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A B C

1 Drug Mech of action (& 2nd Messenger) Uses

2
Repro Drug List
Long acting form of GnRH which down
regulates the GnRH receptors on the
gonadotropin cells (anterior pituitary) -
decrease respond to the normal cyclic
3 GnRH surges and LH (and FSH) will not
be produced. Because of lack of LH,
Leydig cells will not produce testicular and prostate cancer, polycystic ovary dz, as well
testosterone. Suppression of the as endometriosis in women (testosterone is a precursor for
Leuprolide HPGonadal axis estrogen); uterine fibroids, precocious puberty; (BPH?)
Treat BPH, Hirsutism and Other Disorders of Androgen
4
Flutamide Androgen receptor antagonist Excess; tx prostatic carcinoma
Potassium sparing diuretic with
5 Androgen receptor blocking function,
Spironolactone see diuretics Hirsutism and Other Disorders of Androgen Excess
Ornithine decarboxylase inhibitor;
6 mechanism of retarding hair growth is not
Eflornithine cream clear FDA approved for treating hirsutism

5-alpha-reductase type II inhibitor,


7 prevents formation of
dihydrotestosterone from testosterone
(DHT synthesis inhibitor) - physically Useful for treating Benign Prostate Hypertrophy (BPH),
Finasteride reduce size of prostate Alopecia

8 5a-reductase type I & II inhibitor, DHT


synthesis inhibitor - physically reduce Useful for treating Benign Prostate Hypertrophy (BPH),
Dutasteride size of prostate Alopecia

Selective 1A blocker - contracts Benign prostatic hypertrophy, prostate has greater number
Tamsulosin prostate smooth muscle of 1A receptors expressed than other tissues.
A B C

10
Hypertension. See adrengic blockers
Benign prostatic hypertrophy: This use is rapidly being
1-Selective Blockers, see adrenergic supplanted by the 1A selective agents (tamsulosin) which
Terazosin (Hytrin) blockers does not produce orthostatic hypotension

11 Same uses and liabilities as terazosin or prazosin


1-Selective Blockers, see adrenergic Long elimination half-life (24 hr) makes once daily dosing
Doxazosin (Cardura) blockers feasible

12 Estrogen receptor antagonist -


prevents negative feedback to HPO axis,
increases number of follicles to reach
Clomiphene (Clomid) maturity, see extra notes Fertility agent
13 ICI 182,780 (Faslodex): pure anti-estrogen

Parasympathetic (NOT cholinergic!)


stimulation of NO synthetase in the
penis increases NO which increases
14 cGMP which causes vasodialtion of the
corpus cavernosum and spongiosum.
Sildendafil is a phosphodiesterase
inhibitor, which decreases the
Sildenafil (Viagra) breakdown of cGMP Erectile Dysfuntion (4 hr duration)

15
Vardenafil (Levitra) phosphodiesterase inhibitor Erectile Dysfuntion (4 hr duration), faster onset

16

Tadalafil (Cialis) phosphodiesterase inhibitor Erectile Dysfuntion (24-36 hr duration)


Testosterone-enanthate antagonism of prolactin at the mammary suppress lactation before it begins, depot injection given right
17
with estradiol-valerate gland after delivery.

18 Ergot alkaloids: suppresson of lactation


through stimulation of dopamine Treat galactorrhea (by lactation suppression); treat
receptors (D2) and inhibition of prolactin Hypreprolactinemia (especially prolactin secreting
Bromocryptine (Parlodel) secretion adenomas), tx Parkinson's dz
A B C
Treat galactorrhea (by lactation suppression); treat
19 Ergoline derivative: Longer half life Hypreprolactinemia (especially prolactin secreting
Cabergoline (~65 hr) than Bromocriptine adenomas)

Hormonal agent: a Antiestrogen -


20 Chemopreventive agent in women at
high risk for breast Ca; competitive
partial agonist/antagonist of estrogen
Tamoxifen receptors in estrogen-sensitive tumors. Tx estrogen-receptor-positive breast cancer

SERMS (specific estrogen receptor


modulators): Partial agonist-antagonist
21 at estrogen receptors; Estrogen
derivative having estrogen agonist effects
on the bone and limited effects in breast Tx breast cancer (no increased risk of endometrial
and uterus (no stimulatory effect on cancer); Positive effects on bone and lipids (and brain?) - tx
Raloxifene endometrium or breast) osteoporosis, see endocrine section

22

Replacement of estrogen, see extra Menopause: vasomotor flushes, atrophic vaginitis, osteoporsis
Estrogen (HRT - hormonal notes for physiologic effect and (contoversial, and effectiveness gradually decreases),
replacement therapy) preparations coronary artery disease

23
Ethinyl Estradiol
24 Diethylstilbestrol (DES) Non-steroidal estrogen Post coital contraceptive (eg used after rape)
A B C

25

High circulating progesterone & estrogen


mimic luteal or pregnancy hormone
concentrations. These steroids by
"The Pile" (Oral negative feedback suppress the
Contraceptive): preovulatory surge of LH and therefore
Progesterone/estrogen ovulation. Birth control - Contraceptive
Does not prevent ovulation or
fertilization but does prevent
26 implantation either by changing the Birth control - Interfere with implantation; for those women
arrival timing of the blastocyst or by who are at risk for certain estrogen-dependent cancers
"The Mini-Pill": Progestin making uterine conditions (motility or Does not decrease milk production and may be an option for
only secretory) unreceptive. lactating women
silastic tubes implanted subcutaneoulsy,
progesterone is slowly released over an
27 extended period and provides a
pharmacologic effect similar to the mini
Norgestrel (Implant) pill

Progestoren Challenge test!! (see extra notes)


28 Contraceptive; used especially for pt with risk of estrogen
dependent neoplasia;
Amenorrhea (especially in <16yo, as E may interfer with
HPOU axis); oral or IM (depot form), long half-life; good for
women needing estrogen free contraception, (breast feeding,
Medroxyprogesterone sickle cell disease, seizure disorders), and women who cannot
acetate (Depo-provera) Progesterone derivative remember to take the pill (teenagers)
Progesterone derivative (19-nor-
29
Norethindrone testosterone derivatives)

30 Progesterone derivative (19-nor- Used in OCs, (not as androgenic as Norethindrone), treat


Desogestrel testosterone derivatives) hirsutism, see extra notes
Progesterone derivative (19-nor- Used in OCs, (not as androgenic as Norethindrone), treat
31
Norgestimate testosterone derivatives) hirsutism, see extra notes
A B C
Progesterone derivative: (19-nor-
32 testosterone derivatives) 100 times
more potent as a progestin than
Norgestrel norethindrone Used in OCs and implantable contraceptive preparation

Progesterone derivative: very low


33 androgenicity; has even been reported
to have anti-androgenic effects similar in Used in OCs, (not as androgenic as Norethindrone), treat
Drospirenone efficacy to Spironolactone hirsutism, see extra notes; decreased Na and water retention

34
Plan B post coital contraceptive
Levonorgestrel (Plan B) Progesterone derivative Contains high concentration of levonorgestrel (P)

35

Testosterone Androgen
36 Dihydrotestosterone Androgen

37 Androgen; long acting ester of T - Takes


Testosterone Cypionate longer to eliminate
Testosterone androgen: 17-alkyl
38 derivative, this modification increases it
Methyltestosterone elimination time
Androgen; 17-alkyl derivative of Treat anemia caused by deficient RBC (ie Acquired aplastic
39
Oxymetholone testosterone; anabolic; anemia, Myelofibrosis, Hypoplastic anemia)
Progesterone antagonist; also an anti-
40
Mifepristone (or RU486) glucocorticoid t : ~20 hrs Post coital contraceptive
Inhibits the midcycle surge of LH and
41 FSH (feedback regulator, kind of an
estrogen and progesterone
Danazol antagonist) Tx for endometriosis
42 Testolactone aromatase inhibitors
43 Anastrozole aromatase inhibitors
A B C

44
synthetic Prostaglandin F2alpha lifesaving tx. of postpartum hemorrhage due to uterine atony
Hemabate (PGF2alpha) via myometrial contraction

45 potent ripening of cervix & induction of labor; Notice: keeps


Cervidil Prostaglandin E2 (PGE2) ductus arteriosus open
46 indomethacin see NSAIDs Used to close patent ductus arteriosus (PDA)
Preeclampsia (severe) mandates seizure prophylaxis with
47 magnesium sulfate and control of BP with hydralazine or
Magnesium sulfate Ca channel blocker? labetalol

48
hydralazine or labetalol Control BP in pergnancy
49 Pitocin Synthetic oxytocin

50

Protection against HPV types 6, 11, 16 & 18 (reducing


Gardisil chances of developing cervical cancer (squamous))

51 Treatment for non-acute ectopic pregnancy (pts w/ early,


Methotrexate See cancer chemotherapy unruptured ectopics)
Used to maintain patency of ductus arteriosus (ie
52
Alprostadil PGE1 Transposition of the Great Arteries)
53

54
Renal Drug List
55 Diuretics
A B C

Extremely efficacious
1. Emergency & Chronic Tx of edematous states (eg M.I.,
CHF; Pulmonary; Ascites secondary to cirrhosis, Renal failure)
- most efficacious under low Creatinine clearance
conditions; Loop diuretics are used for hypertension with
renal insufficiency; used i.v. for hypertensive emergency
2. Hypercalcemia: causes increased Mg++ and Ca++ loss
(Cause of elevated Ca++ is usually hyperparathyroidism or
malignancy, which must be Tx surgically).
56 Loop diuretics can be used as a temporary measure to reduce
hypercalcemia
3. Hypertension: Use for cases that are not responsive to
thiazides (e.g, HTN in the presence of chronic renal failure)
4. Hyperkalemia: Usually occurs secondary to insufficient
renal excretion, causes loss of resting membrane potential
Sulfonamide; loop diuretic: acting in (cardiac problems). Tx is complex. Loop diuretics are useful
loop of Henle because treating chronic renal failure with a diuretic corrects
Inhibit Na+,K+,2Cl- cotransporter the hyperkalemia (see hypokalemia Side-Effects).
(symporter - transports cations and anion 5. Anion poisoning (eg Fluoride, iodide, bromide); symporter
in the same direction with no counter-ion also reabsorbs these anions, give loop agent with NaCl)
Furosemide (lasix, transport) - transporter used by macula 6. Drug of choice for treating HTN in pts with chronic renal
prototype) densa insufficiency or heart failure.

57 Tx similar as Furosemide, for pts with sulfa allergies or


Ethacrynic acid Loop diuretic, non-sulfa prone to gouty attacks (less hyperuricemia than furosemide)

58
Torsemide Loop diuretic Once daily dosing
59 Bumetanide Loop diuretic

60

1. Prophylaxis of renal failure


Osmotic diuretic: inhibit reabsorption of 2. Decrease the pressure and volume of intraocular fluid &
water and (secondarily) Na+ (More water CSF; tx acute angle-closure glaucoma
Mannitol loss than Na loss) 3. hemodialysis
A B C

1. Seldom used as diuretics (used for metabolic acidosis,


refractoriness)
2. Glaucoma (not a diuretic effect -- they decrease production
of aqueous humor; given topically, do not gain access to
61 systemic circulation in high enough dose to effect kidneys).
3. Alkalinization of the urine: Potential use in poisoning with
aspirin, phenobarbital
4. Epilepsy (mechanism??, Specific to CA inhibition, not a
Carbonic anhydrase inhibitor: Inhibit general effect of diuretics. Tolerance develops quickly.)
formation of H+ and HCO3- from CO2 5. Mountain sickness!!
and H2O (and vice versa); diminished 6. Reduces brain edema!!
Acetazolamide reabsorption of HCO3- and Na+ 7. Pseudotumor cerebri (reduces CSF production)

Purpose: to help eliminate excess volume to treat volume


overload disorders (e.g. edema, CHF)
1. Hypertension (should get a 10-15 mm Hg fall in pressure):
reduce blood volume (volume returns to near normal over 6-
8 weeks, but antihypertensive effect remains); reduce
vascular resistance by relaxation of arterioles (Na+ increases
vessel stiffness, so reducing Na+ relaxes arterioles); reduce
responsiveness of arterioles to NE (also because of lower
62 Na+); DOC isolated systolic HTN
2. Diabetes Insipidus (Vasopressin (ADH) dz): (Generally
controlled with vasopressin replacement), thiazides decrease
urine output by about 50% in these patients, mechanism
unknown
3. Non-emergency edematous states
Thiazide diuretic: Inhibit of Na+,Cl- 4. Hypercalciuria: Volume contraction caused by the thiazide
cotransport (Na/Cl symporter) in distal diuretics stimulates proximal tubule (PT) reabsorption of Ca++
convoluted tubule (DCT); increase urine (?????) So can use to prevent Calcium oxalate stones by
excretion by inhibiting DCT solute and volume contraction (PT will bring more solutes in, including Ca,
Hydrochlorothiazide water reabsorption to decrease Ca in urine, used only profolacticaly until surgery
(HCTZ) corrects)
more potent and has a much longer duraton of action than
63
Chlorothiazide Thiazide diuretic HCTZ
64 Chlorthalidone Thiazide diuretic

65 thiazide-like, indoline derivation


Indapamide

66
Metolazone thiazide-like
A B C

Not very efficacious diuretics by themselves, by this point in


the transit of Na+ in the kidney, there isnt very much left
1. Used to prevent K+ loss, counteract this side-effect of
67 thiazides and loops
2. Drug of choice for primary aldosteronism syndromes
Potassium-sparing diuretic: (rare occurrence)
aldosterone receptor competitive 3. Approved for Class 4 (& 3?) CHF (prevents tissue
Spironolactone antagonist remodeling)

68 Potassium-sparing diuretic:
aldosterone receptor competitive
Eplerenone antagonist see spironalactone

Potassium-sparing diuretic: inhibit


Na+ transport by the epithelial Na
channels (ENaC) in distal tubules (DT)
69 and cortical collecting ducts; because Not very efficacious diuretics by themselves, by this point in
less Na is presented to the Na,K-ATPase the transit of Na+ in the kidney, there isnt very much left
on the apical surface of the CD cells, less 1. DOC for treating primary aldosteronism (in men?)
Amiloride K is excreted 2. DOC for Liddle's syndrome

70 Potassium-sparing diuretic: inhibit


Na+ transport by the ENaC in DT and
Triameterene cortical collecting ducts see amiloride, Liddle's syndrome
71 Other drugs related to HTN

Angiotensin II Receptor (AT1) Blocker


(ARB): This receptor mediates many
angiotensin II effects:
1. Constriction of vascular smooth
72
muscle
2. Release of aldosterone
3. CNS activation of sympathetic
discharge 1. Excellent efficacy as anti-hypertensives
4. Enhanced responsiveness of vascular 2. Blunt the hypokalemia caused by diuretics
Losartan smooth muscle to sympathetic activation 3. uricosuric effect, beneficial for pts with hyperuricemia
(twice daily dosing)
73 1. Excellent efficacy as anti-hypertensives
Angiotensin II Receptor Blockers 2. Blunt the hypokalemia caused by diuretics
Valsartan (ARB) 3. uricosuric effect (for pts with hyperuricemia)
A B C

74

ACE inhibitor: Block conversion of


angiotensin I to angiotensin II by (twice per day)
inhibiting Angiotensin Converting Enzyme Uses of prils in hypertension:
(ACE): decrease angiotensin II-mediated 1. Essential hypertension
release of aldosterone; decrease 2. Efficacious and relatively minimal side-effects
breakdown of bradykinin; decrease 3. High plasma renin
overly active SNS (little reflex 4. Diabetes mellitus (preferred anti-HTN -- dilate efferent
tachycardia), decreasing preload, arterioles, reduces proteinuria)
decreasing afterload which then 5. Renal insufficiency
Captopril [Capoten] decreases BP 6. CHF (preferred anti-HTN decreases mortality)
ACE inhibitor: pro-drug, converted in
75 liver, no SH groups (less allergy than
Enalapril (Vasotec) captopril?) (1-2 per day), same use as captopril
(once daily dosing)
76
Lisinopril (Prinivil, Zestril) ACE inhibitor; not a pro-drug same use as captopril

Calcium Channel Blocker (CCB), a 1. Hypertension (generally preferred for treating hypertension
dyhydropyridine: a member of the over verapamil and diltiazem), efficacious, particularly for
77 dihydropyridines class; decrease Ca++ isolated systolic HTN (esp in diabetics)
influx, resulting in smooth muscle Because of their higher profile of side-effects related to
relaxation; vascular sm selective; therapeutic vasodilation, less preferred than ACE-I or ARBs
Nifedipine Block L-type Ca++ Channels
A B C

78
1. Angina (esp Prinzmetal variant angina)
Calcium Channel Blocker, a 2. Hypertension (Nifedipine is better; Efficacious, particularly
nondyhydropyridine: decrease cardiac for isolated systolic hypertension
contractility and cardiac output, cardiac Because of their higher profile of side-effects related to
myocytes selective (blocks L-type Ca++ therapeutic vasodilation, less preferred than ACE-I or ARBs
Diltiazem Channels)

1. Angina (esp Prinzmetal variant angina)


Calcium Channel Blocker, a 2. Hypertension (Nifedipine is better; Efficacious, particularly
79 nondyhydropyridine: decrease Ca++ for isolated systolic hypertension
influx; decrease cardiac contractility and Because of their higher profile of side-effects related to
cardiac output, cardiac myocytes therapeutic vasodilation, less preferred than ACE-I or ARBs
Verapamil selective, Block L-type Ca++ Channels

80 Used in CHF (produce small increase in myocardial


contracitilty and CO), especially if with concomitant HTN a/o
Amlodipine CCB, dyhydropyridine angina - also no AV block (as with verapimil/ or diltiazem)

81 Used in CHF (produce small increase in myocardial


contracitilty and CO), especially if with concomitant HTN a/o
Felodipine CCB, dyhydropyridine angina - also no AV block (as with verapimil/ or diltiazem)

82 1. (generally replaced by dihydropyridine CCBs)


Hypertension: reduce BP by decreasing systemic vascular
resistance
Must be combined with a beta blocker and a diuretic
Use only with caution in angina or CHF
Arterial Vasodilators: NO formation? 2. Acute severe hypertension in pregnancy
Changes in intracellular Ca++?; open (eclampsia/preeclampsia)!!
vascular ATP-sensitive potassium 3. HF: Typically used with isosorbide dinitrate after a failure of
channels ACEIs (most commonly because ACEIs produced intolerable
Hydralazine cough)
A B C

Arterial Vasodilators: open vascular


ATP-sensitive K channels
(hyperpolarizing): decrease peripheral
83 resistance (PR), causes compensatory
responses (initiated by baroreceptors) of Difficult-to-control HTN in chronic renal failure, must be
increased Sympathetic Nervous System combined with a beta blocker and a diuretic
(SNS) and increased Renin/Angiotensin Use only with caution in angina or CHF
System (RAS); decreases insulin output Used externally for hair growth (alopecia)
Minoxidil (hyperpolarizes beta cells)

Arterial Vasodilators: decrease PR, Hypertension: reduce BP by decreasing systemic vascular


84 causes compensatory responses resistance (Nearly obsolete for hypertensive emergency use)
(initiated by baroreceptors) of increased Must be combined with a beta blocker and a diuretic
Diazoxide SNS and increased RAS Use only with caution in angina or CHF

85 Arteriodilator; D1 agonist (maintains T1/2 = 10 min; Given by i.v. infusion


Fenoldopam renal blood flow) Use in HTN emergencies

86

Uses:
Venoarterial dilator: NO formation by Hypertensive emergencies (see extra note), IV - monitor
increasing cGMP which causes pressure
relaxation; dilates arterioles and veins, CHF (with hydralazine), Short-term therapy in acute HF
Nitroprusside (Sodium) decreasing myocardial oxygen demand Surgery (controlled hypotension)

87

Isosorbide dinitrate see nitroprusside CHF (with hydralazine), Short-term therapy in acute HF
A B C
Nitroglycerin (NTG, see Vasodilator, a nitric oxide (NO) donor,
88
NTG cardio) see cardiac drugs for more detail Angina pectoris (ischaemic heart disease, MI)
89 Labetalol see adrenergics HTN emergencies & drug-induced HTN
90
Na Polystyrene Sulfonate Resin that exchanges Na ions for K in
91
[Kayexalate] large intestine Treat hyperkalemia
92

93 Drugs for UTI


Uncomplicated UTI: Community-acquired, young and females
Complicated UTI: Hospital-acquired infections, older persons, males

94
Structural analogues of p-aminobenzoic
acid (PABA)
Block the incorporation of PABA into folic
acid (dihydrofolic acid) by inhibiting the
Sulfonamide (class) enzyme dihydropteroate synthetase see Co-Trimoxazole
Folate Antagonist - inhibits synthesis of
95 folate; Mechanism of action of
Sulfamethoxazole (SMX) sulfonamide see Co-Trimoxazole

Folate Antagonist - inhibits reduction:


dihydro folate (TH2) to tetrahydro folate
96 (TH4 or FAH4) by blocking dihydrofolate
reductase, FAH4 is a critical precursor of
thymidine, purine, and methionine;
potentiated by Sulfamethoxazole (can
Trimethoprim (TMP) use 1/10 dose) see Co-Trimoxazole
A B C

97
Uncomplicated UTI: E.coli
Complicated UTI: Klebsilla pneumonia & Staphyloccous
saprophyticus & Enterobacter & Acinetobacter
Prostatitis
Acute pyelonephritis.
Used to treat E. coli acute UTI
Cystitis
Combination of TMP and SMX Chronic suppressive therapy for recurrent urinary tract
Co-Trimoxazole (aka Sulfonamide & trimethoprim act infection
TMP/SMX) synergistically Usually oral

Inhibits bacterial topoisomerase II


(DNA gyrase) Active against a variety of gram (+) and gram (-) bacteria
Prevents relaxation of DNA that is Broadspectrum, primarily gram (-)
98 required for transcription and DNA Complicated UTI: multidrug-resistant bacteria
replication (Pseudomonas)
Synthetic fluorinated analogs of nalidixic To treat STDs caused by Gonococcal & Chlamydial infections
Fluroquinolones (aka acid Diarrhea caused by Shigella, Salmonella, E.coli, H. pylori
quinolones, class) Bactericidal Enterobacter, Gonorrhea, Chlamydia (STDs)

99 Prostatitis
Gonorrhea
Ciprofloxacin Fluroquinolone
100 Norfloxacin Fluroquinolone
101 Ofloxzcin Fluroquinolone

Beta-lactam antibiotics
Inhibits bacterial cell wall
peptidoglycan synthesis (cross- DOC for STD caused by Treponema pallidum (syphilis)
linking) Augmentin = Amoxicillin + clavulanate are given orally to treat
102 Inhibits transpeptidase reaction urinary tract infection
Activates autolytic enzyme (autolysin) Not effective against:
Bactericidal agent Klebsiella
Highest activity against G (+), some G Pseudomonas
Penicillin G (-) Indole-positive Proteus
A B C
Uncomplicated UTI by Proteus mirabilis, Enterococcus
103 faecalis
Acute pyelonephritis
Ampicillin a penicillin UTI with pregnancy
104 Amoxicillin a penicillin Greater bioavailability than ampicillin
Ticarcillin, Carbencillin & anit-Pseudomonas penicillins; not Complicated UTI: Pseudomonas (give with penicllin and
105
Azlocillin beta-lactamase resistant clavulanate acid)

Inhibitor of cell wall formaton by inhibiting


106 release of building block carriers
preventing peptoglycan synthesis,
similar to penicillin without beta-lactam Complicated UTI: Enterococcus faecalis (Strep D), S.
Vancomycin (beta-lactamase resistant) aureus (give with aminoglycoside)

Works syndergistically with penicillin/cephalosporin


107 For treatment of UTI caused by gram negative bacteria such
Protein synthesis inhibitor, misreading as Klebsiella, Pseudomonas, Proteus and other gram negative
of mRNA codon message, irreversibly rods
bind 30S, requires O2 dependent Rarely used alone
Aminoglycoside (class) transfer (absent in anaerobes) Used with penicillin or cephalosporin

Used for the treatment of aerobic gram negative bacteria only


Complicated UTI: Enterococcus faecalis & P. aeruginosa
108 (use with ampicillin)
For treatment of UTI caused by gram negative bacteria such
as Klebsiella, Pseudomonas, Proteus and other gram negative
rods
Gentamicin an Aminoglycoside Rarely used alone (Used with penicillin or cephalosporin)

109 For urogenital N. gonorrhea in penicillin allergic patients


Protein synthesis inhibitor - related to to treat gonorrhea caused by beta-lactamase producing
Spectinomycin aminoglycoside, binds 30S ribosome bacteria

110
Beta-lactam antibiotics: Inhibition of
cell wall (peptidoglycan) synthesis (cidal); Complicated UTI: E.coli, Klebsiella pneumoniae (cefazolin),
Cephalosporins (class) does not cross BBB(??) Proteus mirabilis (ceftriaxone)
First line drugs to treat gonorrhea (Neisseria)
111 Complicated UTI: Indole positive Proteus mirabilis,
3rd generation Cephalosporin, good Serratia
Ceftriaxone CNS penetration Acute pyelonephritis; Meningitis; Infectivie Endocarditis
A B C

112
3rd generation Cephalosporin, good First line drugs to treat gonorrhea
Cefixime oral
Used to treat UTI caused by E. coli and Klebsiella in pregnant
patients because co-trimoxazole cannot be used due to risk of
113 kernicterus to the fetus
pneumoniae, Staphylococcus saprophyticus
Uncomplicated UTI: E.coli, Klebsiella pneumoniae!!,
Cefazolin 1st Generation Cephalosporin Staphylococcus saprophyticus!!

114

Protein synthesis inhibitor - Drug of choice (DOC) to treat UTI by Chlamydia


competition with tRNA for A site on 30 S Acute urethral syndrome from Ureaplasma urealyticum and
Tetracyclines (TC, class) subunit of ribosome; Bacteriostatic Chlamydia trachomatis

115

Doxycycline a tetracycline DOC to treat STD caused by Chlamydia Trachomatis


??Used to treat Huntington's Dz (Caspase inhibitor?? with
116
Minocycline a tetracycline neuroprotective effect)??
Protein synthsis inhibitor of aminoacyl Used for Mycoplasma pneumonia, Bordetella pertussis,
117
Macrolide (class) translocation, 50S Legionella
DOC to treat STD caused by Chlamydia Trachomatis, safe
118
Erythromycin a macrolide with pregnancy
Anti-mycoses: inhibits synthesis of
119 ergosterol (fungal cell wall); Blocks
demethylation of lanosterol; Alters cell
Clotrimazole membrane permeability; Fungistatic OTC, Topical azoles; vulvovaginal candidiasis
Anti-mycoses: inhibits synthesis of
120 ergosterol (fungal cell wall); Blocks
demethylation of lanosterol; Alters cell OTC, Topical azoles; Athlete's foot (Tinea pedis), Vaginal
Miconazole membrane permeability; Fungistatic candidiasis

121
Caspofungin Disrupts fungal cell wall sythesis
A B C
enters cell and releases nitro moiety
122 which reacts with DNA and inhibits
Metronidazole duplication of bacteria (bacteriacidal) Trichomonas vaginalis (protozoa) Infection
treat Chronic UTI
123 Daily oral dose (100 mg) for adults in UTI
Nitrofurantoin unknown mech Given for months for chronic UTI

Inhibits viral DNA synthesis; Acyclic


guanosine derivative; competitive
inhibition of dGTP for the viral
polymerase with binding to the DNA
template as an irreversible complex chain
124 termination following incorporation into
viral DNA. Requires three
phosphorylation for activation: it is
converted into monophosphate
derivative by virus specified thymidine
kinase, then to the di- and
triphosphate compounds by hosts DOC for genital herpes (STD); Active against herpes simplex
Acyclovir cellular enzyme virus-1 and -2 (HSV-1 & HSV-2)
125

126
Gastrointestinal Drugs

127

PPIs promote healing of ulcers in the stomach, duodenum,


and esophagus. They are of particular value in patients who
do not respond to H2 receptor antagonists. Especially useful
for treating Zollinger-Ellison syndrome (gastrin producing
Omeprazole (PRILOSECProton Pump Inhibitors (PPIs): tumors). Used in triple therapy for Helicobacter pylori in
OTC) Blockade of Gastric Acid Production Peptic Ulcer Disease and Chronic Gastritis
Proton Pump Inhibitors (PPIs):
128
Esomeprazole (NEXIUM) Blockade of Gastric Acid Production see Omeprazole
A B C
Lansoprazole Proton Pump Inhibitors (PPIs):
129
(PREVACID) Blockade of Gastric Acid Production see Omeprazole
Proton Pump Inhibitors (PPIs):
130
Rabeprazole (ACIPHEX) Blockade of Gastric Acid Production see Omeprazole
Pantoprazole Proton Pump Inhibitors (PPIs):
131
(PROTONIX) Blockade of Gastric Acid Production see Omeprazole

132

H2 antagonists are used for treating duodenal and gastric


ulcers, gastroesophageal reflux disease, stress ulcers,
and hypersecretory states. They also are used as a
H2 Histamine Receptor Antagonists: preanesthetic medication for some surgical procedures to
Cimetidine (TAGAMET) Blockade of Gastric Acid Production reduce the danger of aspiration pneumonitis.
H2 Histamine Receptor Antagonists:
133
Ranitidine (ZANTAC) Blockade of Gastric Acid Production See Cimetidine
H2 Histamine Receptor Antagonists:
134
Famotidine (PEPCID) Blockade of Gastric Acid Production See Cimetidine
H2 Histamine Receptor Antagonists:
135
Nizatidine (AXID) Blockade of Gastric Acid Production See Cimetidine

136

Neutralization of Gastric Acid: use for (1) Simple dyspepsia


Weak bases that react with gastric and (2) as adjuncts to primary therapy with H2 blockers
hydrochloric acid to form a salt and and proton pump inhibitors in duodenal ulcer disease or
water, neutralizing the acid, and raising (3) GERD. Antacid therapy alone (4-8 weeks) is effective for
Antacids the pH of the gastric contents. promoting healing of duodenal ulcers, but not gastric ulcers.
A B C

Neutralization of Gastric Acid; During anesthesia, coma,


137 cesarean section, or endoscopy, aspiration of gastric contents
can cause aspiration pneumonitis - sodium citrate (Bicitra, a
clear liquid antacid) is used prophylactically to neutralize
Sodium citrate (BICITRA) Antacid gastric contents in these situations.

Mucosal Protective Agent


(Cytoprotective Agent): Enhances
secretion of mucus and HCO3- and Effective for treatment and prophylaxis of duodenal and
138 inhibits pepsin activity. Chelates with gastric ulcers, GERD, and diarrhea, especially travelers
proteins in the base of ulcers and may diarrhea. May have an antibacterial action against H. pylori.
form a protective barrier against acid Bismuth subsalicylate is effective in mild-to-moderate
Bismuth subsalicylate diffusion and peptic digestion. Bismuth travelers (infectious) diarrhea. It absorbs bacterial toxins
(Pepto-Bismol) binds and inactivates enterotoxins. and has local anti-inflammatory properties.
139 Bismuth citrate Mucosal Protective Agents See Bismuth subsalicylate

Mucosal Protective Agent: a complex of


sucrose octa sulfate and aluminum
hydroxide that at acid pH polymerizes
140 into a sticky, viscous gel that adheres Sucralfate (1 g, one hour before each meal and at bedtime)
to gastric epithelial cells and the base promotes healing of duodenal and gastric ulcers. It is
of ulcers. This gel layer protects against approved for maintenance therapy of duodenal ulcers. It
acid, pepsin, and bile acid access to should not be administered within 30 min of antacids (it
Sucralfate (CARAFATE) tissue. requires an acidic environment for acitivation).
Mucosal Protective Agents:
Prostaglandin analog - Prostaglandin Misoprostol is a slowly metabolized analog of PGE1 approved
141 E2 and I2, synthesized by the gastric as a second-line agent for treating peptic ulcer. Its primary
mucosa, inhibit the secretion of acid and effect is to inhibit gastric acid production. It is useful for
stimulate the secretion of bicarbonate preventing gastric ulcer disease in patients who require
Misoprostol (CYTOTEC) and mucus. NSAIDs, e.g., for arthritis.
Antagonists of muscarinic cholinergic receptors can decrease
GI motility and can modestly inhibit gastric acid secretion.
142 However, large doses of these drugs are required to achieve
these effects leading to significant side effects. H2 blockers
and PPIs are more efficacious acid secretion inhibitors and
Muscarinic Antagonists see Anticholinergics have far fewer side effects.
A B C

Dopamine Antagonists; Prokinetic (Pro-


motility) Agents - a D2 dopamine
receptor antagonist, also 5-HT4
agonist & 5-HT3 antagonist that Used prior to meals and at bedtime to control nausea and
143
enhances the motility of the smooth vomiting in diabetic gastroparesis, esophageal reflux, and
muscle from the esophagus through the pregnancy. Metoclopramide is used during cancer
proximal small bowel and accelerates chemotherapy as an antiemetic in combination with other
gastric emptying and transit in the drugs. Metaclopramide is the drug of choice for treating
Metoclopramide!! duodenum. Also a cholinesterase diabetic gastroparesis (peripheral andeopathy). Used for
(REGLAN) inhibitor Migraine HA
Dopamine Antagonists; Prokinetic (Pro-
144 Trimethobenzamide motility) Agents - D2 dopamine/5-HT3
(TIGAN) antagonist modest antiemetic. Less effective than metoclopramide.

145
Dopamine Antagonists; Prokinetic (Pro- Parkinson's dz (counteracting the GI effects of levodopa and
Domperidone motility) Agents - D2 antagonist which bromocriptine); for nausea and vomiting associated with
(MOTILIUM) does not penetrate CNS well gastric stasis

D2 Dopamine Receptor Antagonists -


146 Phenothiazines - block D2-like
Chlorpromazine dopamine receptors in the CTZ and
(Thorazine) solitary tract nucleus, see antipsychotics Antiemetic

147

Prochlorperazine D2 Dopamine Receptor Antagonists -


(Compazine) Phenothiazines, see antipsychotics potent antiemetics
Thiethylperazine D2 Dopamine Receptor Antagonists -
148
(Torecan) Phenothiazines, see antipsychotics potent antiemetics
a dutyrophenone, D2 Dopamine
149
Droperidol Receptor Antagonist
A B C

150
Macrolide Antibiotics; Prokinetic (Pro-
motility) Agents - macrolide antibiotic
that binds to motilin receptors -
erythromycin increases the frequency
Erythromycin (many and amplitude of antral contractions and Intravenous erythromycin may be useful short-term for an
brands) initiates gastric phase III contractions. acute exacerbation of diabetic gastroparesis.

Opioid agonist act at and receptors


in the GI tract to decrease normal
peristaltic motion, increased renal
151 sphincter tone, reduce secretory activity,
and enhance NaCl and water absorption.
Opioids slow transit time allowing
more time for absorption. The net
effect of increased absorption and
decreased secretion in the small Diarrhea; Opioids are effective against moderate-to-severe
intestine is to decrease the fluid and diarrhea but should not be used for patients with ulcerative
electrolyte load delivered to the colon. colitis, or acute bacillary or amoebic dysentery. Used for
Loperamide (IMODIUM) See opioids symptoms of travelers diarrhea

152
Diphenoxylate (LOMOTIL) Opioid agonist Diarrhea; use for Irritable Bowel Syndrome (IBS)

153
Difenoxin (MOTOFEN) Opioid agonist Diarrhea
Paregoric (generic,
154 camphorated opium Opioid agonist - antidiarrheal,
tincture, morphine) antitussive, and analgesic properties Diarrhea

Diarrhea; peptide must be given parenterally (SQ);


155 symptoms of tumors of the GI tract (carcinoid, VIPoma,
glucagonoma, gastrinoma, insulinoma), AIDS-related diarrhea,
Octreotide acetate and various motility disorders; variceal bleeding! and
(SANDOSTATIN) Somatostatin Analog orthostatic hypotension.
A B C

Indications for laxative treatment:


156 a) Fecal Impaction - treat immediately.
b) Acute constipation as a result of acute illness, surgery,
perianal disease, severe abdominal or perineal muscle
weakness, drug therapy, irritable bowel syndrome,
uncomplicated diverticular disease, neurological deficits,
severe debilitation, and immobility.
c) Chronic constipation if not relieved after 2-4 weeks of
Dietary fiber bind water and ions, soften nonpharmacological treatment, i.e., dietary fiber.
stools, increase stool bulk, and promote d) Bowel preparation in patients who are to undergo
Bulk-forming Agents colonic bacteria. colonoscopy, barium enema, or colorectal surgery.

Promote accumulation of water and


electrolytes in the colonic lumen and
stimulate motility. Mechanisms include
157 inhibition of Na+, K+-ATPase, increased
permeability of mucosa, increased
leakage at tight junctions, and a possible
increase in synthesis of prostaglandins
Stimulant laxatives and cyclic AMP. increase duky, generally avoided (see bulk-forming agents)

158

Saline laxatives are useful for emptying the bowel prior to


surgical, radiological, and colonoscopic procedures and are a
Act via their osmotic pressure to retain useful adjunct in the elimination of intestinal parasites. May
Saline Laxatives water in the colon also be useful in cathartic doses to treat poisoning.
A B C

Lactulose - Used to lower blood ammonia levels in patients


159
with portal hypertension and hepatic encephalopathy.
Glycerin - rectal suppository softens and lubricates the
Osmotic laxatives are not absorbed and passage of hard stool.
are resistant to digestion, increase Polyethylene glycol-electrolyte solutions (Colyte,
osmotic pressure in lumen and water GoLYTELY) are the drug of choice for bowel preparation for
Osmotic laxatives content of stools. colonoscopy, barium enema, or colorectal surgery.

160

Surfactant Laxatives Stool Softeners

161 NK1 antagonist - Neurokinin A and B act


on Nk1 and Nk2 receptors in the CNS,
Aprepitant and are closely related to substance P Chemotherapy-induced n/v

5-HT3 receptor antagonists are


selective serotonin inhibitors,
162 competitively inhibit the binding of
serotonin to 5-HT3 receptors. Their
antiemetic effects are postulated to stem
from blockade of 5-HT3 receptors
located on the nerve terminals of the
vagus in the periphery and centrally in Antiemetic; Used primarily for cancer chemotherapy and
the chemoreceptor trigger zone of the irradiation-induced nausea and vomiting (N&V), but also some
Ondansetron (ZOFRAN) area postrema. post-operative nausea and vomiting (PONV).
163 Granisetron (KYTRIL) 5-HT3 Antagonists See Ondansetron
164 Dolasetron (ANZEMET) 5-HT3 Antagonists See Ondansetron
165 Alostetron 5-HT3 Antagonists for diarrhea-predominant IBS
A B C

166 use in treating postoperative emesis; prophylactic treatment


Dimenhydrinate Antihistamines - Histamine H1-receptor of motion sickness occurring during mild to moderate travel,
(DRAMAMINE) antagonists , see antihistamines especially if sedation is desired.
Diphenhydramine!! Antihistamines - Histamine H1-receptor
167
(BENADRYL) antagonists motion sickness and vertigo
Antihistamines - Histamine H1-receptor
168
Hydroxyzine (VISTARIL) antagonists motion sickness and vertigo
Antihistamines - Histamine H1-receptor
169
Meclizine (ANTIVERT) antagonists motion sickness and vertigo; given once daily

popular medication for control of inpatient nausea and


170 vomiting; prophylactic treatment of motion sickness occurring
Promethazine! Antihistamines - Histamine H1-receptor during mild to moderate travel, especially if sedation is
(PHENERGAN) antagonists desired.

171 Prototypical muscarinic cholinergic prevention of motion sickness (for rough seas and extended
Scopolamine receptor antagonist, see journeys, transdermal patch is more convenient; less sedation
(TRANSDERM-SCOP) antimuscarinics than dimenhydrinate or promethazine)

172 Cannabinoids - 9- reduce emesis due to moderately emetogenic chemotherapy.


Tetrahydrocannabinol, an active It can also stimulate the appetite and has been used in
Dronabinol (MARINOL) constituent of marijuana, see No, No's patients with AIDS and anorexia.

173 Corticosteroid - suppressing peritumoral


inflammation and prostaglandin Useful adjunct in the treatment of nausea in patients with
Dexamethasone production, see corticosteroids widespread cancer/chemotherapy
Useful adjunct in the treatment of nausea in patients with
174
Methylprednisolone Corticosteroid widespread cancer/chemotherapy
The sedative, anxiolytic, and amnesic properties of these
drugs are useful to reduce the anxiety that may lead to
175 anticipatory emesis that can accompany chemotherapy.
Used alone these drugs have very weak antiemetic properties.
Lorazepam (Ativan) Benzodiazepine, see anxiolytics Also, tx of vertigo
176 Alprazolam (Xanax) Benzodiazepine, see anxiolytics see Lorazepam

Irritable Bowel Syndrome; short-term treatment of


177 constipation-predominant IBS in women; effective in treating
abdominal pain, altered bowel habit (decreased stool
Prokinetic Agent - selective serotonin frequency, hardened stool consistency, straining) and bloating
Tegaserod (ZELNORM) (5HT4) partial agonist associated with constipation-predominant IBS
A B C

178

Alosetron (LOTRONEX) 5HT3 Antagonist Irritable Bowel Syndrome with diarrhea (second line)

179

TCA antidepressant - slow gut transit


time and also may alter visceral afferent Irritable Bowel Syndrome - slow gut transit time and also
Imipramine neural function, see antidepressants may alter visceral afferent neural function
Irritable Bowel Syndrome - slow gut transit time and also
180
Desipramine Antidepressants may alter visceral afferent neural function
181 SSRIs (e.g., fluoxetine) Antidepressants

182

5-ASA Compound; Anti-inflammatory


Drug - affect multiple sites in the
arachidonic acid pathway critical in the
pathogenesis of inflammation, including
inhibition of the cyclooxygenase
Mesalamine pathway and leukotriene formation. Inflammatory Bowel Disease (UC and CD)

183
5-ASA Compound; Anti-inflammatory Inflammatory Bowel Disease, especially Ulcerative cholitis;
Sulfasalazine (Azulfidine) Drug treatment of Rheumatoid arthritis

184
Olsalazine 5-ASA dimer; Anti-inflammatory Drug Inflammatory Bowel Disease (UC and CD)
A B C

185

Anti-tumor Necrosis Factor Antibody


(anti-TNF Ab) - a chimeric mouse-human antibody against TNF that is extremely effective in Crohns
Infliximab [Remicade] monoclonal antibody Disease (CD); used especially to treat CD fistula
Anti-TNF- - decreases the
186 immunoreactivity relative to infliximab by
using an) entirely human monoclonal Ab
Adalimumab to TNF- (see) Rheumatoid Arthritis
187 Clindamycin Antibiotic Colitis
188 Amoxicillin-Ampicillin Antibiotic Colitis, Antibiotic Treatment of H. pylori
189 Cephalosporins Antibiotic Colitis
190 Vancomycin Antibiotic Colitis
191 Metronidazole Antibiotic Colitis, Treat C. difficile
192 Bacitracin Antibiotic Colitis
193 Clarithromycin (BIAXIN) Antibiotic Antibiotic Treatment of H. pylori:
Tetracycline
194
(ACHROMYCIN) Antibiotic
Gastrin receptor blocker (on parietal
195
Proglumide cells)
196 Kaolin (OTC) Adsorbent Discourage use in children for diarrhea
197

198
Liver Drugs
A B C

Potent cytokines that possess antiviral,


immunomodulating, and antiproliferative
actions, activate JAK-STAT tyrosine
199
kinase signal transduction pathway,
leads to the nuclear translocation of a
cellular protein complex that binds to
genes containing an interferon-specific
response element, which synthesis of
over two dozen proteins (causing
inhibition of viral penetration or
uncoating, synthesis of mRNA, Tx Hepatitis (see details below for specific dzs)
translation of viral proteins, and/or viral Tx condyloma acuminatum (papillomavirus)
Interferon- assembly or release)

Synthetic guanosine nucleoside 1. Respiratory syncytial virus (RSV) in infants and young
200 analog children
Active against broad spectrum of RNA & Aerosol, oral, IV
DNA viruses 2. Treat Lassa Fever
Ribavirin Inhibits viral mRNA syntheis 3. Give with INF alpah 2b to treat HCV
201 Interferon -2b See Interferon- Treatment of Hepatitis B

202 Interferon -2a combined


with oral ribavirin See Interferon- Treatment of Hepatitis C

203
Interferon -2b combined
with oral ribavirin See Interferon- Treatment of Hepatitis C
Interferon alfacon-1
204 combined with oral
ribavirin See Interferon- Treatment of Hepatitis C

205 Pegylated interferon -2b


combined with oral
ribavirin See Interferon- Treatment of Hepatitis C (DOC!!)
A B C

206

inhibits reverse transcriptase activity of Treatment of Hepatitis B (long term therapy relative to
Lamivudine both HIV and HBV interferon alfa)

207
phosphonate nucleoside analog,
Adefovir Dipivoxil administered as the oral prodrug, Treatment of Hepatitis B (including variants resistant to
(Hepsera) inhibits replication of HBV lamivudine)

208

Non-NSAID antipyretic/analgesic, a See NSAIDs; Causes liver toxicity (drug-induced


non-narcotic analgesic; hepatitis): severe centrilobular hepatic necrosis when
Very weak anti-inflammartory activity ingested in large amounts in suicide attempts or accidentally
Acetaminophen (Tylenol) (not used for inflammation) by children.
Ursodiol (ursodexoxycholic acid) -
209 primary bile acid that acts by reducing
Ursodiol cholesterol secretion into bile Dissolve gallstones; tx primary biliary cirrhosis
210

211
Cardio drugs
A B C

1. A positive inotrope increase the contractility without


significant increases in HR such that myocardial energy
demands are not significantly increased;
2. Pulmonary Edema: Reduced, due to enhanced stroke
volume, thereby reducing the volume in the heart and volume
backing up into the pulmonary circuit.
3. Cardiac work: Net is uncertain? Increased contractility
increases work, decreased preload decreases work, and
depending on the HR response there will be an increase or
decrease associated with the HR effect. The reason dig is
212 given is because of the tendency to decrease or not change
HR. Most inotropic drugs also increase HR.
Cardiac glycoside: Inhibits cell 4. Cardiac dilation: See pulmonary edema above.
membrane Na/K-ATPase; Relatively 5. Cardiac compliance: Since the end-diastolic volume is
selective for cardiac enzyme; Binds reduced, you will typically move to a portion of the compliance
preferentially to and stabilizes the curve for cardiac diastole which increases compliance.this is
phosphorylated form of the enzyme; GOOD.
Inhibition of the Na/K-ATPase leads to 6. Sympathetic Activity: Enhanced output tends to improve
enhanced Ca++ inside the cell - leads to BP which in turn tends to lead to a reflex-mediated reduction in
more Ca++ stored in sarcoplasmic SNA.
reticulum; Each action potential leads to 7. SVR: If SNA is reduced, SVR will be reduced.
more release of Ca++ from SR, which 8. Ejection Fraction: Increased due to augmented
Digoxin (Digitalis) leads to enhanced contractility contractility

213
Digitoxin (Digitalis) see digoxin see digoxin

Increase pump output


1. Vasodilate: Decrease preload
2. Vasodilate: Decrease afterload, but
selectively constrict efferent arterioles
in the glomerulus (filtration pressure is
214 increased)
3. Decrease Na reabsorption in the
kidney (diuretic)
4. Decrease aldosterone
5. Decrease endothelin Treatment strategies for Acute Decompensated HF (see
6. Decrease NE extra note) - guard against renal insufficiency
Nesiritide (B-Natriuretic Vasodilating without activating either Notice: nesiritide is a peptide so cannot be given orally (give
Peptide) angiotensin or sympathetics IV)
A B C

Relax vascular smooth muscle; Mainly


215 relaxation of large veins which decreases Acute angina
venous return which decreases preload Prinzmetals Angina
which decreases O2 demand of the Congestive Heart Failure (increase Cardiac output)
heart (major effect); smaller decrease After MI
afterload; increase in oxygen supply decrease work of heart (reduces preload)
(transient), effective in prevention of decrease platelet aggregation
Nitroglycerin (NTG) coronary vasospasm (Nitric Oxide, NO) Raynauds disease
slower, less potent than NTG, short and
216
Isosorbide dinitrate long-acting preparations Angina prophylaxis
Beta-Blockers (see
217
adrenergic blockers)

Phosphodiesterase inhibitors:
Inhibition of cAMP phosphosdiesterase Inotropic used in CHF
(PDE)- Increases cAMP: In heart Vasodilatory
218 (increase cardiac output) & in vasculature For short-term therapy
(decrease systemic vascular resistance) Parenteral use
& decrease pulmonary capillary wedge Acute heart failure
Imamrinone (aka pressure Available only in IV formulations
amrinone) Net result: improved hemodynamics Requires a large initial dose for positive inotropic effect

219 Short-term therapy - PDE inhibitor of choice for short-term tx


of acute heart failure
Milrinone Phosphodiesterase inhibitors Parenteral administration
220

221
Antiarrhythmics
no longer used for rhythm control, modestly effective, very
toxic
222 Moderate Na channel Blocker which supraventricular and ventricular arrhythmias like atrial
also blocks K channelsprolongs fibrillation & atrial flutter (moderately effective), ventricular
QRS&QTaction potential; reduce extrasystoles and VT(poorly effective)
Quinidine (Antiarrhythmic automaticity and conduction velocity Major clinical use: atrial fibrillation, atrial flutter, &
Class IA) (Phase 0 and phase 3) ventricular tachcycardia
A B C

Na channel blocker; Prolongs APD


and refractoriness (K channel effect);
slows conduction and decreases
automaticity and excitability of the
223 myocardium and Purkinje fibers. N- Used for Supraventricular and ventricular arrhythmias;
acetyl-procainamide (procainamide acute re-entrant supraventricluar tachycardia and atrial fib and
metabolite) prolongs APD and flutter associated with Wolff-Parkinson-White syndrome
Procainamide refractoriness in atrial and venticular (see extra notes)
(Antiarrhythmic mixed myocardium and prolongs the QT Major clinical use: atrial fibrillation, atrial flutter, &
Class IA & III) interval. (Phase 0 and phase 3) ventricular tachcycardia

moderate Na channel blocker: Increase Broad range of supraventricular and ventricular


224 venticular refractoriness and prolong the arrhythmias (similar to procainamide and quinidine)
QT inverval (reduces automaticity and Moderately effective for atrial arrhythmia and poorly effective
conduction velocity - phase 0), also for ventricular arrhythmia
Disopyramide increases AP duration. (Phase 0 and Major clinical use: atrial fibrillation, atrial flutter, &
(Antiarrhythmic Class IA) phase 3) ventricular tachcycardia

225 modest Na channel blockers (both acute rapid suppression of V arrhythmias, raises
active and inactive Na channels) ventricular fibrillation threshold as well as suppresses
Reduce automaticity arrhythmias caused by abnormal automaticity (observed pt
Lidocaine (Antiarrhythmic Shorten APD (narrow QRS) continuoulsy for SE), no atria effect; very effective membrane
Class IB) Slow conduction velocity stabilizer (numbing)

modest Na channel blockers (both


226 active and inactive Na channels) ventricular arrhythmias & refractory arrhythmias; useful in
Reduce automaticity pts with torsades de pointes (TdP) or long QT syndrome (if
Mexiletine (Antiarrhythmic Shorten APD (narrow QRS) other drugs contra), no effect in atrium; very effective
Class IB) Slow conduction velocity membrane stabilizer (numbing)
modest Na channel blockers (both
active and inactive Na channels)
227 Reduce automaticity
Tocainamide Shorten APD (narrow QRS)
(Antiarrhythmic Class IB) Slow conduction velocity similar to lidocaine
Effective for Atypical Ventricular Tachycardia;
228 Phenytoin [Dilantin] more typically used for seizures (also a membrane stabilizer,
(Antiarrhythmic Class IB ) Na channel blocker arrthymia in brain)
A B C

highly effective Na channel blocker;


229 Prolongs PR and QRS (prolongs AP), Potent inhibitor of ventricular arrhythmia; effective
Flecainide (Antiarrhythmic reduces automaticity and conduction stabilization of atrial rhythm; supraventricular arrhythmias in
Class IC) velocity in A and V; negative inotrope pt with no structural heart dz

highly effective Na channel blocker;


230 Prolongs PR and QRS (prolongs AP),
Encainide (Antiarrhythmic reduces automaticity and conduction Potent inhibitor of ventricular arrhythmia; effective
Class IC) velocity in A and V; negative inotrope stabilization of atrial rhythm;

highly effective Na channel blocker;


Prolongs PR and QRS (prolongs action
231 potential), reduces automaticity and (similar to Flecainide) many arrhythmias, supraventricular
conduction velocity in atria and arrhythmias like atrial fibrillation in pt w/o structural heart dz;
Propafenone ventricles; negative inotrope; structurally potent inhibitor of ventricular arrhythmia; effective
(Antiarrhythmic Class IC) similar to propanolol so= blocker stabilization of atrial rhythm

232 Dofetilide (Antiarrhythmic


mixed Class IC & III) similar to Flecainide similar to Flecainide

See adrenergics; indirect effect via


reduction of sympathetic receptor activity
Blockers and membrane stabilizing activity; mild
233 (Antiarrhythmics class II): effect on automaticity and conduction ventricular tachycardia, supraventricular arrhythmias, also
Propranolol, Timolol velocity; greatest effect is to slow AV AV node re-entry, atrial fibrillation, and atrial flutter; congenital
(nonselective); Metoprolol node conduction, also decrease SA long QT syndrome; prevents recurrent episodes of
& Atenolol node automaticity and increase AV node ventricular tachycardia and reduces symptoms of
(cardioselective) refractory period palpitations and sudden death in pt w/ prior MI

234 & K & Na & Ca channel blocker;


prolongs QT interval and cardiac
Sotolol (Antiarrhythmic refractoriness;slows sinus rate and all types of arrhythmias ie supravent and vent arrhythmias,
Class III) negative inotrope (slows repolarization) cannot be used in patients with heart failure
A B C

235

Amiodarone & K & Na & Ca channel blocker; ONLY used for life-threatening (refractory) Ventricular
(Antiarrhythmic Class III; prolongs PR and QT; slows sinus rate arrhythmias or Atrial fibrillation unresponsive to other
has class I, II, III, and IV (slows repolarization); prolongs AP in antiarrhythmatics (AV nodal re-rentrant tach and Wolff-
activity) fast-response AP Parkinson-White syndrome and sudden death post MI or HF)

236
Ibutilide (Antiarrhythmic K channel blocker; prolongs PR and QT
class III) (slows repolarization) atrial fibrillation or flutter

237
Dofetilide (Antiarrhythmic atrial flutter and atrial fibrillation; maintenance of sinus
class III) K channel blocker; prolongs QT rhythm after reversion
Dihydropyridine group
(nifedipine, amlodipine,
238 nitrendipine, isradipine, Ca channel blockers (CCB), SM
nisoldipine -- selective; see renal CCB; slow
Antiarrhythmic class IVs) conduction velocity, phase 0 of node small effect on AV conduction and arrhythmia
Ca channel blocker; slows AV node
239 Diltiazem (non- conduction (moderately), myocardial
dihydropyridine selective; slows conduction velocity, slows vent rate with atrial fibrillation or flutter and
antiarrhythmic class IV) phase 0 of node prevents AV nodal re-entrant tach

CCB: Most potent to AV node


conduction (also SA node); negative
240 inotrope; myocardial selective; slows Indicated for atrial fibrillatoin and atrial flutter; V response
Verapamil (non- conduction velocity (phase 0) and in SVT and slows V rate w/ A fib or flutter and prevents AV
dihydropyridine increase refractoriness in tissues with nodal re-entrant tach; HTN and peripheral vasospasm
antiarrhythmic class IV) slow-response AP disorders

slows AV node conduction (Vagotonic


action), and depress SA node;
241 conduction velocity and slows V
response to SVT; force of heart
contraction via inhibition of the Na+/K+
Digoxin (digitalis) see also ATPase pump less Na to trade for Ca Atrial fibrillation & atrial flutter; and CHF not be controlled
above - cardiac glycosides to exit cell by other med (not antiarrhythmic)
A B C

242 DOC for acute Paroxysmal SVT caused by re-entry thru AV


Adenosine (antiarrhythmic Slows AV node conduction - causes node;
class V) transient heart block in the AV node diagnostic tool (see extra notes)

Prolongs APD and refractoriness (K


channel effect); slows conduction and
decreasses automaticity and excitability
of atrial and ventricular myocardium and
243 Purkinje fibers. N-acetyl-procainamide
(aka NAPA, procainamide metabolite)
prolongs APD and refractoriness in atrial
and venticular myocardium and polongs Used for Supraventricular and ventricular arrhythmias
the QT interval (Reduce automaticity (similar to quinidine, used if quinidine not effective); acute re-
Procainamide and conduction velocity effects phase entrant supraventricluar tachycardia and atrial fib and
(Antiarrhythmic Class III) 4 and 0) flutter associated with Wolff-Parkinson-White syndrome
244
245 Anticoagulants:

Rapid parenteral anticoagulation (and in vitro


anticoagulation), Heparin is the drug of choice for
parenteral anticoagulant therapy (Usually loading dose
246 followed by continuous infusion)
1. DVT & PE: treatment and prophylaxis.
2. Extra corporeal circulation (hemodialysis and heart-lung
machine); due to in vitro effects
3. Prophylaxis of postoperative and recumbency thrombosis
4. MI and unstable angina - Lessen incidence of secondary
Anticoagulant: Binds with antithrombin peripheral venous thrombosis and PE.
III to inactivates clotting factors IIa, Xa, 5. Disseminated intravascular coagulation (DIC)
IXa, XIa, XIIa, Kallikrein (notice inhibited 6. temporary ischemic attack (TIA) - probably effective, but
(Unfractionated) Heparin active factors) very risky - not used if stoke-in-progress
(UFH) Intrinsic and Common pathways Never given orally or IM
Anticoagulant: Binds antithrombin III,
247 inhibits Xa (greater ratio of anti-factor Xa Prophylaxis of DVT and PE; Used (SQ injection) for
Low molecular weight to antithrombin (IIa) activity and less prophylaxis of DVT associated with hip, knee, and abdominal
Heparins (LMWH) anti-platelet activity) surgery; non ST elevated acute coronary syndrome
248 Enoxaparin LMWH See LMWH
A B C

Slow, sustained, oral anticoagulation (Oral only)


1. General: Usually anticoagulant therapy is started with
heparin and followed with warfarin for long term therapy.
2. Deep venous thrombosis and pulmonary embolism
249 3. Atrial fibrillation (valvular heart disease, CHF, mitral
stenosis, cardiomyopathy)
Anticoagulant: Inhibits vitamin K 4. Myocardial infarction (prevent mural thrombosis and
dependent modification of clotting systemic embolism).
factors prothrombin II, VII, IX, X, protein 5. Rheumatic heart disease (emboli frequently associated with
C and S (notice factors inhibited are not this disorder).
activated); Extrinsic and Common 6. Mechanical prosthetic valves, bioprosthetic mitral
Warfarin (Coumadin) pathways valves.
Antiplatelet drug: Inhibits platelet
250 formation of Thromboxane A2 (TXA2,
Aspirin platelet aggregation) (see NSAIDs) Prophylaxis and treatment of MI and stroke (see NSAIDs)

Prophylaxis of stroke, MI, PAD, and acute coronary


syndrome;
251 Alternate to, or additive with, aspirin for angina (Reduces
platelet aggregation, NO EFFECT ON PROSTAGLANDINS
Antiplatelet drug: Blocks platelet preferred over aspirin if loop diuretic is being used or if
aggregation by irreversibly blocking kidney disease is present)
Clopidogrel ADP receptors Particularly useful in unstable angina

252 2nd prevention of stroke; pts with prosthetic heart values


and as an alternative to aspirin for secondary prevention of
Antiplatelet drug: Blocks platelet acute myocardial infarction, to prevent stroke in patients with
aggregation, inhibits adenosine uptake transient ischemic attacks, and to maintain potency of
Dipyridamole and cAMP phosphodiesterase inhibitor coronary bypass grafts

253 Prevention of thrombotic stroke in patients who have


Antiplatelet drug: inhibits fibrinogen experienced TIAs
binding to platelets and blocks platelet Prophylaxis of recurrent stroke, prophylaxis of thrombosis
aggregation and clot retraction (blocks during stent placement
Ticlopidine ADP receptor). Adverse side effects limit use!
A B C

254 Antiplatelet drug: inhibits cyclic AMP


phosphodiesterase III (increasing
cAMP), blocking platelet aggregation,
Cilostazol causes vasodilation Intermittent claudication, peripheral arterial disease

Acute coronary syndromes; percutaneous coronary


255 Antiplatelet drug: Monoclonal angioplasty; Greater antithrombotic activity than aspirin or
antibody to glycoprotein IIb/IIIa complex, heparin
prevents fibrinogen, thus inhibiting approved for treatment of unstable angina when
platelet aggregation (see extra note for angioplasty or atherectomy planned within 24 hrs.
Abciximab Glanzmann thrombasthenia)

256 Antiplatelet drug: Blocks fibrinogen


binding to IIb/IIIa complex; small peptide Acute coronary syndromes; percutaneous coronary
Eptifibatide analogs of critical domains of fibrinogen angioplasty

257 Antiplatelet drug: Blocks fibrinogen


binding to IIb/IIIa complex; small peptide Acute coronary syndromes; percutaneous coronary
Tirofiban analogs of critical domains of fibrinogen angioplasty

Hemorrheologic Agent = improves


258 blood flow; mechanism is unclear, but
appears to enhance RBC flexibility, intermittent claudication, chronic occlusive arterial disease of
decreases blood viscosity; may decrease the limbs
Pentoxifylline TXA 2 levels and increase PGI2 levels

259 Direct thrombin inhibitor: direct binding


Hirudin to thrombin PE and DVT; alternative to heparin therapy (eg due to HIT)
Direct thrombin inhibitor: direct binding
260
Ximelagatran to thrombin; oral Oral, presently being studied

261
Direct thrombin inhibitor: direct binding Tx of heparin-induced thrombocytopenia (HIT) see extra
Lepirudin to thrombin note
A B C

262

Direct thrombin inhibitor: Direct Percutaneous coronary angioplasty


binding to thrombin, inhibition of platelet Unstable angina
Bivalirudin activation Pt's with HIT

263 Direct thrombin inhibitor: Direct


binding to thrombin (does not require
antithrombin III for antithrombotic activity
Argatroban and is highly selective for thrombin) Tx of HIT; coronary angioplasty in patients with HIT

264

Thrombolytic: Activator of plasminogen, 1. Acute myocardial infarction


Alteplase (rt-PA) dissolve formed fibrin clots 2. Nonhemorrhagic Stroke (make sure pt is not bleeding!!)

265
Thrombolytic: Activator of plasminogen,
Reteplase (r-PA) dissolve formed fibrin clots Acute myocardial infarction

Thrombolytic: Activator of plasminogen,


dissolve formed fibrin clots; mutated form
266 of t-PA with a prolonged half-life,
increased fibrin specificity, and
increased resistance to inhibition by
Tenecteplase (TNK-tPA) plasminogen activator inhibitors. Acute myocardial infarction
A B C

267
1. Acute myocardial infarction
Thrombolytic: Nonenzymatic activator 2. Pulmonary embolism
of plasminogen; stimulates dissolution 3. Deep venous thrombosis
Streptokinase of fibrin clots. 4. Arterial thrombosis
1. Acute myocardial infarction
268 2. Pulmonary embolism
3. Deep venous thrombosis
Urokinase Thrombolytic 4. Arterial thrombosis (?)

269

Thrombolytic: Streptokinase
plasminogen complex, dissolve formed
Anistreplase (APSAC) fibrin clots Acute myocardial infarction

270 Competitively blocks plasminogen


Aminocaproic acid activation Tx bleeding induced by fibrinolytic agents

271
Drotrecogin Alfa [Xigris] Activated protein C Tx of sepsis and DIC
272
273 Antihyperlipidemics
A B C

274

Uses:
1. Elevated cholesterol of all types. Particularly effective at
lowering levels of LDL. If the primary problem is too much
cholesterol, statins are good choices.
HMG-coA Reductase Inhibitor: decrease cholesterol by increasing LDL receptors in the liver
Inhibition of 3-hydroxy-3-methylglutaryl- causing decreased LDL cholesterol (often see a small
coenzyme A (HMG-CoA reductase) from decrease in triglycerides and a small increase in HDL
converting HMG-CoA to Mevalonic acid cholesterol)
-- essential step in cholesterol synthesis. 2. Aggressive therapy in high risk populations: With 2
These drugs are structural analogs of risks, e.g., ischemic disease and diabetes, goal is to reduce
the HMG-CoA intermediate. LDL<70 mg/dL (desirable level without these risk factors is
Leads to increased synthesis of LDL <130); Recent data have shown a 25% reduction in stroke (no
receptors (liver attempts to get more reduction in brain hemorrhage) in at risk populations
Lovastatin (Mevacor) cholesterol from plasma) maintained on statins
275 Atorvastatin

Fibrate Derivatives: increase activity of


lipoprotein lipase (which exist only on
276 endothelial tissue) - cleaves free fatty
acids from triglycerides more readily,
which promotes delivery of triglycerides
to adipose tissue. Decreases VLDL Reduction of triglycerides when VLDL is very high, or when
formation in the liver, leading to IDL is elevated
decrease triglycerides; modest reduction Follow VLDL. If it is elevated, gemfibrozil is a candidate drug.
in LDL (may increase in some patients); If LDL is elevated but VLDL is not elevated, do not use this
Gemfibrozil (Lopid) more impressive rise in HDL drug.
A B C
Fibrate Derivatives: Same mech as
277
Fenofibrate gemfibrozil
278 Clofibrate

Bile Acid Binder (resin): Enhanced


279 excretion of bile acids, leading to
increased conversion of cholesterol to
bile acids in the liver. Uses:
Loss of cholesterol triggers up Hypercholesterolemia, particularly elevated LDL
Cholestyramine regulation of LDL receptors in the cholesterol
(Questran) liver: therefore, decreasing LDLs Follow LDL. If it is elevated, these drugs are potentially useful
Bile Acid Binder: same as
280
Colestipol (Colestid) Cholestyramine same as Cholestyramine
Bile Acid Binder: same as
281
Colesevelam (Welchol) Cholestyramine same as Cholestyramine

282
Inhibits VLDL secretion (probable main Used for both hypercholesterolemia and
mechanism not entirely understood), hypertriglyceridemia - Any lipoprotein disorder, particularly
which leads to decreases VLDL, mixed hyperlipidemia with elevated triglycerides
decreased LDL and increased HDL Have to take gram quantities (NOT acting as a vitamin)
Niacin (Vitamin B3) (catabolism of HDL is decreased) Decreases triglyerides!!

283 Decreases blood glucose, triglycerides,


C-reactive protein levels, and increases
Thiazolidinedion HDLs (and lowers BP in some pts) Metabolic syndrome
A B C

Inhibitors of Intestinal Sterol


Absorption: Inhibits absorption of
phytosterols and cholesterol; Active
form of drug is glucuronidated!!
284 (Phase II metabolism, see extra note)
Travels through the portal vessels to the
bile, and is then brought back to the
small intestine via enterohepatic
recycling.
recycling. This is an unusual feature
nearly all drugs that are conjugated with
glucuronic acid are inactive. Watch for
this bit of information to be tested on Primarily useful for reducing LDL cholesterol
Boards. Excreted with the bile and Decreases cholesterol absorption approx 50%
acts at the brush boarder of the SI to Does not modify triglyceride absorption
inhibit the uptake of dietary and biliary Often used in combination with a statin
Ezetimibe (Zetia) cholesterol into the enterocytes.

Data support multiple mechanisms for cardio protection


285 Antiatherogenic by reducing triglyceride and VLDL
synthesis in the liver
Requires such large amounts of fish consumption that other
Fish oils Omega-3-Fatty Acids factors come into play (e.g., exposure to methylmercury)
286 Hematopoietic Agents
A B C

287

Iron is incorporated into the heme


Iron as complex, which is an essential
Ferrous sulfate, hydrated component of cytochromes, and
Ferrous sulfate, dessicated component of oxygen carrying proteins Treatment of Iron Deficiency Anemia, generally give ferrous
Ferrous gluconate hemoglobin and myoglobin. Many sulfate orally (parenteral for pt who cannot take orally or
Ferrous fumarate biological non-heme functions severely depleted dialysis pt, then give IV iron dextran)

288
Hematopoiesis; production of epithelial
cells; maintenance of myelin. Vitamin
B12 is essential for the synthesis of the
biologically active form of folic acid,
tetrahydrofolate (essential for DNA
Vitamin B12 synthesis). Thus, in vitamin B12
Cyanocobalamin (i.m.) deficiency, there is an internal folate Megaloblastosis Vitamin B12 deficiency, including
Hydroxocobalamin (i.m.) deficiency. pernicious anemia
A B C

289
Purine and pyrimidine synthesis; amino
acid interconversions. Folate is required
for the synthesis of deoxythymidylate
monophosphate, which in turn is required
Folic Acid (p.o./i.m.) for DNA synthesis. Megaloblastosis due to folate deficiency

290

Erythropoietin and the colony stimulating factors are


Colony Stimulating glycoprotein "growth factors" or hormones that regulate blood
Factors cell proliferation and differentiation. See the following

291

Recombinant EPO is being successfully used to treat patients


Erythropoietin (Epoetin Stimulates the division and differentiation with end stage renal disease (chronic renal failure).
Alpha; Epo; Epogen; of erythroid progenitors in the bone Patients infected with the HIV virus (treated with Zidovudine)
Procrit) marrow and cancer pts treated with marrow suppressant drugs.

G-CSF is a lineage-specific stimulator of Decreases the incidence of infection, as manifested by


292 Filgrastim (Granulocyte the proliferation, differentiation, and end- febrile neutropenia, in pts with non-myeloid malignancies
Stimulating Factor; G-CSF; cell function of the neutrophil line (a receiving myelosuppression anti-cancer drugs (ie neutropenia
Neupogen) granulocyte). due to cancer tx)

1. Acceleration of myeloid recovery in patients with non-


Recombinant human GM-CSF produced Hodgkins lymphoma, acute lymphocytic leukemia, or
by a yeast expression system. GM-CSF Hodgkins disease undergoing autologous bone marrow
stimulates partially committed transplantation;
293 progenitor cells to divide and 2. Increases WBC counts in patients with myelodysplastic
Sargramostim differentiate in the granulocyte diseases and in AIDS patients treated with zidovudine;
(Granulocyte Macrophage macrophage pathways.
pathways. Chemotactic, 3. Decrease leukopenia in cancer chemotherapy patients;
Colony Stimulating Factor; antifungal and antiparasitic activities of 4. Corrects neutropenia in aplastic anemia pts
GM-CSF; Prokine; granulocytes and monocytes are 5. Decrease transplantation-associated organ system
Leukine) increased by exposure to sargramostim. damage.
A B C

294 Treatment of thrombocytopenia. Oprelvekin should be an


Recombinant human interleukin-11;
interleukin-11; invaluable aid in the treatment of severe thrombocytopenia
selectively stimulates and help alleviate the requirement for multiple platelet
megakaryopoiesis (ie production of transfusions, which are currently a principal limitation in many
Oprelvekin (Neumega) platelets) chemotherapy regimens.

1. Malignant melanoma, chronic myelogenous leukemia,


295 chronic granulocytic leukemia;
2. sickle cell anemia.
3. The principal use of hydroxyurea has been as a
myelosuppressive agent in the myeloproliferative
Inhibits ribonucleotide diphosphate syndromes, especially chronic granulocytic leukemia,
reductase - inhibits formation of polycythemia vera, and essential thrombocytosis. It is also
deoxyribonucleotides from sometimes used to treat some solid tumors, making these
Hydroxyurea ribonucleotieds tumors more sensitive to radiation therapy.
296

Endocrine Drug List


297

298 Diabetes drugs


Treatment of DM type II, rarely used now for favor of second
299
Acetohexamide (Dymelor) First-Generation Sulfonylureas generation sulfonylureas
Chlorpropamide
300
(Diabinese) First-Generation Sulfonylureas see Acetohexamide
301 Tolazamide (Tolinase) First-Generation Sulfonylureas see Acetohexamide
302 Tolbutamide (Orinase) First-Generation Sulfonylureas see Acetohexamide
A B C

Sulfonylurea (2nd generation, a sulfa


drug); 1) Stimulate Insulin Secretion:
bind to and block an ATP-sensitive K+
303 channel. Blockade of this channel
reduces K+ conductance causing
membrane depolarization and influx of
Ca2+ through voltage-sensitive Ca2+
channels. Ca2+ influx leads to insulin
secretion. 2) prolong binding of insulin to
target tissue receptor 3) reduce serum Oral hypoglycemic agent, Once daily doses with fewer
glucagon levels (indirect inhibition via reported side effects. Can be combined with insulin therapy.
Glimepiride [Amaryl] insulin) Less weight gain than all other sulfonylureas
Oral hypoglycemic agent for T2DM, Potent, intermediate-
304 acting, single dose/day possible; undergoes hepatic clearance
Glipizide [Glucotrol, Sulfonylurea (2nd generation); Stimulate - should be used in pts with mild-to-moderate renal
Glucotrol XL] Insulin Secretion dysfunction
Oral hypoglycemic agent, Potent, intermediate-acting, no
305 Glyburide [DiaBeta, Sulfonylurea (2nd generation); Stimulate longer used (?); Alternative to insulin for Gestational DM
Micronaxe, Glynase] Insulin Secretion (does not cross PBB)

Non-sulfonylurea secretagogues (aka


Meglitinides); Stimulate Insulin
Secretion: binds to the ATP-sensitive
306
potassium channel on pancreatic beta
cells at a different site than
sulfonylureas. The subsequent
depolarization of the beta cell opens the
calcium channel and rapidly increases Oral hypoglycemic agent for T2DM: Short half-life; rapid
Repaglinide [Prandin] insulin secretion. action, taken right before meals
Non-sulfonylurea secretagogues
307 (Meglitinides); Stimulate Insulin Oral hypoglycemic agent for T2DM: Short half-life; rapid
Nateglinide [Starlix] Secretion action, taken right before meals
A B C

308

a Biguanide; antihyperglycemic agent, Oral hypoglycemic agent; treat Type 2 DM, patients with
decreases hepatic glucose production refractory obesity whose hyperglycemia is due to "insulin
& increases the binding of insulin to resistance", also has significant lipid-lowering effect, does
Metformin [Glucophage] its receptor not increase weight; hirsutism

-Glucosidase inhibitor:
oligosaccharide analogs that bind to the
intestinal brush border enzymes that
309 digest complex sugars (disaccharidases
such as -glucosidase). The competitive
inhibition of sugar digestion by these Oral hypoglycemic agent: The effects of -glucosidase
drugs delays the absorption of inhibitors on HbA1c are modest, so these drugs are most
carbohydrates and limits the postprandial useful for newly diagnosed Type 2 patients with mild
Acarbose [Precose] rise in glucose. hyperglycemia.
310 Miglitol -Glucosidase inhibitor

Thiazolidinediones (TZD); Insulin


Sensitizer, increases glucose disposal:
binds to nuclear transcription factors in
adipose tissues that are involved in the
311
insulin receptor signaling cascade
(PPAR- nuclear receptor). TZDs
resensitize the target tissues to insulin. Oral hypoglycemic agent: TZDs are indicated as an adjunct
(Also decreases FFA) Summary: to diet and exercise or for concomitant use with a sulfonylurea
decreases hepatic glucose output & or insulin to improve glycemic control. Rosiglitazone is used
Rosiglitazone [Avandia] improves peripheral insulin utilization as monotherapy or together with metformin; hirsutism
Thiazolidinediones (TZD); Insulin Oral hypoglycemic agent: Pioglitazone is approved for
312
Pioglitazone [Actos] Sensitizer monotherapy or with insulin, sulfonylureas, or metformin.
Thiazolidinediones (TZD); Insulin
313
Troglitazone Sensitizer
A B C

Injectable adjunctive treatment: to Type 1 and Type 2


diabetics who are already using insulin as prescribed but need
Amylin analog: Amylin is a naturally better control of blood glucose, most useful for pts who
314 occurring peptide that is normally co- experience wide glycemic swings or those who are
secreted with insulin. (Amylin secretion insulin-resistant and require large amounts of insulin.
is delayed or diminished in both Type 1 Pramlintide, added to an existing insulin regimen, has been
Pramlintide acetate and Type 2 diabetics.) See metabolic shown to decrease HbA1c levels and also results in
[Symlin] effects extra notes significant weight loss.

Injectable adjunctive treatment: approved for use with


metformin alone, a sulfonylurea alone, or in combination with
315 metformin and a sulfonylurea. When combined with these
more standard treatments, Exenatide is associated with a
Glucagon-like peptide-1 agonist: a significant reduction in HbA1c levels, post prandial
peptide analog of GLP-1 (Incretin) that plasma glucose reductions, and weight loss (increase
Exenatide [Byetta] acts as an agonist at the GLP-1 receptor. satiety).
316 Liraglutide see exenatide

Dipeptidyl Peptidase-4 Inhibitor (DPP-


IV): blocks the Ez that breaks down the 2
incretin hormones glucagon peptide-like
317 peptide-1 (GLP-1) and glucose-
dependent insulinotropic peptide (GIP),
which help regulate glucose metabolism monotherapy or in combination with metformin or a
via increased insulin release, suppressed thiazolidinedione: intended as a replacement for sulfonylureas
Sitagliptin phosphate glucagon release, and delayed gastric in patients who cannot achieve glucose targets with metformin
[Januvia] emptying. or a TZD alone.
318 Vidagliptin see sitagliptin
319 Insulin Preperations
A B C

320
Indications for Insulin Therapy:
SQ (or IV) injections of insulin are the primary therapy for:
1. All Type 1 patients
2. Type 2 patients not controlled by diet and/or oral
hypoglycemic agents
3. Patients following pancreatectomy or with gestational
diabetes.
4. Management of diabetic ketoacidosis.
5. Treatment of hyperglycemic, nonketotic coma.
Lispro [Humalog] Ultra-Short-Acting Insulin (human) 6. Perioperative management of Type 1 and Type 2 patients.

321
Aspart [Novolog] Ultra-Short-Acting Insulin (human) See Lispro

322
Glulisine [Apidra] Ultra-Short-Acting Insulin (human) See Lispro

323
Inhaled insulin [Exubera] Ultra-Short-Acting Insulin (human) See Lispro

324

Regular insulin (R) Short acting insulin (human) See Lispro

325
NPH (neutral protamine
Hagedorn) or Isophane
insulin Intermediate insulin (human) See Lispro
326 Lente Intermediate insulin (human?) See Lispro
A B C

327

Glargine [Lantus] Long-acting basal insulin (human) See Lispro


328 Detemir [Levemir] Long-acting basal insulin (human) See Lispro
329 Ultralente Long-acting basal insulin See Lispro
330 Thyroid & Antithyroid Drugs

331

Levothyroxine [generic,
Synthroid, Levoxyl, DOC for hypothyroid states (always give solucortef first!! -
Levothroid, Unithroid] Natural isomer of thyroxine (T4) reason? Ask Dr. Tanner)

a Thioamide antithyroid drug: Inhibits


332 the thryoid peroxidase enzyme
(organification) and thus interferes with
the incorporation of iodine into tyrosyl
residues of thyroglobulin and with
coupling of iodotyrosyl residues (MIT,
DIT) to form T3 and T4; PTU also acts by
inhibiting the enzyme 5'-deiodinase,
Propylthiouracil (PTU, which converts T4 to the active form Treat hyperthyroid; Propylthiouracil, but not methimazole,
generic) T3. also inhibits peripheral conversion of T4, to T3.
A B C
a Thioamide antithyroid drug, only
333 inhibits oxidation of iodine by peroxidase
Methimazole (Tapazole) (no peripheral effect) Tx hyperthyroid; once daily dosing, no peripheral inhibition

334 inhibits the action of the sodium-


dependent iodide transporter located on
Perchlorate follicular cells' basolateral membranes
335 Thiocyanate see perchlorate

Iodides: (1) inhibit thyroid hormone


release; (2) block iodotyrosine and
336 iodothyronine synthesis by blocking
organification; (3) decrease the Prevent thyroid storm; pre-surgery preperation of the
vascularity of the thyroid gland. The thyroid; short-term control of hyperthyroidism. Iodides are
Potassium iodide inhibitory effect on hormone synthesis is rarely used as sole therapy (PTU or methimazole is used more
solution (SSKI) known as the Wolff Chaikoff effect. typically for pre-surgery thyroid preperation).

1. Hyperthyroidism: relatively safe for treatment of Graves


disease. There is a high incidence of delayed hypothyroidism.
Propranolol and antithyroid drugs can be administered while
337 131I is rapidly taken up by the thyroid, awaiting the effects of the 131I.
incorporated into iodoamino acids and is 2. Hyperthyroidism: with nodular goiter and some
deposited in the colloid of the follicles. metastatic thyroid cancers.
The beta radiation destroys the 3. Diagnostic: for hyper/hypothyroidism and goiter to
Radioactive iodine surrounding parenchymal cells. determine capacity of gland for iodide uptake.

Decrease symptoms of increased adrenergic tone such as


338 heat intolerance, profuse sweating, tremors, and palpitations
Beta Adrenergic Receptor Antagonist: that are associated with hyperthyroid states. MC indications
inhibits thyroxine (T4) conversion to T3 are palpitations and tachycardia. At high doses, beta-
by Ez that catalizes deiodination, see blockers may inhibit conversion of T4 to T3. Use for
Propranolol below for adrenergic antagonistic effects inpatients.
Atenolol (generic,
339
Tenormin) Beta Adrenergic Receptor Antagonist: Outpatient control of symptoms of hyperthyroidism
Metoprolol (generic,
340
Lopressor) Beta Adrenergic Receptor Antagonist: Outpatient control of symptoms of hyperthyroidism
In sufficient quantity, they will
341 Thiocynate, Perchlorate, competitively inhibit the iodine pump
& Pertechnetate (& reducing its ability to concentrate iodine
Llithium) in follicular cell
342 Other endocrine drugs
A B C
Treat acromegaly, also retard development of IGF-1 mediated
343 Somatostatin analogue (aka insulin-like diabetic retinopathy; Carcinoid syndrome; esophageal
Octreotide growth factor, IGF-1) varice bleeds

344 Blocks GH receptors and results in


Pegvisomant decreased IGF-1 synthesis Blocking Tx of Growth Hormone Adenoma

345 Vasopressin, aka ADH used in pts witout P-Pit function. ADH can be insuffalated
Antidiuretic Hormone V1 (vascular receptor, IP3), V2 (renal as powder, injected i.m. for longer control (2-8 hrs) or injected
(ADH) receptor, cAMP) i.m as a tannate derivative for longest control (1-3 days)

346 Bromocryptine & both are alkaloids, stimulate dopamine Treatment of the prolactinoma depress prolactin secretion (a
Ergonovine receptors. prolactin inhibiting factor or PIF)
347 Cabergaline Treatment of the prolactinoma

Estrogens stimulate a generalized


increase in hepatic globulin synthesis
which includes thyroid binding globulins
(TBG) and corticosteroid binding globulin
(CBG). Treatment of the prolactinoma in females (if pregnancy is
348
- Estrogens reduce bone resorption, by not wanted); Will increase total T4 & T3 (not free T4 & T3);
repressing inflammatory cytokine will increase total cortisol as well as slightly increase free
expression and inhibiting effect of PTH ; cortisol.
reduce osteoclast differentiation. - Reduce hip fractures by 50%
Estrogen Rx leads to increased - Reduce CV risk
Estrogen Therapy synthesis of 1,25(OH)D. - Inc skin thickness
SERMS (specific estrogen receptor
modulators): Partial agonist-antagonist
349 at estrogen receptors; Estrogen In post -menopausal women produced a 40 % reduction in
derivative having estrogen agonist effects risk of vertebral fractures, a 3-4 % increase in bone
on the bone and limited effects in breast density. A significant reduction in new breast cancers was
Raloxifene (Evista) and uterus. also observed. Also favorable affect on LDL and cholesterol

Bisphosphonate - Analogues of Reduces hip and spine fractures


350 pyrophosphate (P-C-P); Most effective Tx of postmenopausal and glucocorticoid-induced
inhibitors of osteoclast and bone osteoporosis
resorption by inhibiting farnesyl BPs are the 1st line tx for hypercalcemia of malignancy,
Alendronate diphosphate synthase also used to treat Pagets and tumor bone disease
351 Risedronate Bisphosphonate See Alendronate
352 Editronate Bisphosphonate Older form, no longer used due to mineralization defects
353 Pamidronate Bisphosphonate See Alendronate
354 Androgen Therapy opposite effect to estrogen (above) Will decrease total T4 & T3 (not free T4 & T3)
A B C

Treat Addison's dz, also Congenital Adrenal Hyperplasia


355 (eg 21-hydroxylase deficiency, 11-Hydroxylase Deficiency, 3-
Dexamethasone & strong glucocorticoids with very little Hydroxysteroid dehydrogenase deficiency, 17-Hydroxylase
prednisolone mineralocorticoid activity deficiency, Cholesterol Desmolase Deficiency)
Treat Congenital Adrenal Hyperplasia (eg 21-hydroxylase
356 mineralocorticoi with little glucocorticoid deficiency, 3-Hydroxysteroid dehydrogenase deficiency,
Fludrocortisone activity Cholesterol Desmolase Deficiency)
Used to confirm secondary (pituitary) adrenal cortical
357 block 11-beta hydroxylase to temporarily insufficiency; to sort between primary (adrenal tumor) vs
Metyrapone prevent cortisol synthesis secondary hyperadenocorticalism (Cushing's S.)

358 opens K+ATP channel in beta cell;


Diazoxide inhibits insulin release. Used to treat hyperinsulinism

359
Calcitonin inhibits bone resorption
while formation continues causing a net
increase in bone Ca deposition. Synthetic salmon calcitonin (more potent than human) used to
Calcitionin also lowers Ca by increasing treat bone disease (eg Pagets disease, hypercalcemia,
Calcimar (fish calcitonin) Ca renal clearance (excretion) osteoporosis)

1,25 (OH)2 D3 (calcitriol) is the most


360 potent in stimulating Ca and PO4
transport in the GI and bone
resorption. T 1/2 is relatively short due
to poor binding affinity with serum Vit D
1,25 (OH)2-D3 (calcitriol) binding protein. Tx hypocalcemia
Effective in increasing Ca and PO4
361 reabsorption from kidney; Weak effects
25 (OH)-D3 (calcifediol) on GI absorption of Ca
24, 25 (OH)2-D3 D3
362
(secalcifediol) May stimulate bone formation
363 Ergocalciferol Vitamin D2 Tx hypocalcemia

364

Isotretinoin Tx severe acne vulgaris


A B C
365

366
Pulmonary Drugs
367 Bronchiodilators

368

2-selective adrenergic agonists,


Bronchodilator, see adrenergics; 2-
adrenergic agonists stimulate 2- Asthma (acute, severe asthma), Rapid acting
adrenergic receptor coupled to Gs Therapeutic Use in Asthma and COPD:
protein stimulating adenylyl cyclase and Drug of choice for rapid relief of bronchospasm
an increase in intracellular cyclic AMP. Highly effective and safe for intermittent, prophylactic
Cyclic AMP stimulates phosphorylation treatment of asthma.
cascade that leads to decreased Current Emphasis:
intracellular calcium and smooth Intermittent use on an as-needed basis for relief of acute,
Albuterol (Proventil, muscle relaxation. Also inhibit mediator severe bronchospasm. Not general prophylaxis.
Ventolin) release from mast cells. onset<15 min duration: 2-4 (safe during pregnancy (?))
See albuterol, onset<15 min; duration: 2-4; more active isomer
369
Levalbuterol (Xopenex) new drug, R-isomer of albuterol for effect (more expensive)
370 Pirbuterol (Maxair) see albuterol See albuterol, onset<15 min duration: 2-4

Asthma (acute, severe asthma), Rapid acting; see albuterol,


371 onset<15 min; duration: 2-4; injectable, inhaled, or tablet;
s.c. for emergency/resistant to nebulizer treatments
Terbutaline (Brethaire, Delay pregnancy
Brethine, Bricanyl) see albuterol see adrenergics
A B C
Combined treatment with ipratropium and 2-adrenergic
agonists results in a slightly greater and more prolonged
372 bronchodilation than therapy with either agent alone.
Albuterol + Ipratropium Combined therapy can be considered if severe asthma
bromide (Combivent) Combination exacerbations exist.
2-selective adrenergic agonists,
373 Bronchodilator; a prodrug that must be
Bitolterol mesylate converted to colterol, the active Asthma (acute, severe asthma), Rapid acting; longer
(Tornalate) compound, in the lung. period of useful bronchodilation (3-6 hrs)

374 Long-acting (~12 hrs), selective 2- It is not suitable for treatment of acute bronchospasm.
Salmeterol xinafoate adrenergic agonist with slow onset of Salmeterol is useful for prevention of nighttime asthma
(Serevent) action, Bronchodilator attacks and prophylactic brochodilation (BID)
Long-acting, dry powder inhaler for maintenance therapy
375 of asthma or prevention of bronchospasm in COPD &
2-selective adrenergic agonists, exercise-induced asthma. Not for treatment of acute
Formoterol (Foradil) Bronchodilator attacks.

376 Salmeterol + fluticasone Combination - long acting beta2 agonist


(Advair Diskus) + steroid not used for asthma rescue inhalation

Epinephrine can be give s.c. to patients unable to receive


377 aerosolized 2-agonists because of age or asthma severity.
DOC for treatment of (emergent) anaphylactic reactions.
Give SQ (or IM or IV with dextrose)
Nonselective alpha, beta agonist, see Bronchodilation & Vasoconstriction (maintain BP & decrease
Epinephrine adrenergics edema), Inhibition of mediator release
Inhaled Epinephrine Nonselective alpha, beta agonist, see
378
(primatene mist) adrenergics tempory, brief relief of asthma
379 Racemic Epinephrine aerosol used for pediatric patients (nebulizer)
Asthma; somewhat shorter acting and less selective at 2
380 Metaproterenol & receptors than albuterol - these agents are not frequently
isoetharine Nonselective -Adrenergic Agonists used.

381 Nonselective agonist, see Asthma; nonselective and has a still shorter duration of action
Isoproterenol adrenergics (than albuterol), very potent
A B C

382 Anticholinergic Agents, Bronchodilator,


quaternary amine muscarinic receptor
antagonist (will not cross BBB), block Ipratropium is used exclusively as an inhaled aerosol. The
vagally mediated reflex arcs (blocked principal clinical use of ipratropium is in the treatment of
cGMP) that cause bronchoconstriction, COPD. Also used intranasally to reduce secretion in both the
Ipratropium bromide see anticholinergics; poorly absorbed in upper and lower respiratory tract in allergic rhinitis and
(Atrovent) lungs, GI (less muscarinic SE) chronic postnasal drip syndrome (vasomotor rhinitis).
Anticholinergic Agent, Bronchodilator, Long-acting agent (than ipratropium) used for maintenance
383 quaternary amine muscarinic receptor therapy in chronic bronchitis and emphysema; dry powder
Tiotropium (Spiriva) antagonist inhaler device

Adenosine receptor antagonist (most


likely mech), a Methylxanthine; Formerly a first-line agent for treatment of asthma, now less
Bronchodilator; also inhibit cyclic used: benefits are modest, narrow therapeutic window,
nucleotide (cyclic AMP and cyclic GMP) considerable variation in absorption and elimination between
phosphodiesterases, blocking different patients. Used for both prophylaxis and
384 cAMP/cGMP breakdown (which makes symptomatic relief of broncial asthma and COPD
mast cells less likely to degranulate; May benefit stable COPD pt in combination with other
note: at levels observed for this mech, bronchodilators
drug is toxic - the concentrations required Nocturnal asthma can be improved with slow-release
to inhibit these enzymes is not achieved theophylline, but inhaled corticosteroids and salmeterol are
with therapeutic doses) - relaxes probably more effective.
smooth muscle of the bronchi and Used for status asthmaticus given parenterally (or orally), in
Theophylline (Theo-Dur, pulmonary vessels; also stimulates conjunction with beta-blocker and corticosteroid
Slo-bid) the respiratory center May improve diaphram contractitlity
Aminophylline
385 (theophylline Adenosine receptor antagonist, a
ethylenediamine) Methylxanthine used for emergency brochodilation i.v. infusions
386 Pulmonary Anti-Inflammatory Agents, Corticosteroids
A B C

387 Anti-Inflammatory Agent,


Corticosteroid - bind to intracellular
receptors that translocate to nucleus
and positively or negatively regulate
gene transcription. Inhibit production
and release of cytokines, vasoactive and
chemoattractive factors, lipolytic and
proteolytic enzymes, decrease
mobilization of leukocytes to areas of
Beclomethasone injury, decrease fibrosis. General anti-
diproprionate !! inflammatory effect. Takes time to Asthma (initially given 3 to 4 times daily), inhaled
(Beclovent, Vanceril) effect. See Corticosteroids
Anti-Inflammatory Agent, Asthma, inhaled; (No growth suppression detected in
388
Fluticasone (Flovent) Corticosteroid children)

389
Anti-Inflammatory Agent,
Flunisolide (Aerobid) Corticosteroid Asthma (twice daily), inhaled
Triamcinolone acetonide Anti-Inflammatory Agent,
390
(Azmacort) Corticosteroid Asthma (initially given 3 to 4 times daily), inhaled

391
Budesonide Anti-Inflammatory Agent, Approved for Seasonal & Allergic Rhinitis, inhaled; tx of
diproprionate (Pulmicort) Corticosteroid cough-variant asthma

392 Fluticasone propionate Anti-Inflammatory Agent,


(Fluticasone) Corticosteroid Approved for Seasonal & Allergic Rhinitis only

393 Mometasone furoate Anti-Inflammatory Agent, Approved for Seasonal & Allergic Rhinitis only; (No growth
(Nasonex) Corticosteroid suppression detected in children)
A B C

Systemic Therapy: Systemic (i.v. or oral) steroid therapy is


used in severe asthmatic attacks requiring
hospitalization/status asthmaticus (refractory to
treatment). For severe asthma, prednisone or
methylprednisolone is given i.v., followed by oral doses and
394 gradual tapering of the dose. For acute, severe
exacerbations, oral prednisone is administered for 1 -2 weeks.

In acute exacerbation of COPD, use steroids routinely to


improve symptoms and lung function (FEV1).
Systemic Corticosteroids, see 20-30% COPD pts improve if adminsistered long-term oral
Prednisone immunosuppressants steroid therapy
395 Methylprednisolone Systemic Corticosteroids IV or oral (ED)
396 Hydrocortisone Systemic Corticosteroids IV or oral
IgE Ab, binds free IgE (blocks from
397 binding to its high affinity Fc receptor on
mast cells and basophils, preventing Asthma (tx moderate persisten asthma in pts >12yo whose
Omalizumab mediator release) symptoms are not controlled with corticosteroids))
398 Other Pulmonary drugs

Anti-Inflammatory Agents - Cromolyn


Compounds; may suppress the
activating effects of chemoattractant
peptides on eosinophils, neutrophils, and
monocytes; does not directly relax
399 smooth muscle but after long-term
therapy bronchial hyperreactivity to 1. Allergic Rhinitis
allergens, histamine, and exercise is 2. Primarily prophylactic to prevent asthmatic attacks
significantly diminished. Indirectly inhibit (used in mild to moderate asthma). Ineffective in treating
antigen-induced bronchospasm and ongoing bronchospasm. When inhaled several times daily,
Cromolyn sodium (Intal & directly inhibit the release of histamine cromolyn will inhibit both the immediate and the late asthmatic
Mast Cell Stabilizer Nasal and other autocoids from sensitized responses to antigenic challenge or exercise. Approved for
Spray - Nasalcrom) mast cells. all ages

Anti-Inflammatory Agents - Cromolyn


400 Compounds; indirectly inhibit antigen-
induced bronchospasm and directly
inhibit the release of histamine and other More potent than cromolyn. Nedocromil is approved for use
Nedocromil (Tilade) autocoids from sensitized mast cells. in asthmatic patients > 12yo
Emphysema resulting from genetic deficiency of the plasma
401 proteinase inhibitor 1-antiproteinase (or 1-antitrypsin).
1-antiproteinase Purified 1-antiproteinase (Prolastin) is available for i.v.
(Prolastin) Purified 1-antiproteinase replacement.
A B C

402

Pseudoephedrine Sympathomimetic Agents (-agonists,


(Sudafed) see adrenergic) Nasal decongestants (Allergic Rhinitis)
Phenylephrine (Neo- Sympathomimetic Agents (-agonists,
403
Synephrine) see adrenergic) Nasal decongestants (Allergic Rhinitis)
Oxymetazoline (Vicks
404
Sinex, and others) See Sympathetic Agonists Nasal decongestants (Allergic Rhinitis)

405

1. Approved for children 6 to 12yo (2-5yo low dose);


especially useful for patients who experience aspirin-induced
Anti-Leukotriene Drugs: selective asthma attacks. Must be taken BID.
Montelukast (Singulair) reversible LTD4 receptor antagonist 2. Allergic Rhinits
Approved for prophylaxis and maintenance therapy of
406 asthma in adults and children >12yo; especially useful for
Anti-Leukotriene Drugs: selective patients who experience aspirin-induced asthma attacks
Zafirlukast (Accolate) reversible LTD4 receptor antagonist (Aspirin Sensitivity). Must be taken QID
Blocks production of leukotrienes (from
407 archidonic acid)by inhibiting
Zileuton lipoxygenazse Ez Preventative tx of asthma

408
Guaifenesin (Glyceryl
Guaiacolate) Expectorant - mech unknown Chronic irritating cough
Expectorants: Iodides enhance the
secretion of respiratory fluids, thus
409 decreasing the mucus viscosity. In
addition, iodides may stimulate
Potassium iodide & breakdown of fibrinoid material in
Iodinated glycerol inflammatory exudates. Chronic irritating cough
A B C
Mucolytic agent - acts by facilitating the
410 depolymerization of Chronic irritating cough (COPD); an effective mucolytic
N-Acetylcysteine mucopolysaccharides in dried airway agent but causes irritation. Use is not currently recommended.
(Mucomyst) secretions. May benefit bronchiectasis when delivered by nebulization

411
Mucolytic agent - acts by facilitating the
depolymerization of
Recombinant DNAase mucopolysaccharides in dried airway
(Dornase alpha) secretions. Cystic fibrosis (Chronic irritating cough)

412
Opioid used as an antitussive (cough
suppressant); believed to act at the CNS
level, by suppression of the cough
reflex. May act at non-opioid receptor Acute control of nonproductive cough; often used for in-
Codeine site. See opioids patient treatment.
Non-opioid used as an antitussive - the
d-stereoisomer of methorphan Acute control of nonproductive cough; has no analgesic
413 structurally related to levorphanol, a or addictive properties and does not act through opioid
narcotic (opioid) analgesic (no opioid receptors. Nearly as potent as codeine and produces fewer
receptor activity); NMDA receptor subjective and GI side effects. Available in many over-the-
Dextromethorphan glutamate receptor? counter preparations.

Non-opioid used as an antitussive; Local


414 anesthetics and demulcents probably act
directly on nerve endings in the
pharynx. Antihistaminics mechanism Acute control of nonproductive cough; Control of minor
Benoxonatate (Tessalon) is unknown. transient cough; local anesthetic

415
Diphenhydramine Non-opioid used as an antitussive; see Acute control of nonproductive cough; Control of minor
(Benyline) Antihistamines transient cough; H1 histamine receptor antagonist

416
Ranitidine H2 antagonist, see antihistamines
A B C
417 Smoking Cessation pharmacologic intervention
418 Nicotine polacrilex Nicotine replacement chewing gum; to reduce withdrawl symptoms and relapse
Transdermal nicotine
419 patch (Nicoderm, Nicotrol,
Habitrol) Nicotine replacement to reduce withdrawl symptoms and relapse

420 (see) Antidepressant; enhances CNS nonnicotine aid to smoking cessation, aid to pt who have not
Bupropion (Zyban) nonadrenergic function been able to quit smoking with nicotine replacement therapy
Smoking cessation: is the first treatment that specifically
targets the neurobiological mechanism of nicotine
421 dependence - reduces nicotine withdrawal symptoms and
Stimulates dopamine and blocks nicotine cravings, helping to prevent a full relapse; also blocks the
Varenicline (Chantrix) receptors effects of nicotine if patient begins smoking again.

422
Antimycobacterials
DOC, first line for TB disease (According to NEJM)
1. Isonizid alone should be given for 18mo (recommended
given in conjunction with other drugs)
2. Isoniazid + rifampin given for 9mo
3. Isoniazid + rifampin + pyrazinamide for first 2mo,
423 followed by 4mo of continued Isoniazid + rifampin (total of
6mo, ideal treatment)
4. Unless rate of resistance to isoniazid is known to be <4% in
Bacterialcidal; Inhibits mycolic acid community, add ethambutol or streptomycin until susceptbility
formation in outer membrane (mycolic is known
acid is unique to Mycobacteria). Kills both DOC, first line for TB latent infection, treat for 6-9mo
Isoniazid (INH) intra- and extracellular bacteria Safe for latent TB in pregnancy

1. DOC, first line for TB disease; see Isoniazid for


regiment.
Isolated isoniazid-resistant TB should be treated with
rifampin, pyrazinamide, and ethambutol for 6mo
424 Latent infection: Alternatives to INH therapy for latent TB
Inhibits DNA-dependent, RNA daily: rifampin alone for 4mo or rifampin + pyrazinamide for
polymerase; bacterialcidal 2mo
Combinations with INH and other drugs 2. Leprosy
helps prevent emergence of resistant 3. Effective against gram (+) and gram (-) cocci, some
Rifampin strains enteric bacteria, mycobacteria, and chlamydia

1. A rifampin substitute, used when drug-drug interactions


425 likely, especially protease inhibitors and nonnucleoside
reverse-transcriptase inhibitors (NNRTI) used to treat HIV.
Rifabutin Sim to Rifampin 2.Treat M. avium complex (MAC)
A B C
426 Rifapentine Sim to Rifampin a long-acting rifampin-like agent

1. First (Second?) line TB disease; see isoniazid regiments.


427 Resistance emerges rapidly, use only in combinations
Inhibits mycolic acid synthesis and 2. Latent MDRTB treatment
Ethambutol mycobacterial cell wall synthesis 3. M. avium intracellular (MAI)
1. First line TB disease; see isoniazid regiments; Resistance
428
Pyrazinamide mechanism unknown develops rapidly, use in combinations
An aminoglycosis; Parenteral, First (Second?) line therapy for tuberculosis; Employed
bacteriocidal, protein synthesis when an injectable drug required, especially life-threatening
429 inhibitor; penetrates into cells poorly, so illness, e.g., meningitis or disseminated disease or multi-drug
is active mainly against extracellular resistant TB;
Streptomycin tubercle bacilli. kills aerobic gram- enterics (DOC Yersina Pestis)
430 Ethionamide blocks mycolic acid synthesis Second line TB treatment
431 Capreomycin Second line TB treatment; IM drug for MDRTB
432 Cycloserine inhibitor of cell wall synthesis Second line TB treatment

433
Antifungal Agents

434

Polyene macrolide antibiotic; Binds


ergosterol in fungal cells, increase
membrane permeability; cidal, broad DOC for systemic mycoses
Amphotericin B spectrum, extremely poten Slow parenteral administration necessary

435 block the activity of an enzyme Itraconazole has the broader spectrum of activity and is
necessary for ergosterol synthesis available both orally and IV (of azole's)
Itraconazole

436
Flucytosinne Interferes with thymidylate synnthetase Tx cryptococcosis
block the activity of an enzyme
437
Fluconazole necessary for ergosterol synthesis
block the activity of an enzyme
438
Voriconazole necessary for ergosterol synthesis
A B C
block the activity of an enzyme Tx systemic fungal infections, used to treat Cushings
439
Ketoconazole necessary for ergosterol synthesis disease
Applied topical to skin and mucous membranes
440 complexes with ergosterol (primary Used to treat local candidiasis (thrush, vaginal, etc)
membrane sterol of fungi) and causes Polyene macrolide like Amphotericin B but too toxic for
Nystatin the membrane to become leaky parenteral administration
441 Clotrimazole, Miconazole Topical Azoles
Used for systemic treatment of dermatophytosis (griseofulivin
442
Griseofulvin Interfers with mitotic spindle funtion concentrates inn the stratum corneum)
Used for systemic treatment of dermatophytosis (especially
443
Terbinafine blocks ergosterol synthesis tinea unguium/neil infection)
444

445
Antiviral Agents
446 Prophylaxis of type A influenza; Treatment initiated within 48
Inhibit uncoating of RNA viral nucleic hours after initial appearance of symptoms is effective; Tx
Amantadine acids, Inhibit viral replication Parkinson's dz

447 Inhibit uncoating of RNA viral nucleic Prophylaxis of type A influenza; Treatment initiated within 48
Rimantadine acids, Inhibit viral replication hours after initial appearance of symptoms is effective
inhibits neuraminidase (Ez necessary
448 for viral replication and for release of
Zanamirvir infected cell) Tx and prophylaxis of both influenza A and B
449 Oseltamivir inhibits neuraminidase Tx and prophylaxis of both influenza A and B
1. Respiratory syncytial virus (RSV) in infants and young
Synthetic guanosine analog children
450 Active against broad spectrum of RNA & Aerosol, oral, IV
DNA viruses 2. Treat Lassa Fever
Ribavirin Inhibits viral mRNA syntheis 3. Give with INF alpah 2b to treat HCV

Inhibits viral DNA synthesis; Acyclic


guanosine derivative; competitive
inhibition of dGTP for the viral
polymerase with binding to the DNA
template as an irreversible complex chain
451 termination following incorporation into
viral DNA. Requires three
phosphorylation for activation: it is
converted into monophosphate
derivative by virus specified thymidine
kinase, then to the di- and
triphosphate compounds by hosts DOC for genital herpes (STD); Active against herpes simplex
Acyclovir cellular enzyme virus-1 and -2 (HSV-1 & HSV-2)
A B C
452 Ganciclovir DOC for CMV (eg cytomegalovirus retinitis with HIV pt)
453 Foscarnet
Prevents viral attachment: 3-methyl
isoxazole group binds the floor of the
454 canyon structure at the vertices of the
virion, which normally attach to cell
Pleconaril receptors If administered early, inhibits poliomyelitis infection (polio)
Produces proinflammatory cytokines,
stimulates release of TH1 cytokines,
455 binds to Toll-like receptor of dendritic
cells and M0 and enhances cell-
Imiquimod mediated IR Tx HPV
456

457
Antihistamines

Clinical indications of antihistamines


1. Allergic conditions - DOC for allergic rhinitis and
458
urticaria; vasomotor rhinitis, allergic conjunctivitis, mild,
uncomplicated urticaria and angioedema; ineffective in
bronchial asthma; adjunctive (to epinephrine) therapy in
anaphylactic reactions (parental)
2. Motion sickness/nausea - esp. diphenhydramine,
dimenhydrinate, zines
3. insomnia
Diphenhydramine H1 receptor antagonists: prevents Comments specific for diphenhydramine: Marked
(Benadryl, first generation, phosphoinositol hydrolysis, preventing sedation; anti-motion sickness activity; high
Ethanolamine class) increased intracellular Ca++ antimuscarinic activity

459 Dimenhydrinate (first


generation, Ethanolamine) H1 receptor antagonists Motion sickness/nause; see diphenhydramine

460 Cyclizine (first generation,


Piperazine derivatives) H1 receptor antagonists Motion sickness/nause; see diphenhydramine
Hydroxyzine (first
461
generation) H1 receptor antagonists Motion sickness/nause; see diphenhydramine
A B C

462 Meclizine (first generation,


Piperazine derivatives) H1 receptor antagonists Motion sickness/nause; see diphenhydramine

463
Topical Nasal Spray Antihistamine: given intranasally, with
the advantage of rapid onset of action and the disadvantages
of twice-daily dosing; may be useful in pts with mucosal
Azelastine (Astelin) H1 receptor antagonists irritation and/or epistaxis from nasal corticosteroids.

464 Chlorpheniramine (Chlor-


Trimeton, first generation, See diphenhydramine; common component of OTC cold
Alkylamines class) H1 receptor antagonists medication.

Promethazine
465 (Phenergan, first
generation, Phenothiazine
derivatives) H1 receptor antagonists See diphenhydramine
Ophthamlmic H1 receptor
466 noncompetitive antagonists and
stabilizes mast cells, long duration of
Ketotifen action, little systemic absorption Allergic conjunctivitis

467

Fexofenadine (Allegra,
2nd generation,
Piperidines class) H1 receptor antagonists See diphenhydramine; Newer agent; Allergic Conjunctivitis

468
Desloratidine (2nd Gen) H1 receptor antagonists See diphenhydramine; Newer agent; Allergic Conjunctivitis
Loratadine (Claritin, 2nd See diphenhydramine; Newer agent; longer action; Allergic
469
Gen) H1 receptor antagonists Conjunctivitis

470 Cetirizine (Zyrtec, 2nd


Gen) H1 receptor antagonists Long-acting (24 hr): Allergic Conjunctivitis
A B C

H2 receptor antagonists: selective,


471
reversible competitive blockers of H2
receptors, decreases secretion of Indications
gastric acid; also block the acid 1. Peptic Ulcer
secretion stimulated by gastrin, 2. Gastric ulcer
cholinergic agonists, vagal stimulation 3. Zollinger Ellison Syndrome (see extra notes)
cimetidine (Tagamet) food, insulin, caffeine, etc. 4. Reflux disorder

472
ranitidine (Zantac) H2 receptor antagonists, see cimetidine see cimetidine

473
famotidine (Pepcid) H2 receptor antagonists, see cimetidine see cimetidine

474
nizatidine (Axid) H2 receptor antagonists, see cimetidine see cimetidine
475

476 Sympathetic Agonists (Sympathomimetics):


Drugs that mimic the actions of sympathetic stimulation. Frequently referred to as adrenergic agents. (Catecholamine vs. non-Catecholamine, Direct vs. indi

477
Induces vasoconstriction
Increases BP (arterioles) & Increases cardiac return (veins)
Expect reflex bradycardia. Also
1. Nasal decongestant
2. Infiltration with local anesthetics.
Phenylephrine - Non 3. Pressor agent (drug that increases bp) to maintain bp
Catecholamine Agonist 4. Ocular examination. Mydriasis without affecting
(selective) selective 1 agonist accommodation.
A B C

Agonist at all adrenergic receptors (1,


2, 1, 2, 3).
1. Heart: (beta-1 mediated) Positive
inotropic effect, Positive chronotropic
effect, Increased automaticity (latent
pacemakers become active = increased
ectopic beats. Note: arrhythmias also
may occur because refractory period
following an action potential is reduced);
Increased conduction rate in the AV
node. Epinephrine (E) widens the pulse
pressure because it stimulates 2
receptor on arterioles, causing
vasodilation
478 2. Blood Vessels: Skeletal muscle
arterioles: both 1 and 2 receptors are
present (at physiological quantities see
vasodilatation (2), with pharmacological
doses typically see vasoconstriction
(1)).
Veins: 1 (pure constriction).
Coronaries: vasodilate (2)
Kidney, skin, mucosa: vasoconstriction
(1). 1. Bronchial asthma. Administered by inhalation.
Cerebral: unchanged Bronchodilation (2) and inhibition of antigen-induced
3. Metabolic Effects: Calorigenic effect histamine release.
and tremors in skeletal muscle (2). 2. Anaphylactic shock (give IV or SC) Improves breathing by
Mechanisms related to increased same mechanisms as in 1 above, plus increases blood
glycogenolysis (2) and lipolysis (3) at pressure and reverses edema (a1).
Epinephrine - various organ sites (liver, skeletal muscle 3. Infiltration with local anesthetics.
Catecholamine (Prototype and adipocytes.) 4. Topical for hemostasis.
sympathomimetic) 4. Lungs: Bronchodilation 2
Receptor selectivity. 1, 2 and 1
1. Heart: 1 direct effects (increases
479 Norepinephrine inotropic/chronotropic).
(Levophed)- 2. Vasculature: 1 vasoconstriction, Clinical use: manage hypotension by iv infusion.
Catecholamine (activates baroreceptors) (& treatment of shock)
A B C

1 and 2 stimulant. (no alpha effects).


480 1. Heart: Positive inotropic and
chronotropic effect. Relatively limited because of intense cardiac effects.
2. Vasculature: Vasodilatation of skeletal 1. Bronchial asthma (Aerosol) Relatively limited because of
Isoproterenol (Isuprel)- muscle arterioles (2 receptors on intense cardiac effects. (see Pulmonary drugs)
Catecholamine arterioles). 2. Heart block (give by IV. catheter.)

481
Albuterol - Direct Acting
2 Agents (Selective 2
adrenergic agonist) see
extra notes for additional Direct Acting 2 Agents (Selective 2 Used in bronchial asthma. Aerosol for acute effects and p.o.
beta 2 agonists adrenergic agonist) (post op) for chronic treatment. (see Pulmonary drugs)

482

Ritodrine (Yutopar): Beta-2 Adrenergic Agonist used to delay labor

De-carboxylated tyrosine
No direct effect on receptors
Enters nerve terminal via the re-uptake
483 pump. Massive NE releases
Does not cross BBB to any significant
extent (no CNS effects, contrast this to
amphetamine derivatives, which do cross
Tyramine - Indirect Acting BBB and do cause profound CNS
Sympathomimetic effects)

Blocks re-uptake of dopamine (abuse


mechanism), serotonin, and
485 norepinephrine (effects on heart and
BP)
Cocaine - Reuptake Prolongs and intensifies the actions of
inhibitors NE and E
A B C

Agonist at D1 (& D2) receptors Shock, particularly Hypovolemic shock (and cardiogenic in
D1 (& D2) receptors in kidney; leads to the early stages)
vasodilation in the kidney 1 effects benefit cardiac output
486 Agonist at 1, leads to increased cardiac 1 effects increase blood pressure
output (D1 vasodilation prevents renal failure)
Agonist at 1 (less potent than for D1 Short-term therapy only
and 1), which can lead to Especially useful to increase splanchnic and renal blood
Dopamine (Intropin) vasoconstriction flow

Often switch patients in cardiogenic shock from dopamine (or


occasionally norepinephrine) to dobutamine once blood
pressure is stable. (According to Dr. Olgasby dobutamine is
487 catecholamine - Increase in cardiac used more for cardiogenic shock because of beta1 agony
output; decrease in ventricular filling without the alpha1 vessel increased resistance and bp??)
pressure(??) Short-term support of cardiac output in advanced HF
1(predominant) and 2 agonist effects Tolerance prohibits long-term use. The inotropic effect
Dobutamine (Dobutrex) occurs with little change in heart rate (HR).

Large group of drugs with high abuse


potential (Schedule II). All are indirect
acting non-catecholamines. Release Clinical Uses:
488 NE from adrenergic nerves. Also release 1. Narcolepsy
dopamine in CNS. These agents are 2. Attention Deficit Hyperactivity Disorder children (ADHD).
taken up into nerve terminals via the 3. Obesity; anorexiant effect. No longer FDA approved. Abuse
uptake one mechanism. They also potential is far too great. Derivatives of amphetamine that
compete with and reduce NE and have less abuse potential are still used as anorexiants.
Amphetamines dopamine reuptake.
Pharmacological Actions. Like a longer acting but less
efficacious epinephrine. Ephedrine penetrates the CNS.
489 Ephedrine (eF-a-drine) - indirect (releases NE) but also a direct Cardiovascular: mild positive inotropic effect (may cause
naturally from genus beta-adrenergic receptor agonist (and palpitations and arrhythmias), vasoconstriction
Ephedra alpha agonist, so similar effect to E) CNS: stimulation

490

psuedoephedrine - OTC Nasal decongestant


A B C

OTC Agents for Topical Decongestion: Used for local


vasoconstriction (e.g., nasal decongestants);
Tetrahydrozoline (as Tyzine), Xylometazoline (Otrivin), &
Oxymetazoline (Afrin):
491 Nasal passages have a dense supply of 1 receptors
Tetrahydrozoline (Tyzine, vasculature
Visine), Xylometazoline Edematous fluid can be prevented by squeezing the arterioles
(Otrivin), & and veins of this vascular bed
Oxymetazoline (Afrin) - Tetrahydrozoline (as Visine):
Common OTCs Alpha 1 Effects (direct) shrink injected conjunctiva (soothes red eyes)
492

493 Sympatholytics chemicals


tending to oppose the physiological results of sympathetic nervous activity or of sympathomimetic drugs

Alpha2 agonist
Periphery: 2 receptor is an
autoreceptor on norepinephrine nerve
terminals. When stimulated it decreases
release of norepinephrine.
CNS: stimulation of 2 receptors and
494 imidazolin receptors lowers CNS
sympathetic outflow. Consider the
action as turning down the gain on the
control mechanism regulating HTN emergencies, used for drug-induced HTN (for limited
sympathetic nerve activity. The brainstem duration only), such as cocaine/amphetamine overdose;
is the main site of action as anti- Withdrawal symptom treatment for opiates and sedatives
hypertensive. Part of effect may be via (noradrenergic neurons in the locus ceruleus), see opioids;
Clonidine imidazoline receptors in brainstem May be helpful in reducing craving for cigarettes.
Extremely well studied in pregnancy. If a woman is
495 Methyldopa (aka alpha- Alpha2 agonists (central acting); Pro- hypertensive prior to the start of pregnancy, this is the drug
methyl-DOPA) drug of choice during the pregnancy.
496 Guanfacine Centrally acting alpha-2 agonist Tx of mild to moderate HTN

497 Adrenergic neuronal depleting agent:


blocks vesicular uptake and storage of
NE (and others monoamines). Result is
depletion of monoamines throughout the
Reserpine body, including the CNS Outmoded
A B C
Adrenergic neuronal depleting agent:
Inhibits release of NE from sympathetic
498 nerves and depletes NE from storage
granules. Must be taken up via NE
reuptake pump. Does NOT get into CNS
Guanethidine (highly polar) Outmoded
drug of choice for noemergent HTN in pregnancy (though
499 Olgasby says use methyldopa??????????? (same thing, diff
Aldomet name??)
500

501 Adrenergic Blocking Agents


sin = blocker
lol = blocker

502
Non-Selective, Block 1 & 2
Affinity is 1 = 2 (non-selective)
Also is an agonist at muscarinic and
histamine receptors Pheochromocytoma (see extra notes)-- control acute
Phentolamine is a competitive blocker of hypertensive crisis
alpha receptors. It shifts the NE dose- Treat necrosis due to vasoconstrictors such as NE and
Phentolamine - non- effect curve to the right. Note that the full phenylephrine (should be rare)
selective alpha blocker effect of NE can be re-obtained with Note: non-selective alpha blockers have essentially no use in
(competitively binds) higher NE dose essential hypertension (see extra note).
A B C

1. Vascular. Blocks the effects of


endogenous NE -- reduces blood
pressure.
2. Cardiac. Reflex tachycardia.
Reducing BP causes sympathetic
activation. Because 2 receptors on
adrenergic nerves are blocked, this
further increases NE release at the heart,
503 where NE can act on beta-1 receptors.
3. CNS. Lipophilic agent that crosses
blood brain barrier. 1. Pheochromocytoma: Pre-operative management to treat
Nausea, vomiting and weakness may be vascular effects of high circulating catecholamines.
signs of non-specific CNS effects. Tumor tends to dump NE when physically disturbed (i.e.,
4. Others: miosis, inhibition of surgery).
ejaculation, stuffy nose (related alpha Given in combination with a beta blocker, phenoxybenzamine
Phenoxybenzamine blockade et cetera) protects vasculature; beta blocker protects the heart.
(Dibenzyline) - non- (Notice - Onset is slow (several minutes 2. Peripheral Vascular Disease, e.g. Raynauds syndrome (see
selective alpha blocker for formation of covalent linkages), extra notes)
(covalently binds), aka Offset is very slow, elimination t1/2 of 24 sympathetic tone to peripheral vasculature is high
non-competitive blocker hours. New receptors must be Vascular. Blocks the effects of endogenous NE -- reduces
synthesized.) blood pressure.
A B C

Non-selective competitive antagonist at


1 and 2 receptors (also 3). High
therapeutic doses may also have a non-
receptor-related membrane-stabilizing
effect (?)
1. Heart (decreases CO): Decreases HR
(negative chronotrope); Decreases
contractility (negative inotrope);
Decreases spontaneous pacemaker
504 activity (depresses ectopic foci more than
SA node); Decrease caridac work
(decrease O2 consumption, no effect on
O2 supply); decrease PVR (decreasing 1. Angina pectoris: Reduces cardiac work and O2
O2 demand) consumption.
2. Blood vessels: Reduction in renin 2. Hypertension: blocks renin release (slow working);
release (renin release is controlled by 1 Decrease in cardiac output and decrease in peripheral
receptors in the kidney), leading to resistance (decreased CO allows peripheral vasculature to
decreased angiotensin and decreased relax over time).
aldosterone. Results in a slow developing 3. Migraine headache (Prophylactic treatment)
decrease in peripheral resistance 4. Arrhythmias (see antiarhythmic drugs)
3. Bronchial Smooth Muscle: Blocks 5. Pheochromocytoma
relaxation. Watch out for bronchospasm 6. Thyrotoxicosis
Propranolol (Inderal) - in conditions where sympathetic tone 7. Adjunctive treatment of anxiety (particularly performance
Non-selective competitive maintains the airway (e.g., asthma) anxiety related to fine motor skills)
antagonist at 1 and 2 4. Metabolic: Blocks lipolysis (3) and 8. Reduce mortality post MI
receptors (also 3) glycogenolysis (2). 9. Management of heart failure (non-acute)

505 Non-Selective Beta Blockers (similar to Actions and uses are much like propranolol
Nadolol (Corgard) propranolol); long 14-24hr half-life Very long duration of action (once daily dosing)
Much like other beta blockers for systemic uses (eg HTN,
angina)
506 Treats glaucoma by decreasing synthesis of aqueous humor.
Timolol (Blocarden; Non-Selective Beta Blockers (similar to Administered topically as Timoptic or in various combinations
Timoptic) propranolol) with other drugs.
A B C

507
hypertension, angina & CHF
Slightly preferred (compared to propranolol) in individuals
who also have: asthma, diabetes, peripheral vascular disease
1 (Cardioselective) Blocker; Short (Usual recommendation is to avoid beta blockers in these
Metoprolol half-life limits utility patients if possible)

508 hypertension, stable angina


1 (Cardioselective) Blocker, Metoprolol As compared to metoprolol, only requires once daily dosing
Atenolol (Tenormin) is prototype (advantage over an agent that must be taken 2-3 times daily)

509 Betaxolol (Kerlone; 1 (Cardioselective) Blocker, Metoprolol


Betoptic) is prototype hypertension, glaucoma

510

1 (Cardioselective) Blocker, Metoprolol


Bisoprolol (Zebeta) is prototype hypertension, CHF

Ultra short acting (t1/2 of 10 min)


Structure has ester linkage that is easily hydrolyzed
When infused i.v., steady state is reached very rapidly without
511 the danger of a loading dose
Offset is very rapid when terminated; Onset/Offset
characteristics make this an excellent agent for emergency
use in severely ill patients (e.g. intraoperative and
ultra-short-acting 1-selective postoperative hypertension, and sometimes for
Esmolol (Brevibloc) adrenoreceptor antagonist hypertensive emergencies assoicated with tachycardia))

hypertension, dysrhythmias. Has slight vasodilation


512 Beta1-Selective Partial Agonists (Beta1 (because of slight activation of beta2). Lowers BP by
Blockers with ISA - intrinsic decreasing vascular resistance and appear to supress CO or
Acebutolol (Sectral) sympathomimetic activity) HR less than other beta-blockers
A B C

513

Non-selective partial beta agonists


(Intrinsic Sympathomimetic Activity, see Systemic uses and liabilities of these agents are no different
Pindolol (Visken) Extra Note) than propranolol

514 Systemic uses and liabilities of these agents are no different


Carteolol (Cartrol; than propranolol. Ocupress is an ophthalmic preparation as
Ocupress) Non-selective partial beta agonists 1% drops

515

Benign prostatic hypertrophy (see extra notes)


b.i.d. dosing and orthostatic hypotension limit use of this agent
compared to newer drugs
Hypertension
1-Selective Blockers (block 1 but not Orthostatic hypotension limits usefulness
Prazosin 2 adrenergic receptors). Reflex tachycardia is minimal if at all

Hypertension. Selective 1 blockers can be used, but


because of side-effects, particularly orthostatic hypotension,
which is severe with initial doses, they are used infrequently
516 for that indication.
Benign prostatic hypertrophy: This use is rapidly being
supplanted by the 1A selective agents (tamsulosin) which
Terazosin (Hytrin) 1-Selective Blockers does not produce orthostatic hypotension
A B C

517 Tamsulosin (selective 1A Benign prostatic hypertrophy, prostate has greater number
blocker) Selective 1A blocker of 1A receptors expressed than other tissues.
Same uses and liabilities as terazosin or prazosin
518 Long elimination half-life (24 hr) makes once daily dosing
Doxazosin (Cardura) 1-Selective Blockers feasible

Hypertension: Dilates both resistance and capacitance


vessels; Antihypertensive at doses that do not alter cardiac
520 output; appropriate first-line drug for HTN in pregnancy
Combined Alpha/Beta Blockers: Hypertensive Emergencies (including drug-induced, eg
b1 antagonist coke/amphetamine)
Labetalol (Normodyne, b2 partial agonist Slow onset. Used in combination with shorter acting drugs
Trandate) a1 antagonist Pheochromocytoma

Management of chronic CHF - Critical point is that once


521 patients are stable, therapy with beta blockers extends life
Combined Alpha/Beta Blockers: expectancy. Carvedilol was one of the first drugs used in
Non-selective b1/b2 antagonist clinical trials to document this effect.
Carvedilol (Coreg) a1 antagonist Hypertension
522

523
Cholinergic agonist (Muscarinic Receptor Agonis
Drugs which produce effects similar to those observed during the stimulation of postganglionic parasympathetic fibers i.e., drugs which exert their effec
muscarinic receptors. (Typically) Parasympathetic postganglionic innervation to a muscarinic receptor on cardiac & smooth muscle, gland cells and nerve
have sympathetic muscarinic receptors).

Muscarinic receptors are all G protein


coupled metabotropic receptors (all
524 blocked by atropine):
M1 (nerves) (IP3; DAG)
M2 (cardiovascular) (K+; decrease
cAMP)
M3 (glandular) (IP3; DAG)
M4 & M5 CNS functions unclear
devoid of nicotinic effects (historic basis
Muscarine (naturally for classification of muscarinic receptors), No therapeutic use; of interest only because it is the toxin
occurring alkaloids) resistant to cholinesterases; responsible for mushroom poisoning
A B C
Glaucoma (lowers IOP - intraocular pressure)
525 Dry mouth (xerostomia) (e.g., cancer therapy)
Pilocarpine (naturally Dominant muscarinic actions in periphery and CNS; clinical
occurring alkaloids) Tertiary amine use only as topical

With certain exceptions, muscarinic


effects of acetylcholine are similar to
parasympathetic nerve stimulation (see
Chol Agonist Martin.doc for more detail):
1. Cardiovascular
526
2. Extravascular smooth muscle
3. GlandsIncreased refractory period
Nicotinic effect (see extra note): *
sympathetic and parasympathetic
Acetylcholine - Prototype ganglia, * the adrenal medulla, * skeletal
and choline ester muscle Ophthalmic surgery to produce rapid miosis
Postoperative or neurogenic urinary retention
Bethanechol (increase smooth muscle Postoperative atonic bowel without obstruction
527 tone) has only muscarinic effect, no Lazy bladder syndrome
nicotinic, and is not susceptible to Will not activate nicotinic receptors (so chemical is much
Bethanechol (Choline cholinesterase (not broken down as different than ACh which activates both muscarinic and
esters) quickly as acetycholine) nicotinic receptors)

528 Carbachol (Choline Both muscarinic & nicotinic activity,


esters) but is not susceptible to cholinesterase Glaucoma (lowers intraocular pressure); miosis during surgery
Not a muscarinic drug, but a Tx glaucoma (lowers intraocular pressure by increasing
529
Latanoprost prostaglandin analog aqueous outflow)
(oral medication) for treatment of dry mouth in Sjgren's
syndrome (also dry mouth of cancer pt - xerostomia)
530 Devoid of nicotinic effects; resistant to cholinesterases;
Synthetic muscarinic agonist; M3 Little or no CNS actions
Cevimeline selective Also used for dry eye

531
Methacholine (Choline stimulates sm contractions in the Diagnostic applications: Provocholine (methacholine) for
esters) bronchioles diagnosis of subclinical asthma
532

533 Anticholinergics (Cholinergic receptor antagonis


Drugs that occupy muscarinic receptors and prevent the muscarinic actions of endogenous acetylcholine or other muscarinic agonists. Antimuscarinics
antagonism of acetylcholine binding to muscarinic receptors.
A B C

Non-quaternary compound; Tertiary


amine (enter CNS); 1. Heart: high dose
tachycardia; low dose - bradycardia
(Due to presynaptic inhibition and CNS
effects)
2. Vascular - no (direct) effect (CBP113);
except at toxic doses (some normal Anesthesiology
doses), dilate cutaneous vessels (red as Prevention of bronchial and salivary secretions
a beet) mechanism unknown Prevent bronchospasm
(sympathetic, cholinergic); block Reversal of reflex bradycardia or hypotension during surgery
hypotensive effect of muscarinic agonists Ophthalmology
3. Eye: mydriasis (dilation of iris production of mydriasis and cycloplegia of long or short
sphincter) & cycloplegia (relaxation of duration
534 ciliary muscle) 4. Bronchial: dilation, choice of agent depends upon requirements.
decrease bronchial secretions 5. GI routine examination: short duration; minimal cycloplegia.
Tract: decreased tone, motility many appear in combinations with alpha adrenergic drugs
(antispasmodic effect) 6. Urinary: Gastroenterology:
relaxation of detrusor, ureter; constriction Inhibit gastrointestinal motility - antispasmotic
of sphincter 7. Glands decrease in all Peptic ulcer treatment.
secretions 8. Action at respiratory center Can reduce basal and nocturnal acid secretion
therapeutic dose: faster deeper (other drugs are better, e.g., H2 antagonists)
breathing Reduce pain and prolong actions of antacids
larger doses: depression of respiration Reduce motility for reduction of pain, constipation, or diarrhea
9. Cerebral centers: Irritable bowel syndrome
low doses: sedation Urologic disorders
high doses: restlessness, amnesia, Detrusor hyperreflexia, enuresis
delirium Increase bladder capacity
higher doses: stupor; coma Decrease bladder pressure
Note: with therapeutic doses, atropine Muscarine poisoning: muscarinic mushrooms (Inocybe) or
Atropine - alkaloid & generally has less CNS sedative effects cholinesterase inhibitors
tertiary amine than scopolamine

Non-quaternary compound Motion sickness


535 Tertiary amines (enter CNS); in Scopolamine is useful in prophylactic treatment via CNS action
Scopolamine - alkaloid & prophylactic treatment via CNS action in in vestibular nuclei and reticular formation
tertiary amine vestibular nuclei and reticular formation Muscarine poisoning

Inhalational drug to reverse bronchial constriction and


secretion
536 Quaternary amine compounds: Emphysema, chronic bronchitis (COPD).
Ipratropium (Atrovent) - Due to quaternary structure these do Sometimes asthma
Quaternary amine not enter CNS to an appreciable extent COMBIVENT = albuterol + Ipratropium bromide
compounds See pulmonary drugs
A B C

537 Quaternary amine compounds:


Due to quaternary structure these do inhibit secretions (and inhibit bronchiole constriction???).
Tiotropium (Spiriva) - not enter CNS to an appreciable extent (emphysema, chronic bronchitis; asthma); long acting (24 hr)
quaternary amine See pulmonary drugs QD dosing

Gastroenterology (atropine & dicyclomine have similar


results): Inhibit gastrointestinal motility - antispasmotic
Peptic ulcer treatment - Can reduce basal and nocturnal acid
538 secretion (other drugs are better, e.g., H2 antagonists);
Reduce pain and prolong actions of antacids
Quaternary amine compounds: Irritable bowel syndrome - Reduce motility for reduction of
Propantheline (Pro- Due to quaternary structure these do pain, constipation, or diarrhea; Muscarine poisoning:
Banthine)- quaternary not enter CNS to an appreciable extent poisoning with muscarinic mushrooms (Inocybe) or
amine cholinesterase inhibitors

Quaternary amine compounds:


539 Due to quaternary structure these do
glycopyrrolate - not enter CNS to an appreciable extent
quaternary amine

Peptic ulcer treatment - rarely used now;


Irritable bowel syndrome (reduce motility for reduction of
540 pain, constipation, diarrhea);
Urologic disorders: detrusor hyperreflexia (unihibited
neurologic bladder?, denervated bladder?); enuresis:
Non-quaternary compounds (Tertiary increases bladder capacity, decreases pressure. (enuresis: an
dicyclomine Amines) involuntary discharge of urine : incontinence of urine)
Non-quaternary compound
541 Anticholinergic (Tertiary Amine) with
Oxybutynin antispasmotic properties incontinence, Urologic disorders
Non-quaternary compounds (Tertiary
542
oxyphencyclimine Amines) Peptic ulcer treatment, rritable bowel syndrome
Non-quaternary compounds (Tertiary
543
tolterodine Amines) incontinence, Urologic disorders

544 Ocular: For routine examination, shorter-acting which produce


Non-quaternary compounds (Tertiary little cycloplegia are preferred. Duration of Action 12-48 hr
homatropine - ocular Amines) (least cycloplegia of the three ocular cholinergic blockers)

545 Non-quaternary compounds (Tertiary Ocular: For routine examination, shorter-acting which produce
cyclopentolate - ocular Amines) little cycloplegia are preferred. Duration of Action 12-24 hr
A B C

546 Non-quaternary compounds (Tertiary Ocular: For routine examination, shorter-acting which produce
tropicamide - ocular Amines) little cycloplegia are preferred. Duration of Action 1-2 hr
547

548
Anticholinesterase (Cholinemimetics):
DEFINITION: Drugs that inhibit cholinesterase enzymes and allow acetylcholine released from cholinergic nerves to accumulate, bind to and stimulate posts
are indirectly acting.

549 A non-quaternary compound,


irreversible.
Pharmacological Effects: result from the
increase in concentration of acetylcholine Reserved for reversal of serious atropine or scopolamine
at muscarinic and nicotinic sites which type poisoning where the CNS is involved. Used cautiously
occurs following carbamylation because of its own side-effects. Not routinely used for
inhibition of cholinesterases overdose of drugs with secondary anticholinergic effects. May
(irreversible). Note: these effects occur exacerbate bradyarrhythmias and AV conduction blocks in
Physostigmine (tertiary only where innervation is present. tricyclic antidepressant overdose. Readily distributes to all
amine) - Carbamate See extra notes for ACh organ effect tissues. Well absorbed orally, binds irreversibly.

i) to improve muscle strength in myasthenia gravis (MG)


(Note that MG therapy often involves other measures,
including thymectomy, corticosteroids, or other
550 Variable absorption, p.o. This quaternary immunosuppressive agents) (see Neurology below)
ammonium compound has actions ii) reversal neuromuscular blockade caused by non-
mainly on the peripheral nervous system, depolarizing agents such as pancuronium, vecuronium, etc.
Neostigmine - quaternary binds covalently (carbamylation/ iii) gastric atony (rarely)
amine & a carbamate irreversible). (see Neurology below) iv) urinary retention (rarely)
A B C

i) Diagnostic aid for myasthenia gravis (see extra note) (not


primary diagnostic, but can be used to distinguish MG from
other neuromuscular disorders); also to determine
over/under medication for myasthenia gravis (improves -
551 under medicated, exacerbates - over medicated)
Brief duration of action, rapid onset ii) Differentiation of myasthenia crisis from cholinergic crisis
(essentially, a short-acting neostigmine.) during therapy for myasthenia gravis (infrequently used, not
Only one truly reversible anticholinergic considered reliable) (see Neurology below)
agent, edrophonium, is an alcohol, half iii) Reversal of non-depolarizing neuromuscular blockers (e.g.
Edrophonium (Tensilon, life is 2-10 minutes. (see Neurology tubocurarine)
Reversol) - alcohol below) iv) Treatment of paroxysmal atrial tachycardia (PAT) (historical)
Pyridostigmine -
552 quaternary amine & a same as neostigmine (see Neurology Uses and mechanisms are identical to neostigmine but longer
carbamate below) duration of action and less toxicity

highly lipid soluble group (except a) Treatment of open angle glaucoma.


echothiopate - quaternary) of Echothiopate and isoflurophate (DFP) are used but not
organophosphate agents which bind preferred because of potential for development of cataracts
covalently to and inhibit and other side-effects. Echothiopate is quaternary
cholinesterases. Half life in 100s of ammonium which limits its systemic absorption.
553 hours b) Insecticides: In insects parathion is preferentially
a) The pharmacological actions of these converted to the more toxic compound, paraoxon. (similarly,
compounds are due to irreversible malathion is converted to malaoxon)
inhibition of cholinesterases. Mammals can preferentially oxidize these chemicals to a less
Organophosphates b) Muscarinic and nicotinic actions. toxic compounds. Parathion and malathion are only
(Isoflurophate (DFP), c) Lipid soluble get into CNS. preferentially toxic to insects. In high doses they are extremely
echothiophate, parathion, d) Absorbed by all routes. toxic in man.
malathion, soman, tabun, e) Hydrolyzed slowly in the body by c) Nerve gas: (soman, tabin, sarin). Developed for volatility,
sarin, VX) phosphorylphosphatases. rapid absorption and rapid aging

Cholinesterase reactivation (not an


anticholesterase!!!)
a) Pralidoxime possesses a cationic site
(quaternary ammonium) which attracts it
554 to the anionic site on cholinesterase.
b) The oxime moiety reacts with the
organophosphate bound to the enzyme
forming an unstable complex.
c) The oxime-organophosphate complex
splits off the enzyme and the enzyme is
reactivated.
Pralidoxime (2-PAM) - d) Administration: Slow i.v. infusion. Tx Organophosphate poisoning
A B C
555 Electron Transport Chain Inhibitors

Organic pesticide that inhibitor of


556 complex I (aka NADH dehydrogenase)
of the electron transport chain (binds to
Rotenone the ubiquinone binding site, aka CoQ) Organic pesticide
Barbituate - site of action same as
557
Amytal rotenone
An antibiotic that blocks electron flow
558 from cytochrome b to c1 (blocks
Antimycin A complex III)
Binds to cytochrome c oxidase
559 (complex IV) and prevents electron
Cyanide transfer to oxygen
Inhibit several Ez processes (lipoic acid-
560 containing Ez, such as alpha
ketoglutarate dehydrogenase), also Ez
Arsenic involved in oxidative phosphorylation
Inhibits electron transport chain at
561
Carbon monoxide complex IV (mech??)
Inhibits F0 "stalk" of ATP synthase
562
Oligomycin (F1F0 ATPase) complex V

Uncoupling agent - increases


563 permeability of mitochondrial innner
membrane, causing a decrease of H+
gradient and increased O2 consumption -
2,4-Dinitrophenol no ATP (e- chain continues)
564 Other Poisions
565 Iron Forms reactive oxygen species

566 Interferes with heme synthesis (d-


aminolevulinic acid and ferrochelatase),
Lead alters cell membrane structure
567 Copper Accumulation in Wilson's dz
568

569 Neuromuscular-blocking drugs:


Drugs that interact with nicotinic type cholinoceptors at the motor end plate (NM) to block cholinergic neurotransmission and produce
A B C

Non-depolarizing blockers ; Direct-


acting nicotinic receptor antagonist
1. Occupy NM sites on depolarizing Na+
and K+ channels of skeletal muscle end
plate
2. Prevent channel opening in response
570
to ACh, thereby preventing Surgery setting
depolarization. 1. Facilitate laryngoscopy and endotracheal intubation by
3. Muscle becomes weak and paralyzing muscles of jaw, throat and larynx.
subsequently flaccid and unresponsive to 2. Overcome laryngospasm
stimulation 3. Facilitate surgical exposure
4. Blockade is surmountable so that 4. Facilitate mechanical ventilation.
tubocurarine (prototype of anticholinesterases (e.g. neostigmine) Non-surgical
a non-depolarizing can reverse the neuromuscular 1. Terminate convulsions in status epilepticus
blockers) blockade and paralysis. 2. Terminate convulsions in local anesthetic toxicity

571
mivacurium (non- Non-depolarizing blockers, see
depolarizing blockers) tubocurarine see tubocurarine
Non-depolarizing blockers, see
572
Vecuronium tubocurarine
Non-depolarizing blockers, see
573
Atracurium tubocurarine

574 pancuronium (non-


depolarizing blockers) see tubocurarine see tubocurarine
A B C

Direct-acting nicotinic receptor


agonist
1. Neuromuscular effects are the same
as acetylcholine except they are more
persistent because the drug is
ineffectively metabolized at the synapse.
2. Reacts with NM receptor to open the
channel and cause depolarization of
the end plate. Also enters channel to
575 inhibit ion conductance.
3. Membranes remain depolarized
(repolarization is prevented) and are
unresponsive to additional impulses.
(Phase I block). A phase II (desensitizing)
block may occur subsequently, but is
unlikely to occur under conditions of Surgery setting (intubation, electro-compulsive shock
clinical use. therapy)
4. Effect on muscle is fasciculation 1. Facilitate laryngoscopy and endotracheal intubation by
followed by paralysis paralyzing muscles of jaw, throat and larynx.
5. In contrast to non-depolarizing 2. Overcome laryngospasm
blockers, the neuromuscular blockade 3. Facilitate surgical exposure
produced by succinylcholine is 4. Facilitate mechanical ventilation.
facilitated by anticholinesterase. The Non-surgical
Succinylcholine neuromuscular blockade CANNOT be 1. Terminate convulsions in status epilepticus
(depolarizing blocker) reversed pharmacologically. 2. Terminate convulsions in local anesthetic toxicity
blocks effector cells of skeletal muscle
576 innervated by somatic nerves (NM)
Curare

577
Local anesthetic, Amide class; blocks
Lidocaine (class IB) voltage-dependent Na+ channels Local anesthetics, see antiarrhythmics
578 Bupivacaine Amide class Local anesthetic
579 Etidocaine Amide class Local anesthetic
580 Prilocaine Amide class Local anesthetic
581 Ropivacaine Amide class Local anesthetic
582 Mepivacaine Amide class

583
Procaine Ester class Local anesthetic
584 Benzocaine Ester class Local anesthetic
A B C
585 Chloroprocaine Ester class Local anesthetic
586 Cocaine Ester class Local anesthetic
587 Tetracaine Ester class Local anesthetic

588
Tetrodotoxin (puffer fish) Block voltage-dependent Na+ channels

589 Batrachotoxin (SA


poisonous frog) Open voltage-dependent Na+ channels
590 Hemicholinium Inhibit uptake of choline
591 Vesamicol Block transport of ACh into vesicle
Blocks inhibitory neuronal input by
592
Strychnine binding glycine receptors

593 Inhibits Renshaw cell release of glycine


Tetanus toxin (inhibitor) through presynaptic binding
Botulinum toxin Block vesicle docking and ACh release at
594
(Botox) neuromuscular junction
Black widow spider (Presynaptic binding) causes explosive
595
venom release of Ach
Snake venoms (-
596
bungarotoxin) Block nicotinic receptors (irreversible)

Autonomic ganglion cells of


sympathetic and parasympathetic nerves
597 (NN) blocked by hexamethonium
Adrenal medullary cells and some
adrenergic nerve terminals (NN)
Hexamethonium blocked by hexamethonium
598
599 Anesthetics

600

Halothane depolarizing agent (?) general anesthesia


601

602
Opioid Analgesics and Antagonists
A B C

603

Endogenous Compound - Mu receptor


activation ususally (Opioid receptors are
Beta Endorphin of the Mu, Kappa, and Delta variety) No clinical use found
Endogenous Compound - Delta/mu
604 receptor activation (methionine
Met-enkephalin containing penta peptides) No clinical use found
Endogenous Compound - Delta/mu
605 receptor activation (leucine containing
Leu-enkephalin pentapeptide) No clinical use found

606 Endogenous Compound - Kappa


Dynorphin A receptor activation No clinical use found

607
Endogenous Compound - Kappa
Dynorphin B receptor activation No clinical use found
A B C

High efficacy mu opioid - Prototypic


Opioid Analgesic; binds to all opioid
receptor subtypes; highest affinity is for
mu receptors.
608
low oral:parenteral potency ratio
(Morphine is highly polar; hence, it is
both slowly and incompletely absorbed
after oral administration, both factors are
Morphine (High efficacy important in its lower potency by the oral Useful in pulmonary edema (with SOB, see notes),
opiod (HEO)) route). High efficacy for analgesia analgesia (high efficacy)

609
Meperidine (Demerol) Analgesia; given less due to:
HEO High efficacy mu opioid Shorter elimination half-life

610
High efficacy mu opioid, synthetic, also
blocks NMDA receptors and More efficacious than morphine in difficult to treat pain -
Methadone (Dolophine) monoamine reuptake pumps enhanced by antidepressant effects. Opioid abuse treatment
HEO (antidepressant mechanism) programs

611 High efficacy mu opioid; most lipid Surgery analgesia (particularly cardiovascular) with minimal
soluble, highest potency agents (~100 cardiodepressant effects (due to low dose requirement);
Fentanyl (Sublimaze) HEO x more potent than morphine) transdermal patch for vomiting pts
High efficacy mu opioid; Diacetyl
612 morphine - gets to brain quickly, and is
Heroin (Schedule 1) HEO deacetylated to morphine No clinical use; see No No's

613 High efficacy kappa opioids (& partial Post surgery pain with less potential for respiratory
Butorphanol (Stadol) HEO agonists at mu receptors) depression

614
Post surgery, when patients have respiratory depression,
High efficacy kappa opioids & mu often used to remove the respiratory depressant effects of mu
Nalbuphine (Nubain) HEO antagonist agonists given prior to surgery (still provides analgesia)
A B C

615
Hydrocodone Analgesia: Efficacy is enhanced by adding aspirin or
(Intermediate efficacy acetaminophen. (Numerous formulations exist, including
opioid (IEO)) Partial -opiate agonist Vicodin; Lortab).

616

Oxycodone (Percocet)
IEO See Hydrocodone

617 Moderate kappa agonist with either


partial agonist or pure antagonist at mu
Pentazocine (Talwin) IEO receptors Oral analgesic with limited abuse potential

Propoxyphene Napsylate/
618 Acetaminophen Tablets
[Darvocet] Low efficacy Primarily affects -opioid receptors, Not recommended for use, low analgesic acitivity, unsuitable
Opioid (LEO) partial agonist for severe pain

619 Partial agonists at mu receptors


(kappa antagonist); long duration of
action and high affinity for mu receptor;
Buprenorphine considered an agonist-antagonists; see
(Buprenex) LEO extra notes Narcotic treatment programs
Central-acting analgesic predominantly
by enhancing seroteonergic
620 neurotransmission; also weak mu
partial agonist and inhibits NE transporter
Tramadol [Ultram] funtion Chronic neuropathic pain; used to tx some fibromyalgia
A B C

621 High doses is an agonist at non-mu


receptors (sigma?); slow conversion of
codeine to morphine by
Codeine (High efficacy demethylation, occurs by a cytochrome Opioid of choice for cough, ceiling on analgesia in not limited
see notes) (CYP2D6) by efficacy per se

Opioid agonist act at and receptors


in the GI tract to decrease normal
peristaltic motion, increased renal
sphincter tone, reduce secretory activity,
622 and enhance NaCl and water absorption.
Opioids slow transit time allowing
more time for absorption. The net
effect of increased absorption and Diarrhea; Opioids are effective against moderate-to-severe
decreased secretion in the small diarrhea but should not be used for patients with ulcerative
intestine is to decrease the fluid and colitis, or acute bacillary or amoebic dysentery. Used for
Loperamide electrolyte load delivered to the colon. symptoms of travelers diarrhea

623 Diphenoxylate + atropine


(Lomotril) see loperamide Diarrhea; use for Irritable Bowel Syndrome (IBS)
Difenoxin + atropine
624
(Motofen) see loperamide Diarrhea
Paregoric (generic,
625 camphorated opium Opioid agonist - antidiarrheal,
tincture, morphine) antitussive, and analgesic properties Diarrhea

626
Opioid Antagonist; Prototype, blocks DOC opioid overdose (or even slight possiblitiy, ie coma)
effects of full agonists, blocks mu useful in treating some drug-free addicts
Naloxone (Narcan) receptors Short acting, injected/parentral only (inactive oral)

627
Naltrexone (Revia, Opioid Antagonist; blocks effects of full
Trexan) agonists, block mu receptors Long acting, oral route only
628 Nalmefene (Revex) Opioid Antagonist
A B C

Alpha2 agonist
Periphery: 2 receptor is an
autoreceptor on norepinephrine nerve
terminals. When stimulated it decreases
release of norepinephrine.
CNS: stimulation of 2 receptors and
629 imidazolin receptors lowers CNS
sympathetic outflow. Consider the
action as turning down the gain on the HTN emergencies, used for drug-induced HTN (for limited
control mechanism regulating duration only), such as cocaine/amphetamine overdose;
sympathetic nerve activity. The brainstem Withdrawal symptom treatment for opiates and sedatives
is the main site of action as anti- (clonidine compensates for lack of inhibition in the locus
hypertensive. Part of effect may be via ceruleus (noradrenergic outflow));
Clonidine imidazoline receptors in brainstem. May be helpful in reducing craving for cigarettes.

630 L-alpha-acetylmethadol
acetate (LAMM) Synthetic opioid Prevent heroin relapse (substitution)

631 Non-opioid available OTC; binds NMDA Cough, and when used with opioids increases the cough
Dextromethorphan receptors suppressant activity of the opioid
632

633
Rheumatic Disease & Gout
634 Rheumatic Disease Drugs

635
Hydrochloroquine Malaria tx; mild to moderate (early) rheumatoid arthritis
(Plaquenil) Mechanism of action unknown (rapidly absorbed), safe and convenient
A B C

636

inhibitor of dihydrofolate reductase potent immunosuppressive activity that makes it useful in


(an antifolate); it blocks synthesis of cancer chemotherapy and in the treatment of various immune
Methotrexate!! purines needed for DNA and RNA diseases. It is used at low doses to treat rheumatoid
(Rheumatrex) DMARD synthesis during the S phase arthritis (RA)
Mechanism in RA is not entirely clear
637 (may be related to its ability to inhibit
Leflunomide (Arava) tyrosine kinase activity and inhibit de Alternative to methotrexate and can be given with it to treat
DMARD novo pyrimidine biosynthesis) RA

5-ASA Compounds (derivative of


salicylic acid): Mechanism of action is Tx inflammatory bowel dzs - ulcerative colitis and Crohns
638 unknown, most likely inhibit dz!!
prostaglandin formation in the Sulfasalazine and a newer related drug, olsalazine, are used
intestinal mucosa. A member of the as second-line drugs for the treatment of other autoimmune
Sulfasalazine (Azulfidine) sulfa drug class (other sulfonamides do dzs including rheumatoid arthritis, ankylosing spondylitis,
DMARD not share its anti-rheumatic actions). and seronegative spondyloarthropathy

Inactivates T cells by interfering with


the activation process. T cells are
activated by first binding an antigen-
presenting cell (APC), and then by
639 releasing CD28 that interacts with CD80
or CD86 on the APC, leading to
activation. Abatacept binds to CD80 Pts with moderate to severe rheumatoid arthritis who
and CD86, blocking activation and haven't adequately benefited from methotrexate or TNF-
Abatacept (Orencia) thus it reduces the T-cell-induced inhibitors, are candidates for abatacept. Relieves RA and
DMARD inflammation/joint damage of RA reverse some signs of joint damage disease modification.
A B C

640
RA (usually given with methotrexate) and used for active
Rituximab (Rituxan) Reduces B lympocytes (targets CD20- moderater to severe RA that does not respond to TNF alpha
DMARD containing B lymphocytes) drugs

641

Infliximab (Remicade) Monoclonal antibody which binds TNF- RA Tx - given as an IV infusion every several weeks with
Anti-TNF- (chimeric mouse/human) methotrexate usually
Recombinant protein (genetically
engineered) consisting of the two soluble
642 portions of the TNF- receptor molecule
Etanercept (Enbrel) Anti- and the Fc portion of human IgG. It
TNF- binds two molecules of TNF- RA Tx - injected sub Q twice a week

643 (Decreases the immunoreactivity relative


Adalimumab (Humira) to infliximab by using an) entirely human
Anti-TNF- monoclonal Ab to TNF- RA Tx

644
Recombinant form of human interleukin-1
Anakinra (Kineret) Anti-IL1 receptor antagonist (IL-1ra) Efficacy as good as DMARD for RA Tx
Cyclosporine inhibits T lymphocytes, see Organ transplants & for RA when it fails to respond to
645
(Sandimmune) Immunosuppressants other therapies
Purine antimetabolite that interferes
with purine synthesis and also causes
646 DNA damage through formation of false
nucleotide substrates for DNA synthesis, Cancer, transplant rejection, SLE, and severe refractory
Azathioprine (Imuran) see Immunosuppressants RA
A B C

Analog of the amino acid cysteine that


can slow bone destruction in Immunosuppression: tx rheumatoid arthritis (if other tx have
rheumatoid arthritis by unknown failed); also tx Scleroderma
647 mechanisms;It works by reducing It is used as a chelating agent:
numbers of T-lymphocytes, inhibiting Wilson's dz (binding to accumulated copper and elimination
macrophage function, decreasing IL-1, through urine)
D-Penicillamine decreasing rheumatoid factor, and Cystinuria (binds with the cystine to make it more soluble)
(Cuprimine) preventing collagen from cross-linking. Tx mercury poisoning.

nitrogen mustard alkylating agent,


648 alkylates DNA interfering with synthesis
and function causing T and B cell primarily as an anticancer agent; severe autoimmune
Cyclophosphamide suppression (and all rapidly proliferating disease especially when systemic complications like
(Cytoxan) tissues), see Immunosuppressants vasculitis are present
649 Ifosfamide nitrogen mustard alkylating agent

650 Initially releases substance P, local


Capsaicin (Zostrix) depletion of substance P (long-lasting) Cream applied for relief of pain associated with OA and RA

651 Gold salts probably inhibit the Suppress but do not cure RA. Early active arthritis
maturation and function of especially for diseases which progress despiite NSAID use.
mononuclear phagocytes and of T Water soluble used in intramuscular injections given weekly
Aurothioglucose cells, thereby suppressing immune until 1 gram has been achieved leading to accumulation of
(Solganal) Gold Salt responsiveness gold in the tissue
Gold salts probably inhibit the Suppress but do not cure RA. Early active arthritis
maturation and function of especially for diseases which progress despiite NSAID use.
652 mononuclear phagocytes and of T Water soluble used in intramuscular injections given weekly
Gold sodium thiomalate cells, thereby suppressing immune until 1 gram has been achieved leading to accumulation of
(Myochysine) Gold Salt responsiveness gold in the tissue
Gold salts probably inhibit the
maturation and function of Suppress but do not cure RA. Early active arthritis
653 mononuclear phagocytes and of T especially for diseases which progress despiite NSAID use.
Auranofin (Ridaura) Gold cells, thereby suppressing immune Hydrophobic administerd as oral dose for about 6-9 months
Salt responsiveness better tolerated than injectable but less efficacious
treat tenderness, swelling and pain caused by the
654
Meloxicam [Mobic] inflammation of osteoarthritis and rheumatoid arthritis
655 Gout Drugs
A B C

656 Xanthine oxidase inhibitor (purine DOC for chronic gout (intercritical or tophacious) and
analog competetively inhibits), reduces treats hyperuricemia primary to gout or from malignancy or
Allopurinol (Zyloprim) uric acid production renal failure. Once daily oral dose

657
Uricosuric - block proximal tubular
secretion (low dose) and resorption (both
Probenecid (Benemid) occur at high dose) of uric acid Gout; delayed excretion (secretion) of penicillin

Uricosuric - block proximal tubular


658 secretion (low dose) and resorption (both
occur at high dose) of uric acid; sulfa
Sulfinpyrazone (Anurane) derivative Gout

Binds to tubulin in mitotic spindles


and other microtubular structures causing
659 arrest of cell division, cell mobility, and Use to be the DOC, provides symptomatic relief if
release of granules. This mechanism is administered early, and provides diagnostic confirmation
believed to prevent migration of given it relieves symptoms of gout only; slow onset; commonly
Colchicine granulocytes into the inflamed area used with allopurinol
NSAID: inhibiting prostaglandin synthesis
(analgesic); also, NSAIDs inhibit
660 phagocytosis (M0) of urate crystals (anti-
inflammatory - Note that other NSAIDs
with lower SE can be used, see NSAIDs
Indomethacin (Indocin) below). Initial DOC for acute gout attacks
661

662
Non-Steroidal Anti-Inflammatory Drugs
A B C

Patent Ductus Arteriosus - closure


Low dose aspirin together with diet and exercise is useful for
the prophylaxis of:
coronary artery disease
deep vein thrombosis
unstable angina
prophylaxis and treatment of MI and stroke
Colorectal cancer
Therapeutic Uses: Analgesic/Antipyretics - symptomatic
relief for pain of low-to-moderate intensity:
Headache
Dysmenorrhea (see extra note)
663 Analgesic, Antipyretic, Anti- Arthralgia
inflammatory Myalgia
All NSAIDS inhibit the enzyme Neuralgia
cyclooxygenase (COX), which is a key Arthritis
enzyme responsible for the synthesis of Therapeutic Use as Anti-Inflammatory Agents
prostaglandins. Prostaglandins contribute Rheumatoid Arthritis
to a number of inflammatory processes. Osteoarthritis
Common mechanism of action leads to Gout and Crystal Arthritis
common side effects. Systemic Lupus Erythrematosus
Aspirin covalently (irreversibe and Seronegative Spondyloarthropathy
noncompetitive antagonism) inhibits Arthralgia
COX 1&2, recovery of COX in most Myalgia
tissues is by synthesis of new enzyme, Bursitis, Tendonitis
Platelets cannot synthesize new COX, so External application: salicylic acid is used topically to burn
inhibition is irreversible. (Note, aspirin is off warts, calluses, and corns, i.e., keratolytic. Methyl
Aspirin [generic], OTC - the only NSAID that covalently bind, all salicylate (oil of wintergreen) is found in some liniments as
Osalicylate & prototype others are competitive inhibitors) an external irritant

Used for chronic treatment; commonly used for relief of pain


and fever as over the counter medications. Significant
advantages over aspirin - better tolerated (have all of the
664 detrimental features of NSAIDs). Uses: Rheumatoid Arthritis,
Osteoarthritis (not an inflamatory dz, but does involve pain),
Gout and Crystal Arthritis (acute gouty arthritis), SLE,
Ibuprofen [Advil, Motorin, Seronegative Spondyloarthropathy, Arthralgia, Myalgia,
Nuprin], OTC - Propionic analgesic, antipyretic, anti-inflammatory; Bursitis, Tendonitis, Ankylosing spondylitis, Arthralgia, Myalgia,
Acids COX 1&2 competitive inhibitors Acute Bursitis, Tendonitis, primary dysmenorrhea
A B C

used for chronic treatment; commonly used for relief of pain


and fever as over the counter medications. Significant
advantages over aspirin - better tolerated (have all of the
665 detrimental features of NSAIDs).
Uses: same as ibuprofen
Naproxen [Aleve, analgesic, antipyretic, anti-inflammatory. Used instead of Aspirin during childhood infection with
Naprosyn], OTC - COX 1&2 competitive inhibitor, longer varicella and other viruses, especially the influenza virus
Propionic Acids half-life (14hr) (chose ibuprofen or naproxen)

Used for chronic treatment; commonly used for relief of pain


and fever as over the counter medications. Significant
advantages over aspirin - better tolerated (have all of the
666 detrimental features of NSAIDs).
Uses: analgesia of acute tendinitis, bursitis, and primary
analgesic, antipyretic, anti-inflammatory; dysmenorrhea, rheumatoid arthritis, osteoarthritis, ankylosing
Ketoprofen [Orudis] COX 1&2 competitive inhibitors spondylitis, and acute gouty arthritis.
Never used for routine analgesia
Can be used in resistant rheumatoid disease,
667 osteoarthritis, ankylosing spondylitis, and acute gout.
Indomethacin [Indocin] - more potent than aspirin; COX 1&2 Suppression of uterine contraction in preterm labor and
Indoleacetic Acids competitive inhibitors closure of patent ductus arteriosus
Etodolac [Lodine] - Postoperative analgesia (single dose lasts for 6-8 hours).
668
Indoleacetic Acids relatively COX-2 selective Treatment of osteoarthritis and rheumatoid arthritis.

Can be used orally, IM, or IV; used for 5 days or less


One of only a few NSAIDs that can be given parenterally!!!
669 Used for post-operative pain, as an alternative to opioids
(not obstetrics)
Ketorolac [Toradol] - Potent analgesic, weak antiinflammatory Unlike opioids, it is not associated with tolerance, withdrawal
Heteroaryl Acetic Acids effect; COX 1&2 competitive inhibitors effects, or respiratory depression.

Originally approved for dysmenorrhea, osteoarthritis, and


rheumatoid arthritis (RA), acute post-operative pain
COX-2 specific NSAIDs were preferred for chronic treatment,
670
Selective COX-2 Inhibitors; contains but there use now (Celebrex only) is very controversial.
sulfur Studies show reduction in number of polyps with COX-2
Significantly less GI ulcers (by inhibitors (COX-2 is overexpressed in several human
endoscopy, decreased GI bleeding still cancers). Increasing evidence suggest that COX-2 inhibitors
unproven). may be effective for prevention or treatment, especially for
Celecoxib [Celebrex] Do not effect platelets and bleeding time. colorectal cancer
A B C

671

Valdecoxib [Bextra] Selective COX-2 Inhibitors, Withdrawn

672
Refocoxib [Vioxx] Selective COX-2 Inhibitors, Withdrawn

673 1. Commonly used for relief of pain and fever as over the
counter medications; useful analgesic/antipyretic for
children and those with contraindications to aspirin.
Non-NSAID antipyretic/analgesic, a 2. Initial DOC for treatment of pain in osteoarthritis (which
non-narcotic analgesic; is a non-inflammatory condition)
Very weak anti-inflammartory activity 3. Combined with opioid agonists for additive postoperative
Acetaminophen [Tylenol] - (unknown mech; not used for pain relief [Percocet, Lortab, Vicodin, Darvocet, Tylenol with
non-narcotic, non-NSAID inflammation) Codeine]
Zafirlukast [ACCOLATE] & prophylactic treatment of chronic asthma in patients >
674 Montelukast Anti-leukotriene Drugs - LTD4- 12 years old. As yet, these agents are not approved for
[SINGULAIR] leukotriene receptor antagonists treatment of other inflammatory conditions
675 Sulindac
treat tenderness, swelling and pain caused by the
676
Meloxicam [Mobic] inflammation of osteoarthritis and rheumatoid arthritis
677

678
Corticosteroid Drugs
Glucocorticoids (metabolic) inhibit the production and release of many different cytokines that normally would stimulate the proliferation and function of B and T lym
phospholipase A2 from forming arachidonic acid from phosphoipids.
O=oral; I=injectable; T=topical; Inh=inhaler; E= eye drops
A B C

Rheumatic and autoimmune disorders - Rheumatoid


arthritis, systemic lupus erythematosus, etc.
Chronic inflammatory diseases - ulcerative colitis, Crohns
disease
Organ transplant rejection
679 Asthma: Inhalation localizes drug to the lung and minimizes
systemic absorption; Prophylaxis only - acute attacks treated
with beta2-adrenergic agonists; Emergency treatment of status
asthmaticus
Treatment of Allergic Reactions: Anaphylactic reactions -Epi
first, steroids for delayed reactions
Potent, efficacious anti-inflammatory Important drug for treatment of dermatologic inflammatory
and immunosuppressive agent. reactions and diseases (many different topical glucocorticoids
Glucocorticoids inhibit the production and available, absorption after topical application is enhanced if
release of many different cytokines that covered with an occlusive dressing)
normally would stimulate the proliferation Cancer chemotherapy: Anti-leukemia/lymphoma properties,
and function of B and T lymphocytes. enhancement of antiemetic drug effects
Cortisol: short acting (8-12 hrs) (T, I, O) Cerebral edema and trauma
Lipocortin-mediated inhibition (protein Edematous, Gastrointestinal, Ophthalmic, Sarcoidosis (by
which inhibits) of PLA2 (phospolipase A2) no means an exhaustive list of uses)
Cortisol (aka Suppression/redistribution of leukocytes A single dose, even a large one, is virtually without
Hydrocortisone) Immune/CNS feedback harmful effects

680
Prednisolone Intermediate acting (12-36 hrs) (O, I, E)
Intermediate acting (12-36 hrs) (O); 4
681 times more potent than cortisol, about a
Prednisone third of the mineralcorticoid effect see Immunosuppressant drugs bellow
682 Methylprednisolone Intermediate acting (12-36 hrs) (T, I) Used for spinal injuries, slows progression of degeration
Intermediate acting (12-36 hrs) (O, T, I,
683
Triamcinolone Inh)
684 Beclomethasone Long acting (36-54 hrs) (Inh) See pulmonary drugs
A B C

potent, long-acting; Dexamethasone is also effective in


preventing acute mountain sickness (dexamethasone, 4 mg
685 4 times per day, if the condition is severe). The recommended
Long acting (36-54 hrs) (T, I, O); 30 times prophylactic dosage for adults is 2 mg every 6 to 8 hours. In
more potent than cortisol with no addition, Gingko biloba has been suggested as a useful
Dexamethasone mineralcorticoid effect prophylactic agent but has not been sufficiently studied
Mineralocorticoid (O) (super active, 125
686 or 250 (depending on source) salt-
retaining activity relative to cortisol which
Fludrocortisone is 1) aldosterone replacement (addison's d.)
687 Corticosterone Mineralocorticoid
similar to the insecticides DDT and DDD
688 and has relatively selective toxicity for the
Mitotane adrenal cortex used to treat inoperable adrenal tumors.
Aminoglutethimide inhibitor of the initial and rate-limiting used to decrease hypersecretion of cortisol in patients with
689
[Cytadren] step of steroid biosynthesis Cushings syndrome.
an antifungal agent that at high doses
690 inhibits adrenal and gonadal Tx systemic fungal infections, used to treat Cushings
Ketoconazole [Nizral] steroidogenesis disease
691 Mifepristone [RU-486] progesterone receptor antagonist use (in Europe) to terminate early pregnancy

Potassium-Sparing Diuretic that


competes for the mineralocorticoid
receptor (ie an aldosterone antagonist)
692 and thus inhibits Na reabsorption in the
kidney. It can also antagonize effective for treating hyperaldosteronism. The drug is also
aldosterone and testosterone synthesis. useful for the treatment of hirsutism in women, probably due to
Spironolactone See diuretics competition at the androgen receptor of the hair follicle.
second-line drugs for Rheumatoid Arthritis (along with glod
693
Methotrexate See cancer chemotherapy below salts)
694

695
Immunosuppressant Drugs
A B C

Calcineurin inhibitor: Cyclosporine


binds directly to calcineurin
(cylophilin?); Calcineurin is a cellular
protein that assists enzyme functions and
the complex processes of IL-2 in
signaling between immune cells;
reduction in IL-2 production leads to:
696 1. decreased clonal proliferation of T
cells; 2. decreased IL-2 receptor
expression. 2. reduced activation and
clonal expansion of cytotoxic T cells from
CD8+ precursor cells; 3. reduced
functional activity of effector T-cells that Although it is a potent immunosuppressive agent, it has no
are involved in cell-mediated responses, effect on acute inflammation reactions; Cyclosporin is used
such as delayed type hypersensitivity; 4. alone or incombination with other immunosuppresive agents.
some reduction of T cell mediated B cell It is primarily used for organ transplantation. It has also
Cyclosporine responses. been used to treat psoriasis and asthma.

Calcineurin inhibitor: interfers with the


ability of IL-2 to communicate with the T-
cell receptors, suppressing the activation
and replication of the T-cells. Tacrolimus
697
a) is not structurally related to cylosporin Immunosuppression for organ transplantation. It is effective
and b) binds to an immunophilin for preventing rejection of solid organ transplantation,
binding protein called FK-binding even after failure of standard rejection therapy. On a
protein (FK-BP). The FK-506/FK-BP weight basis tacrolimus is 10- to 100-fold more potent than
complex inhibits calcineurin, inhibiting cyclosporin (and so requires lower dose of steroids in
Tacrolimus (Prograf) IL-2 production. combination therapy).
inhibits signaling from the IL-2
698 receptor - suppress activation and
differentiation of nave T cells (and thus
Rapamycin all IR required of T cells)
Dimeric fusion protein that binds to CD2
on memory-effector T cells, resulting in
699 the inhibition of T cell activation and a
reduced number of memory-effector T
lymphocytes; causes apoptosis of T
Alefacept cells Tx of Psoriasis
A B C

Cytotoxic Agents: kill rapidly


proliferating cells, suppression of WBC
700 proliferation; interfers with purine a. to inhibit the immune response that causes rejection of
metabolism during lymphoid cell kidney transplants.
proliferation that follows antigen b. for the treatment of severe, active rheumatoid arthritis. It
stimulation. Effect nucleic acid is considered a "second-line," or "slow- acting" drug and is
synthesis that is required for cell usually reserved for rheumatoid arthritis patients who do not
proliferation. Cellular immunity (T cell respond to other first-line or second-line medications.
mediated) and both primary and c. to treat Crohn's Disease (inflammatory bowel disease) and
Azathioprine (aka 6- secondary antibody responses are multiple sclerosis.
mercaptopurine, Imuran). blocked by these agents

Immunosuppressive Abs: engineered


monoclonal antibody that targets and
blocks the function T3 or CD3 antigen
expressed on T cells a) associated with OKT3 prevents or reverses graft rejection by blocking the
701 the antigen recognition structure b) is cytotoxic activity of T cells. Reversal of rejection occurs in
essential for signal transduction. Binding about 95 percent of patients given the drug. The major
of OKT3 to T cells results in early problem with this drug has been with side effects. Used to
activation, which leads to cytokine treat patients in the first few weeks after transplant. After
OKT3 (muromonab-CD3 release, followed by blocking T cell termination of OKT3 therapy, T cell function usually returns to
(Orthoclone OKT3)) functions. normal within one week.
Converted to the active metabolite
mycophenolic acid, which inhibits de
702 novo synthesis of the guanine
nucleotid (lymphocyte proliferation
Mycophenolate mofetil dependent upon this purine synthesis) Immunosuppresive therapy
Ab with high-affinity for IL-2 receptor
703
Daclizumab on activated T-cells Immunosuppresive therapy

704 Ab with high-affinity for IL-2 receptor


Basiliximab on activated T-cells Immunosuppresive therapy

705 inhibits T-cell proliferation by binding the


serine-threonine kinase, mTOR, which
Sirolimus is necessary for cell cycle progression Immunosuppresive therapy (minimal renal toxicity)
A B C

Nitrogen Mustard alklayting agent:


prodrug which must be activated by the
liver P-450 mixed enzymes to 4-hydroxy-
cyclclophosphamide; a bivalent
alkylating agent; the effect on
706 lymphocytes appears to be primarily due
to cross-linking of DNA strands. This
decreases the antigen-dependent a. Tx of autoimmune disorders such as systemic lupus
proliferative response in lymphocytes; erythematosus and multiple sclerosis or Wegener's
destroys proliferating lymphoid cells. granulomattosis (an autoimmune hemolytic anemia).
Although similar damage occurs in both T b. Tx of cancers including lymphoma, leukemias, multiple
and B cells, the slower recovery of the B myeloma, mycosis fungoides, neuroblastoma, retinoblastoma,
cells leads to a pronounced effect on and cancers of the breast and ovary.
Cyclophosphamide humoral immunity. c. Immunosuppressive for organ transplantation.
707 Ifosfamide Nitrogen Mustard alklayting agent

Glucocorticosteroid:
1. can reduce the size and number of
cells in the lymph nodes and spleen,
with little effect on erythoid stem cells in
the bone marrow.
2. are cytotoxic to subsets of T cells.
However, immunosuppressive effects are
predominantly due to the modification of 1. suppress organ rejection
function rather than cytotoxicity. a. allergic reactions bee stings, contact dermatitis, allergic
708
4. inhibit the production of drug reactions, allergic rhinitis
inflammatory mediators, such as b. collagen-vascular disorders lupus erythematosus
leukotrienes, prostaglandins, histamine rheumatoid arthritis
and bradykinnin. c. eye disorders allergic conjunctivitis, optic neuritis
5. attenuate chemotaxis and impair d. GI disorders inflammatory bowel disease
bactericidal and fungicidal activity of e. hematologic disorders and malignancies leukemia,
monocytes and neurtrophils, without autoimmune hemolytic anemia, multiple myeloma
altering phagocytic activity. f. Systemic inflammation acute respiratory distress syndrome,
6. can alter leukocyte and neurtorphil gram (-) septicemia to suppress excessive inflammation
distribution causing cells to sequester h. joint inflammatory disorders arthritis, bursitits
in lymphoid tissue. i. neurlogical disorders cerebral edema (to minimize
7. inhibit IL-1 production, leading to postoperative cerebral edema), multiple sclerosis
reduced IL-2 & IFN- production. j. pulmonary disorders bronchial astma, infant respiratory
8. attenuate both cellular and humoral distress syndrome
Prednisone mediated immune responses. k. skin disorders dermatitis xerosis
A B C

Prompt suppression of inflammatory conditions, including


rheumatoid arthritis, systemic lupus erythematosus, acute
gouty arthritis, psoriatic arthritis, ulcerative colitis, and Crohn's
disease. Severe allergic conditions that fail to respond to
709 conventional treatment may respond to
methylprednisolone include; bronchial asthma, allergic
rhinitis, drug-induced dermatitis, and contact and atopic
dermatitis. Chronic skin conditions treated with
methylprednisolone include dermatitis herpetiformis,
pemphigus, severe psoriasis and severe seborrheic dermatitis.
Glucocorticoid: Methylprednisolone is Chronic allergic and inflammatory conditions of the uvea, iris,
a synthetic corticosteroid. Its meachnism conjunctiva and optic nerves of the eyes also are treated with
Methylprednisolone of action is similar to prednisone. methylprednisolone

710
1. control a wide number of disease states which are
characterized by excessive inflammation, including, a) severe
allergic reactions, b) inflammation of the lungs in asthma and
c) inflammation of the joints in arthritis.
2. decrease the numbers of white blood cells and is used
to prevent the rejection of organ transplants
3. treat cancers, including acute lymphatic leukaemia and
myelomas
Glucocorticoids: meachnism of action 4. treat some autoimmune diseases, including systemic lupus
Deflazacort is similar to prednisone erythematosus and rheumatoid arthritis.
711

712 Cancer Chemotherapy


A B C

713

Hodgkins Disease & testicular tumors: used to treat germ


cell tumors of the testis & ovary, squamous carcinomas of
Antitumor antibiotic - Single & double the head and neck, esophagus, and genitourinary tract. It is
strand DNA breaks from free radical often used as a component of combination therapy of
formation; cell cycle specific, G2 Hodgkins and Non-Hodgkins lymphomas. (Does not cause
Bleomycin phase specific. BM suppression!)
activity historically against Hodgkins Disease. Not used
714
Mechlorethamine Nitrogen Mustard, Alkylating Agent commonly anymore due to toxicities associated with it

715
most commonly in the treatment of multiple myeloma or non-
Melphalan Alkylating Agent resectable epithelial carcinoma of the ovary
Alkylating Agent: a Platinum
716
Carboplatin compounds

primary use is in GI malignancy, most commonly as adjuvant


717 therapy or use in metastatic colon cancer, but is also used in
Alkylating Agent: a Platinum other GI malignancies, and is being investigate for use in lung
Oxaliplatin compounds cancers, as well as other malignancies
A B C

718 Alkylating Agent: a Platinum


compounds - Kills cells in all stages of
cell cycle, inhibits DNA synthesis, &
cross-links DNA!! Cell-cycle-active
but non-phase-specific (CCNS, also Bladder Ca, esophageal Ca, head/neck Ca, lung Ca,
Cisplatin known as cycle-independent) osteogenic sarcoma, ovarian Ca, testicular Ca

Oxazaphosphorine, Classic Alkylating


Agent - Highly reactive; spontaneously
transfer their alkyl groups to DNA,
719 protein, or other cell constituents
producing cytotoxic effects. Cross-link
DNA & strand breakage. Non cell cycle-
specific (CCNS) but cells most
susceptible during late G1 and S phases. Bladder Ca, breast Ca, chronic lymphocytic leukemia, lung Ca,
Cyclophosphamide see immunosuppresants above non-Hodgkin's lymphoma, ovarian Ca, soft tissue sarcoma
720 Ifosfamide See cyclophosphamide See cyclophosphamide
Mixture of a mAb directed to CD33 Ag
on hematopoietic cells and the cytotoxic
721 antibiotic, calicheamicin - enters the
lysosomes of CD33+ cells and releases
calicheamicini, which induces DNA
Gemtuzumab ozogamicin strand breaks AML
Tx Chronic lymphocytic leukemia (CLL) annd ovarian cancer;
722
Chlorambucil Nitrogen mustard alkylating agent other lymphomas

723 Atypical Alkylators: old alkylator, used in breast cancer or ovarian cancer and can be given
Thiotepa CCNS intravesically for bladder cancer. It can be given intrathecally.

palliative treatment of CML. In high doses, it has activity in


724 acute leukemia and lymphoma. It is most commonly used
today in high doses as part of a bone marrow transplant
Busulfan Atypical Alkylators, CCNS regimen
A B C

They are the most lipid soluble and also are among the most
carcinogenic.
725 They are used for brain tumors and BCNU has activity
against lymphomas, Hodgkins Disease and melanoma.
They arent used very frequently, except BCNU comes in a
Nitrosureas - alkylating agent; cross wafer form placed in the brain after resection of brain
Carmustine the BBB, CCNS tumors.
726 Lomustine Nitrosureas, see carmustine see carmustine
used in metastatic islet cell tumors of the pancreas
727 Nitrosurea antibiotic: Potent inhibitor (insulinomas!). It also has some activity in lymphomas and
of alkyltransferase, the DNA repair carcinoid tumors.
Streptozotocin enzyme, CCNS Poorly tolerated

An anthracycline - planar multi-ring


structures that are active by 1) insertion
of the planar ring between base pairs
(G-C sequence) of DNA; 2)
728 Topoisomerase II inhibitor & also 3)
generates intracellular free radicals
which are highly cytotoxic 4) disrupts fluid
and ion transport across cellular
membranes. These drugs are Cell Bladder Ca, breast Ca, gastric Ca, hepatocellular Ca,
Cycle Nonspecific (CCNS). Hodgkin's disease, lung Ca, non-Hodgkin's lymphoma,
Doxorubicin Resistance occurs through P osteogenic sarcoma, soft tissue sarcoma. Doxorubicin is
(Adriamycin) glycoprotein mechanism one of the most useful anticancer drugs (Broad spectrum)
See doxorubicin; an antitumor
729 antibody - inserts between DNA bases
Daunorubicin and induces DNA strand breaks
730 Idarubicin See doxorubicin

Derived from Streptomyces sp.; most


active in G1 phase, but is considered cell
731 cycle independent; It intercalates itself
particularly at guanine bases. It
interferes with DNA-dependent RNA
synthesis, which leads to protein Most commonly used in Wilms Tumors (nephroblastomas),
Dactinomycin synthesis inhibition. rhabdomyosarcoma, testicular and uterine cancers.
A B C

Antitumor Enzymes: cleaves


asparagine into aspartic acid and
ammonia. This takes place
extracellularly. Most cells have high
732
levels of asparagine synthetase, so are
not affected, but T cells and many
malignant lymphocytes have low levels
and are therefore reliant on extracellular
pools of asparagine. This leads to protein
L-asparaginase synthesis inhibition and cell death used in ALL and some T cell Lymphomas.

Immunotherapy: creates an
733 inflammatory cascade, attracting
chemokines, cytokines which attract
BCG (Bacillus Calmette- macrophages and T cells which kill tumor originally developed as TB vaccine. Its use is in the bladder
Guerin) cells and provides immunologic memory against superficial bladder cancers.

734 Used in melanoma and renal cell c. (both usually resistant to


Directly modulates the immune chemo), chronic hepatitis B and C; Tx multiple sclerosis
Recombinant Interferon response and directly affects (reduce exacerbations)
alpha-2a proliferation of tumor cells.

Normally secreted by TH1 cells to


735 increases TH1 proliferation (autocrine),
activate CTL, and activate M0 (cell-
Interleukin-2 mediated IR)
Must first be converted to thio-IMP by
HGPRT Ez (purine salvage pathway);
736 thio-IMP acts as purine analog, which
inhibits PRPP Amidotransferase which
inhibits purine synthesis. S Phase indicated for the induction and maintenance of remission of
6-Mercaptopurine specific, Self-limiting ALL
Antimetabolite: derivative of the antiviral used in B lymphocyte malignancies
737
Fludarabine agent, vidarabine Very effective Low grade malignancies

738 Cladribine (2-


chlorodeoxyadenosine, Antimetabolite: analog of
2CDA) deoxyadenosine used in hairy cell leukemia (a B lymphocyte malignancy)
Adenosine analog, that bind and inhibit
739
Pentostatin adenosine deaminase targets lymphoid malignancies; hairy cell leukemia
A B C

Antimetabolite: a nucleoside composed


740 of cytosine and a sugar link (araCTP). It
is analog to naturally occuring
Cytarabine (cytosine deoxycytosin; competitively inhibit DNA ALL, AML, non-Hodgkins lymphoma
arabinoside) polymerase; Inhibits replication It can also be given intrathecally and crosses the BBB readily.

Antimetabolite: a pyrimidine analogs -


Inhibitor of thymidylate synthase;
Inhibits DNA synthesis; strand breakage;
741 Inhibits RNA processing and function -
induce cytotoxicity by serving as false Virtually all adenocarcinomas and some squamous
substrates in biochemical pathways; cell- malignancies; Breast Ca, colorectal Ca, esophageal Ca,
cycle-active and are specific mainly for gastric Ca ; Direct hepatic artery infusions for the treatment of
Fluorouracil (5FU) the S phase. hepatic metastases
Indicated in colorectal adenocarcinoma, as well as other GI
742 It is an oral agent, converted into 5- malignancies, especially when fluoropyrimidine therapy is
Capecitabine fluorouracil preferred. Other indications: breast cancer

743
Levamisole enhances cell-mediated immunity Used in combination with 5FU to tx certain colon cancers

1. Cancer Tx: (higher doses) Acute lymphoblastic leukemia


(ALL), systemic and CNS lymphomas (NHLs), leukemias;
choriocarcinoma (gestational trophoblastic Ca) and
carcinomas of the breast, head and neck, ovary, bladder, and
744 Antimetabolite: a Folic Acid osteogenic sarcoma.
Antagonists - inhibits dihydrofolate 2. Transplant & autoimmune immunosuppressant: (lower
reductase and the conversion of folic doses) severe psoriasis (treats both skin and arthritis), IR in
acid to tetrahydrofolic acid (DHF to THF); GVHD and as an immunosuppressive agent in BM and organ
thus, inhibits synthesis of thymidine, transplant procedures; dermatomyositis, rheumatoid arthritis,
purines and DNA. S phase specific, Wegeners granulomatosis, and Crohns disease; also
self-limiting (?); It crosses the BBB and treatment for non-acute ectopic pregnancy.
Methotrexate can be given intrathecally (High dose therapy with Leucovorin rescue)

Antimetabolite: inhibits the enzyme Chronic myelogenous leukemia (CML), essential


ribonucleotide diphosphate reductase, thrombocytosis; the principle use of hydroxyurea has been
which converts ribonucleotides to as a myelosuppressive agent!! in the myeloproliferative
745
deoxyribonucleotides (XDP to dXDP). syndromes, particularly chronic granulocytic leukemia,
This is a critical and rate-limiting step in polycythemia vera, and essential thrombocytosis; some solid
de novo DNA synthesis. Kills cells that tumors; sickle cell disease (reduces the number of painful
are rapidly dividing during the S phase crises, the frequency of acute chest syndrome and
(those with short G0 phase and cycling hospitalization, and the need for blood transfusions);
Hydroxyurea times); crosses the BBB. HIV/AIDS.
A B C

Hormone agent: a Gondotropin-


Releasing Hormone Analog - Indirect
746 antiandrogen; function as LHRH agonists
cause transient release of FSH & LH
followed by inhibition of release of FSH &
LH, decreasing testosterone levels. Prostate cancer, used with flutamide, bicalutamide, or
Leuprolide Functional castration after 2-4 wks. nilutamide

747 Hormone agent: antiandrogen;


Flutamide androgen receptor antagonist Prostate cancer, used with leuprolide
Hormone agent: antiandrogen;
748
Bicalutamide androgen receptor antagonist Prostate cancer, used with leuprolide

Hormone agent: pure, nonsteroidal


antiandrogen with affinity for androgen
749 receptors (but not for progestogen,
estrogen, or glucocorticoid receptors).
Blocks actions of androgens of adrenal
and testiuclar origin that stimulate growth Tx adenocarcinoma of the prostate. Usually given with
Nilutamide of normal nad malignant prostatic tissue. injections of leuprolide

Hormonal agent: an
adrenocorticosteroids - Lympholytic
750 effects and suppress mitosis in ALL; CLL; Non-Hodgkins lymphoma - very useful in Tx of
lymphocytes; CCNS. See acute leukemia & malignant lymphoma in children and adults.
immunosuppressants or corticosteroids Also useful to reduce edema related to tumors in critical areas,
Prednisone above i.e., mediastinum, brain, spinal cord.
751 Dexamethasone see prednisone see prednisone

752 Hormonal agent: a Antiestrogen -


Chemopreventive agent in women at
high risk for breast Ca; competitive
partial agonist/antagonist of estrogen
Tamoxifen receptors in estrogen-sensitive tumors. Tx estrogen-receptor-positive breast cancer
Plant alkaloid: a Taxane - act by
753 stabilizing microtubules (MT) and
preventing their disassembly, M phase
Paclitaxel (Taxol) specific. Ovarian and breast CA
A B C
Plant alkaloid: a Taxane - act by
754 stabilizing microtubules (MT) and
preventing their disassembly, M phase
Docetaxel specific.

Plant alkaloid: a Vinca alkaloid - bind to


tubulin and cause depolymerization of
MT in the cytoskeleton and mitotic
755 spindle. They block chromosome
segregation during mitosis and thus are
cytotoxic predominately during the M Bladder Ca, breast Ca, Hodgkin's disease, lung Ca, non-
phase of the cell cycle. Resistance Hodgkin's lymphoma, metastatic testicular tumors;
develops due to amplification of P lymphomas, Kaposis sarcoma, neuroblastoma, and
Vinblastine glycoprotein pump. carcinoma of the breast and choriocarcinoma

756

Plant alkaloid: a Vinca alkaloid, see Acute lymphoblastic leukemia, Hodgkin's disease, non-
Vincristine vinblastine Hodgkin's lymphoma, metastatic testicular tumors

Camptothecins: function as
topoisomerase I inhibitors. Topo I
induces single strand breaks in
757 supercoiled DNA. Topoisomerase I (II??)
reseals the break when unwound; block
the dissociation of TOPOI from the DNA
and a double strand break occurs,
Topotecan, irinotecan leading to cell death.

(epi)Podophyllotoxin: a Topoisomerase
II inhibitor. TOPOII is a repair enzyme
that binds, DNA, cleaves the double
strands, causes one strand to pass
758 through the break, and then reseals the
cut. Etoposide inhibits the resealing of
cleaved DNA, leading to irreparable DNA
damage and cell death. S-G2 phase
Etoposide specific Testicular and small cell carcinoma
A monoclonal mouse antibody directed at Diffuse Large B Cell Lymphoma when given with CHOP
759 CD20-positive lymphocytic disease (B (Cyclophosphamide, adriamycin, vincristine and Prednisone),
Rituximab cell) ITP
A B C

760

Monoclonal antibody that binds to


Trastuzumab (Herceptin) Her2/neu, a growth factor receptor Breast Ca

761
Tretinoin or ATRA (all- combination with idarubicin for treatment of promyelocytic
trans retinoic acid) leukemia

762

Imatinib mesylate Interfere with the action of the CML; Gleevec treatment has led to hematologic remission
(Gleevac) abnormal Bcr-Abl tyrosine kinase (control of WBC levels) in almost all patients.
treatment for malignant hypercalcemia from bone mets or from
763 Alendronate, clodrinate, Bisphosphonates - turn off paraneoplastic syndromes such as increased PTH-like
etidronate and osteoclasts; leading increased bone peptide production from squamous cell lung cancer;
pamidronate strength and stabilization Osteoporosis, Paget's dz of the bone
Aromatase Inhibitors: 2nd gen; Either
steroidal or non-steroidal, they work by
764 blocking the conversion of adrenal
androgens into estrogens (non-
Anastrozole steroidal drug???) Breast CA; recurrent and metastatic breast CA
Aromatase Inhibitors: 2nd gen; Either
steroidal or non-steroidal, they work by
765 blocking the conversion of adrenal
androgens into estrogens (non-
Letrozole steroidal drug???) Breast CA; recurrent and metastatic breast CA
Prostate Hormonal Agents: LH/RH
analogs that inhibit gonadotropin
766 secretion, preventing production of
testosterone, which is the source of
Goserelin, leuprolide growth for majority of prostate cancers.
Vascular Endothelial Growth Factor
767
Bevacizumab Receptor Inhibitors
A B C
Epithelial Growth Factor Receptor
768
cetuximab or erlotinib Inhibitors
769 sorafenib or sunitinib Multikinase inhibitors renal cell cancer and melanoma

770 recombinant IL-2, immunostimulant -


enhance circulating numbers of cytotoxic
Aldesleukin T-cells (destroy or remove tumros cells) melanoma

771
Antibiotics
772 Beta Lactams
Competetive inhibitor of the
773 transpeptidase enzyme; inhibits bacterial
Penicillin G cell wall synthesis Strep pneumonia
774 Penicillin V Same
775 Aminopenicillins
776 Amoxicillin Same
777 Ampicillin Same
778 Penicillinase resistant
779 Methicillin Same

780
Nafcillin Same
781 Oxacillin Same
782 Cloxacillin Same
783 Dicloxacillin Same
784 Antipseudomonal
785 Carbenicillin Same
786 Ticarcillin Same
787 Pipercillin Same
788 Mezlocillin Same

789

Cephalosporons
Cephalosporin 1st
790
generation Gram +

791
Cephalothin-1st generation Same

792
Cephalexin-1st generation Same
793 Cefazolin-1st generation Same
794 Cefadroxil-1st generation Same
A B C
Cephalosporin-2nd
795
generation Klebsilla, H. influenzae, and anaerobes
796 Cefamandole Same
797 Ceflacor Same
798 Cefuroxime Same
799 Cefoxitin Same
800 Cefotetan Same
801 Cefmetazole Same
802 Cefonicid Same
803 Loracarbef
Cephalosporin 3rd
804
generation Gram -
805 cefixime Same
806 cefotaxime Same Severely ill ICU patients with pneumonia
807 ceftazidime Same
808 ceftizoxime Same

809 Severely ill ICU patients with pneumonia (especially H.


influenzae, M. catarrhalis, and most strains of S. pneumoniae
ceftriaxone Same and K. pneumoniae); treatment of HACEK (eg endocarditis)
Cephalosporin4th
810
generation Gram + & -
811 Cefepime
812 Carbapenems
Inhibits the bacterial wall synthesis (block
813 peptidoglycan cross-linking) - resistant Broad spectrum, especially enterobacter, anaerobes (and
Imipenem/Cilistatin to beta-lactamases!! most Gram + and -)
814 Meropenem See imipenem See imipenem
815 Monobactams
Tx of gram-negative UTIs, lower respiratory tract, and skin,
816
Aztreonam beta-lactam antibiotic and for intra-abdominal infections
817 Other

818
Bacitracin

819
AntiRibosomal
820 50S-CLEAN
A B C

821 Inhibits prokaryotic


peptidyltransferase (high levels may
also inhibit mitochondrial protein 2nd line antibiotic - tx of serious infections when less toxic
Chloramphenicol synthesis) alternatives are inappropriate

822 Lincosamide; Bind irreversibly to a site Excellent anaerobic coverage, most useful "aboe the
on the 50S subunit of the bacterial diaphragm" anaerobic infections (in part becasuse of the
Clindamycin ribosome, thus inhibiting translocation polymicrobial nature of lung absceseses)

823 Macrolide - Bind reversibly to a site on


the 50S subunit of the bacterial
Erythromycin ribosome, thus inhibiting translocation Ambulatory pneumonia
Pneumonia: Effective coverage to atypical pathogens (eg
824 Legionella and Moraxella (mycoplasm?)), some gram
Azithromycin Macrolide - See erythromycin negative pathogens, and most strains of S. pneumoniae
825 Clarithromycin Macrolide - See erythromycin

826
Linezolid Blocks initiation complex formation, 50S Used for vancomycin-resistant infectons
827 30S-TAG

828

Tetracyclines
Ambulatory pneumonia; Used for renal insufficienct pts,
829 excreted in feces; used prophylactically for chloroquine-
Doxycycline see tetracycline resistant strains of plasmodia/Malaria
Used for renal insufficienct pts, excreted in feces; tx acne
830
Minocycline see tetracycline vulgaris
831 Methacycline see tetracycline
832 Oxytetracycline see tetracycline
833 Demeclocycline see tetracycline
834
A B C

Protein synnthesis inhibitor


(irreversibly bind 30S bacterial ribosomal
subunit, and actis to inhibit the
835 formation of the initiaiton complex,
causes mRNA misreading leading to
non-functional proteins; also induces the Severe infection with gram-negative rods (eg sepsis,
dissolution of polyribosomes during chronic UTI, endocarditis (especially with vancomycin),
Aminoglycosides protein synthesis pneumonia, Pseudomonas infections
836 Gentamicin see aminoglycoside see aminoglycoside
see aminoglycoside, used for preparation for bowel surgery
837
Neomycin see aminoglycoside (kiills bowel flora)
838 Tobramycin see aminoglycoside see aminoglycoside
839 Amikacin see aminoglycoside see aminoglycoside
protein synnthesis inhibitor (binds the
30S bacterial ribosomal subunit, and
840 actis to inhibit the formation of the
initiaiton complex) essentially an
Streptomycin aminoglycoside

841
DNA Gyrase
MC used agent for traveler's diarrhea, UTI, URT, gonococcal
infections, atypical pneumonia; gram negatives
842 (Pseudomonas, Neisseria, Haemophilus, Enterobacter,
Fluoroquinolones Inhibit bacterial DNA gyrase thus causing Legionella, Mycoplasma)
(quinolone) breaks in the DNA DOC for complicated UTI

843
(quinolone) Inhibit bacterial DNA gyrase
Ciprofloxacin thus causing breaks in the DNA Anthrax
Newer quinolone - additional gram-positive
844 coverage/increased activity, especially to S. pneumonia!
Levofloxacin quinolone (some Staph), also covers P. aerguinosa
Newer quinolone - additional gram-positive coverage (S.
845
Gatifloxacin quinolone pneumonia, some Staph
Newer quinolone - additional gram-positive coverage (S.
846
Moxifloxacin quinolone pneumonia, some Staph; Anaerobe coverage
Gets gram + and - including pseudomonas only for severe
847
Trovafloxacin quinolone pnumonia due to LIVER TOXICITY

848
Sparfloxacin quinolone CAP - increased activity, especially to S. pneumonia!
849 Nalidixic acid quinolone Excreted rapidly, rarely used
A B C
metabolized to a compound that
850
Nitrofurantoin damages bacterial DNA Used for recurrent UTI

851
Vaccinations
852

Pneumococcal vaccine Pneumococcal pneumonia


853 Influenza vaccine Influenza

854

Polio vaccine Poliomyelitis


Japanese encephalitis
855
vaccine Japanese encephalitis mosquito-borne dz

856
Yellow-fever vaccine Yellow fever
857 Tyhoid vaccine Thyroid fever

858
Pertussis vaccine

859
Tetanus vaccine Tetanus
860 Varicella vaccine Chickenpox
861

862
Neurologic Drugs
863 Headaches

864
Tension Headaches (Combination: NSAIDS + Butalbital +
NSAIDs (non-steroidal see NSAIDs above; inhibit prostaglandin Caffeine); Tx of Migraine (must be taken very early in the
anti-inflammatories) synthesis attack to be effective!)
A B C

Barbiturate (member of the sedative-


865 hypnotic family); Mechanism is
facilitation of GABA
neurotransmission; Predominant effect Tension Headaches (Combination: NSAIDS + Butalbital +
Butalbital is sedation/anxiolytic Caffeine)

Competitive antagonist at adenosine


receptors! (which are presynaptic on
sympathetic terminals, where the
866 receptor decreases amount of NE, thus
blocking receptor increases NE and
causes vasoconstriction) & at higher
dose they are phosphodiesterase Tension Headaches (Combination: NSAIDS + Butalbital +
Caffeine inhibitors (potentiate beta1 or beta2) Caffeine)

867

Prophylactic Tx of Tension HA; also prophylaxis of


Migrane (give at night due to drowsy SE); useful tx for
Amitryptiline TCA, see antidepressants fibromyalgia
868 Doxepin Older antidepressants (not SSRIs) Prophylactic Tx of Tension HA

869
Imipramine TCA, see antidepressants Prophylactic Tx of Tension HA

870
Sumatriptan (prototype,
Imitrex) (Sumatriptan is prototype) 5HT1 Agent, Tx of Migrane (acute tx, take during prodromal phase);
Rizatriptan (Maxalt) Agonists at 5-HT1b & 5-HT1d sites (Gi Sumatriptan has ~2hr effect (so usually taken several times
Zolmitriptan (Zomig) coupled receptor) - inhibits vasodilation per episode), given both orally and parenterally, not used
Naratriptan (Amerge) (Sub P & CGRP, see extra notes) (5- prophylactically for migrane
Frovatriptan (Frova) Hydroxytryptamine (aka serotonin)) Tx for acute Cluster HA
A B C

871

Ergot Alkaloids; 5-HT1b/1d stimulation


(also dopaminergic, and alpha- Tx of Migranes ONLY (not general analgesic, and efficacious
Ergotamine (Ergomar) adrenergic receptor activity) only if used early in attack)
Tx of Migrane:
Ergot Alkaloids; 5-HT1b/1d stimulation Moderate migraine - Used orally if the migraine is
872 (actually binds all types of 5HT receptors) accompanied by significant nausea
Dihydroergotamine Minimal to no effect on peripheral arterial Severe migraine - If significant functional impairment, used
(Migranal) construction; Potent venoconstrictor i.m. or i.v. in ED (can be given well into attack)

873

Acute Treatment of Migraine, also anti-emetic (See


Metoclopramide (Reglan). Antagonists at D2 receptors gastrointestinal drugs above)
Acute Treatment of Migraine (especially non-responsive pts
874 Chlorpromazine Antagonists at D2 receptors or who have contraindications to vasoactive abortive agents),
(Thorazine) (neuroleptic) also anti-emetic
Acute Treatment of Migraine (especially non-responsive pts
875 Prochlorperazine Antagonists at D2 receptors or who have contraindications to vasoactive abortive agents),
(Compazine) (neuroleptic) also anti-emetic
Prophylaxis of cluster!
876
Verapamil CCB Prophylaxis of Migraine
Non-selective beta-blockers, see
877
Propranolol & Timolol adrenergic blockers above Prophylaxis of Migraine

878
Valproate see Seizure Medication Prophylaxis of Migraine; Prophylaxis of Cluster
A B C

879
Prophylaxis of Migraine:
Ergot derivative; blockade of 5-HT2a and Without benefit when given during an attack
5-HT2c receptors (blocks serotonin Protective effect develops over 1-2 days.
Methysergide receptors) Prophylaxis of Cluster HA

880

Treatment of Cluster Headaches (DOC) - acts in ~5min


Oxygen (issue is it is a pain to carry around)

881

1) Chronic Cluster HA (Narrow theraputic range before


toxicity, monitor closely)
Lithium See Mood Stabilizers 2) Tx Carbon monoxide poisioning!! (100% O2 antidote)
Prophylaxis of cluster HA; treatment of Giant Cell Arteritis (aka
882
Steroids temporal arteritis)
883 Motor Disease and Muscle Spasticity Drugs

884

Antimuscarinic (Anticholinergic):
Centrally-acting competitive inhibitors of Early stage treatment of Parkinson's Dz (if under 65yo) -
Biperiden muscarinic cholinergic receptors. Improve tremor and rigidity, but not bradykinesia.
Antimuscarinic (Anticholinergic):
885 Centrally-acting competitive inhibitors of Early stage treatment of Parkinson's Dz (if under 65yo) -
Trihexyphenidyl muscarinic cholinergic receptors. Improve tremor and rigidity, but not bradykinesia
Antimuscarinic (Anticholinergic):
886 Centrally-acting competitive inhibitors of Early stage treatment of Parkinson's Dz (if under 65yo) -
Benztropine muscarinic cholinergic receptors. Improve tremor and rigidity, but not bradykinesia
A B C

887 Selective inhibitor of MAO-B at


relatively low doses. MAO-B is the
Selegiline (Deprenyl; isozyme responsible for the degradation
Eldepryl) of DA (dopamine) in the striatum Early stage treatment of Parkinson's Dz (neuroprotective)

888
Rasagiline (Azilect) Selective inhibitor of MAO-B Early stage treatment of Parkinson's Dz (neuroprotective?)

889 May influence synthesis, release, or


reuptake of DA. Has anticholinergic and Early stage treatment of Parkinson's Dz (benefits short
Amantadine antiglutamatergic! effects as well lived)

890 Dopamine replacement: Historic


treatment for disabling-PD involves the
DA precursor levodopa, which can be
converted to dopamine in
catecholamine neurons via the enzyme Treatments for Disabling-Parkinsonism (especially
dopa decarboxylase. Therapy with the akinesia/bradykinesia) - Currently less popular as initial
precursor levodopa is necessary treatment in disabling-Parkinsonism because of perceived
Levodopa (l-dopa; L- because DA itself does not penetrate the advantages of DA agonists (see below). Do not give L-DOPA
DOPA) CNS. without carbidopa!

891 Dopamine replacement. Carbidopa Treatments for Disabling-Parkinsonism (Carbidopa reduces


Levodopa/Carbidopa prevents peripheral DA conversion the on-off phenomenon, and the smooths out end-of-dose-
[Sinemet] (Carbidopa does not cross BBB) faliure phenomenon)

892
Dopamine replacement (D2); ergot
Bromocriptine alkaloid (Old) Treatments for Disabling-Parkinsonism

893
Dopamine replacement (D1/D2); ergot
Pergolide alkaloid (Old) Treatments for Disabling-Parkinsonism
A B C

894
New Treatments for Disabling-Parkinsonism (especially
akinesia/bradykinesia); Possibly a neuroprotective agent.
Dopamine replacement (D3, part of the Effective in both early and advanced PD as monotherapy or in
D2 family); Non-ergot dopamine combination with levadopa. Neuroprotective as it is an
Pramipexole agonists; (antioxidant) antioxidant. Midigates on-off phenomenon
Dopamine replacement (Relatively Effective in early or advanced PD alone or in combination;
895
Ropinrole selective D2 agonist) Midigates on-off phenomenon

Catechol-O-Methyltransferase
inhibitors (COMT inhibitor): Inhibition of
dopa decarboxylase causes activation of
COMT pathway, increasing 3-O-
896 methyldopa (3OMD); 3OMD is
associated with poor therapeutic
response to levodopa (competes for the capones may smooth response to levodopa and may
absorption into brain); only active in the permit lowering of levodopa dose for PD (only used with L-
Entacapone periphery DOPA); typically started with L-DOPA/carbidopa therapy

Spasmolytics of the CNS; GABA


897 analogue; GABA-B receptor agonist,
causes hyperpolarization by increased
K+ conductance. Inhibits release of
excitatory amino acids and substance P
(may reduce pain). Target is intrafusal Tx spasm: less effective in cerebral accident; more effective in
Baclofen (Lioresal) afferent (Ia) of muscle spindle spinal injury and MS. effective in ALS.
Antiseizure drug (see seizure medication below); has been
898 studied in patients with MS with positive results
Gabapentin (Neurontin) Spasmolytics of the CNS Neuropathic pain, Trigeminal Neuralgia

899 Centrally acting skeletal muscle relaxant


that is structurally related to tricyclic muscle spasm or a strianed muscle (skeletal muscle
Cyclobenzaprine antidepressants relaxant)
CNS depression (no direct action on the Muscle relaxation - adjunct to rest, physical therapy, and
900 contractile mechanism of striated muscle other measures for relief of discomfort in various
Methocarbamol or nerve fiber) musculoskeletal conditions)
A B C
Spasmolytics of the CNS; Mechanism
901 not clear: spasmolytic effect likely due to For treatment of ALS, spasmolytic effects reported. Extends
Riluzole (Rilutek) inhibition of glutamate release survival and time to tracheostomy

Spasmolytics of the CNS; Analogue of


902 clonidine; CNS mechanism not
understood; Reinforces inhibitory effects Spasm associated with cerebral palsy, multiple sclerosis, and
Tizanidine (Zanaflex) in spinal cord, reduces pain conduction stroke

Spasmolytics of the CNS; Acts by


increasing GABA-Aergic
903 neurotransmission, leading to
enhanced presynaptic inhibition Most effective for MS, spinal lesions. Less effective for
(internuncial neurons); Target is cerebral lesions. Not effective in ALS
intrannuncial (inhibitory interneuron). May be used in combination with baclofen to control night-time
Diazepam (Valium) See Seizure Medication spasms (MS) See Seizure Medication

Spasmolytics of the PNS; skeletal


904 muscle relaxant; interferes with release 1) Cerebral spasticity; not used for ALS
of Ca ions from sarcoplasmic 2) i.v. for malignant hyperthermia (eg D2 blocker induced
reticulum; can reduce contractions by such as antipsychotics)
Dantrolene (Dantrium) only 75% 3) external sphincter hypertonicity
Other nervous system
905
drugs

906
Mineralocorticoid, see corticosteroids;
resorbing Na at kidney (K and H lost) Treat orthostatic hypotension due to autonomic
Fludrocortisone causing retension of water dysfunticon

907
Midodrine Alpha agonist (see adrenergics) Treat orthostatic hypotension due to autonomic dysfunticon
908 Benzodiazepines Dystonias
909 Botox Dystonias
910 Anticholinergic drugs Dystonias
911 Alprazolam Essential Tremor
912 Propranolol Essential Tremor
913 Primidone Essential Tremor (usually given with propranolol)
914 Seizure Medication
A B C

915

Generalized tonic-clonic seizure (grand mal, GTCS)


Voltage gated Na+ Channel Blocker Partial seizures (simple and complex)
(Antagonist) - limits the capability of (Makes absence (petit mal) worse)
neurons to fire at high-frequency rates Non-sedative
Phenytoin!! (Dilatin) (increases refractory period) Note cardiac uses: digitalis-induced ventricular arrhythmia
Voltage gated Na+ Channel Blocker;
916 same as phenytoin but has phosphate
group attached so that it doesnt sting (?) Prodrug for parenteral use, see dilatin (doesn't sting when
Fosphenytoin (Cerebyx) Thus can give faster IV given IV)

917 Partial seizures (Jacksonian);


Generalized tonic-clonic
Voltage gated Na+ Channel Blocker Makes absence (petit mal) worse
Carbamazepine!! (Antagonist) - limits the capability of Note use for obsessive compulsive disorder, trigeminal
(Tegretol) neurons to fire at high-frequency rates neuralgia, bipolar affective disorder
918 Topiramate inhibits neural cell Na channels Epilepsy

919
less potent, fewer adverse effects, fewer drug interactions than
Oxcarbazepine Voltage gated Na+ Channel Blocker Carbamazepine; 3/d dosing - compliance issue

920 Prevents and reverses absence seizures (petit mal)!! without


Inhibits T-type Ca++ current, GTCS;
decreasing glutamate release in Never used to treat GTCS of any origin
Ethosuximide (Zarontin) thalamus. No effect on seizure spread Not sedative
A B C

Effective against partial & generalized tonic-clonic &


absence seizures!!
Increased use as monotherapy for generalized tonic-clonic;
921 Treat Juvenile Myoclonic Epilepsy
Valproic Acid aka Block BOTH Na+ & Ca++ channels; Possibly prophylactic following head injury
Valproate (Depakene, Also increases brain levels of GABA Note: use for migraine and bipolar affective disorder
Depakote) (indirect, mech unknown) Epigastric distress reduced by Depakote

Adjunct for Partial seizures & Generalized tonic-clonic


Labeled for adjunctive use or monotherapy when withdrawn
from phenytoin or carbamazepine; increasing use as first-line
922 agent
Well-tolerated in the elderly
Effective against absence seizurescalcium channel
mechanism
Lamotrigine Block BOTH Na+ and Ca++ channels Also used in bipolar disorder
923 zonisamide Adjunct use for partial seizures

Barbiturate - direct GABA(A);


924 ( duration Cl- channel opening) long
acting
Glutamate receptor (AMPA receptor) less
important
Barbiturates stimulate chloride flux Generalized tonic-clonic seizures
(chloride ionophore), thereby facilitating Alternative for febrile convulsions in children <5 years
Phenobarbital GABA-induced inhibition Simple partial seizuresrelatively larger doses

Benzodiazepines - direct GABA(A); (


frequency Cl channel opening) short
acting (addiction); benzodiazepine
925 allosteric site - GABA-mediated
inhibition via Cl- ionophore; elevates
seizure threshold and limits spread.
Suppresses spread from epileptogenic
foci; does not abolish the abnormal focal
Diazepam (Valium) discharge Status epilepticus

926
Benzodiazepines - direct GABA(A), see
Lorazepam!! (Ativan) Diazepam Status epilepticus
A B C
absence; myoclonic, akinetic, atonic seizures
927
Clonazepam (Klonopin) Benzodiazepines - direct GABA(A) Infantile Spasms (Wests Syndrome)
Benzodiazepine - indirect GABA(A);
928
tiagabine Uptake inhibition

929 Benzodiazepine - indirect GABA(A);


Inhibit degradation; Irreversible inhibitor Wests Syndrome
Vigabatrin of GABA-transaminase. adjunctive therapy of partial seizures

930
Enhances GABA activity; Blocks
glutamate activity; but many other
mechanisms, including other ion
Alcohol channels Good Anticonvulsant?
Antiseizure drug; has been studied in patients with MS with
931 Benzodiazepine - indirect GABA(A); positive results
Gabapentin (Neurontin) unknown mech; Spasmolytics of the CNS Neuropathic pain, Trigeminal Neuralgia

932
Corticosteroids (eg
corticotropin, prednisone,
dexamethasone) (Mechanism unknown) Infantile Spasms (Wests Syndrome)
933 Multiple Sclerosis Drugs & Myasthenia Gravis

Inhibits IFN-gamma (TH1 cytokine


which activates M0); (Slows freqency and
934 accummulation of physical
disability/clinical exacerbations)
modulating conversion of TH1 to TH2. Treatment of Multiple Sclerosis
Interferon-1a (Avonex; May form Ab (NAb) (The rate of NAb Reduce attack rate of MS
Rebif) & Interferon-1b production is probably less with IFN-1a Relapsing/remitting MS
(Betaseron) treatment than with IFN-1b treatment) Secondarily progressing MS
A B C

935 (Mechanism in MS is not established) -


Mimics myelin basic protein (?IS
attacks the glatiramer instead of self
myelin?) May affect bodys IR by
converting the TH1 type to a TH2 type
IR. Neutralizing antibodies do not Treatment of Multiple Sclerosis (Approved for Relapsing
Glatiramer (Copaxone) arise Remitting MS)

Suppresses cell-mediated immunity,


936 which may reduce immune cell attack of
Mitoxantrone the myelin sheath Tx for secondary progression (?) MS

Monoclonal antibody directed to specific


937 adhesion molecules, reduces leukocyte
Natalizumab entery into the CNS Tx MS

Used for Myasthenia Gravis;


938 Indicated for acute and/or chronic use in a number of immune-
mediated disorders
Relapsing Remitting MS acute exacerbation (only during
Corticosteroids See immunsuppresants above exacerbations).

Decreased lymphoid cell production;


Azathioprine converted to
mercaptopurine; interferes with purine
939 nucleic acid metabolism, dramatically
interferes with the wave of lymphoid-cell
proliferation that normally follows
antigenic stimulation Used for Myasthenia Gravis
Azathioprine See Immunosuppresants above Often used in MS, but evidence-based medicine is lacking

Inhibits the production of helper T-


940 cells; works more quickly than
azathioprine, usually within one or two
months.
Cyclosporine See Immunosuppresants above Used for Myasthenia Gravis
A B C

Long Hx of use for treating various conditions where


concentration of gamma globulin is low
941 I.V. Ig: Gamma globulin, immune Also effective in autoimmune disorders (such as MG;
globulin, intravenous immunoglobulin mechanism in these conditions is unknown)
(slows down membrane attack Used for immediate improvement in MG pts (much faster
IVIG [Gammagard] complex???) than azathioprine or cyclosporine)

A procedure that filters the blood's


plasma component (blood is
centrifuged, plasma portion is removed.
942 Cells are returned to the pt, diluted with Main uses:
fresh plasma or a substitute (to reduce relieve a myasthenic crisis
allergic rx, usually a substitute)). patients scheduled for a thymectomy and post-operatively
Plasmapheresis Used to remove abnormal antibodies in covering the increased weakness that may occur when
(Treatment modality) specific cases (as in lupus or MG). corticosteroid treatment is begun

943

see Anticholinesterases above; DOC for Myasthenia Gravis (long acting); Use in conjunction
Quaternary drugs do not penetrate with an antimuscarinic to block excess ACh in the
Pyridostigmine CNS, so no intoxication/seizure problem parasympathetic nervous system

944 see Anticholinesterases above; Used for Myasthenia Gravis; Use in conjunction with an
Quaternary drugs do not penetrate antimuscarinic to block excess ACh in the parasympathetic
Neostigmine CNS, so no intoxication/seizure problem nervous system

945
Uses
Diagnostic aid for myasthenia gravis (not primary
diagnostic, but useful for distinguishing MG from other
Alcohol; see Anticholinesterases neurological disorders)
above; brief duration of action, rapid Differentiation of myasthenic crisis from cholinergic crisis
Edrophonium (Tensilon) onset (iatragenic). see Tensilon test extra notes
946 Alzhemier Drugs
947
Tacrine Acetylcholinesterase Symptomatic Tx of Alzhemier dz
A B C
948 Donepezil Delays progression of Alzheimer dementia
949

950
Antidepressant Drugs

951

Selective Serotonin Reuptake


Fluoxetine (generic, Inhibitors (SSRIs) - selective inhibition
Prozac) of 5HT (serotonin) reuptake Treat depression

952

Sertraline (Zoloft) SSRI Treat depression

953

Paroxetine (generic, Paxil) SSRI Treat depression

954

Citalopram (generic,
Celexa) SSRI Treat depression

955
Escitalopram (Lexapro) SSRI Treat depression
A B C

956 Fluvoxamine (generic,


Luvox) SSRI only labeled for obsessive-compulsive disorder (OCD)

2nd & Subsequent Generation


Antidepressants; Negligible actions on
NE & 5-HT reuptake; at therapeutic
957 concentrations occupies about 25% of
DA uptake sites; Inhibitor of neuronal
nicotinic receptors. (inhibitor of both DA
Bupropion (generic, uptake and neuronal nicotinic Treat depression; Also used in smoking cessation (helps with
Wellbutrin) cholinergic receptors) cravings???)
Bupropion with altered
958
dosage [Zyban] See bupropion Smoking cessation (nicotinic receptor inhibition)

Heterocyclic anti-depressant;
959 Marketed as an SSNRI (selective
serotonin and norephinephrine
reuptake inhibitor - inhibits 5-HT and
NE reuptake); more potent at 5-HT site;
Venlafaxine (Effexor) hence, at low doses acts like an SSRI Treat depression
inhibits neuronal uptake of serotonin
and NE; acts as an antagonist of
960 postsynaptic 5-HTA receptors and of
alpha1-adrenergic receptors. Not
chemically related to SSRI, tricyclic,
Nefazodone tetracyclic, or MAOI Tx depression and anxiety; no sexual SE or weight gain

961 2nd & Subsequent Generation


Antidepressants; a 5-HT2 antagonist
Trazodone (generic, and a weak, selective 5-HT reuptake
Desyrel) inhibitor Treat depression

962 Treat depression; particularly useful in the treatment of


2nd & Subsequent Generation painful physical symptoms of depression. It has received
Duloxetine (Cymbalta) Antidepressants; SSNRI FDA approval for treating diabetic neuropathic pain.
A B C

Heterocyclic anti-depressant;
marketed as an NaSSA (Noradrenergic
and Specific Serotonergic
Antidepressant),
963 Blocks 2-adrenergic autoreceptors
which increases NE release; & increase
in 5-HT cell firing due to increase NE
release and block of 2-adrenergic
heteroreceptors on 5-HT nerve terminals
Selective stimulation of 5-HT1
Mirtazapine (generic, receptors due to blockade of 5-HT2 & Treat depression (refractory major depression who need to
Remeron) 5-HT3 receptors. gain weight)

Treat depression!
964 Other Clinical Uses:
Tricyclic Antidepressant (TCA): block chronic pain!
monoamine reuptake (NE, 5-HT, DA), Enuresis
Amitriptyline (generic, down-regulate NE and/or 5-HT Panic disorder
Elavil) receptors Attention deficit hyperkinetic disorder
Nortriptyline (generic,
965
Aventyl, Pamelor) TCA see amitriptyline
966 Imipramine TCA see amitriptyline
967 Clomipramine TCA Tx obsessive-compulsive disorder

968

Monoamine Oxidase Inhibitors


Phenelzine (Nardil) (MAOIs): irreversible inhibitor Treat atypical depression (not used commonly)
Tranylcypromine
969
(Parnate) MAOIs: reversible inhibitor Treat atypical depression (not used commonly)
970 Iproniazid MAOI Treat atypical depression (not used commonly)
971 Isocarboxzid MAOI Treat atypical depression (not used commonly)

972
Selective norepinephrine uptake
Atomoxetine (Strattera) inhibitor Treatment of attention deficit hyperactivity disorder (ADHD)
A B C

973
Mood Stabilizers

974 Mood Stabilizing Drug: Substitutes for


Na in generating action potentials,
substitutes for Na in Na/NA exchange
across membrance, variable effects on
neurotransmitters (DA, 5HT, ACh), many
of these seen acutely though it must be
taken for 2-3 weeks before clinical effect
is seen; depletion of PIP2; other May be used prophylactically. Main use is for bipolar
Lithium mechanisms, see extra notes disorder (though 20-40% do not respond)

975 Valproic Acid + Sodium Mood Stabilizing Drug: May act through Anticonvulsant mood stabilizer and the combo of these two
Valproate = Divalproex increasing GABA, see Seizure causes less GI distress. Both for acute and maintenance
Sodium Medication above therapy (see notes about therapy approaches)

976 Partial, secondarily generalized seizures. Labeled for


Mood Stabilizing Drug: Sodium channel adjunctive use or monotherapy when withdrawn from
blocker (and/or Ca) voltage dependent phenytoin or carbamazepine.
inactivation of channels; anticonvulsant, Bipolar disoder; not effective in acute mania.
Lamotrigine see neuro drugs Can be used as a potentiating agent for antidepressants

977 Partial, general tonic clonic seizures


Obsessive compulsive disorder
Mood Stabilizing Drug: Sodium channel Trigeminal neuralgia
Carbamazepine (Tegretol) blocker Bipolar affective disorder
A B C

978 Olanzapine, Haloperidol,


Risperidone, Quetiapine, With bipolar dz, primarily for acute mania.
Ziprasidone, and MC used for Tx of Psychosis and Schizophrenia, see
Aripiprazole Antipsychotics antipsychotics below

979 Given to control acute mania (biploar dz, often as an adjunct


Benzodiazepine, see neuro drugs and to treatment with an antipsychotic drug or other mood
Clonazepam (Klonopin) anxiolytics stabilizing drug) - typically given with a mood stabalizer
980 Lorazepam (Ativan) Benzodiazepine, see clonazepam see clonazepam

981
Antipsychotics

982

Original Atypical Antipsychotic - block


DA receptors (esp D2) receptors as
well as higher affinity as antagonists
for 5-HT2 receptors (both actions
appear important to their efficacy in
schizophrenia. Efficacious for positive Tx of Psychosis and Schizophrenia; Most efficacious
and negative symptoms!! See extra antipsychotic, particularly against negative symptoms
Clozapine!! (Clozaril) notes
Tx of Psychosis and Schizophrenia; Frequently prescribed
983 atypical has replaced olanzapine as most prescribed of this
class
Quetiapine (Seroquel) Atypical Antipsychotic Being promoted for use in bipolar disorder
A B C

984
Atypical Antipsychotic: blocking D2
receptors & block 5-HT2 receptors;
Olanzapine is rapidly becoming the
standard against which both typical and Tx of Psychosis and Schizophrenia
Olanzapine (Zyprexa) atypical antipsychotics are judged Bipolar dz - primarily for acute mania

985 Atypical Antipsychotic - in addition to


high affinity to antagonize 5-HT2
receptors, also has high affinity to
antagonize D2 receptors with little Tx of Psychosis and Schizophrenia
Risperidone (Risperdal) affinity for muscarinic receptors Bipolar dz - primarily for acute mania

Atypical Antipsychotic - partial


dopamine agonist; efficacy against both
schizophrenia (as a weak partial-agonist
it blocks the full agonist, dopamine) and
986
depression (efficacy as a partial agonist
is enough to provide therapeutic efficacy
think of the mechanism of bupropion). Efficacious against positive & negative symptoms of
1) D2 partial agonist schizophrenia as well as depression. This drug is becoming
2) 5-HT2 antagnoist a tremendously popular choice when prescribing an
Aripiprazole (Abilify) 3) 5-HT1a partial agonist antipsychotic.

987
Ziprasidone Atypical Antipsyychotic - IM formula Rapid relief of agitation and distress; weight neutral
A B C

988

Typical Antipsychotic - Butyrophenone;


Relatively clean D2 antagonist
Some anti-serotonergic and alpha- Tx of Psychosis and Schizophrenia; Highly effective against
adrenergic effects, but relatively minor; positive symptoms; some effect against negative symptoms
Haloperidol!! (Haldol) high potency ED use for aggressive pts (calms everybody!)
Injectable depot preparation form - used for tx of noncompliant
989
Haloperidol Decanoate Haloperidol ester, long-acting pts

Typical Antipsychotic - Phenothiazine;


prototype - block DA receptors,
990
particularly the D2 receptor. Their
clinical efficacy against positive
symptoms is relatively well correlated
with this action. Not particularly Because of SE profile and other reasons chlorpromazine is
Chlorpromazine efficacious against negative symptoms; generally of historic interest for Tx of Psychosis and
(Thorazine) low potency Schizophrenia;
Typical Antipsychotic - Phenothiazine;
991
Fluphenazine (Prolixin) high potency Tx of Psychosis and Schizophrenia

992
Thioridazine Typical Antipsychotic - Phenothiazine Tx of Psychosis and Schizophrenia

993 Promethazine (Phenergan Typical Antipsychotic - Phenothiazine;


special use) first-generation H1 receptor antagonist Anti-nausea use; Tx of Psychosis and Schizophrenia

994 Prochlorperazine
(Compazine special use) Typical Antipsychotic - Phenothiazine Anti-nausea use; Tx of Psychosis and Schizophrenia

995 Typical Antipsychotic? - Thioxanthene;


Thioxanthixene S2 antagonist (also alpha1 and H1) Tx of Psychosis and Schizophrenia

996
Anxiolytics & Hypnotics
997 Anxiolytics
A B C

998

BZD are generally used for situational care (and not long term
care)
Anxiolytic, hypnotic
Muscle relaxant
Pre-anesthetic (anesthetic + above)
Blocks convulsions in ethanol or BZD withdrawal
Benzodiaezepin (BZD) - prototype: 2nd line status epilepticus (given i.v.; Second behind
Increases Cl- conductance on GABA lorazepam - see extra notes)
Diazepam (Valium) channels; long half-life (approx 50+ hrs) - Alcohol withdrawal
Prazepam, quazepam,
999
and flurazepam See diazepam See diazepam
Used for anxiolytic and hypnotic effect
some potential for early morning awakening
1000 said to be less sedative than other BZDs (use as hypnotic
Benzodiaezepin - Increases Cl- may be based on anxiolytic effect)
conductance on GABA channels; Often a BZD of choice for pts PRN (eg fear of flying)
Alprazolam (Xanax) Intermediate acting Panic disorder; generalized anxiety

Benzodiaezepin - Increases Cl-


1001 conductance on GABA channels; much DOC for status epilipticus
more water soluble (than diazepam) - so Used for anxiolytic and hypnotic effects
Lorazepam (Ativan) rapid acting; intermediate acting Alcohol withdrawal (with liver dz)

1002
Benzodiaezepin - Increases Cl-
conductance on GABA channels;
reliable pharmokinetics, especially for Anxiolytic and for sleep induction
Oxazepam (serax) the elderly; intermediate acting Alcohol withdrawal (with liver dz)
A B C
Temazepam and
1003
chlordiazepoxide Benzodiaezepines

1004 Benzodiaezepin - Increases Cl-


conductance on GABA channels; short
Triazolam (Halcion) acting See Hypnotics below

Used i.v. as anesthetic pre-op; significant amnesia


1005 (anterograde)
Benzodiaezepin - Increases Cl- Anxiolytic, plus patients are sleepy but can be aroused
conductance on GABA channels; Water (useful feature for moving patients to O.R. table)
Midazolam (Versed) soluble - very short acting Muscle relaxant
Post anesthesia (quicker recovery if midazolam is still on
board)
1006 **BZD overdose (only for acute use of BZD, not if BZD
Benzodiaezepin antagonist - non- dependence, see SE)
Flumazenil (Romazicon) competitive antagonist **mixed poisoning (no longer approved)

Tx Anxiety (If SSRIs are ineffective in controlling anxiety,


recommendation is often buspirone either tried alone or added
1007 to the SSRI);
5HT1a partial agonist - increase K No efficacy in sleep disorders
conductance via same channels as (No sedation; no motor impairment)
Buspirone (Buspar) GABAb receptors Better effects for OCD if given with SSRI than SSRI alone
Prevents jitters associated with excess stimulation of b2
receptors
1008 Used for tx of performance anxiety - use where
Beta blocker, see adrenergic blockers sympathetic outflow is high and serves no purpose (e.g., stage
Propranolol (inderal) above fright)
1009 Hypnotics

1010

Benzodiezapam - Increases Cl-


Triazolam (Halcion) conductance on GABA channels Sleep
A B C

1011 BZD alpha 1 subunit Selective Binder


(bind selectively to GABA receptors alpha
Zolpidem (Ambien) 1 subunit); Not a BZD, see extra notes Sleep

1012 Sleep (shorter half life though than zolpidem) Pushed as PRN
before bedtime or upon awakening in the middle of the
Zaleplon (Sonata) Same as zolpidem; very short half life night (if more than 4 hours remain in sleep cycle)

1013
Pineal hormone that regulates useful for sleep problems related to jet-lag or changing
Melatonin sleep/wake cycle (peaks at 2 am) day/night working hours

1014
Binds melatonin receptors (MT1 and
Ramelteon (Rozerem) MT2) and not GABA Sleep

Barbituates - indirectly potentiate


GABAa receptor activity in the brain,
thereby increasing the flow of Cl- to
1015 hyperpolarize cell membrane, Sedative (tx anxiety and insomnia)
Pentobarbital, decreaseing acitivty of the neurons of Phenobarbital for seizure control
Secobarbital, the CNS; high does may cause direct SUPERVISED use of other agents for sleep i.e., they should
Phenobarbital activity, see extra notes only be used in medical facilities, not on out-patient basis
1016 Theopental Barbituate induction of anesthesia
1017 antihistamines (e.g. hydroxyzine)??????????
1018 chloral hydrate

1019
Additional Psych Drugs
1020 ADHD Drugs

CNS stimulant, enhances dopamine


(DA) in the synapse; enhanced
norepinephrine (NE) neurotransmission
1021 in the CNS is probably involved as well
(facilitation of release of central DA and
NE). Mech in ADHD is unknown (as an
amphetamine-type drug, presumably is
Methylphenidate (Ritalin) dopamine) ADHD
A B C
Methylphenidate ADHD - extended release version Concerta effects last 12-14
1022
(Concerta) SAA hours so no administration needed during school

Indirect acting non-catecholamines;


release NE from adrenergic nerves,
also release DA in CNS; these agents
are taken up into nerve terminals via the
1023 uptake one mechanism and thus interfer
with active uptake (at presynaptic neuron
membrane as well as at the transporter
into the vessicle) amphetamine
interfers with both processes some
Amphetamines (Adderall claim it actually reverses these
is a combination product) transporters ADHD (immediate affect)

1024
Structurally similar to methylphenidate;
Pemoline (Cylert) relatively long duration of action (7-h) ADHD; essentailly no abuse potential

Treatment of attention deficit hyperactivity disorder in


1025 children & adults (ADHD). Non-stimulant, low abuse
Selective norepinephrine uptake potential, long acting (once a day) equal to methylphenidate in
Atomoxetine (Strattera) inhibitor effectiveness
1026 Narcolepsy
1027
d-Amphetamine See above ADHD drugs Narcolpesy, used at low dose typically

1028
Methylphenidate (Ritalin) See above ADHD drugs Narcolpesy

1029
Amphetamine related by structure, DEA DOC for narcolpesy and sleep disturbances associated with
Modafinil (Provigil) Schedule IV drug jobs that involve shift changes (day shift to night shift)
1030 Appetite Control
A B C

1031

Amphetamine-related anorexiant:
Modification of NE and dopamine; work Weight loss, decreased appetite, loss of interest in food, less
in appetite control centers of the pleasure from eating, increased satiety with eating, decrease
Benzphetamine (Didrex) hypothalamus (likely a NE mechanism) in total energy intake

1032
Diethylproprion (Tenuate) See Benzphetamine Extended release available, See Benzphetamine
Previosly used with fenfluramine (Fen-Phen) popularity
1033 See Benzphetamine; Long acting increased once fenfluramine removed from market; See
Phentermine (Fastin) sympathomimetic Benzphetamine
1034 Fenfluramine (Not avail) See Benzphetamine No longer available

1035 Fluoxetine (generic, Non-sympathomimetic anorexiant -


Prozac) SSRI, see antidepressants Produces satiety ("fullness") rather than anorexia.

Non-sympathomimetic anorexiant:
1036 Inhibits reuptake of 5HT and NE (SNRI
reuptake inhibitor), as well as being an
Sibutramine (Meridia) MAOI Weight loss; take without regards to meals

Non-anorexiant derivative of lipstatin -


covalently binds and inhibits gastric
1037 and pancreatic lipases preventing
hydrolysis of triglycerides to absorbable
FFA and monglycerols; not absorbed
Orlistat (Xenical) systemically Weight loss

1038
Herbals See extra notes Weight loss
A B C

1039 Progesterone derivative - increases


Megestrol appetitie Weight gain (associated with antineoplastic therapy)

1040
Drugs of Abuse & Treatment
1041 Alcohol

1042

GABA gated Cl- channel is facilitated;


Glutamate gated Ca++ channel is 1) Pleasure (recreation) to abuse to dependence
inhibited; EtOH used because it has a 2) Cardiovascular benefit (~1 drink/d)
higher affinity (lower km) for alcohol 3) Methanol (MeOH) & Ethylene Glycol (antifreeze)
Alcohol (Ethanol or Ethyl dehydrogenase -- inhibit formation of Poisoning (used in conjunction with hemodialysis, emesis,
Alcohol) toxic aldehydes gastric lavage, correction of acidosis and supportive care)

1043 Reduces cravings in alcoholics; (also opioid OD, see


Naltrexone Mu selective opioid antagonist opioids)
Treating abstinent alcoholics (meaning alcoholic with a
1044 problem getting a drink), reduces cravings in alcoholics (Not
Blocks NMDA (glutamate) receptors metabolized, not contraindicated if there is hepatic
Acamprosate and activates GABA(A) receptors impairment)
A B C

1045

Alcohol consumption treatment: with ethanol consumption,


produces acetaldehyde syndrome - used for court ordered
Disulfiram (Antabuse) Blocks aldehyde dehydrogenase aversive therapy
aka 4-methylpyrazole; inhibit the action
1046 of alcohol dehydrogenase thereby
reducing the synthesis and accumulation
Fomepizole (Antizol) of toxic aldehydes. Methanol (MeOH) & Ethylene Glycol (antifreeze) Poisoning
1047 Other Terribly Delicious No, No's

1048

Psychostimulants; blocks DA
transporter (also binds NE and 5-HT
transporters); (benzoylecgonine
Cocaine metabolie in plasma 1-3 days) Local anesthetic effect
A B C

1049

Psychostimulants; presynaptic release


of DA (amphetamine runs the re-uptake
transporter in reverse); in plasma for 1-2
Amphetamines days; see ADHD drugs ADHD & Narcolepsy
1050 Ammonium chloride Acidify urine Hasten amphetamine excression

1051

Psychostimulants; agonist at CNS &


peripheral nicotinic sites; (Cotinine
metabolite in plasma 1-2 days);
Stimulates the release of dopamine and
Nicotine glutamate.

1052

LSD; LSD-like drugs (eg


mescaline and
psilocybin) Hallucinogens
A B C

1053

Hallucinogen; non-competitive blocker


Phencyclidine (PCP) of NMDA receptors

1054

Hallucinogen; non-competitive blocker


Ketamine of NMDA receptors

1055
Methylenedioxy-
methamphetamine
(MDMA) Hallucinogen

Dronabinol (Marinol): L-delta-9-transtetrahydrocannabinol


(delta-9-THC)
Glaucoma - advantage not established
Nausea/vomiting (cancer chemotherapy; advent of 5-HT3
1056 agents has minimized this use; FDA has disapproved
marijuana for this. Dronabinol, a synthetic delta-9-THC analog
is approved for antiemetic effects)
Marijuana (Pill form: Hallucinogen; binds to cannabinoid Anorexia - for weight loss in AIDS
Dronabinol (Marinol)) receptors Non-medical
1057 Fentanyl analogs Opioid effects
1058 Heroine See opioids above

1059
Related to GABA, but mechanism not
Gamma-hydroxybutyric known; detectable in plasma only for
acid (GHB) hours
A B C

1060
BZD; detectable in plasma less than 7
Flunitrazepam days

1061
Inhalants: Organic
solvents

1062 Inhalants: Used medically to relieve pain in people with heart disease,
Nitrates/Nitrites (amyl amyl is a vasodilator -- it causes blood vessels to open wider,
nitrite, butyl nitrite and easing the heart's labors, allowing blood to flow more freely,
isobutyl nitrite) Amyl is a vasodilator and temporarily increasing the pulse rate.
D E F
1 Side Effects & Toxicies Contraindications Memory Technique

st 2

Pt with severe vertebral dz or


3 bladder obstruction as Rem: Lou lied (Leuprolide) about taking his
temporary surge of T (before hormones (sGnRH) for his prostate cancer so
functional castration) may he wouldn't be castrated and get boobies. He
worsen symptoms by feeding wants to still be able to play his skin flute (flut-
prostate cancer amide used together)

7 5% ejaculation problems Rem: that's a fine ass 2 ride (Fin-as-te-ride, 2 =


10% erection problems type II), but oops, no erection. The man has a
5% libido problems (all from androgen tupe to cover his balding head, but notices hair
blockade) growth
5% ejaculation problems
8 10% erection problems
5% libido problems (all from androgen Rem: Do taste the BPH, see if its ripe (large)
blockade) (Du-taste-ride)

Retrograde ejaculation (more than


Terazosin), incidence increases over time
D E F

10
Retrograde ejaculation, orthostatic HTN
(light headed, syncope with first dose);
Asthenia ("feel" weak, will not show
objective evidence); Stuffy nose
Retrograde ejaculation, orthostatic HTN
(light headed, syncope with first dose)
11 though this is minimal with time; Asthenia
("feel" weak, will not show objective
evidence); Stuffy nose

12
Rem: "clone me friend, many times." (Clo - mi
Multiple births - phene)
13

Tx with nitrites/nitrates,
Patients with angina are at
14 Blindness is rare (unique to Sildenafil), risk; BP < 90/55
some pt complain of a "blue aura" in visual Warning: ED drugs of sildenafil-
field and decreased visual accuity; type should not be used within 4
Headache (15%), Flushing, G.I. upset, hrs of alpha blockers (does not Put your penis on the (window) sill, then the fill
Nasal congestion (4%), priapism apply to tamsulosin) (of the vagina with semen)Sill-den -da -fill
Headache (15%), Flushing, G.I. upset,
15
Nasal congestion (4%), priapism see sildenafil

16
Headache (15%), Flushing, G.I. upset,
Nasal congestion (4%), priapism see sildenafil

17

18
plagued by high incidence of nausea and
vomiting
D E F

19

20 Hot flashes; thrombo-embolism; vaginal


bleeding & discharge (vaginitis);
thrombocytopenia peripheral edema,
increased risk of endometrial cancer

21

Rem: relax, I'm fine, I'm on a partial agonist, I


might even give a SERMon

22 Rem: Sertoli, the gay Italian, converts


testosterone to estradiol with his aromatics
(aromatize)
Rem: estriol I o Little baby (placenta), E3 =
history of venous thrombosis; es-tri-ol
Cancer of the breast (past, Rem: Estrone I own you says the big mean
present or family history); old lady (rone~own), E1 = Estr1
Cancer of the endometrium (Eone=estrone)

23
24
D E F

DVT is absolute
25 contraindiction; Pregnancy;
Women with Hx of E-dependent
Thromboembolism, Cardiovascular risk, neoplasms or breast cancer; Hx
Hypertension. Because high doses of thromboembolic disorder or liver
steroids, side effects range from minor disease; Heavy smokers
discomfort (water retention, nausea) to (cardiovascular risk is higher if
cosmetic (chloasma) to dangerous >35yrs of age) (big
(hypertension, embolic disorders) contraindication); Migrane HA

26
Some women may hoave moral or ethical
objections to the mini pill but not the standar pill

27

N/V!
Weight gain, 5lbs at 1 year, lbs by the
2nd, 12lbs by the 5th.
Massive weight gain in 1-2 % of patients.
Bone loss!
28 Should use for no longer than 2 years
without a break
Slow return to fertility
average 10 months, can be as long as 2
years
Some metabolise quickly, some very slow
Pt keeps eatting heavily too

29
Androgenic effects such as hirsutism

30
higher risk of thromboembolism

31
D E F

32
very high androgenicity

33

Rem: Dro-spirenone similar to spirono-lactone

34

35

36

37

38

39

40
Rem: Are you for 86ing this pregnancy (RU486)

41
Rem: Dan - you have endometriosis??; Dan-an
tagonist (Danazol)
42
43
D E F
Rem: abate/stop the hemorrhage (Hemabate);
44 Rem: PGF2 For Fucks sake, save that
woman; or Fuck that baby (2nd trimester
pregnancy termination)

45
Rem: PGE2 E-gads, get that baby out
46

47

48
49

50

Rem: Guard dis li vagina (gar-dis-il)


Perform a laparoscopy for acute ectopic
51 Stomatitis, neutorpenia (usually pregnancy (hemodynamically stable pt), or
moderate), rarely alopecia laparotomy (hemodynamically unstable pt)

52
53

st 54

55
D E F

Should be used under careful medical


supervision
56 Excessive fluid and electrolyte loss:
1. hypokalemia (watch out for CHF
patients on digoxin), K+ is lost in the CD,
not the loop or the DT 2. hypokalemic
metabolic alkalosis: Metabolic alkalosis is
secondary to hypokalemia (Excess Na+ at
CD drives K+ and H+ into lumen) 3.
hyperuricemia (hypovolemia enhances
reabsorption of urate at proximal tubule) 4. Remember: a ferocious (Furosemide) lion
hypomagnesemia 5. ototoxicity (usually jumping through a firey loop and pissing
reversible -- watch for patients also taking (diuretic) out fire; notice the SE - bunch of
aminoglycosides) 6. hypovolemia 7. hypo's and 2 hypers (glycemia and uricemia)
interstital nephritis (furosemide) and an oto

57

58
59

CHF - Transient expansion of


extracellular fluid volume,
hyponatremia (mannitol is
distributed in the extracellular Non-electrolytes, but highly polar; Confined to
compartment and draws water ECF (doesn't enter cells); Freely filterable at
60
from the intracellular glomerulus; Not reabsorbed; Provide a higher
compartment, can result in solute load in the nephron osmotic pressure
cardiac failure and/or pulmonary prohibits normal water reabsorption; More
edema. Do not use these agents water loss than Na loss; Poorly absorbed, given
Headaches, nausea, vomiting in patients with diminished parenterally
Long-term: hypernatremia, dehydration cardiac capacity)
D E F

61

1. Hyperchloremic metabolic acidosis, K+


depletion
2. Renal stones!! Remember: throw an ace ta soul of mine (Ace-
3. Hypersensitivity reactions (rare): rash, ta-zol-a-mide), splitting my carbon (carbonic)
fever, bone marrow suppression body, breaking it

1. Hypokalemia (watch digoxin)


2. Hypokalemic (hypochloremic)
metabolic alkalosis
3. Hyperuricemia
(These 3 above are same toxicities and
same mechanisms as for Loops)
62 4. Hyponatremia with hypovolemia
5. Hyperglycemia: decrease insulin
secretion -- may unmask latent diabetes
mellitus, usually clinically important only at
high dose Usually reversible with correction
of hypokalemia
5. Increase serum cholesterol usually
clinically important only at high dose
6. Allergic reactions
7. Erectile dysfunction: Frequency is
even greater than with beta-blockers
8. hypercalcemia

63
64 a sulfa based drug
thiazide-like; have key portion of Remember: India (indapamide) produces
65 sulfonamide structure hypersensitivity cheap thiazide knockoffs (thiazide-like), many
cross-reactions people allergic (HS)
Remember: thiazide ring made from metal
66 thiazide-like; have key portion of (Metolazone), many people have allergy (HS);
sulfonamide structure hypersensitivity or me to lazy to get up and go to bathroom so
cross-reactions I'll pee right here
D E F

1. Hyperkalemia (esp. with ACE inhibitors,


NSAIDs, b-blockers); Most common when
67 co-administered with K+ supplement, which Remember: tell potassium to take a SEAT
is not rational 2. Anti-androgen effect (Spironolactone, Eplerenone, Amiloride,
(steroid structure leads to competitive Triameterene), all of the K spareing diuretics;
inhibition of androgen receptors): Rem: spiro no!! (no spiral shaped erection), but
gynecomastia; impotence Renal failure man with gynecomastia
Intended in development to be an
aldosterone antagonist with no
68 antiandrogen effects; Side-effect profile
shows gynecomastia, consequently, little
different from spironolactone Renal failure

69 1. G.I. (nausea, vomiting)


2. Dizziness Remember: Amelia (Amiloride) riding a shinny
3. Leg cramps K horse, but the horse refuses to lick Liddle's
Renal failure Fiddle of salt lick
1. G.I. (nausea, vomiting) Remember: try a meteor (triameterene) for
70 2. Dizziness breakfast made from K, the meteor splashes
3. Leg cramps into the milk (Ca) which splashes onto your
4. Nephrolithiasis Renal failure kidneys (nephrolithiasis)
TN 71

Side-effect profile approaches placebo


72
(Dr. Dubin scoffs at this statement)
Avoid during pregnancy (2nd & 3rd
trimester), teratogenic: If pregnancy occurs
while on these drugs, no adverse effects Remember: lo sartan means the frying pan or
occur if the drugs are discontinued early taint of him, so Angi was tense because
on. Toxic to the developing kidneys someone blocked her boyfriend's taint receptor

73
see losartan
D E F

Predictable, typically mild, dose-related


side-effects: 1. Cough!! 2. Initial dose
hypotension, esp. if hypovolemic; also
initial dose rise in creatinine and K
(transient, also find with ACEI use) 3. Skin
rashes/neutropenia (is captopril worse than
others?) 4. Acute renal failure in renal Rem: Cap full of Ace's that were stolen from
74 artery stenosis!! (bilateral stenosis or men's hypertension club poker game
single kidney stenosis) 5. Angioedema!! Rem: ACEI - think CAPTOPRIL:
(d/t bradykinin - swollen tongue, etc, can be Cough (dry)
life threatening) 6. African-Americans and Angioedema/ Agranulocystosis
elderly may not respond well 7. Proteinuria/ Potassium excess
Contraindicated in 2nd & 3rd trimester Taste changes
pregnancy, teratogenic (fetal Contraindicated in 2nd & 3rd Orthostatic hypotension
malformations (thin facial bones), trimester pregnancy, Pregnancy contraindication/ Pancreatitis/
hypoplasia of lungs, hypotension and renal teratogenic (fetal malformations Pressure drop (first dose hypertension)
failure(anuria)), probably not good in first (thin facial bones), hypoplasia of Renal failure (and renal artery stenosis
trimester either 8. Hyperkalemia possible lungs, hypotension and renal contraindication)/ Rash
(esp. if combined with other drugs that failure(anuria)), probably not Indomethacin inhibition
increase K) good in first trimester either Leukopenia/ Liver toxicity

75

76

Side Effects associated with excessive


77 vascular dialtion: HA, postural
dizziness, flushing, peripheral edema Pt with CAD, do not use Rem: knee fed a pen (ni-fed-i-pine) blocking
especially ankle edema, parethesia, dihydroopyridine CCBs and knocking his Ca teeth into his dilated
gingival problems. without a beta blocker vessels
D E F

78

1. headache; flushing; orthostatic problems


2. potential problem of heart block if
verapamil and diltiazem are used with Remember: tilling an angina heart with a dill
beta-blockers pickle (dil-tia-zam), Ca flying everywhere

1. Constipation!!
2. headache; flushing; orthostatic
problems
79 3. potential problem of heart block if
verapamil and diltiazem are used with Remember: a bear (ver) rapping (rap), falls with
beta-blockers pain of angia, chocking on Ca so bad that he
4. CHF can't poop

80

81

1. Hypotension (orthostatic) is a
significant side-effect for most patients.
Profound reflex SNS activation and
tachycardia as well as peripehal edema.
Consequences of increased myocardial O2
consumption - angina; increased
myocardial work - induction of CHF is more
82 likely; hypotension side-effects such as
palpitation, pounding headache,
flushing; edema secondary to Na+ and
H20 retention; GI
2. tachyphylaxis
3. Drug induced systemic lupus (hapten
mech - high doses, slow acetylators,
reversible)
4. Coronary Steal syndrome in pts with remember: pregnant hydra with using visin for
ischemic dz the butterfly rash around face
D E F

83

see hydralazine
Adverse effects: SNS activation, angina,
edema, hirsutism

84
see hydralazine Remember: an ox in the day opening all of the
window (arteries)
Remember: "Fen? old o pam, she's D one
85 Typical arteriodilator toxicities who's got the HTN problem, but great kidneys",
says her old friend

86

excessive hypotension
cyanide/thiocyanate toxicity with
prolonged use
Tolerance!!

87

Tolerance, give at night (see extra notes)


D E F
88
89
90
91
Hypokalemia
92

I 93
ng and females
er persons, males

Drug interactions of
sulfonamides - Displace
bilirubin from plasma albumin -
94 bilirubin is then free to pass into
central nervous system, cause
Act synergistically with sulfonylurea kernicterus (neural symptoms
hypoglycemia by increasing the release of associated with high levels of Rem: Sulfonamides (eg Sulfamethoxazole)
insulin bilirubin) - contraindicated block dihydropteroate Synthase, TRimethoprim
reduce blood glucose level during pregnancy blocks dihydrofolate Reductase

95

96
D E F

97
Toxicity:
Crystalluria Drug interactions of
Hemolytic anemia in G6PD deficient sulfonamides - Displace
patients (Afro Americans) bilirubin from plasma albumin - Remember: TMX/SMX: T = tree or respiration
Stevens-Johnson syndrome: severe and bilirubin is then free to pass into (S. pneumonia and H. inflenazae); Mouth = GI,
usually fatal conditions involving blistering central nervous system, cause diarrhea (Shigella, Salmonella, E.coli); Pee =
of the skin, mouth, eyes and genitalia, often kernicterus (neural symptoms UTI, urethritis, prostatitis (enterics such as E.
accompanied by fever, polyarthritis, and associated with high levels of coli); SMX = Syndrome or AIDS (profolactive to
kidney failure bilirubin) - contraindicated prevent P. Carinii when T count below 200, also
Hyperkalemia during pregnancy T gondii)

Toxicity: n, v, d
98 Achilles tendonitis, tendon rupture
CNS such as HA, insominai, restlessness Contraindicated with patients
Epigastric distress under 18 years of age;
Damage cartilage do not give to children as
Suprainfection with streptococci, Candida causes cartilage damage

Contraindicated with patients


99 under 18 years of age;
do not give to children as
causes cartilage damage
100
101

102

Safe drugs to use


Only side effect is allergy & hypersensitivity
D E F

103
Allergy and hypersensitivity
104
105

106 Remember: the people in the AV club don't go


out much, stay entero (inside) (A
-aminoglycoside, V-vacomycin), entero-
enterococci

Very toxic agent:


Auditory (ototoxicity)
Contraindicated during pregnancy.
107 Causes hearing loss in the fetus or
newborn Rem: A stripper (Streptomycin), a G'
Vestibular dysfunction (loss of) (gentamicin), Mr. T (Tobramycin), and Neo
Nephrotoxicity Contraindicated during (Neomycin) are all hangin out with a mean guy
Neurotoxicity pregnancy (aminoglycoside)

108

see aminoglycoside, causes polyuria

109
Remember: You 'spectin to get gonorrhea

110

MRSA and enterococci are


Allergy & hypersensitivity resistant to cephalosporins

111 Remember: all 3rd gens have t in them


(except cefotetan, a 2nd gen), and apparently
Cefixime
D E F

112 Remember: cefixime, easy way to get your oral


fix, and need to fix cefixime by putting a t in the
word to make it fit with the other 3rds

Remember: 1st generation have ph in them, to


113 know 1st gen must have a PhD, however
cefazolin doesn't have a pph, don't let that faze
you (and don't let the red current jelly faze you
(Klebsiella)

Relatively toxic
Contraindicated during
pregnancy
cross the placenta to reach the
114 fetus and cause deformity and
Teeth discoloration, bone deformity in growth inhibition
children, Fanconi's syndrome damage to teeth, bones, and Remember: VACUUM your Bed Room Tonight:
(aminoaciduria, phosphaturia, acidosis, and nails of the fetus Vibro cholera, Acne, Chlamidia, Ureaplasma
glycosuria), photosensitityity Renal toxicity Urealyticum, Mycoplasma pneumonia, Borrelia,
Suprainfection Rickettsia, Tularemia,
Do not give during pregnancy:
Congenital limb abnormalities,
115 tooth discoloration, inhibition of remember: a daschund (dog, doxicycline) on
bone growth in fetus, bicycle coming out of your ass (excreted in
suprainfection. feces)

116

117

118

119
Oral therapy causes GI disturbances. Remember: clostridium for clottage cheeze

120
Remember: Miconazole for fungus of the toe;
severe GI disterubances also Azoles hate ergosteroles
Rem: Casper the ghost messin with the fungus
121 wall synthesis (moving around all the pieces
needed), the fungus just doesn't get why it can't
complete its wall
D E F

122 Remember: GET out of its way, Giardia,


Entamoeba, Trichomonas

123

124

Nausea, diarrhea, headache, renal


insufficiency, neurologic toxicity
125

Drugs
126

127
Generally well tolerated; occasional
nausea, diarrhea, abdominal colic,
headache, dizziness, skin rash. PPIs are
metabolized and can inhibit cytochrome
P450 (CYP2C19 & CYP3A4, especially
omeprazole) and therefore decrease the Prazole = PPI; Rem: pray so (pra-zole) the
clearance of other drugs such as pumps stop pumping acid onto our heads;
benzodiazepines, warfarin, phenytoin, and Rem: put your H. pylori CAP on (tx with
others. clarithromycin, amoxicillin, and PPI)

128
see Omeprazole
D E F
129
see Omeprazole

130
see Omeprazole

131
see Omeprazole

Cimetidine (but not other H2 blockers)


inhibits the activity of cytochrome P450,
132 thereby slowing the metabolism of many
drugs (phenytoin, theophylline,
phenobarbital, cyclosporine, some tidine = H2 blocker; Rem: tied up in (tid-ine) an
benzodiazepines, carbamazepine, H2 hummer; Rem: see me (Ci-me-tidine) tied
propranolol, Ca2+ channel blockers, up with all sorts of drugs In the H2 (inhibits
quinidine, sulfonylureas, warfarin, and P450); Rem: Major Cytochrome P-450
tricyclic antidepressants). If drug inhibitors: FREaCKI Grapefruit gets stuck in
interactions must be avoided, use an H2 Ez - Ketoconazole, Isoniazid, Cimetidine,
blocker other than cimetidine. Fluoxetine, Ritonavir, Erthyromycin, Grapefruit

133
Very little SE

134
Very little SE

135
Very little SE

Change in bowel habits, systemic cation


absorption and alkalosis (usually only if
renal impairment present). Low sodium
content is recommended, especially for
hypertensive and CHF patients. Drug
interactions result mainly from changes
in GI motility or pH. Alumina and
136 magnesium change mobility and can
change absorption of other drugs. Al3+
can cause precipitation of some drugs in GI
tract, reducing their absorption. Changes
in luminal, serum, or urinary pH can change
absorption or elimination rates of many
drugs. Advice: Do not take antacids
within 1-2 hours of administration of
other drugs.
D E F

137

138

Causes black stools and sometimes Rem: bi - bicarb increased, mu - mucus


black tongue. increase (Bi-s-mu-th), and bismuth besmirches
Extremely safe at recommended doses. your tongue black
139

140
Rem: Ralph was sucking (Suc-ral-fate) on a
sticky viscous sucrose and aluminum sucker
that coated his stomach and relieved him of the
Constipatoin fate of his ulcer just to give him constipation

141
potential abortifacient, Rem: Miso-prostol is Prosta-glandin soup, but
therefore it is contraindicated in causes Japanese baby abortions; miso is good
Causes diarrhea in 30% of patients pregnancy. for the belly; prost = prostaglandin

142
D E F

143
Side effects are significant, especially
with chronic treatment, and include: Rem: Me is such a dope (anti-D2) that me toe I
hyperprolactinemia, galactorrhea, breast cloped (Me-to-clop-ramide), screaming like a
tenderness, menstrual irregularities, girl (giving me girly stuff (SE)) while my GI
extrapyramidal symptoms, anxiety, and functions better with the diabetes. Rem: Me to
depression. D 2 (D2 and DM2)
Rem: try meth Ben (Trimethobenzamide), its a
144 dope (dopamine) used to prevent vomiting and
nausea "2 dope" he exclaims

145
Rem: the PD pt cracked open a bottle of
central side effects less than (Domperidone) now that his gastric stasis is
metoclopramide solved

146

SLE SE

147

148

149
D E F

The major side effects of erythromycin and


other macrolide antibiotics relate to
150
abdominal pain and cramping (51%);
nausea (up to 37%); diarrhea (24%); and
vomiting (7%). These side effects are
especially troublesome in patients with
gastroparesis who may already suffer from
similar symptoms. Rem: Macrolide bind Motilin receptors

151

Prolongs fever in pts with shigellosis, toxic Rem: the pt took Loperamide and is now
megacolon in pts with C. difficile; and HUS lopping around from the opioid (opioids work at
in children infected with Shiga toxin- Ulcerative colitis, or acute the MD receptos, mu and delta); or Rem: (the)
producing E. coli. Should be avoided in pts bacillary or amoebic dysentery; l'opera makes you slow, opiods make on lop;
with bloody diarrhea bloody diarrhea lopping amide the diarrhea in the streets

152 Rem: Dip the ox and hen in a vat of opium so


they stop with their diarrhea (Dip-hen-ox-ylate)

153 Rem: dive in (Dif-en-oxin) the opioid haze; or


Rem: dip ox (dif-en-ox-in) in opium vate

154
Schedule II

155 Rem: an octopus tree (Octreotide) stand in the


sand (somatostatin) with tumor diarrhea,
orthostatic HTN, and esophageal varices on
the branches
D E F

156

Phenolphthalein causes pink to red


colored urine and feces, gastric irritation,
electrolyte imbalance, and allergic
157 reactions are possible.
Anthraquinone derivatives: may produce
an excessive laxative effect and abdominal
pain and yellowish brown to red urine. May
cause nephritis

158

Adverse effects such as dehydration and


electrolyte imbalances can be caused by
injudicious use of these agents.
D E F

159

Rem: like to loose (Lac-tu-lose) your ammonia


and portal HTN and hepatic encep

160

161
Rem: a prep for chemo puking - Aprepitant, "No
Kidding" as he pokes you (NK1 antagonist)

162
setron = antiemetic; Rem: seeing Tron won't
make you puke, in fact, it will make you feel
pretty good (seritonin receptor); Rem: Tron
throwing his frisbee at the seritonin receptor
inhibiting it; or Rem: O' dan is so strong
(Ondansetron), you can give him 5 hits in 3
rounds (5HT3)
163
164
165
D E F

166
Rem: Men die from saying hi to nate, (Di-men-
hy-dri-nate, Hi is H1 antagonist)

167

168

169
Rem: zine = H1 blocker

Rem: a pro method magazine that has photos


170 of skaters pulling methods with snot pooring
Dizziness, dry mouth, nausea and vomiting, out (rhinitis), splattering on the camera (camera
rash man vomits up mushrooms - muscarinic SE)
Very high incidence of anticholinergic
171 side effects when given orally or
parenterally. It is better tolerated as a
transdermal patch.
Hallucinations, disorientation, vertigo, and
172 other adverse effects limit the use of these
drugs to patients refractory to other Rem: the stoner was a drone (Dronabinol) from
therapy. all the Cannabinoids

173

174

175 Rem: Lora is scared of ze Pam, so takes


Benzodiazepines to relax; Lora's ass is so nice,
it will hypnotize you
176

177 Rem: (Tegaserod) touch the gas with the rod


and it expodes, punching a hole through the
Removed from market due to CV SE (ie MI, IBS; or to gas and shit right when your IBS is
unstable angina, strokes) treating you wrong, tegaserod
D E F

178
This drug was previously withdrawn due to
very serious adverse effects, including setron = antiemetic; Rem: seeing Tron won't
ischemic colitis and serious make you puke, in fact, it will make you feel
complications of constipation. pretty good (seritonin receptor);

179

Rem: tricyclic antidepressants prey on the mind


(pra-mine)

180
181

182

183 Rem: Sal farting sulfer cause relief to his UC


(sulf-a-sal-azine); 5-ASA compound -
BM suppression, n/v, HA, malaise sulfASAlazine

184
D E F

185
Must check for latent TB and other
infections before administration. One side
effect is a lupus-like syndrome, which is
rare and reversible after stopping the drug.
Anti-double-stranded DNA antibodies occur Rem: to fix CD, inflict a flick to their bowel
in 9% but are not associated with clinical (Infliximab), don't flick too hard or will give them
lupus. TB SLE or knock free the TB

186

187
188
189
190
191
192
193
194

195
196
197

198
D E F

systemic "flu-like" symptoms, marrow


199
suppression, emotional lability,
autoimmune reactions (especially
autoimmune thyroiditis), and
miscellaneous side effects such as
alopecia, rashes, diarrhea, and numbness
and tingling of the extremities. With the Rem: Jak, stop interferoning with me stat! or I
possible exception of autoimmune am gonna synthesize over 2 dozen proteins on
thyroiditis, all these side effects are your ass
reversible upon dose lowering or cessation (interferon turns on jak stats and they make a
of therapy. bunch o crap)

Rem: Lassa is so skinny, her Rib's avirin from


200 her side, covered with guano, and she is
having a hard time breathing, has turned yellow
for all to C (Guanosine analog, breathing is
anemia teratogenic RSV, and yellow plus C = Hep C)
201 See Interferon-

202
See Interferon-
See INF-alpha; Very rarely, interferon alfa-
203 2b, recombinant used alone or in
combination with ribavirin capsules may be
associated with aplastic anemia.

204
See Interferon-
See INF-alpha; Very rarely, interferon alfa-
205 2b, recombinant used alone or in
combination with ribavirin capsules may be
associated with aplastic anemia.
D E F

206

Negligible

Usually well tolerated; asthenia, headache,


207 diarrhea and abdominal pain High dose
are risk factors for azotemia and renal
tubular dysfunction. Hepatitis flares may Rem: What B AILing you (Adefovir, interferon
occur after adefovir is stopped. alpha 2b, and lamivudine for treating B)

208

alcoholic liver disease

209

210

s 211
D E F

212

GI most predominate, see extra notes for


all side effects. Loop diuretics may
exacerbate digitalis associated
hypokalemia (and hypomagnesemia); do
not give with quinidine (displaces digoxin
from binding sites on albumin)

213
see digoxin

214

B for brain; Rem: "Neh, sir, the tide is changing


(Ne-sir-i-tide), where gonna bring this pt back
hypotension from certain death (acute decomp)"
D E F

Headaches, dizziness (Monday disease


people who work (factory) with nitrates
often experience worse HA/dizziness
immediately after the weekend because
215 tolerance is lost over about 24 hr)
Orthostatic hypotension & reflex
tachycardia. Drugs for erectile dysfunction --
Tolerance - Dose/frequency dependent afils are contraindicated with
(Try to maintain patients nitrate free for at nitrates: sildenafil, tadalafil &
least 8-hr /day; mechanism?; Drug holidays vardenafil (the afil class), Rem: put your dick on a sill and it will fill (afil,
can alleviate) including severe hypotension. sildenafil)

216
See NTG

217

218 GI (nausea, vomiting)


Thrombocytopenia
Abnormal liver function
If used long term, increased mortality

Short Term - Fewer than amrinone, so


219 preferred
Long Term - Increased Mortality, Half-life = 30-60 minutes
Arrhythmias
220

cs 221

Increased TdP = hypotension syncope


and sudden death within the 1st few
222 days; Nausea, diarrhea, abdominal
cramping; Cinchonism = vertigo, HA,
tinnitus, psychosis, blurred vision; rash, Do not use in pt with long QT
thrombocytopenia, hemolytic anemia;lupoid syndrom, TdP history, or
hepatitis and 2X to 3X increase in mortality hypokalemia (increases TdP) Put Na in your tonic and call it quinidine
D E F

223
Salty (Na) old man weiding his cain in NAPA
valley, whacking hot Lupus chick, giving her
lupus-like syndrome!! arrhythmia may be Do not use in pt with long QT butterfly rash; Rem: its not HIPP to get drug
aggravated, development of TdP; syndrom, TdP history, or induced-LE - (Hydralizine, INH, Phenytoin,
agranulocytosis, BM depression hypokalemia Procainamide)

224

Remember: dis o' pyramid sitting in sand of Na,


anticholinergic SE - stops peeing, can't piss or poop (anticholinergic), just wants 1
pooping, salivating impaired ventricular function Ass (1A) movement

CNS symptoms: seizures!! (mental


225 status changes), drowsiness, dyarthria,
dysesthesi, and coma; can depress cardiac Remember: class I be (B) ventin (works only on
function leading to decreased clearance, ventricle) with the short fuse temper (shortens
and produce greater SE; sinus node AP)
dysfunction
CNS symptoms: seizures!! (mental
status changes); dose related tremor, Remember: the Mexican (Mexiletine) injected
226 visual blurring, dizziness, dysphoria, and his toe (tocainamide) with lidocaine to numb
nausea; thrombocytopenia and postivie the 1 Bee sting (class IB), but goes into a
ANA; worsen heart block with high seizure and wishes he'd injected dilantin
concentration instead

227

228
Remember: die laughing so had a seizure
D E F

proarrhythmia!!; CHF; CNS=blurred drug interactions: cimetidine


229 vision, headache, ataxia;decreases LV its clearance its half-life;
function and depresses the SA node in pt digoxin, propranolol, & Remember: flick a cain in someones one eye
with SA node dysfunction amiodarone its levels and they can't see (1C)

230

proarrhythmia!!

drug interactions: increases


digoxin, theophylline,
231 cyclosporine levels and warafin
effects;cimetidine increases its
proarrhythmia!! nausea, vomiting, metallic levels;phenobarbital, phenytoin, Prop a phone against Kofi in one sea (1C), the
taste to food rifampin decreases its levels sea is rough (proarrhythmia)

232
similar to Flecainide

Severe systolic heart failure


233 (from massive myocardial
damage, RV infarction, or acute
high doses=fatigue and depression; valvular regurgitation) and
bronchospasm, bradycardia and AV block, active wheezing from reactive
myocardial contractility, impotence, CHF airway dz

proarrhythmia, bronchospasm, worsens


heart failure;instability in pt w vent Remember: Jaba the Hut saying Sotolol
234 arrhythmias post MI;TdP in those w (meaning solo) for Han Solo, who is a master
bradycardia, prolonged QT intervals, and bounty hunter and will pull in any criminal,
hypokalemia;normal side effects of including & K & Na & Ca channel blocker
blockers criminals
D E F

irreversible pulm fibrosis!!


hepatotoxicity (jaundice and cirrhosis);
235
hyper- & hypothyroidism, corneal Remember: Amy and Yoda sitting together
deposits; agranulocytosis, bluish eatting bananas (K), yoda got corneal deposits
discoloration of skin & photodermatitis, in eyes and is bitch'n because he has
nausea, constipation, bradycardia, drug interactions: digoxin and pulmonary fibrosis and toxic liver, but stoked
hypotension with IV due to contractility cyclosporine levels and cause he can have a prolonged orgasm (half
and peripheral vascular resistance wafarin effects life)
dont give to those w
236 TdP (esp in women w vent function or hypokalemia,
electrolyte disoders--all TdP), heart hypomagnesemia or a QTc
block, hypotension, nausea >440msec
TdP; drug interactions which increase Rem: Do fret, I lied (Do-fet-i-lide)
237 levels: erythromycin, diltiazem, cimetidine, - though your heart can be fixed
or ketoconazole; causes massive by bananas (K), it causes
diarrhea! massive diarrhea

238
reflex tach due to vasodilation; edema
and orthostatic hypotension

239
moderate in LV contractility,
bradycardia and hypotension

240 peripheral edema, moderate in LV


contractility (V. Fib.) and hypotension
(peripheral vasodilation); constipation; CHF (because of decreased
hemodynamic collapse inotropic effect)

promotes atrial and vent irritability;


hypokalemia, loss of appetite, nausea,
vomiting, diarrhea, blurred vision & yellow-
241 green halos (xanthopsia), confusion,
drowsiness, dizziness, nightmares, Wolff-Parkinson-White
agitation,depression; do not give with syndrome (direct
quinidine (displaces digoxin from binding connection/reentry tachy - dig
sites on albumin) would exacerbate)
D E F

facial flushing, dyspnea, or chest pressure dont use for AFib, sick sinus
242 lasts <60 sec; sometimes nausea, syndrome, or 2 and 3 heart
lightheadedness, headache, sweating, block unless they have a
palpitation, hypotension and blurred vision pacemaker

243

Arrhythmia may be aggravated, Do not use in pt with long QT


development of TdP; lupus-like syndrome, TdP history, or
syndrome; agranulocytosis hypokalemia
244
245

1. Hemorrhage from inadvertent overdose,


bleeding from undiagnosed disease site Active bleeding!!
(ulcer, carcinoma). Also: severe HTN, aneurysm,
2. Hematoma formation at surgical site or hemophilia, thrombocytopenia,
from SC or IM injection intracranial hemorrhage, active
3. Heparin-induced thrombocytopenia tuberculosis, ulcerative lesions
246 (HIT). Heparin induces transient of the GI tract, threatened
thrombocytopenia in as many as 25% of abortion, or visceral carcinoma;
patients but his usually resolves withhold during/after surgery of
spontaneously. However, in approximately the brain, eye, or spinal cord;
5% of patients a severe thrombocytopenia lumbar puncture or regional
can evolve days after the initiation of anesthetic block; visceral Remember: hepar-in-trinsic Remember: PiTT -
therapy (Ab formation, see extra note). carcinoma The drug should be intrinsic, Brad Pitt is a hep dude (heparin) and
4. Less common side effects include acute used only where clearly gets a suck on Angalena Jolee's TT's (thrombin
hypersensitivity, alopecia, platelet indicated in pregnant women, time); Remember: The hemaphiliac (A) ate
aggregation, osteoporosis (1 year therapy), despite its apparent lack of (eight) nine Christmas Bees (B), see (C) at
and priapism. transfer across the placenta. eleven (11) on the news

247
Bleeding
248 Bleeding Rem: Enoxaparin = LMWHeparin
D E F

1. Hemorrhage (bleeding): incidence 2


4%, serious bleeding approximately 1%
249 2. Anorexia nausea, vomiting, diarrhea
3. Cutaneous lesions: skin necrosis
(usually associated with protein C or S
deficiency causing hypercoagulation and Remember: PeT - extrinsic, walk your PeT
thrombus), begins as bulla that may be down on the Warf (warfarin); Remember: slow
purpuric or show dermatitis, urticaria, prolonged bloody war, as told by the oral
alopecia - followed by necrosis Contraindications are similar to tradition, don't let the pregnant woman listen
4. Drug-Drug Interactions!!! heparin, but include pregnancy (teratogen), it's too horrible for their fragile state

250

251 Clopidogrel increases the risk of


bleeding during coronary bypass surgery, Remember: clop/slap the ADP receptors face
so this drug usually is not started if the to piss them off so they will stop aggregating,
patient is considered to be a surgical so we can drill (clopidrogel) prophalactically
candidate. open the a. of brain and heart

252
Rem: Love cAMPing outside a pyramide,
planned go into the pyramide but passout from
vasodilation and die from eatting spicy mole
(though drug prevents stroke)

Life-threatening hematological adverse


reactions, including
neutropenia/agranulocytosis, thrombotic
253 thrombocytopenic purpura (TTP) and Remember: tickling opie (Ticlopidine) while he
aplastic anemia; severe diarrhea. Use dines spagetti (fibirin) and meatballs (platelets),
should be reserved for pts who are but the spagetti and meatballs will not mix, and
intolerant or allergic to aspirin therapy or worse, he spills his blood wine
who have failed aspirin therapy. (neutropenia/anemia)
D E F

254 Rem: she'll stall all (cilostazol) the platelets


(blocking them) and vasodilates open their
faces so she won't be lame for the cAMPing
CHF trip at CHF park

255

Remember: ET learning his ABCs in jail


(Eptifibatide, Tirofiban, ABCiximab, jail =
IIb/IIIa)

Remember: ET learning his ABCs in jail


256 (Eptifibatide, Tirofiban, ABCiximab, jail =
IIb/IIIa); Remember: go up to the fibrinogen tide
(Ep-ti-fiba-tide) and stop it by mimicing it

257 Remember: the tyranny (tiro-fiban) of fibrinogen


will end by replacing it during heart surgery
(PTCA) with a analog

258
Remember: a pent up ox in a RBC that that is
doing yoga to become more flexible

259 Bleeding; Disadvantage of the direct


thrombin inhibitors is lack of revesibility
Bleeding; Disadvantage of the direct
260
thrombin inhibitors is lack of revesibility

261 lepard attacks heparin and rudely (lepirudin)


Bleeding; Disadvantage of the direct latches on with its claws, so heparin HIT the
thrombin inhibitors is lack of revesibility lepard
D E F

262

In the bivouac (bivalirudin) the solider was rude


Bleeding; Disadvantage of the direct to the thrombin and platelet commanders,
thrombin inhibitors is lack of revesibility jutting his fingers into their hearts (PCA)
Remember: needed a direct thrombin binding
drug, so went into the LAB to create it
263 (Lepirudin, Argatroban, Bivalirudin);
Remember: Argatroban, an aligator bites and
Bleeding; Disadvantage of the direct sticks (binds) to thrombin, and so is banded
thrombin inhibitors is lack of revesibility from the HIT club on Miami beach

264

Remember: alteplase alters the plasminogen to


active plasmin, also alto (stops) at the boarder
hemorrhage of the thrombus, also stops the MI

265 Remember: rent a place (Reteplase) to


"activate" plasminogen - a seedy hotel room
deep in the getto (clot), its so good you don't
hemorrhage have a MI

266

hemorrhage
D E F

267

Active or recent internal Remember: SARA T. is thrombolytic (heart


bleeding; intracranial surgery or throb) - Streptokinase, Alteplase, Reteplase,
hemorrhage pathology Antistreplase (APSAC), tenecteplase

268 Active or recent internal


bleeding; intracranial surgery or
hemorrhage pathology

269

Remember: a nap sack (APSAC) filled with


inactive steptokinase and plamin complexes,
but seeps through the sack, becoming active
hemorrhage and bloody-fibrin lysed blood dripping
Rem: the amgios (aminos) gonna cap the
270 rollers, killing them before they can kill (Amino-
Thrombosis cap-ro-ic)

271
272
273
D E F

Numerous, but incidence is low and


severity is relatively lesser than with other
lipid lowering drugs. Most frequent is
hepatic damage (1-2%). Elevated serum
hepatic enzymes occur, and they can
cause hepatitis. Monitor liver enzymes after
1-2 months and then every year.
Increasing number of reports of peripheral
neuropathies. Appear reversible on
discontinuation of the drugs.
Watch for myalgia (1-5%), myopathy
274 (<1%) and rhabdomyolysis (rare).
Monitor for myopathy more carefully when
combining with niacin (2%) or fibrate drugs
(5%), which can cause the same toxicity).
These toxicities occur more frequently.
Monitor creatine phosphokinase (CPK; CK)
Avoid combining with erythromycin (dec.
metabolism of statins, with inc. myopathy);
also verapamil, diltiazem & grapefruit juice
(increases statin levels).
Test on Board examinations: Lovastatin
and simvastatin cross BBB and may cause Contraindicated in hepatic
sleep disturbances disease
Frequency of toxicities is generally low, Contraindicated in pregnancy
most are reversible on discontinuation of (fetus needs cholesterol for
drug formation of cell walls)
275

(relatively long list, but low incidence):


Blood cell deficiencies, skin rash and other
hypersensitive rx
G.I. problems
liver enzyme abnormalities (usually
276 transient)
myositis -- myopathy and
rhabdomyolysis are reported when
combined with HMG-CoA reductase
inhibitors Remember: the gem (gemfibrozil) VLDL (very
lithiasis (increase biliary cholesterol luminuous during lumination) is found in Brazil;
excretion). Do NOT use in pts with gall Also notice Fibrate Derivatives have fibr inside
bladder problems. pts with gall bladder problems. their name (gemifibrozil and fenofibrate)
D E F
Remember: the fen fenofibrate fell over and
277
vibrated, breaking the gems (VLDL)
278

GI distress: Constipation and a feeling


of bloating, also causes steatorrhea
279 Text says this is easily controlled with a Do not use in pts with multiple
high fiber diet. However, patient compliance other medications as bile acid
is not good because of these side effects. sequestrants are notorious for
Unpalatable binding other medications,
Increase Triglycerides!! (associated with particularly beta-blockers,
atherosclerotic plaques that rupture) thiazides, digoxin, and warfarin

280
same as Cholestyramine same as Cholestyramine

281
same as Cholestyramine same as Cholestyramine

Itching, flushing and unpleasant


sensation of being warm.
Prostaglandin mediated - give aspirin
(blunts, but does not remove, this effect).
G.I. distress (may activate ulcers)
282
Elevates transaminase levels and may
(rarely) cause hepatitis
Glucose intolerance aggravates
diabetes
Inhibits urate secretion. Hyperuricemia in
20% of pts.

283 Rem: I am Thiazolidinedione, I can decreases


blood glucose, triglycerides, C-reactive protein
levels, and increases HDLs, what can you do?
D E F

Relatively benign side-effects, particularly


compared to the g.i. effects of the bile-acid
binding resins. Angioneurotic edema.
Reversible change in liver function.
Like statins, if pushed to aggressively with
dose, may see myalgia/rhabdomyolysis
phenomena. The literature is somewhat
284 unclear on this point, but my reading is that
the incidence is less than with statins.
When combined with a statin, the
probability may be higher. Note, however,
that the most popular form of this drug
(Vytorin) is in a fixed dose combination with
simvastatin. On balance this is not like
combining a statin with a fibric acid drug,
which clearly has greatly enhanced Remember: Tim is all pissed at you because
prospects of rhabdomyolysis. your eating to much plantsterols (seeds) and
(Very low systemic toxicities because choleterol, so you say "Easy, Tim, I be donnin
majority of drug isolated to intestine) much betta" in a Jamacin accent

285

286
D E F

287

GI distress is the most prominent adverse


effect of oral iron therapy (15 to 20% of
patients). Abd pain, n/v, or constipation
often lead to noncompliance. Although
small doses of iron or iron preparations with
delayed release may help somewhat, GI
SE are a major impediment to the effective Rem: (Deferoxamine) talk to da farrow cat to
treatment. save your kid from the iron overdose

288

Rem: the co-balla (Cyanocobalamin) flying a


B12 bomber (plane been around for a while =
long storage in body), but co-balla probably
shouldn't be flying it because of his neuro
damage
D E F

289

290

291

292 Rem: Fill gas (Fil-gras-tim) in BEN's car so we


can go pick up some granulocytes (BEN -
basophil, eosinophil, neutrophil)

293

Rem: Sargent Slaughter (Sar-gramo-stim) will


stimulate BEN and macrophages to get back to
work
D E F

294 Rem: Oprea thought that by being vegan


Fluid retention and must be used (Opre-l-vekin) she could get ride of her
cautiously in patients with CHF or cardiac thrombocytopenia, but instead she had fluid
arrythmias. This drug may harm the retension by eating those 3 carrots (3 carrots =
fetus and pregnant women. I-ll)

MC SE include myelosuppression
(leukopenia, thrombocytopenia, anemia),
GI symptoms (eg n/v, stomatitis, anorexia,
appetite disturbances), and dermatologic
toxicity (eg rashes, skin ulcerations, facial
erythema). Rarely (at high doses)
295 neurologic disturbances (eg drowsiness,
dizziness, HA, and convulsions, altered
renal function, alopecia). Mutagenic
potential is unknown, avoid when possible
in pregnant women. Causes
macrocytosis, may mask the incidental Rem: hydrated urine (hyrdoxy-urea), when
development of folic acid deficiency, give pissed on R to D 2 (ribonucleotide to
prophylactic folic acid deoxyribonucleotide) shuts him down
296

List
297

298
Rem: first generation sulfonylureas have
299
-amide

300
alcohol-induced flush!!
301
302
D E F

303

Rem: use a cell phone (sul fon) to call


Hypoglycemic reactions, including coma potassium to throw a insulin releasing party -
- caution in elderly patients with renal Pts with Type 1 DM, sulfa Sulfonylurea. Rem: 'ide' drugs are commonly
failure and others predisposed to allergies, pregnant or nursing hypoglycemic agents Rem: (Glimepiride)
hypoglycemia; HS rxn - many pts are mothers, and significant Glee, my pride for doing so well with my new
allergic to sulfa's hepatic or renal insufficiency. DM drug. Let's throw the insulin party

304
Hepatic insufficiency, sulfa
See Glimepiride allergies, pregnancy Rem: Glee (Glipizide) and ide

305
See Glimepiride See Glimepiride Rem: Glee (Glyburide) and ide

306

Adverse effects are comparable to


sulfonylureas but these drugs should be Rem: 'gli' and 'ide' drugs are commonly
used cautiously in the elderly and those hypoglycemic agents - but 'glinide' are Non-
with liver dysfunction. sulfonylurea secretagogues
Rem: 'gli' and 'ide' drugs are commonly
307 hypoglycemic agents - but 'glinide' are Non-
sulfonylurea secretagogues
D E F

Metformin should not be


administered to patients with
308 renal impairment (CI if
>1.5mg/dL), hepatic disease, a
history of lactic acidosis,
cardiac failure, or chronic
Lactic acidosis!!; abdominal discomfort, hypoxic lung disease because
anorexia, nausea, metallic taste, and of the concern for the
diarrhea development of lactic acidosis.

309
Rem: a car and bus (Acarbose) filled with
diabetic ketoacidosis, cirrhosis, people with explosive diarrhea, their splatter
inflammatory bowel disease, splattering their sugar lolly pops such that they
flatulence, diarrhea and GI upset due to colonic ulcers, or partial don't want to eat them (inhibits glucose
undigested carbohydrate intestinal obstruction. digestion)
310

311

moderate weight gain, edema and mild Rem: the glitter zone (glitazone), everyone is
anemia, all due at least partly to fluid here in the nuclear gliter zone, sensitized to
retention; can precipitate frank anemia. insulin's hypnotic music - P-party!! (PPAR-) -
Potential liver damage Heart dz and liver dz! the heart and liver weren't invited

312
See rosiglitazone Heart dz and liver dz!

313
Hepatotoxic (monitor LFTs) Heart dz and liver dz!
D E F

314
Risk of hypoglycemia and nausea. Other
side effects include decreased appetite, Rem: the new baby Amylin in the pram
vomiting, stomach pain, tiredness, (flatbottom boat or baby carrige, Pram-lintide)
dizziness, or indigestion. is so fat it already has DM

315
Nausea, vomiting, diarrhea and upper
respiratory symptoms are the most Rem: I threw my ex in the tide (Ex-en-a-tide) to
common adverse effects. Incidents of drowned because of her glib tongue (GLP), that
hypoglycemia are relatively low. fat diabetic bitch
316

317

Rem: Sit the Ez that breaks down GLP by


punching, smashing it in the face (Sit-a-GLP,
SitaGLiPtin);
318
319
D E F

320

Rem: Lis is a pro (Lis-pro) at having her ass


pulled apart for quick insulin insertion
Rem: use GLUT to (GLUT2) activate insulin
production at islets of Langerhans
Lispro is associated with a lower risk of Rem: use GLUT for (GLUT4) glucose (and aa)
hypoglycemia (than Regular insulin). transportation to muscle (and adipose)

321 Rem: pull her ass apart (as-part) and quickly


insert insulin (ultra-short-acting) - no do it faster
Rem: Lis got sick of her ass being rapidly
322 pulled apart so she glued it closed, now it
glissens (Glulisine)

323

324

325

326
D E F

327

Rem: the diabetic glared at you for a very long


time (Glargine), he was very determined
(Detemir)
328
329
gs 330

331

332
Toxicity to thioamide drugs occur in 3-12%
of treated patients. The most common
adverse effect is a maculopapular pruritic
rash (super itchy!!). The most dangerous Rem: they are for (pro) piling (pyl) up the iodine
(potentially fatal) complication occurring in because drug blocks Ez that forms MIT, DIT,
0.3 0.6% of patients is agranulocytosis and thyronines. Rem: Theo Huxtable amist
(BM failure) heralded by a sore throat (thio-amide) all the trendies with ther peroxide
and fever. Goiterogen bleached hair (peroxidase)
D E F

333 congenital scalp defects (aplasia cutis),


see propylthiouracil Pregnancy, see PTU extra note

334

335

336

337

338

339

340

341
Remember: Perchlorate prefers it makes active
Goitrogen receptors to chocolate than iodine
342
D E F
Remember:: the orc tree had acromegaly so
343 was chopped down to prevent it from growing
(GH inhibiter) taller - Octreotide
Rem: a ginormous Peg (Pegvisomant) standing
344 on Camp bowie blocking traffic (blocks GH
receptors)

345

Remember: His/'Er breasts are gone, a vine


346 plugged up the leaky milk and took the breasts
away - Ergonovine
347

Bloating, Breast tenderness and uterine


bleeding.
348
Women who have an intact uterus must
take a progestin to avoid risk of
endometrial carcinoma.
Long term use increases risk of
thromboembolism and might increase risk
of breast cancer

349
Adverse effects. Hot flashes and leg
cramps. Also increase risk of
thromboembolic disorders.

Heartburn, esophageal irritation and reflux,


abdominal pain and diarrhea; To avoid GI
350 discomfort take orally after an overnight
fast with 8 oz of plain water; Calcium
supplements taken at the same time may Rem: drowned nate (Alen-dro-nate) in milk
interfere with the absorption of BPs. (Ca) because he is pro-osteoclast
351
352 mineralization defects
353
354
D E F

355

356
Remember: flood (flud) the mineral mine

357 Remember: cortisol met Tyra and fell inhibited


-metyrapone

358 Remember: insulin dies so (dia zo) K channels


can live, K channels are open - Diazoxide

359

Vit D3 is converted to metabolites in the liver


360 (25 hydroxy-D3) and kidney (1,25 and 24, 25
dihydroxy D3) Rem: 1 liver and one number
one type (25 hydroxy-D3), 2 kidneys and 2
T1/2 is relatively short due to poor binding numbers and 2 types (1,25 and 24, 25
affinity with serum Vit D binding protein dihydroxy D3)

361

362
363
Dry skin and chelitis!! Pseudotumor
cerebri, vision impairment, HA, myalgias,
364 arthralgias; also BM suppresion, Teratogen - must confirm pt is
hepatotoxicity, hypertriglyceridemia and not pregnant with two negative
pancreatitis; depression and suicide pregnancy tests
D E F
365

gs
366

367

368 Exceeding the recommended


dosage will intensify side effects,
SE more apparent by the oral route: but a greater danger is the
hypotension, muscle tremors, (relflex) tendency of patients to continue HS type I (Allergic Asthma): Early phase:
tachycardia, hypokalemia (low [K+] in self-medication during periods Allergen-IgE mediated release of preformed
blood), see extra notes. Effects on blood when their symptoms are mediators causes bronchospasm and
glucose are variable. escalating. To avoid a medical infiltration of more mast cells.
Caution in hyperthyroidism, DM, emergency, patients should Late phase: hours later, eosinophils,
cardiovascular disorders be encouraged to seek neutrophils, and other inflammatory cells can
Skeletal Muscle Tremors (2 receptors on medical attention as soon as cause reactive hyperemia, edema, cellular
skeletal muscles mediate increased energy possible after they detect a inflammation, bronchospasm.
production, excess high energy compounds marked decline in the efficacy Repeated exposure: heightened bronchial
are reduced by muscle contraction - of their usual therapeutic reactivity to specific and nonspecific stimuli.
tremors)
see albuterol, fewer effects on the heart regimen.
rhythm (ie tachyarrhythmia) and fewer
369
occurrences of tremors
370 see albuterol

371
see albuterol, use with caution in pts with Remember: Terbutaline - tear a butt to help
CHF or history of arrhythmias person breath and delay pregnancy
D E F

372

see albuterol, ipratropium

373 Rem: Bite old turd role (Bit-ol-ter-ol), bad taste,


but opens your lungs for longer than albuterol;
Bitolterol has a disagreeable taste. best to eat turd when riding a colt (colterol)

374 Salmeterol - a salmon swimming slowing in


lungs, it is wearing a night cap (used for
nighttime asthma)

375 Rem: for motor roles (Formoterol), put COPD


and exersize-induced asthma pt in charge of
vehicle maitenance, will role the car fo-sho

376

377 Typically, epinephrine is administered by s.c.


injection. It causes vasoconstriction that limits
edema and swelling of the upper airways,
produces bronchodilation, and inhibits mediator
release from mast cells.

378
379

380

IV not recommended for


381 treatment of asthma because of
risk of MI
D E F

382
Quaternary compounds can block nicotinic
receptors and may have ganglion or a rat from Ip was rowing his boat with four
neuromuscular blocking action paddles (quaternary) because he thought the
Overdose with quaternary more likely to be sea air would open his lungs (reverse bronchial
fatal because of neuromuscular constriction), his boat was overflowing with
blockade. sizziling mushrooms
Tio is spanish for uncle, the uncle of
383 ipratropium who tries to spit, but sizzling
see ipratropium mushrooms in his mouth wont let him

Theophylline should only be used where


384 methods to periodically measure blood
levels are available (hepatic metabolism
varies amongst pts). Normal plasma
concentrations are 5-20 mg/L. Anorexia,
nausea, vomiting, abdominal
discomfort, headache, and anxiety often
occur if blood levels reach 15 mg/L.
Higher drug levels may cause seizures or
arrhythmias.

385

Corticosteroids
386
D E F

Potential Adverse Effects Associated with


Inhaled Glucocorticoids, see
corticosteroids for more complete list
a. Hypothalamic-pituitary-adrenal axis
suppression - low risks until high dosages
are used.
b. Bone resorption/ osteoporosis/
asseptic necrosis of femoral head
387 c. Effects on carbohydrate and lipid
metabolism - minor risks
d. Cataracts and skin thinning - dose-
related
e. Purpura - dose-related
f. Dysphonia - usually resolves with no
consequences
g. Candidiasis - incidence reduced with
use of a spacer device and rinsing mouth Be close to the "method zone"
after dosing. (Beclomethasone) for greatest asthma relief,
h. Growth retardation - of concern when that what all the roid bodybuilders do; no not
high doses used in children. blow (beclo), inhale

388
See corticosteroid SE

389
See corticosteroid SE

390
See corticosteroid SE

391
Budda is so nice (Budesonide) to alleve pt of
See corticosteroid SE allergic/sesonal rhinitis
flew to kazakhstan (Flu-ti-casone propionate) to
392 apropriate drugs for my rhino (seasonal/allergic
See corticosteroid SE rhinitis)
mo' meat is on (Mometasone) this rhino
393 (allergic/seasonal rhinitis), let your kid ride on
See corticosteroid SE his back (no growth retardation)
D E F

394

See corticosteroid SE
395 See corticosteroid SE
396 See corticosteroid SE

397

398

399

Conan saying "Crom" (his god) while bear


hugging a mast cell, preventing release of
Essentially no local or systemic toxicity. histamine

400 Need a crow mill (Ned-o-cro-mil) to make a


potent (than cromlyn) asthmatic liquor, aged at
Adverse effects are infrequent and least 12yrs, out of ground up crows - the drink
generally mild. of Conan - the Mead of Crom

401
D E F

Rebound congestion is a problem with


these agents; insomnia, excitability,
402 headache, nervousness, palpitations,
tachycardia, arrhythmia, hypertension,
nausea, vomiting, and urinary retention;
Used topically they are likely to cause
systemic effects; Rhinitis medicamentosa
Rebound congestion is a problem with
403
these agents.

404

405
Dyspepsia (indigestion) is the most
common side effect. Liver toxicity has lukast - inhibits leukotriens. Monte is a young
been noted in some patients and the drugs boy (6-12yo) with asprin triggered asthma, so
are contraindicated in patients with he takes lukast but gets a stomach ache
abnormal liver function. instead.

406
see Montelukast

407

408
Rem: fence in the throat guana (sputum),
delivered from throat (Gua-i-fenesin)

409
Because of the potential for adverse effects
(?), other agents are usually preferred.
D E F

410
causes irritation

411

Rem: re-combine mucous with a cystic fibrosis


pt and get a depolymerized pt - they are broken
up into tinny bits sugar (polysaccharide)

Adverse effects (Most common with


codeine)
1. CNS: euphoria, depression of respiratory
and vasomotor centers
412
2. GI: constipation, nausea, vomiting 3.
GU: urinary hesitancy or retention 4. Drug
Interactions: additive CNS depression with
sedative hypnotics, phenothiazines, and
tricyclic antidepressants. 5. Opioid
dependence supported by codeine

413 Rem: give the damn dextrose (sugar) to the


damn meth orphan (Dextro-meth-orphan) so
he'll stop his damn non-productive coughing, so
Less constipation than codeine what if its actually opium

Rem: Ben knocks on Nate's taint


(Benoxonatate) which happens to be in the
414 back of his mouth at the pharynx, numbing it
with locally so he doesn't cough (antihistamine
effects), Nates pissed, cause its not opium, its
non-opium

The General made non-history (antihistamine),


415 when he drove his army green hummer H1 and
died into a fire-hydrant (Di-phen-hydramine)
but he wasn't coughing
The rich bastard ranted to Dean (ranitidine),
416 because some ran into his H2 hummer (H2
histamine)
D E F
intervention
417
418

419
local skin irritation

420

421
nausea, vomiting, gas, headache and Rem: I am very inclined to stop smoking (Var-
insomnia. enicline)

ials
422

423 Rem: I saw Red Pyre (Isoniazid, rifampin,


pyrazinamid) buring a liver (hepatitis); "I son, I
Elevated liver enzymes and hepatitis (risk am a TB lung zit, pop me" (I son I a zid); Major
increases with age); peripheral neuritis Cytochrome P-450 inhibitors: FREaCKI
(treat with pyridoxine HCL (vit B6)); drug Grapefruit gets stuck in Ez- Ketoconazole,
interactions Isoniazid, Cimetidine, Fluoxetine, Ritonavir,
Fatal OD Erthyromycin, Grapefruit

Can cause body secretions to turn orange


(harmless); rifampin strongly induces
cytochrome P450 enzymes which
424 increases the elimination rates of
numerous other drugs (warfarin, Rem: Rifampin - think Red (Red body fluids,
glucocorticoids, narcotics, oral also inhibits DNA dependent-RNA polyermase);
antideabetics, estrogen, decrease effect of Rem: orange flavored TB rye (ri) toast; Rem:
contraceptives); hepatitis, fever, RC PP induces P450 (rifampin,
thrombocytopenia carbamazepine, phenobarbital, phenytoin)

425 Rem: rif with a button, an AIDS pt jammin on


the guitar, playing a happy song cause his TB
is undercontrol
D E F
426

SPIRE TB (streptomycin (2nd), pyrazinamide


427 Can cause optic neuritis (may present as (1st), isonazid (1st), rifampin (1st), ethambutol
painful loss of vision), red-green color (2nd); Rem: AM (etham) radio or TB on the
blindness radio, TV shows only red and green colors
GI intolerance; hyperuricemia; hepatic
428
effects

429 Auditory, vestibular, and renal effects,


eosinophilia; hypokalemia;
hypomagnesemia
430
431
432

nts
433

Severe side effects


Delayed nephrotoxicity major dose-
limiting toxicity, Renal hypokalemia
(increased CRT, BUN)
Acute reaction to IV - fever, chills,
434 headache, nausea, vomiting, hypotension,
tachypnea
Weight loss, malaise, anemia,
thrombocytopenia and mild leukopenia can
occur
Usu given with steroid, heparin, and
antihistamine to reduce SE; usu give KCl
supplement
potent inhibitors of cytochrome P450
(CYP3A4) and can lead to unacceptably
435 high levels of co-administered drugs that
are normally metabolized by CYP3A4
(especially some HIV drugs)
HIV pts (may cause BM
436
suppression)

437

438
D E F
439

440

441
442
Pregnancy

443
444

ts 445

Lady has a man to dine (amantidine) with who


446 keeps trying to undress but she keeps stopping
him (prevents uncoating) so she dont get
CNS SE in elderly pregnant (teratogenic)

447
CNS SE in elderly

448

449

450

anemia teratogenic

451

Nausea, diarrhea, headache, renal


insufficiency, neurologic toxicity!
D E F
452
453

454

455 Rem: She had to quit the mods cause their


leader gave her HPV (Imi-qui-mod), she's got
to pay the toll when she rides her scooter
456

es 457

Side Effects: Sedation most common


(less prominent with newer drugs); Other
CNS effects: dizziness, tinnitus,
nervousness, insomnia, fatigue, blurred
vision; GI: nausea, vomiting, loss of
appetite; Antimuscarinic; dryness of
458
mouth, nasal passages; urinary retention,
frequency; Hypersensitivity reactions
Poisoning:
1. Central effects: child excitation;
hallucinations, ataxia, incoordination and
convulsions
2. Fixed dilated pupils with flushed face Rem: The General made non-history
and fever are common (antihistamine), when he drove his army green
3. Terminally there is deepening coma with hummer H1 and died into a fire-hydrant (Di-
cardiorespiratory collapse and death phen-hydramine)but he wasn't coughing
Rem: men die from saying hi to nate (Di-men-
459 see diphenhydramine; Marked sedation; hydri-nate) because they have runny noses by
high antimuscarinic activity choking on mushrooms
Rem: 'zines' are H1 antagonists with slight
460 sedation; anti-motion sickness activity; and no
see diphenhydramine; Slight sedation antimuscarinic activity

461
see diphenhydramine
D E F

462
see diphenhydramine

463
Rem: has a lasting (az-e-lastine) effect when
At very high doses (280x), is squirt this up the rhino's nose (allergic rhinits),
sometimes leaving a bitter taste, and teratogenic in mice; dont use but he gets pissed cause the bitter taste in his
sometimes causing sedation. during pregnancy. mouth

464 Rem: stick the chloride (Chlor-phen-ir-amine)


down the histamines ear to burn it so bad its
Slight sedation nose stops running

Rem: a pro method magazine that has photos


465 of skaters pulling methods with snot pooring
Marked sedation; antiemetic and out (rhinitis), splattering on the camera (camera
antimuscarinic activity. man vomits up mushrooms - muscarinic SE)

466

467

free of sedative effects; decreased risk of


arrhythmia (e.g., Terfenadine (Seldane) and
Astemizole (Hismanal)).

468
Rem: Lo-ratidine is lo-nger actingin 2nd gen H1
469
little sedation. antagonist

470
D E F

Adverse Effects - low incidence


Antiandrogenic effects (cimetidine)
gynecomastia, galactorrhea
471
GI - constipation, nausea/vomiting,
diarrhea (cimetidine)
CNS - headache, dizziness, hallucinations
Hematologic - agranulocytosis,
thrombocytopenia, etc.
liver toxicity Rem: all of the H2 antagonist have 'tidine'
The rich bastard ranted to dean (ranitidine),
472 because some ran into his H2 hummer (H2
see cimetidine histamine)

473
see cimetidine

474
see cimetidine
475

pathomimetics):
476
amine vs. non-Catecholamine, Direct vs. indirect acting, Re-uptake inhibitors)

477

Increases BP (arterioles)
Expect reflex bradycardia. Remember: phenylephrine is a picky hot bitch
Increases cardiac return (veins) who feels (phenyl) out ephrine (who is similar
to epinephrine) and only takes his 1 qualities.
D E F

478

Contraindications
1. Hypertension
2. Shock (non-anaphylactic??)
3. Hyperthyroidism - E may have
enhanced cardivascular actions
in pt with hyperthyroidism. If E
1. Arrhythmias - particularly in conjunction is required in such an indivildual,
with the gaseous anesthetic halothane; E the dose must be reduced. The
increases the frequency of ectopic beats in mechanism appears to involve
Purkinje fibers by accelerating spontaneous increased production of
depolarization. adrenergic receptors on the
2. Cerebral hemorrhage vasculature of the hyperthyroid
3. Necrosis distal to site of injection individual leading to a Rem: I had a cat named NED
(potential problem with infiltration) hypersensitive response. (Catecholamines; NE, E, Dopamine) - all
4. CNS effects: anxiety, headache 4. Angina pectoris derived from tyrosine (which is derived from
phenylalanine)

479
slow, forceful (pounding) heart beat,
elevated BP, anxiety, headache.
D E F

480

Common: tachycardia, flushing, headache,


rapid pounding heart.
Serious: arrhythmias, angina

Usual side effects more apparent by the


oral route: hypotension, muscle tremors,
tachycardia, hypokalemia (low [K+] in
blood). Effects on blood glucose are
481
variable.
Skeletal Muscle Tremors (2 receptors on
skeletal muscles mediate increased energy Remember: Terbutaline - tearing a butt to help
production, excess high energy compounds person breath and delay pregnancy; Salmeterol
are reduced by muscle contraction - - a salmon swimming slowing in someones
tremors) lungs
Skeletal Muscle Tremors (2 receptors on
skeletal muscles mediate increased energy
482 production, excess high energy compounds
are reduced by muscle contraction - Give mother ritodrine to prevent early arrival of
tremors) ritoline (sp?) kid

Potential for hypertensive crisis in patients


on MAO inhibitors.
Tyramine is found in many foods (red wine,
aged cheeses, peanuts, etc)
483 It normally is subjected to such a large first-
pass effect by MAO in the gut and liver that
it never enters the circulation
Watch out in pts taking MAO inhibitors.
A classic drug interaction. Disastrous
hypertension.

485
D E F

Tachycardia (worse than dobutamine)


486 At higher doses, increase in systemic
vasuclar resistance; mechanism is alpha
agonist
Dobutamine is generally a better choice

487
Atrial fibrillation; Tachycardia with possible
increase in myocardial oxygen
consumption (angina)

Side effects:
488 insomnia, anxiety, arrhythmias, nausea,
vomiting
Toxicity:
Acute: convulsions, coma, death
Chronic: abnormal mental state (paranoia),
weight loss, psychotic reactions.

489 Like amphetamine (dopamine mechanism),


ephedrine has abuse potential; now
banned in the U.S.

Oral decongestants have a preolonged


490 duraton of action but may cause more
systemic effects, including nervousness,
excitability, restlessness, and insomnia
D E F

491 Side-Effects: Rebound edema (typically


happens with prolonged or excessive-dose
use). Clears in 24-48 hrs.
Toxicities: Necrosis of the nasal tissue.
(This occurs only with gross overuse,
usually in combination with cocaine abuse)
492

emicals
493
tivity or of sympathomimetic drugs

CNS: drowsiness/sedation, dry mouth,


494 depression
Rebound hypertension (from abrupt
discontinued oral administration, can elicit
hypertensive crisis, common board Remember: the clone goes into the bank to
question) make a withdrawl so he can by cigarettes,
Do not give with beta blocker because cocaine, heroine, (used to treat drug withdrawl)
excessive bradycardia and he is agonizing over his need (alpha 2
Inhibits insulin secretion agonist)

495 May cause autoimmune hemolytic Remember: give meth and dopa to pregnant
anemia and SLE woman with high bp
496

Unacceptable side effects:


CNS -- depression!!, nightmares (dont
use if history of depression)
497 nasal stuffiness
unopposed parasympathetic activity: Remember: red (re) serpent/snake (serpine)
miosis, bradycardia, aggravation of ulcers, Do not give with beta blocker, crawls into your brain and drains the body of
diarrhea may cause excessive monoamine causing depression and
fluid retention bradycardia nightmares
D E F

498 Remember: Adrenergic guana/poop


(guanethidine) got everywhere, except your
Na+ and water retention are marked (given head (CNS) - sucks the happiness from
with diuretic) NEbody (NE depletion, depression)

499

500

g Agents
501

502

Orthostatic hypotension
Tachycardia
Combined alpha blocking and
muscarinic/histamine agonist actions Remember: the phens are hens that are bitchy
Diarrhea and charge a tole to all the alpha males that is
Nausea too steep for them to pay, so they keep them
out/block them.
D E F

503
1. Cardiac. Reflex tachycardia.
Reducing BP causes sympathetic
activation. Because 2 receptors on
adrenergic nerves are blocked, this further
increases NE release at the heart, where Remember: Phen is Hen and
NE can act on beta-1 receptors. they're bitchy birds that block all
2. CNS. Lipophilic agent that crosses blood alpha's, and the word is
brain barrier. impressive -
Nausea, vomiting and weakness may be PhenoxyBENZAMINE -
signs of non-specific CNS effects. showing its strength to
3. Others: miosis, inhibition of ejaculation, irreversibly bind to the alpha
stuffy nose. receptors covalently
D E F

"KISS and KICK till you're SICK of SEX"


(QISSS and QIQ till you're SIQ of SQS) = Gq,
Gi, or Gs. Receptors are in alphabetical order,
starting twice:
1. AV block!! alpha1=Q
2. Severe Bradycardia alpha2=I
3. Bronchospasm and respiratory beta1=S
distress in asthma, COPD!!! beta2=S
4. Exacerbation of acute CHF and beta3=S
pulmonary edema!! M1=Q
504 5. CNS effects: dizziness, tiredness, M2=I
nausea, depression, vivid dreams (& M3=Q
nightmares) Contraindications: D1=S
6. Impotence Asthma D2=I
7. Constipation, diarrhea Obstructive pulmonary dz H1=Q
8. Severe reactions: rash, purpura, fever. Cardiogenic shock H2=S
9. Hypokalemia Acute treatment of heart V1=Q
Chronic use: Hypertriglyceridemia, failure (contrast this to use of V2=S
increased VLDL and decreased HDL beta blockers in management of Rem: A cutesie (A-q-C; alpha1 is a Gq protein
cholesterol; 28% increased risk of stable heart failure) causing phospholipase C to make PIP2 which
developing NIDDM!!; rebound angina 3rd degree heart block, 2nd forms IP3 (which increases Ca from ER) and
Propranolol Drug Interactions: Additive degree heart block. DAG (which activates Protein Kinase C)
with hypotensive agents; Prolongs Contraindications with Rem: drugs that are inotropic: GAP (gycosides
hypoglycemia in patients taking unstable angina are reactive (cardiac), adreneroreceptor antagonists,
hypoglycemic agents. Mask signs of airway disease, sinus node phosphodiesterase inhibitors) - slave drivers at
hypoglycemia & mask symptoms of dysfunction or AV block, and the GAP whipping their employees to work hard
hyperthyroidism severe heart failure. (increasing force of contraction)

505 Remember: propranolol says to nadolol that it


has to keep working, and nadolol says na-doie

506

Timmy from south park uses for his glacoma


D E F

Dyslipidemia
AV block!!
All 1-selective drugs lose selectivity at
high doses.
507
Use very cautiously if at all in patients with
reactive (asthma) airways.
Symptomatic hypotension common initially
Fluid retention: may have to increase
diuretics remember: lol blocks beta, me too (meto)
Heart failure may worsen initially selective for beta 1
Rem: Aten, very selective for who he is a god
of (beta 1), he is a (long lasting) god; Rem:
508 beta1 blockers is "A BEAM" straight to the
heart (cardioselective; acebutolol, betaxolol,
esmolol, atenolol, metoprolol)

509 They must be used very cautiously if at all


in patients with reactive (asthma) airways.

All 1-selective drugs lose selectivity at


high doses.
Use very cautiously if at all in patients with
510 reactive (asthma) airways.
Symptomatic hypotension common initially
Fluid retention: may have to increase
diuretics Remember: biso-prolol is busy taking care of
Heart failure may worsen initially CHF

511

eskomos are short, especially metoprolol


eskomos

512

May exacerbate angina ace but means 1 but = 1 beta


D E F

513

pin doll (pindolol) of propranol, not as effective


May exacerbate angina as the full blow thing

514

shopping cart partially full of propranolol

Generally reflex tachycardia and orthostatic


hypotension are less prevalent than with
non-selective alpha blockers.
Syncope is noted when first administered
515 in a large group of patients, first-dose
hypotension (can be severe), caution
patients to avoid sudden postural
changes.
Increased risk for aggravating or causing
CHF
Nasal congestion
Salt and water retention (must use diuretic)
Orthostatic hypotension, including chronic sin is alpha blocker, prazosin is short word so
fatigue and light headedness only blocks the 1

516
Note: non-selective alpha blockers have
essentially no use in essential hypertension
(see extra note at phentolamine).
D E F

517

518

520
Orthostatic hypotension - alpha blocking
effects make this more likely than with pure
beta blockers contraindication similar to
Others side effects are like propranolol. propranolol

Orthostatic hypotension (and see


propranolol side effects)
Use very cautiously if at all in patients with
521 reactive (asthma) airways.
Fluid retention: may have to increase
diuretics contraindication similar to Rem: Carving with a dildo, which cut the alpha
Heart failure may worsen initially propranolol and beta receptors off
522

Receptor Agonists):
523 i.e., drugs which exert their effects largely via activation of peripheral
tic fibers
c & smooth muscle, gland cells and nerve terminals. (Notice eccrine sweat gland
ors).

Contraindications for
cholinoceptor agonist drugs
Potential Side Effects of Muscarinic Bronchial asthma (constricts
Agonists bronchiols)
Bradycardia Urinary obstruction (force urine
524 Syncope (caused by asystole) against ob)
Orthostatic hypotension Peptic ulcer (already too much
Cardiac dysrhythmias acid secr.)
Gut or urinary urgency Gastrointestinal lesion or
Diaphoretic effects (sweating) obstruction
Sialogogic effects (salivation) Hyperthyroidism (precipitates
Abdominal cramping arhythmia)
Coronary insufficiency (would
slow heart further)
D E F

525 a pine tree pealing a car open to release its


see muscarine aqueous fluid (mushrooms flooding in aqueous
See Muscarin side effects contraindications fluid)-pilocarpine to treat glacoma.

526

see muscarine
See Muscarin side effects contraindications

527
See Muscarin side effects, also no nicotinic see muscarine Beth-ann was agonizing over lossing her
effect contraindications boyfriend, who started dating a mushroom

528 see muscarine


See Muscarin side effects contraindications

529

530
see muscarine s'have (cev) you eat a melon (meline) for you
See Muscarin side effects contraindications dry mouth.

531
see muscarine Remember: the method (Metha) to diagnose
See Muscarin side effects contraindications asthama.
532

ceptor antagonist):
533
er muscarinic agonists. Antimuscarinics exert their effects through competitive
inic receptors.
D E F

534

Toxicity of Atropine-like drugs :


Xerostomia, constipation, Urinary
retention, hyperthermia, Mydriasis,
headache, Blurred vision, Dizziness Contraindications for
Flushing, dry skin, Excitement Heart Antimuscarinics: Glaucoma
palpitation, Mental confusion, memory loss, Prostatic hypertrophy
hallucinations Toxicity more severe in children

Contraindications for Antimuscarinics: Contraindications for


535 Glaucoma Antimuscarinics: Glaucoma
Prostatic hypertrophy Prostatic hypertrophy A skull (sco) spining on a pole (pol), to signify
Toxicity more severe in children Toxicity more severe in children motion sickness

Quaternary compounds can block nicotinic


receptors and may have ganglion or a rat from Ip was rowing his boat with four
536 neuromuscular blocking action Contraindications for paddles (quaternary) because he thought the
Overdose with quaternary more likely to Antimuscarinics: Glaucoma, sea air would open his lungs (reverse bronchial
be fatal because of neuromuscular Prostatic hypertrophy, Toxicity constriction), his boat was overflowing with
blockade. more severe in children sizziling mushrooms
D E F

Quaternary compounds can block nicotinic


receptors and may have ganglion or
537 neuromuscular blocking action Contraindications for
Overdose with quaternary more likely to Antimuscarinics: Glaucoma, Tio is spanish for uncle, the uncle of
be fatal because of neuromuscular Prostatic hypertrophy, Toxicity ipratropium who tries to spit, but sizzling
blockade. more severe in children mushrooms in his mouth wont let him

538
Contraindications for bunch of ladies standing in line picketing (pro)
Antimuscarinics: Glaucoma for pans and have 4 (quaternary) pans each
Prostatic hypertrophy that are frying mushrooms (muscarinic
Toxicity more severe in children antagonist)

Contraindications for
539 Antimuscarinics: Glaucoma
Prostatic hypertrophy
Toxicity more severe in children

540

541

542

543

544
remember: can drive home (hom) after
contraindicated in pt with BPH ophthamologist treats eye with hom-atropine

545 A pen got caught in the cycle spoke and fell


because at eye doc and now too late
D E F

546
Got eyes checked to see well in the tropics
547

nemimetics):
548
o accumulate, bind to and stimulate postsynaptic cholinergic receptors. Thus, they

549

predictable (parasympathetic overactivity)


plus CNS stimulation followed by coma.

550

Toxicities are readily predictable from


knowing distribution of AChE. Note that
drug does not cross into the CNS.
D E F

551

Rem: Ed's on the phone to give you the


Toxicities are limited because of brief diagnosis (MG) and he was a little tense
duration of action and poor penetration to (tensilon test) so he had a couple of drinks
CNS (alchohol)
Remember: a pirate-door (Pyridostigmine)
552 stuck open for a long time (long lasting) on my
thenia's ass (myasthenia gravis)

In overdose, initial signs usually relate to


parasympathetic overactivity. If the dose
is high enough, death occurs via
553 asphyxiation due to muscle paralysis. If the
victim survives these initial insults, a variety
of CNS and ANS signs may occur until
recovery or death.
Treatment (for organophosphate
posioning): Support respiration; Atropine
"heroic doses" (muscarinic receptor
antagonist); Cholinesterase reactivator
pralidoxime (2-PAM)

554

Side effects: weakness, dizziness,


headache, diplopia, nausea, tachycardia.
D E F
bitors
555

556

557

558

559

Rem: the city of LA is poison (lead, arsenic),


560 would die there, murder capitol (di-mercaprol
tx) of the West if without dimercaprol (and
penicillamine)

561

562
Rem: 0ligomycin inhibits the F0

563 Rem: the nitro speed the e- chain train so fast,


it popped off its track and slammed through the
wall (Di-nitro-phenol; punches holes in the
membrane)
564
565 Rem: tx with De-fer-oxamne (ferrous = iron)

566
Rem: LEAD - EDTA
567
568

ng drugs:
569
olinergic neurotransmission and produce muscle paralysis.
D E F

1. Blockade of ganglionic nicotinic


receptors (NN) contributing to hypotension
(Tubocurarine)
570
2. Release of histamine (also resulting in
hypotension) (tubocurarine, mivacurium)
Tubocurarine: Toxicologic effects
Apnea
bronchial constriction
cardiovascular collapse
Treatment
neostigmine, edrophonium Notice 'cur' in middle of all non-depolarizing
artificial respiration neuromuscular blocking drugs names

571
Release of histamine (also resulting in
hypotension) (tubocurarine, mivacurium)

572

573

574 Block of cardiac muscarinic receptors


(tachycardia)(pancuronium)
D E F

575
Depolarizing blocker (succinylcholine)
(effects predictable based on similarity to
acetylcholine)
1. Stimulates SA node muscarinic
receptors and ganglionic nicotinic receptors
and may produce various cardiac
arrhythmias.
2. Low doses produce negative
chronotropic effect (blocked by atropine)
whereas higher doses may produce
positive inotropic and chronotropic effects Psuedocholinesterase
via activation of ganglia. deficiency - idosyncratic apnea
Malignant hyperthermia, see extra notes (monogenetic response) (this is
Hyperkalemia (succinylcholine promote K not predictable); Malignant
efflux from muscle cells) hyperthermia

576
Amazonian Indian arrow poisons

577
puffer fish has needles filled with lidocaine
578
579
580
581
582

583 Rem: Ester took cocaine with Ben, who says


he's gonna Professionally inject Tetrado-fish
with Cloro (Spanish for Chlorine)
584
D E F
585
586
587
588
Puffer fish gets caught in the Na channel

589 Frog sends his bat which rakes your back,


opening your Na+ channels and parylising you
590
591 Vesam blocks transports to vesicle

592

593

594
Remember: an blackwidow storm
595
(acetylcholine storm)
Beavis saying "bungaro" with a smoke (nicotine
596
receptor) as he is bitten by a snake

597

598
599

600 cardiac arrythmias, or in


situations related to high Rem: drugs that cause hepatic necrosis: "Very
Malignant hyperthermia; lethal hepatitis catecholamine levels such as Angry Hepatocytes" - Valproic acid,
(hapten mech) pheochromocytoma Acetaminophen, Halothane
601

Antagonists
602
D E F

603

Most opioids have an abuse potential.


General rule the greater the efficacy
against pain, the higher potential for abuse

604

605

606

607
D E F

Rem: FM (MM) radio HErOine plays musak


(Fentanyl, Morphine, Meperidine, Methadone,
Heroine - all High Efficacy Opiods - mu
608
receptors)
Rem: for tx of acute MI - MONA B (Morphine,
O2, Nitrates, Aspirin, and Beta Blockers); when
MI pt discharged - ABC2 (Aspirin, Beta-blocker,
Captopril (ACEI) and Cholesterol-lowering
See extra notes!! drugs

609 Rem: "Me pear I dine on (prickly pear, Me-per-


Metabolites can cause seizures!! See e-dine) caused me to go into seizures, and me
extra notes lips to go numb (analgesia)," says the pirate

610

See extra notes


Rem: Fentanyl - Fat (lipid soluble), Rem: a fat
611 tan man with a big punch (the blow causes the
If given IV can quickly cause truncal receiver to go stiff (truncal rigidity) like a
rigidity; see extra notes cartoon)

612
Schedule 1
Rem: Bo tore his flannel (Bu-tor-phanol) in his
613 state of dysphoria after Luke was capped
Dysphoria (kappa agonists) Schedule 4 (kappa), trying to be a HErO

Rem: Bufred (Nal-buph-ine) kapped the surgen


because he kept changing the musak channel
614 (antagonist of mu receptor). Rem: if you
kap(pa) someone, they aren't going to have
respiratory distress (cause their dead - ghost -
Dysphoria (kappa agonists) Schedule 4 dysphoria/disassociation)
D E F

615

Nausea and vomiting

616

Rem: drugie Limbaugh


Rem: the drug dealer was pent up in jail from
617 the sin of kapping his girlfriend, but only
partially blowing her mutha f&#ckin face off
(Pent-azo-cine; mu partial agonist)

618
Abuse potential is higher than analgesia Rem: a pox on any physician who recommends
potential propoxyphene

619
Rem: give Buprenorphine to the orphine to
Not readily reversed by an opioid treat his drug habit, but only give him a partial
antagonist (e.g., naloxone); difficult to dose (partial mu agonist) cause he's weak
reverse respiratory depression (LEO)

620

Seizures epilepsy
D E F

621
Non mu receptor action may cause
unpleasant side effects and limit abuse
potential (ceiling of efficacy due to sigma?
mediated SE)

622

Prolongs fever in pts with shigellosis, toxic Rem: the pt took Loperamide and is now
megacolon in pts with C. difficile; and HUS lopping around from the opioid (opioids work at
in children infected with Shiga toxin- the M/D receptors, mu and delta); or Rem: (the)
producing E. coli. Should be avoided in pts l'opera makes you slow, opiods make one lop;
with bloody diarrhea lopping amide the diarrhea in the streets

623 Rem: Dip the ox and hen in a vat of opium so


they stop with their diarrhea (Dip-hen-ox-ylate)
Rem: dive in (Dif-en-oxin) the opioid haze; or
624
Rem: dip ox (dif-en-ox-in) in opium vate

625
Schedule II

626
Precipitate withdrawal symptoms on
individuals dependent on mu agonists
(chronic users of opioids)

627

628
D E F

629
CNS: drowsiness, dry mouth, depression
Rebound hypertension (from abrupt
discontinued oral administration, can elicit
hypertensive crisis, common board Rem: the clone goes into the bank to make a
question) withdrawal so he can buy cigarettes, cocaine,
Do not give with beta blocker because heroine, (used to treat drug withdrawl) and he
excessive bradycardia is agonizing over his need (alpha 2 agonist)

630

631
Less constipation than codeine
632

& Gout
633

s 634

Well tolerated but toxicities are numerous


and include ocular (most dangerous)
635 inclusing corneal deposits, extraocular
muscular weakness, loss of accomodation,
and retinopathy with may lead to Rem: got hydrochloride in your eye and now
irreversible vision loss you're blind (Hydrochloroquine, SE)
D E F

Nausea & mucosal (oral & GI, aka


stomatitis) ulcers are the MC SE
observed at the doses used for treating RA;
At higher doses or with longer-term therapy,
severe depression of white blood cell
count (bone marrow depression), liver
636 cirrhosis, pneumonia-like syndrome
(pneumonitis!!) renal toxicity,
osteoporosis, & alopecia can develop.
Most of these SE are reversible upon
termination of the drug; however, the
pneumonitis does not necessarily improve
when methotrexate is stopped. Milder than Rem: Me so tricky/tricksie (Methotrexate), I
at chemo therapy range doses and convinced cancer to die by giving it a
compliance is higher as compared to water/folate reduction sauce (dihydrofolate
other medications, so has the highest reductase) over its fibrotic lung dinner, but
possibility of still being used after 5 years Leucovorin came to its recue
Elevated liver enzymes (monitor liver Ez); Rem: "Le flu no mide" is translated the flying of
637 other toxicities are related to suppression no mind, meaning the RA pt figuratively flew
of fast-turnover cells (GI problems, when leflunomide stopped their arthritis, and as
alopecia) he flew, so to did his liver Ez elevate

Rem: Sal farting sulfer cause relief to his UC


(sulf-a-sal-azine); 5-ASA compound -
638 sulfASAlazine; Rem: Put the RA pt in a relaxing
sulfur bath, with a inflammatory bowel
magazine to read, easing their joint pain (Sulfa-
Hypersensitivity reaction to sulfa drugs sal-azine); hope that it is not so relaxing that
and mild gi problems they shit the hot tube (IBD)

639
Rem: take a bat and beat the T cells 80 to 86
times, to stop them (A-baT-acept blocks
CD80/86) from harming the RA pt; but a COPD
pt jumps you first smashing the back of your
COPD as it can make it worse head with his O2 tank (COPD contraindicated)
D E F

Rem: wear your tux (Rituximab) when you


diffuse the B-bomb (Diffuse Large B Cell
Lymphoma); with it diffused you can then get
640 Flu like symptoms, and occasional back to the party with your hot 20yo RA date
profound reactions: breathing problems, (who has a flu, lots of snot and breaths loud
cardiac rhythm disturbances, cardiogenic through her nose) (CD20, flu SE, breathing
shock most of which occur after first dose problems)

Rem: to fix Chrons's Dz inflict a flick to their


641
bowel (Infliximab) and their joints (RA), don't
URI, and since it is chimeric mouse/human flick too hard or will give them SLE or knock
antibody immunological reaction may free the TB; also notice that infliximAb = Ab to
occur; drug induced-lupus TNFalpha

642 Rem: Dr. Tanner grabing two TNF-alpha


cytokines and tying them into pretzils (E-taner-
long term safety concerns still an issue cept)

643
Rem: add the whole Ab for less IR (Ad-alimum-
Ab)

644 Generally well tolerated; Injection site


reactions, pneumonia at a higer rate, when Rem: (Anakin-ra) Anakin Skywalker is the ill
combined with TNF alpha inhibitor, high one (IL-1), meaning both bad-ass and sick with
incidence of severe infection seen infection

645
Expensive and renal toxicity

646 Bone marrow suppresion (pancytopenia)


and heaptotoxicity; allopurinol increases
levels
D E F

647 Rem: Da penicillin (D-Penicillamine) that


wanted to be an amino acid (cysteine), got no
Prolonged treatment leads to bones about dressing up like an amino acid
dermatological problems, nephritis, and (analog, slows bone destruction, bone also for
aplastic anemia!! B6 deficiency aplastic anemia)

648

hemorrhagic cystitis
649 hemorrhagic cystitis

650

MC SE associated with the use of gold


compounds involve lesions of the skin
651 and mucous membranes, usually of the
mouth. Skin reactions vary from simple
erythema to severe exfoliative dermatitis.
Other less frequent SE include kidney
damage and severe blood dyscrasias

652

See Aurothioglucose

653

See Aurothioglucose

654
NSAID gastropathy
655
D E F
MC hypersensitivity reactions (rashes),
656 precipitate an acute attack of gout (low Acute attack (increases pain
dose to minimize this). Hepatotoxicity even though decreasing uric
(rare, lethal) acid)

657
Low incidence of GI irritation, used with
caution in pts with history of ulcers. Impaired renal function or
Hypersensitivity, sulfa allergies patients prone to urate stones
May induce hypoglycemia by inhibiting
metabolism of oral hypoglycemics.
658 Hepatic metabolism of warfarin
impaired. GI irritation in 10-15%; sulfa
allergies

Diarrhea, nausea, vomitting, and


659 abdominal pain (wickly toxic in GI track).
Long term use may lead to myopathy,
agranulocytosis, aplastic anemia, and
alopecia

660
GI toxicities; BM suppression and renal do not give with renal
damage insufficiency
661

matory Drugs
662
D E F

Gastrointestinal Side Effects:


Epigastric distress
Nausea
Vomiting
Microhemorrhage
Ulceration
Anemia
Prolonged bleeding time (anti-platelet
effect) Use of aspirin and salicylates
Patients scheduled for surgery taken off of are associated with the
663 aspirin for one week prior development of Reyes
Hypersensitivity syndrome (severe hepatic
asthma, nasal polyps, chronic urticaria injury and encephalopathy).
predisposed The use of salicylates in children
progresses from hives, nasal secretion and or adolescents with varicella
edema to acute asthma attack, severe (chicken pox) or influenza is
dyspnea, hypotension, and shock contraindicated.
Drug-drug interactions (This high Salicylism - see extra note
degree of protein binding is a potential Overdose = acute medical
source of drug-drug interactions, 50- emergency; fever, dehydration,
99%): delirium, hallucination,
antacids convulsions, coma, respiratory
protein displacement; phenytoin, thyroxine, and metabolic acidosis, death;
thiopental children especially vulnerable
risk of bleeding for patients on Avoid use during third
anticoagulants trimester unless absolutely
uricosuric effect in gout patients necessary

Hypersensitivity to aspirin.
Patients intolerant of aspirin also
may suffer a severe reaction
from ibuprofen-like drugs. Alter
664 platelet function and prolong
bleeding time. These
compounds can cause GI side
effects, but these effects are
usually less severe than with
aspirin
D E F

Hypersensitivity to aspirin. alter


platelet function and prolong
665 bleeding time. These
compounds can cause GI side
effects, but these effects are
usually less severe than with
aspirin

Hypersensitivity to aspirin. alter


platelet function and prolong
bleeding time. These
666 compounds can cause GI side
effects, but these effects are
usually less severe than with
aspirin
Toxicity (worse than aspirin) limits its
usefulness. GI bleeding, severe frontal
667 headache, associated with long-term Hypersensitivity to aspirin; do
administration, not commonly used for not give with renal
therapy as an analgesic or antipyretic insufficiency

668
Hypersensitivity to aspirin

669
Rem: key-toe roll ack (Ketorolac) is an attack
that is so effect that it actually eliminates pain,
Hematologic toxicity minor or chronic pain but its so strong it cause blood toxicities

670

Contraindicated in aspirin
HS reaction to sulfa allergy, 3rd trimester pregnancy,
No effect on platelets and bleeding time. and pts with a family Hx of
But caution with patients on warfarin. CAD!
D E F
Valdecoxib is associated with an increased
rate of serious and potentially life-
671 threatening skin reactions (e.g., toxic Lesser incidence and less serious GI side
epidermal necrolysis, Stevens-Johnson effects (than aspirin and other non-COX2
syndrome, erythema multiforme) Hypersensitivity to aspirin inhibitor NSAIDs)

672
Hypersensitivity to aspirin

673
Well tolerated, lacks many of the side
effects of aspirin (especially GI, platelet
(bleeding), uric acid excretion)
Acute Overdose: can be fatal due to
delayed liver damage (fatal hepatic
damage, self-poisonings and suicides
has grown), see Liver drugs

674

675
676
677

rugs 678
e the proliferation and function of B and T lymphocytes. Also Corticosteroids inhibit
m phosphoipids.
= eye drops
D E F

HPA axis suppression and withdrawal


Most frequent problem - flare-up of the
underlying disease.
Most severe complication - acute adrenal
insufficiency
Less severe withdrawal - fever, myalgias,
arthralgias, and malaise.
Toxicity Due to Continued Use of
Supraphysiological Corticosteroid
Doses (Consequences of
679 Immunosuppression):
Poor wound healing
Opportunistic infections (& reactivation of
latent tuberculosis)
Cushings Habitus
Toxicity:
Hyperglycemia
Hypertension
Peptic ulcers
Myopathy (proximal)
Behavioral changes
Cataracts
Osteoporosis
Growth retardation
Suppression of HPA axis and life-
threatening susceptibility to stress upon
withdrawal.

680

681

682
683
684
D E F

685
Rem: I'll bet-a deck-a cards that I can piss
further (Betamethasone and Dexamethasone;
longest half-life)

686

687

688

689

690
gynecomastia
691

692

693
694

t Drugs
695
D E F

696
Toxicites are numerous and frequent. They
include a) nephrotoxicity, b) HTN c)
hyperglycemia, d) liver dysfunction, e)
hirsutism and f) hyperkalemia
Increased risk of lymphoma, karposi's
sarcoma and skin cancer have also been
documented.
also toxic to nerves, kidneys, and can
cause diabetes; metabolized by P450

697
also toxic to nerves, kidneys, and can
cause diabetes and hyperkalemia; HTN;
risk of developing post transplant Remember: an organ rolling in tacks, creating a
lymphoproliferative disorders & tack shield that prevent IL-2 from reaching T
lymphomas & de novo nonlymphoma cells inside, steps on some kidneys while he
solid tumors; neutropenia is a rare does it

698

699

Lymphopenia
D E F

Remember: Use as a thigh opener


(Azathioprine), to reach in that thigh and tear
out WBC by the puny purines. But as you tore
700 in, blood poured out causing leukopenia,
leukopenia, anemia and/or anemia and/or thrombocytopenia; and a
thrombocytopenia, resulting in an pregnant woman carring a child in arms and
increased risk of infections; nausea, womb began lapping up the blood but you told
vomiting, and loss of appetite; liver her to stop because it will get to the baby she is
toxicity; bacterial infection, cancer nursing and the baby she is carrying. She
(these last two pretty common for most looks at you, mad from her gout pain, and
immunosuppressants); allopurinol begins to scream but only cancer comes out
increases levels Pregnancy/nursing her mouth

When side effects occur, they typically are


701 seen within a few hours after the first dose.
With the first or second doses, flu-like Remember: "OK, call in the T3 (terminator3)"
symptoms, headaches, chills and fever, as he can fight the steroid resistant acute graft
and nausea, diarrhea, and breathing rejection. He doen't need no stinking steroids,
problems have been reported. as he is an ANTI-BODY (an etherial being who
doesn't require a corporal form). He aint cute

702

703
Rem: Dac-LI2-zu-mab Daclizumab
Rem: fresh basil growning on a T cell IL-2
704 receptor, and Basiliximab comes along and just
puts his mouth right on it and sits there
minimal renal toxicity, though synergistic
705 renal toxicity if mixed with cyclosporine;
hyperlipidemia, thrombocytopenia, and
lekopenia
D E F

(Sim to Mustard gas) Immediate


toxicities include a) nausea and vomiting,
b) cardia toxicity (vascular insult leading to
myocardial hemorrhage) and c)
electrolyte imbalance; BM suppression, Remember: a cyclops who weilds a
706 hepatotoxicity. phosphamide sword to slay WBC, at the cross
Delayed toxicities include a) alopecia and roads of DNA (by cross-linking) but accidentally
hemorhagic cystitis, b) increased risk of catches his own bladder with the hilt, which
non-Hodgkin lymphoma, bladder cancer, starts to bleed profusely and then becomes
acute non-lymphoblastic leukemia and skin bladder cancer. The WBCs then see this and
cancers. rebel, cursing him with the nons: non-Hodgkins
Bladder cancer occurs in about 10% of lymphoma and non-lymphoblastic leukemia.
patients treated cronically with He then lays down from burden and finally gets
cyclophosphamide. skin cancer
707 hemorhagic cystitis

Metabolic side effects include the following:


1. Iatrogenic Cushing's syndrome
(rounding and puffiness of the face (moon
faces)). 2. redistribution of fat to the trunk
708
and neck 3. increased growth of fine hair
on face thichs and trunk 4. acne 5.
insomnia 6. increased appetite 7.
increased need for insulin with weight gain
8. development of insulin resistant
diabetes. Other side effects include 1.
peptic ulcers 2. masking the effects of
bacterial and mycotic infections 3.
nausea, dizziness and weight loss 4.
hypomania or acute psychosis (large Glucocorticoids must be used
doses) 5. increased intraocular with caution in patients with
pressure, posterior subcapsular peptic ulcer, heart disease of
cataracts and glaucoma 6. impaired HTN psychosis, tuberculosis After excluding common causes, one should
wound healing 7. hypocalcemia and diabetes osteoporosis of also consider prednisone-induced neutropenia,
osteoporosis glaucoma although this aetiology is rare.
D E F

Side effects include fluid retention, weight


gain, high blood pressure, potassium loss,
headache, muscle weakness, puffiness of
709 the face, hair growth on the face, thinning
and easy bruising of the skin, glaucoma,
cataracts, peptic ulceration, worsening of
diabetes, irregular menses, growth
retardation in children, convulsions, and
psychic disturbances. Psychic disturbances
may include depression, euphoria,
insomnia, mood swings, personality
changes, and even psychotic behavior.

a) insomnia, b) depression, c) glaucoma, d)


weight gain, e) irregular menstrual cycle, f)
secreased functioning of the adrenal gland
710
(adrenal suppression), g) thinning of the
bones (osteoporosis), h) ulceration of the
stomach or intestine, i) increased
susceptibility to infections, j) acne, k)
increased risk of fractures of the bones, l)
increased hair growth (hirsutism), m)
vaginal yeast infection (candidiasis), n)
suppression of growth in children and
adolescents and o) muscle wasting and
weakness
711

erapy
712
D E F

713

Rem: mycin sounds like an antibiotic, which


Bleomycin ~is but for cancer, but pt will not be
Nausea & vomiting; fever pneumonitis; able to blow (bleo) with pulmonary fibrosis.
pulmonary infiltrates & fibrosis; little Also, Bleo wanted to be a G too (G2 cell cycle)
myelosuppression; fever with so he joined a radical group (forms free
administration. This can develop rapidly radicals) and is initiated by fire (fever) and balls
with hyperpyrexia, hypotension and shock. stomping (tx testicular cancer)

714
BM suppression and GI upset

bone marrow toxicity leading to


715 pancytopenia, which is sometimes delayed
It is considered the most leukemogenic of
the classic alkylators

716
BM toxicity!! Rem: -plantin = Platinum Alkylating Agent

717 short-term neurotoxicity that is related to


cold:a sensation of burning associated
with cold objects or foods (~72hrs) Rem: -plantin = Platinum Alkylating Agent
D E F

Renal tubular damage, ototoxicity Rem: Plantin' (Cis-platin) a platinum tree with
718 Extremely toxic CH3s hanging off branches (alkylating agent),
Nausea & vomiting!! and its roots form an X (cross-links). The tree
Bone marrow suppression! is so beautiful it causes you to vomit up your
GI irritation kidney (renal failure), which causes you to
Gonadal suppression sceam, however it only falls on deaf ears
Secondary leukemias (ototoxicity)

Hemorrhagic cystitis!!
719 Extremely toxic
Nausea & vomiting
Bone marrow suppression
GI irritation
Gonadal suppression
Secondary leukemias see immunosuppresant
720 See cyclophosphamide

721

myelosuppression and hypersensitivity

722
Rem: tx ChLorambuciL

723

most feared complication is pulmonary


fibrosis.
724 It can cause hepatic veno-occlusive
disease and the oral form is preferred to Rem: MC BB pulm toxicity (rhyme it) -
help prevent HVOD. methotrexate, carmustine, bleomycin, busulfan
D E F

725 Rem: MC BB pulm toxicity (rhyme it) -


methotrexate, carmustine, bleomycin, busulfan;
Put some super charged nitro urine (urea) in
Carmustine associated with pulmonary your brain, that will cure the brain cancer;
toxicity (fibrosis?), BM suppression; N/V! mustine must enter your brain
726 Rem: mustine must enter your brain

727
N/V!

728
Rem: the bison (ru-bicin) rode his bike (anthra-
cycline) over topo (Topoisomerase inhibitor)
Nausea & vomiting, Bone marrow because it was infected with anthrax (anthra-
depression; cardiotoxicity (especially cycline) which caused his giant heart to
dysrhythmias); alopecia; stomatitis; explode from his little body (cardiotoxicity) thus
hyperuricemia,; leukemia freeing the radicals from his tyranny

729

730

731

Rem: Tackin' (Dactin-) between the guanine on


BM suppression the giant tumor on the kids kidney
D E F

732

733

flu-like syndromes; *Depression is a major


side effect that needs to be recognized
734 early and treated and if depression is not
controlled, the drug needs to be stopped.
Suicide is common in those depressed on
IFN.

flu-like symptoms, but a deadly side effect


735 of Capillary Leak Syndrome; delirium,
due to CLS and brain edema.

736

737
Inhibits T cells (sim to AiDS pt) Rem: ribine/rabine are antimetabolites
Rem: clay dripping from your hair; ribine/rabine
738 are antimetabolites; give the man 2CD-A
Very toxic in large dose, give in short doses (canadian saying it) for catching the hairy
over several days monster

739
D E F

740
Profound myelosuppression
GI toxicity, oral mucositis Rem: ribine/rabine are antimetabolites

Rem: Flew over a carousel (Flu-or-ouracil), but


a woman's thigh made me late (thy-midy-late
synthase) cause I "thought" about it too long,
and had to run to the plane which prohibited
741 me from metabolizing my dinner
(antimetabolite), and on the way I tripped and
Nausea & vomiting, bone marrow fell, spilling of my BM out like a snake (S
depression, palmar-plantar phase), and the snake bit my palm and foot
erythrodysesthesia!! causing erythrodysesthesia

742
Rem: ribine/rabine are antimetabolites
Rem: Levi missles (Leva-misole) will make your
743
immune system bad ass

744
Nausea & vomiting, oral and GI
ulceration, bone marrow depression Rem: Me so tricky/tricksie (Methotrexate), I
(anemia and thrombocytopenia), convinced cancer to die by giving it a
pulmonary infiltrates & fibrosis, liver water/folate reduction sauce (dihydrofolate
cirrhosis, renal toxicity, osteoporosis, reductase) over its fibrotic lung dinner, but
alopecia, others Leucovorin came to its recue

Nausea & vomiting, bone marrow


depression; produces a predictable
745
leukopenia that is usually reversible within
days of discontinuing therapy. Rem: CML (country music lover) going to show
Gastrointestinal toxicity is usually mild. this weekend for some R&R (ribonucleotide
Patients receiving long-term hydroxyurea diphosphate reductase), but pissed cause
therapy may develop mild dermatologic gotta bring the sickle cell kid, that kids in a
changes. Sucky phase of his life (S phase)
D E F

746 Rem: Lou lied (Leuprolide) about taking his


hormones (sGnRH) for his prostate cancer so
he wouldn't be castrated and get boobies. He
wants to still be able to play his skin flute (flut-
Hot flushes, impotence, gynecomastia amide used together)

747

748

749

Rem: need a night light (Ni-lut-amide, slow dark


Delayed adaption to the dark (from the adaption) to see your massive metastatic
light; sec to min) prostate

750
Fluid retention (?used to reduce edema??),
hypertension, diabetes, increased
susceptibility to infection, moon facies.
751 see prednisone

752
Hot flashes; thrombo-embolism; vaginal
bleeding & discharge (vaginitis);
thrombocytopenia peripheral edema, Rem: Tammy on an ox with big ol lumpy
increased risk of endometrial cancer breasts covered with estrogen receptors

753 Rem: 'taxel' are Taxanes which tack MT


Hypersensitivity reaction, Bone marrow together, preventing their release; and anytime
depression, peripheral neuropathy your talking MT your talking M phase
D E F

754 Rem: 'taxel' are Taxanes which tack MT


together, preventing their release; and anytime
your talking MT your talking M phase

755

Tissue damage with extravasation, Bone


marrow depression, Peripheral Rem: Vin blasted christine and depolarized her
neuropathy; Also alopecia, paralytic ileus MT and M phase; vin-blastin your bones (BM
(Neurotoxicity?) suppresion)

see vinblastine; Neurotoxicity!! is dose-


limiting with vincristine and is manifested as
756 peripheral sensory neuropathy and/or
an autonomic neuropathy. With
continued use of the agent, a motor Rem: Christine is very neurotic (neurotoxicity),
neuropathy may develop. she'll drive you crazy

757

Rem: Topo inhibitor - Topotecan,

758

Rem: Topo inhibitor - Etoposide; Pasidin


(Greek God = II = roman arches) sows his oats
BM suppression (sow = testicles, oast = small cell)
Rem: wear your tux (Rituximab) when you
759 diffuse the B-bomb (Diffuse Large B Cell
Lymphoma); -mab = monoclonal Ab
D E F

760

Rem: it tries to zoom (Trastuzumab) in her two


new (Her2/neu) breasts; Rem: -mab =
cardiotoxic monoclonal Ab

761

762

Rem: Country music lover's (CML) stop at the


road side vendor and by some local Imatinib

763
Rem: -dronate ~ bisphosphonate

Rem: Anastrozole steals the soul (zole) from


764 aromatase, the man cannot become the
May have increased risk for osteoporosis woman (inhibits androgens conversion to
compared to Tamoxifen estrogen)

Rem: Let-ro-zole steals the soul (zole) from


765 aromatase, the man cannot become the
May have increased risk for osteoporosis woman (inhibits androgens conversion to
compared to Tamoxifen estrogen)

766

767
D E F
768
769

770 Rem: I'll just dust some IL-2 on your back and
then whipe the melanoma right off. (al-des-
leukin)

771

772

773
Allergic reaction; rare hemolytic anemia
774
775
776
777
778
779 Interstitial nephritis!! I met a nasty ox

780
Interstitial nephritis!! Also neutropenia I met a nasty ox
781 I met a nasty ox
782
783
784
785
786
787
788

789

790

791

792
793
794
D E F
Rem: I met man tanned the foxes fur; all have
795
f's - all 2nd generations
796
797
798
799
800
801
802
803
804
805
806
807
808

809
Eosinophilia, thrombocytosis, and
leukopenia

810
811
812
Seizures (especially renal insufficency pts
813 or previous CNS pathology), allergic
reaction Rem: see, it stays in (C-il-istat-in)
814 See imipenem
815
816
817

818

l 819

820
D E F

821

Gray baby syndrome

822

Major Cytochrome P-450 inhibitors: FREaCKI


823 Grapefruit gets stuck in Ez- Ketoconazole,
Erythromycin mimics motilin so it causes Isoniazid, Cimetidine, Fluoxetine, Ritonavir,
increased GI motility; inhibit p450 Erthyromycin, Grapefruit

824
inhibit p450
825 inhibit p450
826
HA Rem: the Godzilla Lizard (linezolid)
827

Teeth discoloration, bone deformity in


children, Fanconi's syndrome (diminished
828 absorption in the proximal tubules -
aminoaciduria, phosphaturia, acidosis, and
glycosuria), photosensitityity, pseudotumor
cerebri

829

830
831
832
833
834
D E F

Nephrotoxicity (acute tubular necrosis,


especially cephalosporin); otoxicity
(especially loop diuretic use); teratogen;
835 neuromuscular blockade (especially
when administered with neuromuscular
blocking agents or pts with impairment of
neuromuscular transmission such as Rem: amiNOgycoside - Nephrotoxicity,
myasthenia gravis) Ototoxicity (Rem: two o's in oto, two o' in loop)
836
837
838
839

840

841

842 Arthropathy, myalgias, and leg cramps in


children <18yo (tendonitis and tendon
rupture)
GI irritability like erythomycin and
doxycycline, damages cartilage (avoid in
843 children), achilles tendonitis, rare CNS
effects like headache, restlessness, and
insomnia

844 Drink this moxi take my gat and lev this


pneumonia dead
Drink this moxi take my gat and lev this
845
pneumonia dead
Drink this moxi take my gat and lev this
846
pneumonia dead

847
PHOTOSENSITIVITY and prolongs the QT Sun burned boxer gyrating and sparring for a
848
interval QT
849
D E F
GI upset, neuropathy, hemolytic anemia in
850
G6DP

s 851

852

853

854

855

856
857

858

859

860
861

gs 862

863

864

see NSAIDs above


D E F

865
Rebound HA (with overuse); abuse Do not take with alcohol Rem: (But-al-bital) , Barbiturate - relaxes
potential (schedule 3 with tylenol) (additive effects) muscles

Excess dose:caffeine causes palpitations


866 and anxiety
Termination of taking caffeine in patients
who are dependent on caffeine provokes
headaches. Rem: Caffeine Aids in antagonizing you (Aden
antagonist)

More anticholinergic than other


antidepressants. Side-effects are typical of
atropine (in the low dose range = dry
mouth & urinary retention; as the dose Rem: Amy tripped (Ami-trip-tyline) so much she
867 increases = tachycardia and CNS got horrible migranes and depression (anti-
intoxication - lethal arrhythmias!); Deadly in overdose. Alters depressive), so she pulled a very tight condom
selected for evening administration cardiac electrical properties; over her head (prophylaxis for tension and
because they cause sedation and difficult to dialyze due to large migranes), the condom was dry (no urine or
drowsiness at the start of each dose. volume of distribution. spit - anticholinergic)
868 See Amitriptyline
Less toxic and less anticholinergic than
869
amitriptyline

870 Most frequently encountered are mild in


severity: Altered sensation (tingling,
warmth, dizziness, muscle weakness), pain
at site of injection. Contraindications:
Rarer (1-5% in various studies), but more Coronary artery disease
important, is chest discomfort!! (occurs Prinzmetal angina (triptans can Rem: Triptans are BD (B and D receptors)
because of vasoconstriction!); can cause cause coronary vasospasm) this is Never gonna work (naratriptan is the
HTN crisis!! Uncontrolled hypertension slowest onset)
D E F

As opposed to triptans, significant SE,


including nausea. At higher doses,
including those that can be reached with
871
repeated use for long-lasting migraine, they Rem: I got a HA, ergo I took an ergot alkaloid
are dangerous because of alpha agonist ergo I got nausea, ergo I hallucinated; Rem:
effects (peripheral vasoconstriction); Just remember that ergot mold is where LSD
hallucinations & bizarre behavior, came from and then picture yourself tripping
gangrene and abortion (with eating moldy and all of a sudden you have an abortion, your
rye-bread) Do not use with Triptans fingers fall off (gangrene)

872
see Ergotamine, less nausea than
ergotamine, but still requires anti-emetic Rem: Dihydroergotamine is an ergot alkaloid

Side effects are significant, especially


with chronic treatment, and include:
hyperprolactinemia, galactorrhea, breast
873 tenderness, menstrual irregularities,
extrapyramidal symptoms, anxiety, and
depression.
Rapidly Occurring Neurologic SE (rare; due
to Extra-pyramidal effects), three main
types: Parkinsonism!! Dystonias!! (seen
most frequently when treating migraine),
Neuroleptic Malignant Syndrome

874
See Metoclopramide, drug induced SLE

875
See Metoclopramide

876
see CCB above

877
asthmatics, COPD
hepatotoxicity & thrombocytopeina, weight
878
gain
D E F

Do not give in combination


Usually mild and transient - GI (burning, with a triptan
diarrhea, nausea & vomiting) Potentially hypertension/vasospasm risk;
879 serious: inflammatory fibrosis, including Note: if methysergide is being
retroperitoneal fibrosis, used prophylactically and a Meth is your guide to turn on the AC cuz it is so
pleuropulmonary fibrosis and coronary migraine headache occurs, damn hot and you have been up for 2 days
fibrosis. Usually reversible on treatment options are decreased (protects you after 2 days) with your
discontinuation dramatically inflammatory fibrosis

880

Polydipsia & Polyuria (common, even at


therapeutic levels)
Tremor (clear sign of excessive dose)
Gastric distress (common)
881 Edema
Weight gain Picture a bunch of bipolar people clustering
Hypothyroidism together (lithium used for bipolar disorder)
Cardiac conduction problems peeing all over themselve, shaking, and all fat
Mild cognitive impairment and shit

882

city 883
Drugs

884
Classic side effects of antimuscarinics (dry
mouth, urinary retention, constipation etc). Prostatic hyperplasia,
Will make dementia worse (especially obstructive GI disease,
Alzehimers, antimuscarin exacerbates). glaucoma

885
See Biperiden See Biperiden

886
See Biperiden See Biperiden
D E F

Metabolites include amphetamine,


methamphetamine, and
887 desmethylselegiline, the last of which may Interactions:meperedine, Rem: sell the gel (selegiline) that, when you
be anti-apoptotic. Amphetamine & trcicyclics, SSRI's. Nonselective pour it over the MAOist (MAOI), they stop their
Methamphetamine appear responsible MAOI's should not b eused destruction of the dope (dopamine) cultures.
for insomnia, and eventually psychosis (HTN crisis) Rem: MAOist never sleep (insomnia)
Does not have metabolites of Selegiline,
888
therefore decreased SE profile
Many SE: insomnia, restlessness,
889 depression, GI disturbances. Toxic
psychosis in overdose but normally well-
tolerated. Seizure disorders, CHF

Nausea and vomiting with tolerance after


4-6 weeks. Cannot use phenothiazine
(H1 receptor antagonists) antiemetics to
relieve this side effect. Cardio arryhtmia
due to increased catecholamines. Rem: an Athen/Greek slithering around on the
890 Dyskinesia - 80% of patients: chorea, ground (athetosis); remember: you call that (ca
ballismus, athetosis, tics, tremor; occur in dat) a striped tiger? (caudate nuclei) plus bitch
face trunk or limbs. Cant treat with man who is always in both, hes the bitch of the
haloperidol or other dopamine-receptor ganglia (putamen) = striatum.
blocking drugs. See extra notes. Also, Rem: So putamen, ganglias bitch, and the
dose-related fluctuations in motor globe (globus pallidus) celebrating lent world
function that tend to worsen in late PD wide = lenticular nucleus.
under levodopa therapy. Postural
hypotension!! Arrhythmias

Rem: curb (carbi) the L-DOPA from forming


891 dopamin in periphery (and 5-hydroxytryptophan
from forming serotonin (?)), makes them both
bit the curb.

erythromelalgia, vasospasm;
892 Psychotomimetic and dyskinetic effects
typical of dopaminergic treatment of PD;
Postural hypotension nausea, somnolence,
mental disturbances, hallucinations
See bromocriptine; also cardiac Rem: (Pergolide) Pergo lied about her age, she
valvulopathy involving one or more valves said she was 21 (D1/D2) but she was really old
893 - consistent with the valvulopathy (old treatment of PD), you could tell by the
associated with carcinoid syndrome and horrendous sound of her cardic valve
with the use of other ergot alkaloids. flapping/snapping
D E F

894
No ergot associated side effects; postural
hypotension (D2 agonists are hypotensive
via peripheral DA receptors in vasculature), Rem: the Parkinson's pt felt so good after
dyskinesi, nausea, somnolence, Mental taking his Pramipexole he primed his pecks
disturbances, hallucinations, etc. (Pra-mi-pex-ole) for his new date tonight.

895
See Pramipexole

Rem: the Capones make an offer that meth


896 trafficers (Catechol-O-Methyltransferase) can't
refuse, and so they lower the cost (amount) of
Adverse effects related to increased dopa (in the system). The Capones listen to
levodopa exposure (lower dose by 30% in OMD on the way in the car (poor theraputic
first 48 h to avoid complications) response)

897

drowsiness, fatigue and hypotension Rem: Baclofen has an l and an a (la)

898

Anticholinergic SE: somnolence,


899 xerostomia, mydriasis, and tachycardia;
also blurred vision, urinary retention and
constipation

900
D E F

901 Many adverse reactions: GI hemorrhage,


sepsis, convulsions, neoplasm Contraindications: Lactation Rem: Riluzole treats Lou Gehrig's dz (ALS)

Rem: the doc exclaims "Ti-zan (a-dine)" as he


902 Adverse effects - result from alpha-2 sprinkles Tizanidine over the spasming pt, and
agonist adrenergic effects (hypotension, they stop but begin grotesquely dividing into
drowsiness) clones (clonidine)

903

Rem: Dan was able to get back to working at


the Whataburger cause he's taking his
Dantrolene for his cerebral spasticity, dan-tro-
904 lean, if you got time to lean you got time to
clean. (notice, you need peripheral limbs to
muscle weakness (avoid use in ambulatory lean and clean well, and enjoy a milk shake
patients); dose-related hepatocellular injury (Ca inhibitor) (PNS))

905

906
(if give at night, it will cause really high bp,
so only give in morning and at noon)

907
908
909
910
911
912
913
914
D E F

Antiepileptic drug idiosyncratic rxns (see


extra note)
Cerebellar and vestibular systems (ataxia,
nystagmus, vertigo, diplopia), pt looks
915
drunk;
gingival hyperplasia (20% of patients on
chronic medication), pt has bad breath;
hypertrichosis, hirsutism, osteomalacia,
megaloblastic (RBC) anemia
hypersensitivity, hyperexcitability in children Designated FDA category D
Induce P450 (increases metab of (benefits outweigh risks) based
contraceptives); also increase steroid H on considerably greater
binding prt pregnancy risk associated with Rem: RC PP induces P450 (rifampin,
Teratogen: Cardiac damage, cleft palate uncontrolled seizures carbamazepine, phenobarbital, phenytoin)

916

Antiepileptic drug idiosyncratic rxns (see Rem: zepine and zepam seems to be generic
extra note) Toxicity: ataxia, rash, blood for seizure; Rem: A car exploded (Car-bam-a-
917 dyscrasias (leukopenia or aplastic zepine), set by a group of salt mine workers
anemia!!), diplopia, teratogen (Na) who are angery and protesting because
Induce P450 (increases metab of they got seizures from their working conditions;
contraceptives); also increase steroid H FDA pregnancy category D Rem: RC PP induces P450 (rifampin,
binding protein. Hyponatremia carbamazepine, phenobarbital, phenytoin)
918 Sedation, weight loss, nephrolithiasis
Rem: the ox driving the car (Ox-car-bazepine)
919 eating fries, heavily salted (Na channel blocker)
Serious: Hyponatremia (more common in - the ox keeps dumping more Na on to fix his
elderly), rash hyponatremia

Blood dyscrasias; Skin reactions; GI


(diarrhea, nausea, vomiting, anorexia) and
920 CNS (headache, dizziness, etc.) effects.
Tolerance develops to GI effects; Rem: Ethel sucks a mean one (Ethosuximide),
Behavioral effects (restlessness, anxiety that's why she's absent today (petit mal, Ca T
and aggressiveness) Tubule), swallow the milk
D E F

Rem: Val is such a pro (Valproic) she can


921 reduce both Na and Ca will increasing GABA,
Possibility of hepatotoxicity (do not give too bad she's a drunk (hepatotoxicity); she is
to Hep B/C pt); Thrombocytopeina; FDA pregnancy category D also such a bad ass that she can treat GTCS,
Idiosyncratic rxns (see extra note) partials (simple or complex), and absence

Nonserious: Tics and insomnia


Serious: Rash, including Stevens
Johnson and toxic epidermal necrolysis
(increased risk for children, also more
922 common with concomitant valproate use
and reduced with slow titration); Rem: the lamo trying again to stop the seizures
hypersensitivity reactions, including risk of (Lamo-tri-gine) to block both Na and Ca
hepatic and renal failure, and arthritis. channels, then you can hang out with the old
Idiosyncratic rxn people and Steve Johnson
923 Weight loss

Induces P450; Idiosyncratic rxn; sedation


(but tolerance may develop); subtle
cognitive impairment
Respiratory depression!!
osteomalacia (interferes with vitamin D
924 metabolism and Ca2+ absorption)
rash (1-2%)
paradoxical hyperactivity in children
megaloblastic anemia
sudden reduction or elimination of dosage Pregnancy, pts with liver dz, Rem: Phenobarbital is a Barbiturates; Rem: RC
may cause status epilepticus pts with porphyria; pts taking PP induces P450 (rifampin, carbamazepine,
Teratogen? Recent studies show low risk alcohol or BZD phenobarbital, phenytoin)

Idiosyncratic rxn; Benzodiazepines:


Toxicity
IV: cardiovascular and respiratory
925 depression (high dose)
chronic oral: sedation and ataxia (some
tolerance to sedation and ataxia, but not as
much as with barbiturates)
seizures are sometimes exacerbated
behavioral disturbances

926 Rem: Lora's ass is so nice (Lorazepam), it


would put anyone into status epilepticus -
Idiosyncratic rxn (see diazepam) ZEPAM! (or take them out)
D E F
927
Idiosyncratic rxn Rem: Clonazepam treats myoclonin
Nonserious: weakness; Serious: Stupor or
928
spike wave stupor; Idiosyncratic rxn
Rem: the vegan (viga-batrin) battered her infant
indirectly (indirect GABA) by throwing (GABA-
929 transaminase) the baby from a moving car to
another moving car while on a road trip West
Idiosyncratic rxn (West syndrome)

Lowers seizure thresholds; Binge


drinking triggers microseizures - spiral
930 effect (makes further seizures more likely);
Cessation of drinking (withdrawal)
increases seizure risk due to upregulation
of glutamate and downregulation of GABA;
Idiosyncratic rxn

931 Weight gain, peripheral edema, behavioral


changes; Idiosyncratic rxn

932

Idiosyncratic rxn
enia933
Gravis

Injection site inflammation


Depression
Flu syndrome: fever, myalgias. Note that
934 much of the unpleasant muscle symptoms
of the flu result from the bodys production
of interferon.
Liver function monitoring is recommended. Rem: Interferon-1a (Avonex; Rebif) &
These side-effects abate to level of placebo Interferon-1b (Betaseron) & Glatiramer
at 1-year (Copaxone) the ABC drugs for MS
D E F

935 Generally well tolerated; Injection site


irritation (itching and inflammation), Rotate
site of injection to minimize;
Transient reactions (~15 minutes in
duration, flushing, chest pain, dyspnea, Rem: the glatiator (Glatiramer) had MS, so
urticaria, these occur after several months instead of fighting he playing shell game,
of treatment) switching TH1 to TH2

936

Rem: Natalie has MS, but it makes her


937 stripping that much more exciting (Natali-
zumab)

938

See immunsuppresants above See immunsuppresants above

939
Bone marrow suppression (leukopenia), GI
signs (diarrhea, vomiting typical of high
dose); Allopurinol increases 6-
mercaptopurine levels
Toxicities are numerous and frequent;
nephrotoxicity and hypertension are
940 notable -- limits use in patients with pre- Toxicities are numerous and frequent;
existing renal disease or uncontrolled nephrotoxicity and hypertension are notable --
hypertension. See Immunosuppresants limits use in patients with pre-existing renal
above disease or uncontrolled hypertension.
D E F

During the infusion: headache, muscle


aches, chills
Post-Infusion:
941 MC are fatigue, fever and nausea (lasts
approximately 1 day); rarer but more
problematic are migraines and allergic
reactions

Pt may experience dizziness, nausea,


numbness, tingling, or lightheadedness
942 during or after the procedure. These effects
usually pass quickly, allowing the patient to
return to normal activities the same day.
Also - infection, particularly when a central
line is used.

943

see Anticholinesterases above

944
see Anticholinesterases above

945

see Anticholinesterases above


946

947
D E F
948
949

rugs
950

951 sexual dysfunction - decreased libido /


decreased arousal / anorgasmia (all three
can be seen with SSRIs, but anorgasmia
most prevalent); initial agitation & initial
insomnia (very common with fluoxetine);
initial nausea, weight loss (??), Potential
for many drug interactions due to potent
inhibition of 2D6 and long half life. MAOI
sexual dysfunction - decreased libido /
decreased arousal / anorgasmia;
952 sedation; most likely of the SSRIs to
produce GI disturbances (diarrhea); Low
potential for drug interactions due to P450 Rem: Ser-traline = ser-otonin; Serah had
interactions. MAOI diarrhea; ine can mean SSRI

sexual dysfunction - decreased libido /


decreased arousal / anorgasmia;
953 Discontinuation Syndrome; more weight
gain, sexual dysfunction and
discontinuation symptoms than other
SSRIs; Potential for many drug interactions
due to potent inhibition of 2D6. MAOI

954

sexual dysfunction (especially


anorgasmia), Low potential for drug Rem: Sital will keep the jizz inside (Cital-
interactions due to P450 interactions. MAOI opram), but you won't be depressed
sexual dysfunction (especially
955 anorgasmia), Low potential for drug Rem: a skittle will not help you have an orgasm
interactions due to P450 interactions. MAOI (E-scital-opram)
D E F

956 Rem: the voice (vox) said Fluvoxamine, said


MAOI Fluvoxamine, said Fluvoxamine..

957

Stimulating effects and little or no sexual


dysfunction. contraindicated in those with a
Potential for seizures at high doses seizure disorder (epilepsy Hx).

958

Low sedative and antimuscarinic effects.


959 Dose-related hypertension &
tachycardia (NE effects)!!
More intense withdrawal than SSRIs
Greater toxicity in overdose than SSRIs
acts more like a TCA

960

Strong inhibitor of cytochrom P450 IIIA4

First antidepressant developed that was not


lethal in overdose
few antimuscarinic effects Rem: Travis dawned a swollen, purple boner
961 highly sedating (individual differences) that almost killed him (Traz-o-done) and he fell
sometimes used in combination with asleep in the ED with everyone stairing
MAOIs which disturb sleep (serotonin sedation); the cock almost killed him,
Can cause life-threatening priapism not the OD

962 Rem: this drug is deluxe (duloxe-tine) cause


not only does it treat pain, but also treats DM
pain
D E F

963

very significant sedation!! (due to potent


antihistaminergic effects)
increased appetite / weight gain

964 Multiple side effects including


antimuscarinic & antihistaminergic
effects (see extra notes) such as Rem: Anti-HAM effects: histaminic, adrenergic
precipitating acute narrow glaucoma. and muscarinic
High toxicity in overdose!!
see amitriptyline; can affect sexual
965
performance by lowering blood pressure
966 see amitriptyline
967

MAOIs are rarely used because of the risk


of interactions with many foods (those
968 high in tyramine) & drugs
(sympathomimetic agents: ephedrine,
methylphenidate, phenylephrine and
pseudoephedrine)
Serotonin syndrome if used with SSRIs SSRI

969
See Phenelzine SSRI
970 See Phenelzine SSRI
971 See Phenelzine SSRI

Rem: Adam was an atom bomb of activity in


972 dry mouth, then urinary retention (ContraI the class till they gave him an atom of
in males with BPH, glaucoma); also Atomoxetine - will inhibit NE-body (NE reuptake
idiosyncratic liver damage inhibitor, effects both child and adult)
D E F

rs
973

Narrow therapeutic window!! (acute 1-


1.5 meq/L, maintenance ~0.6-1.2 meq/L,
toxic at 2.0 meq/L) so monitor plasma
levels. Worsens extrapyramidal syndromes
produced by older antipsychotic drugs.
Tremor!! (MC effect, treated with
974 propranolol or atenolol), decreased
thyroid function! (usually
nonsymptomatic, monitor serum TSH every
6-12 months), mild cognitive impairment,
transient acne eruptions, leukocytosis,
renal dysfunction (polydipsia and (thiazides, NSAIDs, see extra
polyuria) see extra notes. Gastric distress notes) Brady/tachycardia
(use divided dose), edema, weight gain (SICK SINUS) as it depresses
(30% pts and not from edema) the sinus node.
GI distress (n/v), idiosyncratic
hepatotoxicity (can be lethal), congenital
975 neural tube defects, thrombocytopenia,
alopecia, and increased appetite and
weight gain Pregnancy

Rash (including Steven Johnsons and toxic


epidermal necrolysis increased for kids,
976 and more common with concommitant Rem: the lamo is super excited to try again
valproate use and reduced with slow (bipolar) to stop the seizures (Lamo-tri-gine) by
titration), hypersensitivity reactions (hepatic pouring salt and milk on the twitcher (Na and
or renal failure, arthritis), blurred or double Ca channels blocker), Steve Johnson just
vision, loss of coordination, dizziness watches

Blood dyscrasias (aplastic anemia),


ataxia, rash, pharmacokinetic tolerance
977 through autoinduction of metabolism,
hyponetremia (~3%), diplopia, ataxia, GI Car exploded from the p450 time bomb set by
upset, sedation, wt gain, teratogen may salt mine workers who were upset about their
worsen other seizure types (petit mal) anemias and flipper babies
D E F

978

979

980

cs 981

982

Essentially devoid of extrapyramidal motor


side-effects
Blood dyscrasias (agranulocytosis)!! in
2% of pts - monitor blood, particularly
between 6th and 18th week, can only be Rem: claw the crazy out of their head, lots of
prescribed under a blood-monitoring bleeding (Cloz-apine, blood dyscrasias);
program Rem: atypical antipsychotic drugs work Due 2
Other SE are strong sedation, 5-HiTs 2 the CROw, "AQ it squacks",
anticholinergic effects (urinary retention), antagonizing it (Clozapine, Risperidone,
seizures, and hypotensive effects Olanzapine, Aripiprazole, Quetiapine)

983
Somewhat more sedative (give at night); Rem: Quetiapine quites the voices in the
Implicated in type 2 diabetes incidence schizo's head
D E F

With the exception of weight gain and


somnolence, the SE profile is much more
acceptable with this drug. Recent
controversy concerning this drug (and most
atypical antipsychotics) causing type 2
984
diabetes. Perhaps because of this, and
perhaps because of remarkable efficacy
against both schizophrenia and depression, Rem: "O' land ho" screams the voice in the
aripiprazole (see below) is sweeping the schizo's head, (O-lanzapine); "land ho? Looks
market since its introduction in autumn, more like Land O'lakes" butter with that weight
2002. gained - fattie gonna get DM2

Because of higher affinity for D2 sites (this


drug most like old typicals), it has a higher
potential than other atypical
985 antipsychotics for extrapyramidal SE,
including a small propensity for tardive
dyskinesia; SE include: Anxiety,
Somnolence, Extrapyramidal symptoms,
Dizziness, Type-2 diabetes, weight gain

986

Remarkably low incidence of SE, including Rem: Ari only gave the schizo a partial slice of
no tardive, and less weight gain than pie (Ari-pi-prazole; partial D2 agonist), even
olanzapine; No incidence of Type 2 though he wasn't gonna get the diabetes or get
diabetes; akathisia very common fat
Potential for polongation of QTc intervals
987 (caution pts with hx of AV block and
arrhythmia)
D E F

Greater potential for neurologic


(extrapyramidal) motor SE than many
typical (and all atypical) antipsychotics
Extrapyradmidal effects include:
Dystonias
988 Parkinsonism
Neuroleptic Malignant Syndrome
Also dyphoria, and tartive dyskinesia with
long term use (especially haloperidol);
transient leukopenia or leukocytosis, many
other SE, see extra notes
Galctorrhea and ammenorrhea (females),
gynecomastia (males)

989

Orthostatic hypotension because of


alpha-receptor blockade
Dry mouth and urinary retention because of
anti-muscarinic effect
Extrapyradmidal effects, dyphoria, tartive
990
dyskinesia, and many more - see extra
notes
Galctorrhea and ammenorrhea (females),
gynecomastia (males)
Drug Induced Liver Dz - idiosyncratic Rem: all of the typicals are azine (except
(slow metabolizers) hadoperidol)

991
See Chlorpromazine

992
See Chlorpromazine

993 See Chlorpromazine; dizziness, dry mouth,


nausea and vomiting, rash

994
See Chlorpromazine

995 Little significant SE???, anticholinergic


effects

notics
996

997
D E F

998

Benzodiezapam SE: Sedation, altered


mental status, ataxia; Tolerance; Physical Rem: your GABAa ABCs (a and alcohol) B
Dependence (Abstinence (barbiturates and benzodiazepines) and C
Syndrome/Withdrawal) (Cl-)

999
See diazepam

1000
Potential for early morning awakening,
tolerance/dependence if over used Rem: -am = BZD

1001
Leukopenia; mild elevation of lactate
dehydrogenase

1002
D E F
1003

1004 Rebound insomnia and other withdrawal


signs particularly with conitnued use. Rem: of the zolam's, Triazolam and Midazolam
Amnesia, tolerance with continued use both work for a short TM (= short TiMe)

1005

Watch out for precipitated withdrawal;


1006 Seizures!! (potentially lethal gran mal and
cardiac collapse ) the big issue in BZD
dependence/withdrawal BZD dependent pt

1007 10% can't tolerate because it increasses Rem: can drive the bus (no motor impairment,
anxiety; High dose can cause anxiety. Bus-pirone), to the zoo to see the Piranhas (no
Poor patient acceptance, dizziness, anxiety to see them) and throw 5 partial
nausea, vomiting. MAOI will increase BP bananas (K+) to the monkeys

1008

1009

Rebound insomnia!! and other withdrawal


1010 signs, particularly with continued use.
(some individuals show mild aspects of this
phenomenon with a single dose);
antegrade amnesia; Tolerance with Rem: Triazolam, z for zzz's (sleep) and am for
continued use BZD
D E F

1011 Just as likely to potentiate the


lethal effects of alcohol as a
Slight grogginess next day BZD Rem: Zolpidem gets your zzz's

1012 Just as likely to potentiate the


lethal effects of alcohol as a Rem: Zaleplon gets your zzz's; also shorter
Less grogginess due to short half life BZD word for short half life, and PRN (zaleplon)

1013
Depression or hx of depression
is contraindicated

Do not use with fluvoxamine


1014 (inhibits ramelteon metabolism)
and careful in folks with history Rem: R for receptor, mel for melatonin (R-a-
of depression mel-teon)

1015 Poor Therapeutic Index; Profound CNS


depression!! (anesthesia and coma) Pregnancy, pts with liver dz, Rem: Phenobarbital is a Barbiturates; Rem: RC
respiratory depression, abuse potential; pts with porphyria; pts taking PP induces P450 (rifampin, carbamazepine,
induce P450 alcohol or BZD phenobarbital, phenytoin)
1016
1017
1018

Drugs
1019

1020

Schedule II agent - potential for


abuse/dependence.
Some risk of dependence/abuse if ADHD
persists to adulthood
1021 Other predictable toxicities:
Insomnia
Anorexia
Weight loss and growth retardation may HTN, glaucoma, anxiety, seizure Rem: Ethyl was a funny date (Methyl-pheni-
occur with long-term therapy disorders date) cause she was high on her kids ritalin
D E F
1022

1023
Schedule II agent - potential for
abuse/dependence.
Insomnia!!, reduced weight, emotional
lability (flip flop), significant potential for
diversion (parents, ADHD patient, other
siblings) HIGH ABUSE POTENTIAL
Rem: pommelling the liver (Pemoline,
1024 hepatoxicity), riddling (same as ridalin) your
Less used due to hepatotoxicity but no liver with bruises (no abuse, or can't see
abuse potential (essentially) abuse)

Rem: Adam was an atom bomb of activity in


1025 the class till they gave him an atom of
Dry mouth, then urinary retention ; also Atomoxetine - will inhibit NE-body (NE reuptake
idiosyncratic liver damage Males with BPH, glaucoma inhibitor, effects both child and adult)
1026
Abuse and dependence make this drug
1027
less than optimal

1028

Less abuse potential than other


1029 amphetamines (schedule IV), still get
insomnia, appetite suppresion, etc (less Rem: "the mode to stay awake - finally! A shark
intense however) fin in my butt" (Mod-a-finil)
1030
D E F

Unusual reactivity to sympathomimetics


(amphetamines, E, isoproterenol, Cardiovascular disease
phenylephrine, pseudoephedrine, Glaucoma
terbutaline); dental problems (reduce Moderate or severe HTN
salivary flow causing periodontal disease Hyperthyroidism
and other dental problems), insomnia, Psychosis
1031 increased BP, anxiety, tremor, potential Alcoholism
for abuse (psychosis, dependence) use 4- History of drug
6 hours before bedtime (complicates tx of abuse/dependence
nighttime hunger). INTERACTIONS: thyroid
Overdose: arrhthmia, confusion, diarrhea, hormones (increase stimulant
fever (though less than cocaine), assultive effects), MAOI (HTN crisis), Rem: Ben's feta cheese is so nasty, you'd loss
behavior, hallucinations (even small dose anesthetics (esp, halothane weight (Benz-pheta-mine) and jack up your
shifts thought to paranoid thinking so high lethal arrythmias) teeth; no antidote for his nasty feta cheeze and
does can lead to psychosis), circulatory Benzphetamine (specifically): will stimulate sympathomimetics and cause
collapse and coma precede death. No Class III CI in pregnancy psychosis. Don't eat he's cheese before
antidote!! (category X) surgery or will die with halothane
Class IV associated with blood dyscrasias Rem: Ethyl will die from her blood diet (Di-
1032
(rare); see Benzphetamine See Benzphetamine ethyl-proprion, blood dyscrasias)

1033 Primary pulmonary HTN, See Rem: it's fun to mine (Phen-ter-mine), cause
Benzphetamine See Benzphetamine you lose weight
1034 Lethal SE

1035
Tolerance develops within days or weeks
Rem: Sir Butt Rammin' (Sibutramine) is taken
Serah (serotonin) in the @$$, (though he can
1036 Dry mouth, headache, constipation, F&%k NEbody), he's thinking she needs to loss
insomnia, some risk of increased BP weight - maybe she will after she fixes the
(monitoring required) constipation

1037
Initial flautlence and loose stools which
may occur after high fat meals
(steatorrhea)

1038
D E F
Rem: Meg wanted to eat, so she eat Mega-
1039 struddles (Meg-e-strol)and gained all sorts of
weight

eatment
1040

1041

1042

Rem: Trex bitting the liver (don't give to pt with


1043 Impaired liver function and pts liver dz); also Trex has been around for a long
being treated with opioids time (long lasting) (Nal-trex-one)

1044 Rem: a camper prostrated himself, asking God


to treat his alcohol problem (and cravings) and
spare his liver (A-cam-prosate)
D E F

1045

1046
Rem: my piss is foamy from the antifreeze in it
(Fome-piz-ole)
No's
1047

1048
D E F

1049

1050

1051

Rem: the metabolite of nicotine has the same


letters rearranged - cotinine

1052
D E F

1053

1054

1055

1056

1057
1058

1059
D E F

1060
Rem: Flunitrazepam is the flun (fun)
benzodiazepine

1061

1062
Toxicity related to vasodilation -
headache, peripheral pooling of blood, combination of Viagra and
decreased myocardial flow poppers can be deadly
G H
1 Extra Notes Extra Note

Testosterone analog that blocks production of dihydrotestosterone


7 (growth H resonsible for H-dependent growth of the prostate), Saw palmetto (Serenoa repens): Suggested to inhibit 5-
leads to reduction in size of gland, reduces symptoms, and alpha reductase
can decrease the PSA by up to 50%. No impact on PSA
May get retrograde ejaculation Similar side effects to Finastride

BPH S&S:
More frequent urination, especially at night
Sub sets of alpha1A, B, and D (all three seen in prostate, alpha1A Feeling an urgent need to urinate
9 predominates in prostate; alpha1B predominates with arterials) Having difficulty urinating or straining
both have mosaics of receptors. There is also an alpha2 family (A, Pause/prolonged amount of time before the urine flow starts
B, and D); all of these receptors are most likely expressed on A very weak urinary stream
receptive tissues, but the relative amount changes (eg A urine stream that starts and stops
preponderance of alpha1B in arterials) Feeling of incomplete emptying of the bladder
G H

10
Relaxation of muscle (Relatively few alpha-1 receptors in the body
of the bladder)
Sympathetic stimulation causes contraction of trigone, therefore Symptomatic improvement
blocking this results in relaxation and hence voiding Does not arrest or reverse the underlying prostatic hyperplasia

11

Mech: Clomiphen occupies hypothalamic and pituitary estrogen


receptors preventing negative feeback effects on LHRH, LH, and
12 FSH. As a result the pituitary continues to release LH and
FSH allowing more follicles to reach maturity together. (Why
does ovulation then occur if cannot respond to E2 surge? - give LH
surge/dose)
13

Phosphodiesterase Type 5 Inhibitors:


14 Increase arteriolar flow - Excess blood engorges the tissue and
compresses veins Both male and female cock and clit expand with drug
Flaccidity is brought about by normal sympathetic tone (increased engorgement); note pt not always ready to hump
Note: many types of PDE, Type 5 is predominant in arterioles of just cause of drug, pt must have libido and sexual stimulus
cavernosa; Some Type 5 also found in arteries and veins (organ is much more responsive) - see Nitrates in No, No's

15

Tadalafil:
Much longer lasting, with a significantly greater likelihood of
16 priapism
Much less visual disturbance (if any)
Higher incidence of muscle ache complaints (5%)
One advantage with this drug, the mother may change her mind
17
and suckling will usually override the effect.
Bromocriptine and Cabergoline can be taken orally, or
administered intra-vaginally to reduce nausea. Nausea associated
18 with bromocriptine is due to: effect of Dopamine on CTZ
(chemoreceptor trigger zone) via D2 receptors. The CTZ is a
group of cells situated close to the area postrema on the floor of
the fourth ventricle
G H

19 Better tolerated and considered to be more effective than


bromocriptine

20

21

22 Estradiol (E2): Patch (bipass first pass effect), micronized E2


(oral), Vaginal ring (local administration to vagina, ie vaginal 3 major forms of naturally occurring estrogens (estrogen
dryness) generic term (3 forms):
Ethinyl estradiol ethinyl group reduces first pass effect 1) 17-estradiol made primarily by the
Diethylstilbestrol (DES) non steroidal estrogen, post coital ovary
contraceptive 2) Estrone & Estriol some made in
Conjugated equine estrogens (contains estrone sulfate, equilin ovary, mostly made by conversion from
sulfate, etc.) aka Premoran?, MC post menopausal estrogon androgens in liver and/or adrenal glands
Ethinyl Estradiol is the most commonly used estrogen in OCs
23
(Ovral, Orthotricyclen)
24
G H

25
The progestagenic component should have low androgenic
activity (ex. Desogestrel)
Reduce free androgens by increasing the amount of plasma
SHBG
The pill does not stop follicular development and when not taken Sequential (E, then P) or E alone oral contraceptives will
for one or more days ovulation may occur. Must be taken faithfully inhibit the H-P-G axis, thus reducing ovarian androgen
(99% effective) production

26

Norplant system:
Injectalbe effective for long-term contraception Also effective for long term contraception - releases much
27 Not good for women who want to get pregnant soon after less steroid as oral agents;
discontinuation of treatment Disadvantages include need for surgical implantation and
Takes awhile for H to be cleared removal, and some irregular bleeding

Sources for progesterone (naturally occurring progestin)


In female:
- produced primarily by ovary (corpus luteum)
Physiological effects of Progesterone: - during pregnancy, placenta produces progesterone
28 Progesterone is involved in the development of the secretory Follicular phase (levels) in women ~ that in males (0.03g/dL)
apparatus in the breast Luteal levels: 0.5 2 g/dL
Causes maturation of the endometrium
Prepare uterus for implantation
Increases body temperature CNS (hypothalamic) effect
Depressant effects, sedative or hypnotic effects (probably
mediated by metabolites of progesterone like Allopregnanolone)

29

Oral contraceptives (containing the not so androgenic


30 Rank order of progestagenic potency: Norgestimate, Desogestrel), influence binding globulin
Desogestrel > norgestrel > norgestimate norethindrone reducing bioavailability, less synthesis of androgens

31
Prodrug: Norgestimate converted to L-norgestrel
G H

32
Rank order of androgenicity:
Norgestrel >> norgestimate > norethindrone > desogestrel

Drespirenone progestin (Yasmin)


33 have excretion of excess sodium and water
excellent for acne
Similar to spironolactone
Levonorgestrel only (Plan B)
34 0.75 mg ASAP and 2nd dose 12 hrs. later
Due to mechanism of action, is unlikely to work if fertilized egg has preferred formulation, lowest side effects and failure rate
already implanted (this interfers with uterine line formation) Now available OTC for patients 18 and older

35
Sources for testosterone:
In male: Testosterone is principally bound to SHBG (sex H binding
- produced primarily by testis (Leydig cells) globulin) or albumin (only about 2% is free-circulating
- only about 5% produced by adrenals hormone the bioavailable amount). Converted to DHT
Levels in women: ~0.03ug/dL (dihydrotestosterone) by 5-reductase type II (but also by
Levels in men (post-pubertal): 0.6ug/dL type I, especially CNS)
36
Propionate, cypionate esters of testosterone can be administered
37 parenterally. While they have greater activity, they have prolonged
absorption times

38 Alkylation at the 17-position: results in more orally active


androgens (ex. Methyltestosterone, Oxymetholone)

39

40

41
Danazol: Can bind to AR, GR and PR, but not ER;
By binding to SHBG, may increase clearance of hormones
42
43
G H

44
Rem: hem-abate = blood stop
PGE2 keeps ductus arteriosus open, thus large ingestion of
45 aspirin may cause fetal death

46

47 Chronic hypertension is treated with alpha methyl dopa


(Aldomet), calcium channel blockers, and labetalol

48
49

Females 9-26 years old


Protection against types 6, 11, 16 and 18
3 doses; now and in 1 and 6 months
50 Cost around $500( $120 per dose plus office visits)
Can be given with other vaccines
No need to test before giving vaccine
Non-live vaccine, can be given to immunosuppressed

51
Tell pt to stop taking multi vitamins (for the folate)

52
53

54

55
G H

Drug Interactions:
Aminoglycosides: Ototoxicity!! Normal physiology: Symporter is electrically neutral,
Digitalis (digoxin/digitoxin)!!: Enhanced efficacy of digitalis however, net result is excess K+ in the ascending loop cell.
56 (mechanism related to hypokalemia) enhanced likelihood of K+ follows concentration gradient back into lumen. Therefore,
arrhythmias the lumen become positively charged. Positive lumen charge
Sulfonylureas used for Type II diabetes: Hyperglycemia drives divalent cations out of the lumen via paracellular
Lithium (used in treating bipolar disorder): Na is preferentially pathway.
excreted Loop Diuretic: Na+, K+ transport is blocked. Note: Almost
NSAIDs (e.g., aspirin, ibuprofen): Blunted diuretic response; also immediately after the (blocked) symporter segment of the thick
blunts response to loop's ability to reduce pulmonary edema ascending loop, a different transporter exists for K+. K+ is
(mech related to prostaglandins released by the kidneys to cause essentially entirely reabsorbed at this site . Net loop diuretic
vasodilation and rapidly reduce pulmonary edema) result across these segments is increased loss of Na+ without
Thiazides: Diuretic synergism - use thiazide and loop diuretic loss of K+; block of Na+, K+ transport leads to a relative loss
together to help tx CHF refractory to loops alone (thiazide blocks of positive charge in the lumen (less driving force for K+ to
distal Na resorption) back diffuse). This in turn leads to less reabsorption (potential
for greater urinary loss) of Ca++ and Mg++

57

Remember: torso (torse-mide) of mine sliding down the loop,


58
blocking function
59

60
G H

61

Note there are 2 sites of action (both are important): Net effect is
reduced HCO3- going back into blood, and less H+ available in Carbonic anhydrase is also present in the eye, where it is
nephron to serve as counter ion for Na+ reabsorption. involved in the production of aqueous humor

62 Thiazides: JNC-7 Virtually unsurpassed in preventing the


cardiovascular complications of hypertension
Usually prescribe thiazides first, less potential for harm as Well tolerated
compared to loop agents. Satisfactory alone for Stage 1 African Americans respond better to thiazides than do
hypertension Caucasians
At low doses, side-effects are minimal Although hyperuricemia may occur, gout is uncommon,
Slow onset; long lasting particularly when the dose is modest (watch out for Boards,
Less efficacious than loop diuretics which will pick on this side-effect)
But capable of fluid and electrolyte disturbances Although lipid profiles can change unfavorably, this is usually
hypokalemia, hyponatremia insignificant when the dose is modest (watch out for Boards,
Important to note that thiazides do not directly block K+ which will pick on this side-effect)
reabsorption

63
64

65

Resistance occurs to loop agents; if so, add metolazone (thiazide-


66 like diuretic, but it also has a slight efficacy at proximal Na re-
uptake site. This accounts for the greater efficacy of metolazone
vs other thiazides)
G H

Aldosterone receptor antagonist:


67 Recently demonstrated to improve mortality and morbidity in
patients with severe (NY Class IV) CHF
Spironolactone significantly decreases mortality rates for pt Lends support to hypothesis that aldosterone effects on the
with NY Heart Association class III and IV CHF; does not increase heart are a major contributor to tissue remodeling
clinically significant hyperkalemia Approved for Class 4 CHF

68

69

70

71

ARB Advantages: Excellent efficacy as anti-hypertensives


ARB effects, uses are similar to ACE-inhibitors, but side-effects are Side-effect profile approaches placebo
72
even less troubling. Note: ACE-I drugs elevate bradykinin, which Blunt the hypokalemia caused by diuretics
accounts for many of the ACE-I side-effects. In contrast to ACE-I, Mechanism: decreased aldosterone release
ARBs do not elevate bradykinin. ARBs, therefore: do not cause Little orthostatic hypotension
cough (a frequent side-effect of ACE-I drugs), have significantly Little reflex activation of SNS
less chance of producing angio-edema (also known as No effect on triglycerides, cholesterol
angioneurotic edema)

73
G H

74

ACE is also the same enzyme as Kininase II, which is the enzyme
that inactivates bradykinin. Note that bradykinin is: Tissue irritant, Mechanism and Effects:
vasodilator, a candidate for why ACE-I drugs inhibit cardiac Block conversion of angiotensin I to angiotensin II by inhibiting
hypertrophy Angiotensin Converting Enzyme (ACE):
ACEI cough: 3-39% of pts decrease angiotensin II-mediated release of aldosterone
Elevated bradykinin in the lungs produce dry, non-productive, decrease breakdown of bradykinin
Irritating cough; dose-related, but seen in the therapeutic range; decrease overly active SNS (little reflex tachycardia),
not seen with ARBs; elevated bradykinins!! also may rarely decreasing preload, decreasing afterload which then
cause angioedema (Remember: Greg Brady entering the vessels decreases BP
and tissue swells with his offspring abundance)

75
Remember: not anal (Enalapril) cause its pro-drug, pril - ACEI

76

Advantages: Ca++ is critical for smooth muscle contraction: Myosin light-


Efficacious, particularly for isolated systolic hypertension chain kinase phosphorylates (activates) myosin, block Ca++
77 low incidence of side-effects compared to many older entry and smooth muscle will relax
antihypertensives Nitric oxide (NO) is critical for smooth muscle relaxation: cyclic
Disadvantages: GMP promotes dephosphorylation of myosin, NO promotes
headache; flushing; orthostatic problems cGMP formation, and smooth muscle will relax
G H

78

Advantages:
Efficacious, particularly for isolated systolic hypertension
low incidence of side-effects compared to many older
antihypertensives Diltiazem and verapamil are relatively selective for cardiac
myocyte Ca channels

Advantages:
79 Efficacious, particularly for isolated systolic hypertension
low incidence of side-effects compared to many older
antihypertensives Not used with pt with CHF (actually accelerates CHF, has
negative inotropic effect)

80
Not associated with AV block (as beta blockers)

81

82

Mechanism is unknown
Decreases systemic vascular resistance (decreases
General effect: afterload), which leads to increased stroke volume
decrease PR, causes compensatory responses (initiated by Has minimal effects on venous capacitance. Therefore, most
baroreceptors) of increased SNS and increased RAS. effective when combined with venodilators
Consequences of SNS and RAS activation: increased SNS with When combined with isosorbide dinitrate, the
arterial block but venous constriction, increased HR and CO, Na+ combination has been shown to decrease mortality in
and H2O retention CHF (but not as effective as ACEIs)
G H

83

Efficacious, long duration of action (metabolite)

84

85

Hypertensive Crisis: Emergent or urgent


Hypertensive emergencies: acute BP greater than 220/140 with
progressive target organ dysfunction such as myocardial or
cerebral ischemia/infarction, pulmonary edema, renal failure, or
papilledema; tx - gradually decrease BP by 10% in 1st hour then
by 15% over next 3-12 hrs with target of 170/110
86 Hypertensive urgencies: no obvious end-organ damage, blood
pressure control should be achieved within 24 hrs. Get diastolic
pressure to 100-110, then move it to normal over the next few
days; Avoid excessive decrease in BP. Avoid too rapid decrease
in BP; Either can result in cerebral or cardiac hypoperfusion. Use
drugs parenterally in emergencies; Use drugs parenterally and
occasionally orally for urgencies. Overly aggressive therapy is
associated with severe hypotensive problems, including
insufficient circulation to the CNS; Insufficient therapy is
associated with end-organ damage, including stroke.

ORGANIC NITRATES: (ie nitroprusside, NTG, Isosorbide


dinitrate)
Combined with hydralazine, decrease mortality (especially Pharmacodynamics
87 isosorbide dinitrate) - decreases venous return, decreasing Decrease preload
pulmonary edema (esp used for nocturnal dyspnea) Increase exercise capacity
Used by themselves, they decrease congestion Decrease symptoms of congestion
Nitroglycerin is used i.v. in acute HF to decrease ventricular filling Tolerance is a significant issue such that pts must be drug
pressures free 6-8 hrs per day. Drug is given at night to facilitate sleep.
G H
88
89
90
91
92

93

94

95
Does not work on anaerobes

96
G H

97

Uncomplicated cystitis: short term therapy (typically 3 days)


includes Trimethoprim-sulfamethoxazole (co-trimoxazole);
amoxicillin or sulfisoxazole are also useful. Fluoroquinolones
are reserved for treatment failure due to multidrug resistant
Most effective against Klebsiella with E. coli bacteria or patients allergic to co-trimoxazole or amoxicillin.

Pharmacokinetics
98 Rapid absorption following oral administration
Oral absorption impaired by divalent cations-antacids
Excellent tissue/fluid distribution
Excreted mainly through kidney by tubular secretion & by
glomerular filtration

99

100
101

Resistance
Mainly due to production of beta-lactamases; Due to reduction of Blood level of penicillin can be raised by simultaneous
102 permeability of the outer (porin pores) of gram negative bacteria; administration of probenicid, impairs tubular secretion of
Due to modified penicillin-binding sites penicillin
Pharmacokinetics Susceptible to beta-lactamases, used in combination with
Excreted rapidly via the urine; 10% glomerular filtration; 90% beta-lactamase inhibitors such as clavulanic acid,
tubular excretion; probenecid prevents tubular secretion sulbactam, and tazobactam
G H

103

104
105

106

107 Resistance
Plasmid dependent resistance
production of adenylylating, phosphorylating, acetylating enzymes
destroy the drug
P/C open bacteria to allow AMP to reach target

108 Resistance
Plasmid dependent resistance
production of adenylylating, phosphorylating, acetylating enzymes
destroy the drug Antibiotics causing poluria: demeclocycline, methacillin,
gentamicin

109
Note the difference between spectinomycin and streptomycin

110
Resistance
Very similar to penicillin
Degraded by beta-lactamases

111
G H

112

113
Most effective against Klebsiella (even though first gen are most
effective against gram +)

Resistance
114 Transmitted by plasmids TC affects both pro- and eukaryotic cells
TC resistance genes are closely associated with those of AMG, Mammalian cells have both the uptake and the efflux systems
sulfonamides, CAP for TC
Plasmids usually transmits resistance to multiple drugs rather than Bacteria have only uptake system. Can concentrate TC
TC alone Resistance bacteria have active efflux system

115 Doxycycline less effective than others TCs


Doxycycline is excreted in feces
Other TCs is excreted through kidney

116

117

118

119

120

121
G H

122

123

124
Resistance
Through alteration in viral thymidin kinase
Through alteration in viral DNA polymerase
Pharmacokinetics
Used orally or intravenously for treating genital herpes
Cleared by glomerular filtration
Safe during pregnancy
125

126

Mechanism of Action: The ultimate mediator of acid secretion is


the H+, K+-ATPase proton pump of the apical membrane of
the parietal cell. This pump is unique to parietal cells. PPIs Pharmacological Properties: PPIs are unstable at a low pH.
irreversibly inhibit the activity of the proton pump. PPIs are The oral dosage forms (delayed release) are supplied as
considered prodrugs. At neutral pH, they are chemically stable, enteric-coated granules encapsulated in a gelatin shell
lipid soluble, and are devoid of inhibitory activity. These neutral (esomeprazole, omeprazole and lansoprazole) or as enteric-
weak bases reach parietal cells indirectly, by first being absorbed coated tablets (pantoprazole and rabeprazole). It is clinically
into the blood, diffusing into the secretory canaliculi, where they important to note that these drugs are destroyed by acidic
127
become protonated and thus trapped. The protonated drug conditions. Therefore, if their microencapsulation is
chemically rearranges and covalently modifies sulfhydryl destroyed before swallowing - for example, if the patient
groups on the proton pump protein, irreversibly inactivating it. breaks open or chews the gelatin-coated capsule before
These drugs produce a profound inhibition of acid secretion and swallowing - the neutral pH in the mouth and esophagus
inhibition persists after the drug disappears from the plasma. The will break down the microencapsulation, and the drug will
specificity of these drugs derives from the selective distribution of be exposed to degradation in the acidic contents of the
the H+, K+ATPase, from the requirement for acidic conditions to stomach. When taken properly, the drug is released after
generate active drug, and from the trapping of the drug at sites the granules have left the stomach and is rapidly
adjacent to its target enzyme. PPIs may also have antimicrobial absorbed from the intestine. Co-administration of H2
activity against H. pylori. blockers may also diminish the efficacy of the PPIs.

128
G H
129

130

131

Enterochromaffin cells (ECL cell) release histamine, the


primary stimulus for acid production from the gastric parietal
cell.
Histamine activates the H2 histamine receptor, causing
elevation of cAMP levels, that leads to recruitment of the H+,K+
ATPase (the Proton Pump) to the membrane surface and activates
secretion of protons (acid) into the gastric lumen.
132 Acetylcholine (ACh) released from the vagus nerve or from
interneurons activates at muscarinic receptors (M1, M2, M3). M3
receptors on parietal cells directly stimulate acid production via a
Ca++-dependent pathway. ACh also acts indirectly by stimulating
histamine release from ECL cells. The superficial epithelial cells secrete cytoprotective factors,
Gastrin released from G cells of the gastric antrum acts at mucus, and bicarbonate. Prostaglandin I2 and ACh stimulate
gastrin receptors (G, cholecystokinin, CCK2) on the ECL cell production of these factors. Prostaglandin I2 and E2 inhibit
stimulating histamine release and also stimulates parietal cell acid cAMP formation in the parietal cell and inhibit acid production.
production directly via a Ca++-dependent pathway. Prostaglandins also enhance mucosal blood flow.

133

134

135

136

Antacids should be prescribed on an as-needed-basis for During anesthesia, coma, cesarean section, or
symptom relief, but only if the patient reports symptomatic relief endoscopy, aspiration of gastric contents can cause
after antacid administration. Drawbacks include: lack of patient aspiration pneumonitis - sodium citrate (Bicitra, a clear liquid
compliance, nocturnal acid secretion, and interaction of antacids antacid) is used prophylactically to neutralize gastric contents
with other medications. Antacids typically only provide short-term in these situations. Oral or IV administration of H2 blockers is
symptom relief but act rapidly. also used for this purpose.
G H

137

138

139

140

141
Misoprostol and H2 antagonists are the only agents with proved
efficacy in preventing NSAID-induced mucosal injury.
Pirenzepine is an antagonist relatively selective for the M1 receptor subtype in the stomach and is being tested as a potential
antisecretory drug. Other, older compounds, particularly quaternary amines with few CNS side effects find limited use as GI
142 antispasmodic agents, e.g. dicyclomine (Bentyl). Other available cholinergic antagonists such as hyoscyamine sulfate (Levsin,
IB-Stat) glycopyrrolate (Robinul) are still used occasionally for their GI antispasmodic activity but are associated with typical
anticholinergic side effects such as dry mouth, urinary retention, and tachycardia. Muscarinic agonists, such as bethanechol, find
some limited use for stimulating GI motility.
G H

The neural regulation of gastric motility involves stimulation


by cholinergic neurons, inhibition by adrenergic neurons, and
the complex modulatory influence of the enteric nervous
system in which dopamine and serotonin play a role.
143
Metoclopramide is a central and peripheral dopamine (D2) Antagonists of D2 and 5-HT3 receptors and agonists of 5-
receptor antagonist; a serotonin (5-HT4) agonist; a serotonin HT4 receptors can stimulate gastric motility, frequently in
(5-HT3) antagonist (at high doses); and a cholinesterase ways that depend on cholinergic neurotransmission. In
inhibitor. Metoclopramide is used during cancer chemotherapy as addition, the GI peptide, motilin, has potential as a prokinetic
an antiemetic in combination with other drugs. Metaclopramide is agent and derivatives of the antibiotic erythromycin act as
the drug of choice for treating diabetic gastroparesis. agonists at motilin receptors in the antrum and duodenum.

144

Does not interfere with treatment of Parkinsons disease, so is


useful for counteracting the GI effects of levodopa and
bromocriptine. However, this drug does elevate serum prolactin.
145 Used for nausea and vomiting associated with gastric stasis, may
be used in reflux esophagitis if hypomotility is prominent and
omeprazole treatment is insufficient. Not FDA approved in the
USA

146

Prochlorperazine, thiethylperazine, and chlorpromazine are


among the most commonly used general purpose antinauseants
147 and antiemetics. Compared to ondansetron or metoclopramide,
these drugs are not uniformly effective in cancer chemotherapy-
induced emesis. However, they also possess antihistaminic and
anticholinergic activities, which are of value in other forms of
nausea such as motion sickness.

148

149
G H

SE - By initiating a phase III contraction in the digestive rather


than interdigestive period, erythromycin may
inappropriately cause the delivery of large undigested
particles into the small bowel. Subsequently,
150
malabsorption or a dumping syndrome may result.
Erythromycin is a macrolide antibiotic that binds to motilin Erythromycin may cause QT prolongation, cardiac depression,
receptors. Motilin receptors are G protein-coupled receptors and and possibly torsades de pointes. These cardiac toxicities are
are located throughout the enteric nervous system. As a motilin usually seen at higher intravenous dosages. Furthermore, the
agonist, erythromycin increases the frequency and amplitude of chronic use of erythromycin may result in tachyphylaxis or the
antral contractions and initiates gastric phase III contractions. down-regulation of motilin receptors.

These opiodes penetrate into the CNS poorly and can inhibit
151 diarrhea at doses that produce few central effects.
Atropine is added to diphenoxylate and difenoxin preparations,
primarily so that the unpleasant anticholinergic side effects will Agents Used to Treat Diarrhea - General Considerations:
discourage abuse. Atropine may have some capacity to slow Excessive fecal loss of fluid and electrolytes that characterizes
motility, but usually much higher doses are required to achieve this diarrhea is an important aspect of many infectious and non-
effect. Loperamide alone or in combination with antibiotics infectious GI diseases. Although nonspecific drug therapy for
(trimethoprim, trimethoprim-sulfamethoxazole, or a diarrhea is the norm clinically, knowledge of the types of
fluoroquinolone) has been effective in controlling the symptoms of diarrhea can help determine when to use nonspecific agents
travelers diarrhea. or more specific agents.
Atropine is added to diphenoxylate and difenoxin preparations,
152 primarily so that the unpleasant anticholinergic side effects will
discourage abuse.
Atropine is added to diphenoxylate and difenoxin preparations,
153 primarily so that the unpleasant anticholinergic side effects will
discourage abuse.

154

peptide must be given parenterally (SQ); useful for treating the symptoms of tumors of the GI tract (carcinoid, VIPoma,
glucagonoma, gastrinoma, insulinoma), AIDS-related diarrhea, and various motility disorders. Octreotide can inhibit the secretion
of hormones involved in vasodilation. This property makes octreotide useful in treating variceal bleeding and orthostatic
155 hypotension. Octreotide increases splanchnic arteriolar resistance and decreases gastrointestinal blood flow, hepatic-vein
wedge pressure, hepatic blood flow, portal vein pressure, and intravariceal pressure. Decreased blood flow to the portal vein
reduces portal venous pressure in patients with cirrhosis or portal hypertension. A majority of patients with portal hypertension
have a reduction in variceal bleeding when given octreotide.
G H

GI Water Flux and Motility - Approximately 9 liters of fluid


Dietary Fiber and Bulk Forming Laxatives enter the small intestine daily, but normally only 0.1 liter is
a) Dietary fiber is plant cell wall that is resistant to digestion. Usual passed with the stool. The small intestine absorbs about 8
sources are whole grains, bran, vegetables, and fruits. These bind liters per day. Any reduction in this absorption adds to the
water and ions, soften stools, increase stool bulk, and promote burden of the colon, which can absorb from 4-5 liters per day.
colonic bacteria. The presentation to the colon of fluid in excess of this amount
156 b) A variety of dietary supplements are available containing wheat or of a load of non-absorbable solutes will increase the
bran, psyllium (e.g., Metamucil), methylcellulose (e.g., Citrucel), passage of fluid and produce diarrhea. Conversely, excessive
or carboxymethylcellulose. Polycarbophil compounds (e.g., reabsorption of water will result in desiccated feces and
FiberCon) are non-absorbed, hydrophilic polyacrylic resins. constipation. Intestinal motility dictates the time available
c) Bulk-forming laxatives are effective within 2-3 days, are well for absorption of solutes and fluid. The extent of
tolerated, and are safe for long-term use in conjunction with absorption generally parallels transit time, such that altered
increased dietary fiber. motility contributes to either diarrhea or constipation. GI
d) Choice of product depends on the patients acceptance of motility also is an important component of vomiting and
texture, taste, other ingredients (sugar free, low sodium, etc.), and enhanced gastric emptying is a significant aspect of the
cost. actions of some antiemetic agents.

Stimulant Laxatives
1) Diphenylmethane derivatives: phenolphthalein (Modane, Ex-Lax, Feen-a-Mint, Correctol, etc.) and bisacodyl (Dulcolax,
157 Carters Little Pill). Effective doses vary widely among patients. Soft or semiliquid stool occurs within 6-24 hours.
Phenolphthalein causes pink to red colored urine and feces. Can cause gastric irritation, electrolyte imbalance, and allergic
reactions are possible. Use of these agents should be limited to 7 days at most.
2) Anthraquinone derivatives: senna, cascara, rheum (rhubarb), and aloe. Produce laxation after about 6 hours. These agents
may produce an excessive laxative effect and abdominal pain and yellowish brown to red urine. May cause nephritis.

Saline laxatives:
Magnesium sulfate (Epsom salt) - intensely bitter taste may
produce nausea; magnesium hydroxide (Milk of Magnesia)
liquid suspension of Mg(OH)2 or as tablets; magnesium citrate
oral solution, or sodium phosphates oral solution (FLEET
158
PHOSPHO-SODA) is relatively pleasant tasting
Sodium phosphate (FLEET) enema is the DOC for fecal
impaction.
Saline laxatives produce laxation with a delay of 6 to 8 hours in
lower laxative doses and a thorough fluid evacuation in less than
3 hrs when administered at higher cathartic doses.
G H

Osmotic laxatives
a) are not absorbed and are resistant to digestion, increase osmotic pressure in lumen and water content of stools.
b) Lactulose is a disaccharide broken down by bacteria in the GI to fructose and galactose. These metabolites are only partially
absorbed and increase osmotic pressure in the GI lumen. Used to lower blood ammonia levels in patients with portal
hypertension and hepatic encephalopathy.
159
c) Glycerin administered as a rectal suppository softens and lubricates the passage of hard stool.
d) Sorbitol and mannitol are sugars administered rectally, orally, or as an enema.
e) Polyethylene glycol-electrolyte solutions (Colyte, GoLYTELY) are the drug of choice for bowel preparation for colonoscopy,
barium enema, or colorectal surgery. These preparations are mixtures of sodium sulfate, bicarbonate, and chloride, and
potassium chloride in an isotonic solution containing ethylene glycol. Patient drinks four liters of solution over 3-5 hours. Causes
most complete evacuation of GI tract; copious, watery diarrhea.

Surfactant Laxatives: act primarily as stool-wetting and stool-


softening agents.
Docusate salts: produce minimal softening of the feces in 1-3
days; Poloxamers: anionic surfactant and mild stool softener;
160
Dehydrocholic acid: a bile acid, safe and effective as an oral
laxative; Caster Oil: has been used for ages as a cathartic
laxative; from oil of the castor bean, contains ricinoleic acid, has
very bitter taste; adult dose 15-60 ml on empty stomach produces
one or two copious and semi-fluid stools within 1-6 hours. Too
strong a cathartic effect to be used for common constipation.

161

The 5-HT3 subtype of serotonin receptors mediate


neurotransmission at several sites in afferent pathways
controlling emesis, including in the chemoreceptor trigger zone
(CTZ), in the stomach and small intestine, and in the solitary
162 tract nucleus. Blockade of these receptors by selective
antagonists, such as ondansetron, very effectively inhibits emesis, Emesis is a complex process coordinated by the vomiting
even emesis due to high doses of chemotherapeutic drugs or center in the lateral reticular formation of the medulla.
radiation therapy. These drugs are given orally or IV, have plasma The vomiting center receives input from a number of different
half-life of 3-4 hours, and are generally well tolerated. Used neural pathways that utilize various neurotransmitters,
primarily for cancer chemotherapy- and irradiation-induced nausea including dopamine, acetylcholine, histamine, and serotonin.
and vomiting (N&V), but also some post-operative nausea and Therefore, a wide variety of drugs that block receptors for
vomiting (PONV). these neurotransmitters have antiemetic properties.
163
164
165
G H
Some H1 antagonists are useful for suppressing vertigo. Used
alone, these agents have only very modest efficacy against
166 chemotherapy-induced emesis but are included in combination
regimens to reduce the extrapyramidal side effects of D2
antagonists.

167

168

169

170

171

172

173

174

175

176

Unlike cisapride, which also has 5HT4 agonist activity, tegaserod


has not demonstrated any significant adverse Tegaserod, as a selective serotonin (5HT4) partial agonist, stimulates the peristaltic reflex. Intestin
electrocardiographic effects. Tegaserod has also shown positive involved in motor, sensory and secretory functions. Peristalsis occurs due to release of inhibitory and
177 effects in the treatment of gastroesophageal reflux disease neurotransmitters via activation of the intrinsic afferent neurons in the GI mucosa. Additionally, increa
(GERD), but confirmatory studies are needed. While not approved and water secretion produce a softer stool. In animal models, tegaserod has also been shown to red
for chronic constipation, tegaserod has shown positive results in a firing (i.e., through the spinal cord) and thus visceral pain sensation. These actions result in the
randomized, controlled trial for this use. and altered stool form associated with constipation-predominant IBS.
G H

Alosetron (Lotronex) is a 5-HT3 antagonist that has been


approved with limiting indications for the treatment of patients with
178 severe IBS with diarrhea. Only patients who have failed on
conventional treatments and who have severe disease are
candidates for alosetron treatment. This drug was previously
withdrawn due to very serious adverse effects, including ischemic
colitis and serious complications of constipation.

In addition to their mood-elevating effects, antidepressant


medications have several physiological effects that may be
beneficial in IBS. In diarrhea-predominant IBS patients, the
179 tricyclic antidepressants, such as imipramine and desipramine,
slow gut transit time and also may alter visceral afferent
neural function. Newer trials with selective serotonin reuptake
inhibitors (SSRIs) have also demonstrated symptomatic
improvement.

180
181

The principal drugs used in the treatment of chronic


inflammatory bowel disease (IBD: ulcerative colitis [UC] and
The mainstay of therapy for mild to moderate UC and CD are the Crohns disease [CD]) are salicylate derivatives (5-ASA),
anti-inflammatory derivatives of the non-absorbed salicylate, 5- corticosteroids, other anti-inflammatory/immunosuppressive
aminosalicylic acid (5-ASA). 5-ASA (mesalamine) can affect agents, and, when indicated, metronidazole (+ ciprofloxacin).
182 multiple sites in the arachidonic acid pathway critical in the UC is an inflammation of the mucosal layer of the colon and
pathogenesis of inflammation, including inhibition of the rectum that leads to chronic diarrhea, rectal bleeding, and
cyclooxygenase pathway and leukotriene formation. However, 5- abdominal pain. CD is a granulomatous inflammatory process
ASA itself is too toxic to the upper GI tract to be taken directly that may involve any part of the GI tract from the mouth to the
unless coated in special resins (Pentasa, Asacol, Rowasa). anus. Unlike UC, the inflammation of CD involves multiple
These formulations of 5-ASA release drug slowly throughout the tissues layers (transmural) and this leads to deep ulcerations,
GI tract or only in the terminal ileum and colon. Alternatively, the adhesions, and fistula formation. Both diseases are
drug is linked to other chemical moieties such that the active drug characteristically chronic and episodic with a clinical course of
is released in the lower GI tract by action of bacterial enzymes. exacerbations and remissions.

Sulfasalazine (Azulfidine), olsalazine, and balsalazide combine 5-


183 ASA linked to sulfapyridine, another 5-ASA molecule, or an inert
carrier, respectively. These 5-ASA compounds have been shown Notice: steroid the DOC for acute flare ups of IBS -
to induce and maintain remission in up to 75% of patients. predinose for CD, Hydrocortisone suppositories for UC

184
G H

Of active CD patients refractory to glucocorticoids, 6-MP, or 5-


ASA, 65% will respond to intravenous infliximab; one-third will
185 Tumor necrosis factor (TNF) is a key inflammatory cytokine and enter complete remission. Patients who experience an initial
mediator of intestinal inflammation. The expression of TNF is response will respond again to repeated infusions of infliximab
increased in inflammatory bowel disease. Infliximab is a every 8 weeks up to 44 weeks. Thus infliximab may also be
chimeric mouse-human monoclonal antibody against TNF that is efficacious in maintaining remission. However, more trials
extremely effective in Crohns Disease. It blocks TNF in the serum need to be completed on remission maintenance after
and at the cell surface and likely lyses TNF-producing infliximab therapy. Infliximab is also effective in CD patients
macrophages and T cells through complement fixation and with refractory perianal and enterocutaneous fistulas, with a
antibody-dependent cytotoxicity. 68% response rate and a 50% complete remission rate.

186

187
188
189
190
191
192
193
194

195
196
197

198
G H

Interferons (IFNs) are potent cytokines that possess antiviral,


immunomodulating, and antiproliferative actions. There are
three major classes of IFNs, alpha, beta, and gamma. Clinically
used IFNs are recombinant proteins of the alpha class.
Endogenous alpha-interferons are secreted by leukocytes (e.g.,
macrophages, B lymphocytes, and non-B non-T lymphocytes) in
response to viral infection or various synthetic and biological
inducers. All alpha-IFNs share common biologic activities
199
generated by the binding of interferon to the cell-surface receptor.
Interferon binding to the cell surface receptor is followed by
activation of the JAK-STAT tyrosine kinase signal transduction
pathway and leads to the nuclear translocation of a cellular
protein complex that binds to genes containing an interferon-
specific response element. This in turn leads to synthesis of IFN stimulates the production of several enzymes such as 2'-
over two dozen proteins that contribute to antiviral effects, 5'-oligoadenylate synthetase (2'-5'-OAS) and beta2-
such as inhibition of viral penetration or uncoating, synthesis microglobulin. Expression of major histocompatibility antigens
of mRNA, translation of viral proteins, and/or viral assembly by IFNs may also contribute to antiviral activity by enhancing
or release. the lytic effects of cytotoxic T lymphocytes.

Oral ribavirin combined with injected interferon is effective for


treatment of chronic hepatitis C!! Aerosolized ribavirin is
200 approved for treatment of RSV bronchiolitis and pneumonia in
hospitalized children. Ribavirin is teratogenic, embryotoxic,
oncogenic, and gonadotoxic. Pregnant women should not directly
care for patients receiving ribavirin aerosol.
201

202

203

204

Peg interferon plus ribavirin is the treatment of choice for


205 chronic hepatitis C; it provides sustained viral responses of 54%
to 63%. When used as monotherapy, peg interferons once weekly
are more effective than standard preparations.
G H

IFN-a and lamivudine are quite comparable in efficacy as first-line


therapy for chronic hepatitis B. Interferon requires only brief-
duration therapy, too limited in duration to support viral variants,
206 but requires subcutaneous injections and is associated with a high
level of intolerability. Lamivudine requires long-term therapy in
most patients and, when used alone, fosters the emergence of
viral variants. On the other hand, lamivudine is taken orally, is SE are negligible, indistinguishable from those observed in
very well tolerated, leads to symptom improvement and is placebo recipients. Long-term monotherapy with lamivudine is
effective even in patients who fail to respond to interferon. associated with mutations in a key motif of HBV DNA
Although some prefer to begin with interferon, most physicians and polymerase, analogous to mutations that occur in patients with
patients prefer lamivudine as first-line therapy. HIV infection treated with this drug.

Adverse effects: Doses of adefovir used for HBV are


generally well tolerated but may be associated with asthenia,
headache, diarrhea and abdominal pain. Higher than
207 recommended doses (30-60 mg/d) and pre-existing renal
Some experts recommend adefovir over lamivudine for long-term impairment are risk factors for azotemia and renal tubular
treatment of HBeAg-negative or cirrhotic patients because of the dysfunction. Hepatitis flares may occur after adefovir is
high risk of emergence of lamivudine resistance. stopped.

At prescribed doses: Acetaminophen may be converted in


the liver by cytochrome P450 to a quinone type of reactive
A single dose of 10-15 g, or occasionally less, may produce clinical intermediate that is rapidly transformed to a glutathione-
evidence of liver injury. Ingestion of 25 g or more usually, but not type conjugate (mercapturate), when the levels of
208 always, causes fatal fulminant disease. Nausea, vomiting, glutathione are not limiting. With normal levels of the drug,
diarrhea, abdominal pain, and shock are early manifestations this pathway is only of minor significance. However, with
occurring 4-12 hours after ingestion. Then 24 to 24 hr later, when massive drug overdose, glutathione becomes depleted
these manifestations are decreasing, hepatic injury begins to and the quinone reactive intermediate may reach
become apparent. Hepatic failure may not be evident until 4-6 sufficient concentrations to react with nucleophilic
days after ingestion, and aminotransferase levels approaching groups of tissue constituents. Hepatic and renal necrosis
10,000 units are not uncommon. Renal failure and myocardial can result. An antidote, N-acetylcysteine (Mucomyst), take
injury may also be present. the place of the depleted glutathione in the reaction.

209

210

211
G H

212

An inverse relationship exists between extracellular K+ and


Generally well absorbed phosphorylation of the cardiac ATPase
Gut bacteria (Eubacterium lentum) in 10% of population rapidly Elevated K+ decreases the affinity of the ATPase for cardiac
metabolize digoxin to inactive metabolites glycosides
Likely accounts for variability in dosing Low levels of K+ increases the affinity of the ATPase for
Digoxin cardiac glycosides!!
Excreted unchanged by kidney Watch out for hypokalemia!

These drugs have a low therapeutic index


213 Metabolized in liver, then excreted in bile Because longer acting drugs manifest toxicity for longer
Enterohaptic circulation creates long elimination t1/2 periods of time, there are significant disadvantages in using
May be useful in kidney failure pts digitoxin.

214 Nesiritide is particularly useful for short-term vasodilating


Treatment strategies for Acute Decompensated HF: actions
Although pts are edematous, monotherapy with a loop diuretic Hx: natriuretic peptides were first discovered as products
is inappropriate - activates Renin-Angiotensin-Aldosterone and released from the atrium (ANP). In the hunt for similar
sympathetic nervous system - vasoconstriction is increased, so substance, a compound was isolated from brain (BNP) that
much so that GFR declines. was even more efficacious in causing vasodilation. (Note this
Pts must receive a diuretic and vasodilation (nesiritide) is not beta-natriuretic peptide, it is B-natriuretic peptide.)
G H

215 In healthy subjects, nitric oxide (NO) dilates coronary


arteries
Old hypothesis was that NO improved perfusion to hypoxic
areas of heart. This hypothesis is incorrect
NO (from nitrates or endothelium) causes endothelial cells to In angina of effort, direct infusion of NTG into heart does not
activate Guanylyl cyclase to convert GTP to cGMP, causing relieve angina, but sublingual NTG does. Thus, heart is not
dephosphorylation of Myosin Light Chain causing relaxation the critical site of action.

216

217

218

219

220

221

Class 1A:
222 1. Reduce automaticity (phase 4, reduce slope of upstroke,
AP becomes broader)
Rarely used;has a vasodilator effect so can be used in reduced 2. Prolong action potential duration
vent function or HF; also has a indirect anticholinergic effect that 3. Reduce conduction velocity (phase 0, slope also reduced)
will decrease vagal tone and may facilitate condion in the AV node Note: (phase 3 affected, not 4, according to Lange)
G H

Antiarrhythmic Class III: prolong duration of cardiac action


223 potential (AP) and refractoriness;most potent class of
antiarrhythmic drugs, effective for rhythm disturbances in all
Absorbed rapidly and is 100% orally bioaviable; i.v. loading tissues; combo of blocker, Ca channel blocker and Na
dose must be given slowly, so limited to clinical situations with Channel blocker along with primary effect on repolarization
adequate time available; Does not increase digoxin levels; current (basically does everything the other classes do put
cimetidine and ranitidine decrease clearance 10-50% together)

224 Loading dose not recommented, risk of HF or anticholinergic SE;


rapid fluctuations in plasma concentration; Phenytoin, rifampicin,
and phenobarbital increase hepatic metabolism (elimination); Antiarrhythmic Class IA include quinidine, procainamide,
depression of contractility from co-admin with beta-adrenergic of and disopyramide - increase venticular refractoriness and
CCB prolong the QT inverval

Class 1B
Reduce automaticity
Shorten APD (narrow QRS)
225 Slow conduction velocity
Have little or no effect on atrial tissue Antiarrhythmic Class Class IB include lidocain, mexiletine,
all other classes work above ventricles and tocainide - modest Na channel blockers that shorten
Moderately effective for ventricular arrhythmia the action potential duration (APD) and refractoriness with
only used for V!! little effect on PR, QRS, or QT intervals

226 Typically hepatic metabolism (CYP2D6), can be increased with


phenobarbital, phenytoin, or rifampicin; Pts with hepatic CYP2D6
deficiency are dependent on renal excretion. (notice, quinidine
inhibits the CYP2D6 Ez)

227

228
G H

Antiarrhythmic Class Class IC include flecainide and


229 propalenone - potent Na channel blockers that slow
eliminated by the liver (CYP2D6) and kidney(so not effected by conduction velocity, little effect on repolarization, and increase
CYP2D6 deficiency except in renal insufficiency) PR and QRS intervals, little change on QT interval

230

231
eliminated by the liver CYP2D6; if CYP2D6 deficiency have slow
elimination of propafenone and develop significant receptor
antagonism at low doses

232

Antiarrhythmic Class II: beta adrenergic antagonist, effective


233 for supraventricular arrhythmias and tachyarrhythmias caused
by excessive sympathetic activity; limited efficacy for severe,
life-threatening ventricular arrhythmias; mech unknown; only
esmolol, ultra short half life=9min, used for atrial fibrillation and drugs effective in preventing sudden cardiac death with
atrial flutter after surgery MI survivors

Most potent class of antiarrhythmic agents (meaning Class III)


234 Effective for rhythm disturbance in all tissues
Agents possess combination of mild beta blocker, calcium
almost as good as amiodarone; eliminated by the kidney w half life channel blocker and sodium channel blocker activity along
of 12hrs with primary effect on repolarization current (K current)
G H

Amiodarone:
prolonged half-life of 30 days - makes difficult to use to
reach steady state (4-5 half lives) requires half a year (3
months for effect), and if make a mistake, takes 5 half lives to
get ride of , must follow pt closely (have foresight)
235
Rapid effect when given IV
Side Effects
Hepatotoxicity
Hypo and hyperthyroidism
metabolized to desethyl metabolite (DEA) in the liver; half life of Corneal deposits
5hrs to 30days (Cecil says 103days); IV HAS A RAPID EFFECT Irreversible pulmonary fibrosis (permanent)

236
oxidative hepatic metabolism and cleared by the kidney

237
eliminated by liver (CYP3A4) and kidney; half life=8-10 hrs but
12% to 18% lower in women
Antiarrhythmic Class IV: Ca channel antagonists; dont
affect the Phase2 plateau???; poor effect as direct
238 antiarrhythmic for atrial or vent arrhythmias, most effective
on slowing conduction velocity (Phase 0) in nodal
tissues; useful for the control of vent rate in SVT

239 CCB and beta blockers have ~same effect in heart - slow
conduction velocity in the AV node (prevent SVT from getting
to V)

240

241

derived from digitalis


G H

242 Used diagnostically to determine whether ventriclar


Half life of 1.5 to 10 sec (shortest half life of any drug); tachycardia was induced supraventricularly or
metabolized in the plasma ventricularly

243

Absorbed rapidly and is 100% orally bioaviable; i.v. loading


dose must be given slowly, so limited to clinical situations with
adequate time available; Does not increase digoxin levels; Antiarrhythmic Class III: prolong duration of cardiac action
cimetidine and ranitidine decrease clearance 10-50% potential (AP) and refractoriness
244
245

Thrombin Time: Dilute thrombin is added to the patients


246 Activated Partial Thromboplastin Time (aPTT) is used to plasma and a control plasma and the clotting time are
monitor heparin anticoagulant therapy: compared. Since no Ca++ is added to the plasma, clotting
Normal = 35-45 sec; aPTT = 1.5 to 2.5 times control time is independent of reactions involved in the
(theraputic goal with heparin); Ca++ ion, "partial generation of thrombin and depends only upon the
thromboplastin", and a charged surface contact are added to reactions initiated by adding the weak exogenous
plasma and clotting time is compared to a control plasma sample. thrombin. A long thrombin time may be caused by increased
The aPTT measures the activity of the intrinsic coagulation antithrombin activity, for example when plasma contains
pathway including the factors deficient in the two forms of heparin. Dilute thrombin is added to the patients plasma and
hemophilia, hemophilia A (factor VIII deficiency) and hemophilia a control plasma and the clotting time are compared. Heparin
B (factor IX deficiency). The aPTT is used to monitor prolongs both the aPTT and the thrombin time; at higher
anticoagulant therapy with unfractionated heparin. doses can also prolong the PT time
LMWH preparations have been developed with the goal of
247 decreasing bleeding episodes while still retaining
Longer duration, simpler kinetics, clotting tests not usually anticoagulant activity, especially for the prevention of deep
required venous thrombosis (DVT) in surgical patients.
248
G H

Prothrombin Time (PT): Plasma will clot in 12 to 14 seconds


249 after addition of calcium ion and "thromboplastin" (a saline
extract of rabbit or human brain that contains tissue factor and
phospholipids). Warfarin anticoagulant therapy leads to
inactivation of several clotting factors (especially VII, X, and
thrombin) and prolongs the clotting time in the PT test. The INR
(see below) is used to normalize PT test results and monitor
warfarin therapy. The International Normalized Ratio (INR): is a Monitor therapy with INR (PT test); PT time (corrected to an
format for reporting prothrombin times of patients on warfarin. INR) INR = 2.0 to 3.0

250

Clopidogrel:
Alternate to, or additive with, aspirin Approved for the prophylaxis of stroke, MI, peripheral arterial
Inhibits ADP pathway in platelets disease, and acute coronary syndrome. This drug
251 Reduces platelet aggregation irreversibly inhibits platelet fibrinogen binding. Clopidogrel
NO EFFECT ON PROSTAGLANDINS preferred over aspirin: selectively inhibits the binding of adenosine diphosphate
if loop diuretic is being used (ADP) to its platelet receptor and the subsequent ADP-
if kidney disease is present mediated activation of the glycoprotein GPIIb/IIIa
Particularly useful in unstable angina complex, thereby inhibiting platelet aggregation.

Inhibits platelet function by increasing cyclic AMP levels (inhibits


phosphodiesterase and raises adenosine levels which stimulates
cyclic AMP synthesis). It has coronary vasodilator activity as well,
252 but has been mostly disappointing in clinical trials. Dipyridamole is
now indicated in patients with prosthetic heart values and as an
alternative to aspirin for secondary prevention of acute myocardial
infarction, to prevent stroke in patients with transient ischemic
attacks, and to maintain potency of coronary bypass grafts.

253
Ticlopidine (Ticlid) inhibits the platelet ADP receptor and inhibits
the binding of fibrinogen to activated platelets, and thus blocks
platelet aggregation and clot retraction. The effect on platelet
function is irreversible for the life of the platelet.
G H

inhibits cyclic AMP phosphodiesterase III, suppresses cyclic AMP


degradation, and the resultant increase in cAMP in platelets and
blood vessels leads to inhibition of platelet aggregation and
254 vasodilation. Cilostazol is indicated for the reduction of
symptoms of intermittent claudication, as indicated by an
increased walking distance. The use of this drug is
contraindicated in patients with CHF of any severity.

Glanzmann Thrombasthenia: congenitally deficient or


Monoclonal Ab that prevents clot formation by binding the inactive GpIIb-IIIa platelet surface receptors (noncleaved
glycoprotein IIb/IIIa receptor, thus inhibiting platelet aggregation. fibrinogen is an important cofactor), ADP induces a
255 The drug has greater antithrombotic activity than aspirin or confromational change of the GpIIb-IIIa platelet surface
heparin. Abciximab is used as an adjunct in high-risk angioplasty receptors so that they can bind fibrinogen. Fibrogen then acts
and in acute coronary syndromes. During angioplasty procedures, to connect multiple platelets together to form large aggregates
the balloon device can cause formation of blood clots that can (during platelet aggregation phase, after adhesion and
cause restenosis of the artery and lead to cardiac arrest. secretion)
Eptifibatide and tirofiban, are small peptide analogs of critical
domains of fibrinogen that inhibit platelet aggregation by Combined antiplatelet and antithrombotic therapy (ie
256 blocking ligand binding to the IIb/IIIa receptor. These two drugs heparin plus platelet glycoprotein Iib/IIIa inhibitor) is
are also used to percutaneous transluminal coronary angioplasty superior to heparin alone in reducing morbidity and
(PTCA). mortality in pts with acute coronary syndromes

257

258

Derived form the saliva of the medicinal leach (Hirudo


259 medicinalis), does not require cofactors and is not inactivted by
platelet factor 4 or plasma proteins. Monitor therapy PTT

260

Heparin-induced Thrombocytopenia unfractionated heparin


261 induces formation of Ab that activate platelets (HIT II, antibody
mediated), endothelial injury, and prothrombin state. Use low
molecular weight heparin to prevent.
G H

Bivalirudin is a short-acting, synthetic direct thrombin binding


inhibitor approved for patients with unstable angina
undergoing coronary angioplasty. Most patients in the USA
262 with acute coronary syndromes undergoing angioplasty are
now treated with platelet glycoprotein IIb/IIIa receptor
The direct thrombin inhibitor bivalirudin has been recommended antagonists (eptifibatide, tirofiban, or abciximab) plus aspirin
as an improvement over heparin during angioplasty and is the and low doses of unfractionated heparin. This drug is very
agent of choice in patients with heparin-induced expensive compared to more conventional treatments.
thrombocytopenia. ($456.00 versus $68.00 Lovenox or $1.20 for UFH)

263

Intravascular clots dissolve as a result of the action of


plasmin, an enzyme that digests fibrin. Plasminogen, an
inactive precursor, is converted to plasmin by cleavage of a
single peptide bond by tissue plasminogen activator (t-PA),
a protease released from endothelial cells. The normal
264 t-PA is the natural protease activator of plasminogen. It has been fibrinolytic system is regulated such that unwanted fibrin
purified and is now produced by recombinant DNA technology. thrombi are removed, while fibrin in wounds persists to
Three forms of recombinant t-PA are now available, alteplase (rt- maintain hemostasis. A major factor in this regulation involves
PA), the full-length form, reteplase (r-PA), a shorter, genetically greater fibrinolytic activity when plasmin is bound to the fibrin
engineered mutant form, and tenecteplase (TNK-tPA), a mutated in a clot than to fibrinogen free in circulation. t-PA is rapidly
form with a prolonged half-life, increased fibrin specificity, and cleared from blood and/or inhibited by circulating inhibitors
increased resistance to inhibition by plasminogen activator (such as 2-antiplasmin) and thus does not normally effect
inhibitors. circulating plasminogen.
Reteplase does not bind fibrin so tightly, allowing the drug to
diffuse more freely through the clot rather than binding only to
265 the surface the way t-PA does. Also, this redesigned t-PA in high
concentrations does not compete with plasminogen for fibrin-
binding sites, thus allowing plasminogen at the site of the clot to be
transformed into clot-dissolving plasmin.

266
G H

Streptokinase has been shown to be effective when given IV for


dissolution of intracoronary thrombi in myocardial infarction.
267 Therapy is most beneficial when instituted early (within 90 Nonenzymatic activator of plasminogen extracted from
min) after the onset of symptoms. Streptokinase has also been beta hemolytic streptococci. It forms a complex with
used to treat pulmonary embolism, deep venous thrombosis, and plasminogen and accelerates conversion to plasmin. Most
peripheral vascular disease. Bleeding (especially cerebrovascular) patients have antibodies to streptokinase resulting from
is a serious adverse reaction. previous exposure to streptococci.

268

(Anisoylated Plasminogen Streptokinase Activator Complex;


APSAC) is the inactive form of the plasminogen streptokinase
activated complex that becomes activated once in the blood.
269 This preparation can be given by rapid IV injection and has greater
selectivity for plasminogen associated with clots, i.e., has less
effect on free plasminogen in plasma and thus less chance of a
generalized fibrinolytic state. It has been shown to have beneficial
thrombolytic effects especially when administer early after an
ischemic attack in myocardial infarction.

270

271
Also give broad spectrum Abx and Xigris for sepsis and DIC
272
273
G H

274

Mechanism causing rhabdomyolysis is not entirely clear


HMG-CoA inhibitors also inhibit Q10 (ubiquinone), and this
mechanism is most likely. Various statins do so differentially, and
those most efficacious in inhibiting Q10 are also most likely
offenders
Mevalonic acid is a constituent of cell wall molecules, and HMG-CoA reductase inhibitors, cholesterol uptake inhibitors,
blockade of their formation is also implicated, although this and bile acid binding resins primarily used for
hypothesis is losing favor hypercholesterolemia

275

276
G H
277
278

279 Fibric acid derivatives: Used for hypertriglyceridemia in which


VLDL is elevated
Bile Acid-Binding Resins: Used for hypercholesterolemia with
normal triglycerides
Cholesterol uptake inhibitors: Block cholesterol absorption in
intestine

280

281

282

Taking with food, or aspirin or anithistamine 30 min before can


minimize SE

283
G H

Phase I and Phase II reactions are biotransformations of


chemicals that occur during drug metabolism.
Phase I metabolism usually precedes Phase II, though not
necessarily. During these reactions, polar bodies are either
introduced or unmasked, which results in (more) polar
metabolites of the original chemicals. Phase I reactions may
284 occur by oxidation, reduction or hydrolysis reactions. If the
metabolites of phase I reactions are sufficiently polar, they
may be readily excreted at this point. However, many phase I
products are not eliminated rapidly and undergo a subsequent
reaction in which an endogenous substrate combines with the
newly incorporated functional group to form a highly polar
Note: unlike bile acid binders, this drug does not decrease conjugate.
absorption of other fatty substances Phase II reactions usually known as conjugation
Well tolerated reactions (e.g., with glucuronic acid, sulfates, glutathione or
No inhibition of cholesterol synthesis in the liver or increase amino acids) are usually detoxication in nature, and involve
in bile acid secretion. the interactions of the polar functional groups of phase I
metabolites.

285

286
G H

287

Treatment of Iron Deficiency Anemia Prophylaxis: Generally, prophylactic use of iron preparations
The severity and cause will determine the appropriate approach should be reserved for individuals at high risk; pregnant and
to treatment. lactating women, low birth weight infants and infants
Symptomatic elderly patients with severe iron deficiency anemia maintained on unsupplemented milk formulas. Other
and cardiovascular instability may require red cell transfusions. patients at high risk include rapidly growing children (low
For the majority of cases, oral iron therapy is sufficient. meat diets) and in adults with chronic blood loss.

All dividing cells are undergoing DNA synthesis and require the
precursors and cofactors necessary for synthesizing the purine
and pyrimidine bases in DNA. Two of these essential factors are
288 vitamin B12 and folic acid. Deficiencies in either of these two
substances lead to impaired DNA synthesis and abnormal
maturation and functioning of cells. These changes occur in Megaloblastic anemia: In vitamin B12 or folic acid deficiency
any dividing cells, but tissues which normally undergo rapid cell there is decreased DNA synthesis, but continued RNA and
division, i.e., hemopoietic cells and GI epithelium, are the most protein synthesis which leads to a characteristic production of
susceptible. Anemia is the chief finding in patients with Vitamin large (macrocytic) red blood cell precursors (megaloblasts)
B12 or folic acid deficiency; GI symptoms may also occur. that do not mature properly into circulating red cells. The
Neurological abnormalities may also occur in Vitamin B12 bone marrow is hypercellular and the red cells formed are
deficiency, but not usually in folic acid deficiency. more susceptible to destruction.
G H

Folates are readily absorbed (50-200 ug/day) from ingested


food. Folic acid is stored (5-20 mg) in numerous tissues,
Sources: Richest sources are yeast, liver, kidney, green especially the liver. Folates are excreted in the urine and stool
289 vegetables. Folic acid deficiency, unlike B12 deficiency, is often and are also destroyed by catabolism. Folates are unlike
caused by inadequate dietary intake of folates. Elderly people, vitamin B12 in that there is more breakdown, less storage,
poor people, food faddists, and alcoholics are groups of patients and greater demand, and therefore, folic acid deficiency can
who are prone to diets lacking in fresh vegetables, eggs, and develop within 1-6 months after adequate intake stops.
meat. Deficiency may also occur in pregnant women and patients Certain drugs interfere with folate absorption or metabolism
with intestinal disease, cancer, or undergoing dialysis. (phenytoin, isoniazid, methotrexate, trimethoprim).

Colony stimulating factors (CSFs) have only been recently purified and their physiologic functions and mechanisms of action are
incompletely understood, but these molecules hold great promise for treating anemias and myelodysplastic disorders.
a. SCF (Multi CSF): stimulates bone marrow production of RBCs, granulocytes, macrophages, and platelets.
290
b. GM CSF: stimulates production of granulocytes and macrophages.
c. G CSF: stimulates granulocyte proliferation and differentiation.
d. M CSF: stimulates monocyte macrophage proliferation.
e. Other cytokines: numerous other factors influence bone marrow derived cell proliferation, differentiation, and function
including the interferons (alpha, beta, gamma), the interleukins (1-12), and other factors.

When an increase in EPO levels in the circulation occurs in


response to acute onset of anemia, new proerythroblasts
and normoblasts appear in the bone marrow within 2 to 4
291 days, and new reticulocytes begin to appear in the
Erythropoietin: a glycoprotein synthesized by the kidneys in peripheral blood within 3 to 7 days. Reestablishment of
response to hypoxia and stimulates the division and normal numbers of circulating erythrocytes and normal tissue
differentiation of erythroid progenitors in the bone marrow. It has oxygenation results in reduced production of EPO and a
been purified, cloned, and the recombinant human hormone is reduced rate of production of erythrocytes back to the normal
being produced by genetic engineering techniques. basal level.
The human G-CSF gene has been inserted into E. coli which
produce the protein. Endogenous G-CSF is produced by
292 monocytes, fibroblasts and endothelial cells. It is a lineage-
specific stimulator of the proliferation, differentiation, and end-cell
function of the neutrophil line.

293

Sargramostim increases the cytotoxity of monocytes toward


certain neoplastic cell lines and activates polymorphonuclear
neutrophils to inhibit the growth of tumor cells.
G H

Oprelvekin has been shown to have non-hematopoietic


properties. The drug enhances healing of gastrointestinal
294 lesions and currently in clinical trials for the treatment of Crohn's
disease. Oprelvekin also has been shown to induce protein
synthesis, inhibit adipogenesis, inhibit pro-inflammatory
cytokine production by macrophages, increase production of
osteoclasts, and stimulate neurogenesis.

Mech: Inhibits ribonucleotide diphosphate reductase, the


enzyme that converts ribonucleotides to
deoxyribonucleotides and is a crucial and probably rate-
limiting step in biosynthesis of DNA. Hydroxyurea causes an
immediate inhibition of DNA synthesis without interfering with the Hydroxyurea is approved for treating adults with sickle cell
295 synthesis of ribonucleic acid or of protein. The drug is specific disease. The drug reduces the number of painful crises, the
for the S phase of the cell cycle. It causes cells to arrest at frequency of acute chest syndrome and hospitalization, and
the G1-S interface. Since cells are highly sensitive to irradiation the need for blood transfusions. Known pharmacologic
in the G1 phase of the cycle, combinations of hydroxyurea and effects of hydroxyurea that may contribute to its beneficial
irradiation cause synergistic toxicity. Hydroxyurea also potentiates effects include increasing hemoglobin F levels in RBCs,
the antiproliferative effects of other cancer chemotherapeutic decreasing neutrophils, increasing the water content of
agents such as cisplatin, alkylating agents, topoisomerase RBCs, increasing deformability of sickled cells, and
inhibitors, and antimetabolites. altering the adhesion of RBCs to endothelium.
296

297

298
First-generation sulfonylureas vary considerably in their half lives,
299
duration of action, and extent of metabolism

300
301
302
G H

Sulfonylureas: Mechanism of Action


A. lower blood glucose levels by stimulating insulin
release from pancreatic cells. Initially (first few months of
303 treatment), fasting plasma insulin levels and insulin responses
to oral glucose are increased. With chronic administration,
circulating insulin levels decline to those that existed before
treatment, but, reduced plasma glucose levels are maintained.
Type 2 DM patients often fail to respond adequately to a single B. Sulfonylureas bind to and block an ATP-sensitive K+
agent and are then treated with a combination of oral drugs or are channel. Blockade of this channel reduces K+ conductance
switched to intensive therapy with insulin. Patients with Type 1 causing membrane depolarization and influx of Ca2+ through
diabetes are treated with insulin and do not respond to oral voltage-sensitive Ca2+ channels. Ca2+ influx leads to insulin
hypoglycemic agents. secretion.

304

305

Repaglinide & nateglinide are structurally different from Repaglinide and nateglinide were developed to manage meal
sulfonylurea drugs; they are meglitinides. Meglitinides binds to the related glucose loads. The rapid action of these drugs
ATP-sensitive potassium channel on pancreatic beta cells at a (taken right before a meal) makes them useful for patients
different site than sulfonylureas. The subsequent who are erratic eaters. For example, if a meal is skipped so is
306
depolarization of the beta cell opens the Ca channel and rapidly that dose of drug and hypoglycemia is avoided. Only the first
increases insulin secretion. Thus, these drugs are sometimes phase of insulin secretion is stimulated because of the rapid
called non-sulfonylurea secretagogues. Both of these drugs are metabolism of the drugs. These drugs are approved for
well absorbed and reach peak levels within 30 to 60 minutes. monotherapy or combined with metformin. Adverse effects
These drugs are rapidly metabolized by the liver to inactive are comparable to sulfonylureas but these drugs should be
metabolites that are excreted in the bile or urine. used cautiously in the elderly and those with liver dysfunction.

307
G H

Metformin has been used as sole therapy to treat Type 2 DM


Metformin has an antihyperglycemic action; not a or can be added to sulfonylurea or TZD treatment if only
hypoglycemic action. Unlike the sulfonylurea drugs, It does not partial reductions of plasma glucose have been achieved.
directly effect insulin release. It does not cause hypoglycemia Metformin is most often prescribed for patients with
308 even at high doses. Metformin appears to produce the following refractory obesity whose hyperglycemia is due to "insulin
effects: resistance". Because metformin is an insulin sparing
reduce hepatic glucose output by inhibiting gluconeogenesis. agent and does not cause weight gain or provoke
increase insulin action in peripheral tissues (increases anaerobic hypoglycemia, it offers advantages over sulfonylureas and
glycolysis), i.e., decreases insulin resistance; insulin in treating obese, insulin-resistant patients. It also has
increase glucose uptake and utilization by muscle; a a significant lipid-lowering effect, i.e., it decreases total
reduces intestinal absorption of glucose cholesterol, LDL, and triglycerides.

309

The most common side effects are flatulence, diarrhea and GI


upset due to undigested carbohydrate. These adverse effects
lead to poor patient compliance.
310

311

TZDs increases glucose uptake and glucose oxidation in both


muscle and adipose tissue, while reducing hepatic glucose
output and lipid synthesis in muscle and fat cells. Insulin Free fatty acids (FFA) increased insulin resistance (FFA
release is not directly stimulated. increased in obesity)

312

313
G H

The identified metabolic effects of pramlintide are:


suppression of endogenous glucagon production, especially in
314 the postprandial state.
reduction of postprandial hepatic glucose production.
reduction of gastric emptying time. Pramlintide is delivered by subcutaneous injection before
centrally-mediated induction of satiety meals and cannot be mixed with insulin. Thus, use of
reduction of postprandial glucose levels pramlintide requires an additional 2 to 3 injections per day.

Among GLP-1 and Exenatides (and Dipeptidyl Peptidase


Inhibitors) proposed effects are:
glucose-dependent enhancement of endogenous insulin
secretion and perhaps insulin sensitivity.
315 inhibition of endogenous glucagon secretion.
possible appetite suppression and satiety induction. Glucagon-like peptide 1 (GLP-1) is a peptide hormone
reduction in speed of gastric emptying. produced by the cleavage of the proglucagon precursor. It is
possible stimulation of islet growth, differentiation and secreted by intestinal L cells. The analog Exenatide was first
regeneration. discovered in the salivary secretions of the Gila monster.
316

Among GLP-1 and Exenatides (and Dipeptidyl Peptidase


Inhibitors) proposed effects are:
glucose-dependent enhancement of endogenous insulin
317 secretion and perhaps insulin sensitivity.
inhibition of endogenous glucagon secretion.
possible appetite suppression and satiety induction.
reduction in speed of gastric emptying.
possible stimulation of islet growth, differentiation and
regeneration.
318
319
G H

In solution, insulin can exist as a monomer, a dimer, or as a


320
hexamer (six molecules).The various insulin preparations
crystallize differently. This is an important determinant of how
fast the hormone crystals dissolve after subcutaneous
injection. Since only insulin free in solution can be
Insulin is a protein hormone. cells of the pancreatic islet absorbed, the rate of dissolution of injected insulin
synthesize insulin from a single chain precursor = preproinsulin crystals along with local blood flow determines the rate of
that is further shortened to form proinsulin. Proinsulin folds and onset and duration of action of the preparation. When the
disulfide bonds form. In the Golgi complex, proinsulin is packaged hormone is absorbed and the local concentrations fall, the
in secretory granules along with the enzymes that remove the hormone dissociates into monomers, the active state of the
connecting peptide (C peptide) to form insulin. molecule.

321

322

323

Regular Insulin is short - acting insulin and is simply a solution


of regular crystalline zinc insulin dissolved in a buffer at neutral pH.
Regular insulin has a fairly rapid onset of action (30-45 min) and a
324 short duration of action (4-8 hr). Regular and aspart are the only
types of insulin that can be administered as IV infusions.
Regular, aspart, glulisine, and lispro insulin can be used in
subcutaneous infusion pumps.
Intermediate-Acting Insulins are formulated so that they dissolve
more gradually when give S.C., their duration of action is therefore
325 longer.
NPH insulin is a suspension (not dissolved) of insulin in a
complex with protamine (a highly charged protein) and zinc in a
phosphate buffer.
326
G H

Glargine (or Detemir or Ultralente) [Basal-Bolus] Regimen: A


pre-breakfast dose of Glargine (or detemir or ultralente) and
ultrashort or regular insulins is taken along with additional
doses of ultrashort or regular insulin at lunchtime and
327 dinnertime. Glargine insulin provides a basal requirement for
insulin, while the rapid acting insulin meets the postprandial
Ultra-Long-Acting Insulins are formulated to dissolve very slowly demand. To achieve more uniform basal levels, the dose of
when injected SQ and thus, these insulins have a very slow onset basal insulin is sometimes divided into morning and evening
and prolonged, relatively flat peak of action. doses.
328
329
330

331 Thyroid hormone receptors belong to the superfamily of


hormone-responsive nuclear transcription factors that are
similar in structure and mechanism of action. Other members
of this family include receptors for steroid hormones, vitamin
Thyroid Hormones: The thyroid gland is the source of the thyroid D, and retinoids. These receptors are activated by hormone
hormones, thyroxine (T4) and triiodothyronine (T3). Normally 80 binding and bind to specific sites on DNA (hormone
100 microg of thyroxine and 30 microg or triiodothyronine are response elements, HRE) in the promoter/regulator regions
produced within 24 hrs, released into the blood stream, and taken of genes. Activation of the receptor results in either activation
up by all tissues. or repression of specific genes.

Indications: The thioamide antithyroid drugs are the preferred


treatment for children, pregnant women, and young adults with
uncomplicated hyperthyroidism. These patients have some
332 chance of spontaneous remission and this is the only treatment
modality that leaves the thyroid gland intact and does not carry
the added risk of hypothyroidism that often accompanies
radioactive iodine treatment and surgery. Treatment for Hyperthyroid states: Exophthalmic goiter, Grave's Disease
uncomplicated Grave's disease typically lasts several years. (diffuse toxic goiter) - The clinical state of thyrotoxicosis is
These drugs are also used to hasten recovery while awaiting the characterized by: nervousness; weight loss; hyperphagia;
effects of radioactive iodine or to control the disorder in heat intolerance; increased pulse pressure; fine tremor of
preparation for surgery. Unfortunately, with antithyroid drug outstretched fingers; elevated BMR; exophthalmos; lowered
treatment alone, there is a 60-70% incidence of relapse. peripheral vascular resistance; increased cardiac output.
G H

333

334

335

Iodides are rarely used as sole therapy. The most important


Iodides: (1) inhibit thyroid hormone release; (2) block iodotyrosine pharmacological effect of the iodides is their ability to promptly
and iodothyronine synthesis by blocking organification; (3) inhibit thyroid hormone release. Therefore, iodide therapy is
336 decrease the vascularity of the thyroid gland. The inhibitory effect useful in the management of thyroid storm (sudden, intense
on hormone synthesis is known as the Wolff Chaikoff effect. This exacerbation of the symptoms of thyrotoxicosis) and when
represents an inherent autoregulatory function of the gland to relatively short-term control of hyperthyroidism is
prevent excessive synthesis of hormone. However, the thyroid can necessary. Beta adrenergic blockers, such as propranolol, are
"escape" from this block even with continued iodide use. also useful for the management of thyrotoxic symptoms.

131I is rapidly taken up by the thyroid, incorporated into


337 iodoamino acids and is deposited in the colloid of the follicles.
The beta radiation destroys the surrounding parenchymal
cells. The x-rays can be detected externally and allow for
Physical properties - 131I emits beta particles and x-rays, with estimation of quantity of 131I in the thyroid. When small
a decay half life of 8 days. doses of 131I enter the thyroid, function is not affected.

Beta-blockers (except those with sympathomimetic activity)


decrease symptoms of increased adrenergic tone such as heat Propranolol, which is dosed t.i.d. or q.i.d. is more suited to
intolerance, profuse sweating, tremors, and palpitations that are use in inpatients. Outpatients can be treated with either
338 associated with hyperthyroid states. Due to their relatively rapid atenolol or metoprolol, both of which are more beta-1
onset of action, they can be used to alleviate symptoms until a receptor selective. Patients with hyperthyroidism may require
thioamide takes effect. The most common indications for using a twice the usual doses of beta-blockers to control symptoms
beta-blocker are palpitations and tachycardia. At high doses, beta- and heart rate. As the biochemical hyperthyroidism resolves,
blockers may inhibit conversion of T4 to T3. beta-blocker doses can be tapered down.

339

340

341 Technesium scan: Pertechnetate (T1/2 = 6hrs) radioisotope


concentrated by the thyroid, can be used to visualize the functional
anatomy of the thyroid
342
G H

343

344

345

346 dopamine antagonists may produce hyperprolactinemia and


inappropriate lactogenic effects.
347

348
Osteoprosis Tx: Combination of estrogen-calcium or estrogen-
BPs; Statins also prevent fractures and enhance bone formation in
rodents
Combination of estrogen-calcitonin or estrogen-BPs appears to
have additive effects in increasing BMD.

349

Analogues of pyrophosphate (P-O-P) in which oxygen has been


replaced by carbon (P-C-P) with various side chains.
Concentrate in bones and they are to date the most effective
350 inhibitors of osteoclasts and bone resorption. They inhibit
farnesyl diphosphate synthase which leads to decreased
prenylation of small G proteins essential for osteoclast activity and
survival.
351
352
353
354
G H

355

356

357

358

Pagets Disease: Etiology unknown but a slow virus is suspected;


characterized by uncontrolled osteoclastic bone resorption
359 with secondary increases in bone formation. The new bone is
poorly organized. Goal of treatment is to reduce bone pain, and
stabilize or prevent other problems such as deformity, hearing loss,
hypercalcemia and high out put cardiac failure.
Rx. Calcitonin (SQ or IV) and bisphosphonates are used to reduce
osteoclast activity. Patients may become refractory to calcitonin.

Vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol)


are found in diet.
Vitamin D derivatives are also formed from a prohormone that
360 Hypocalcemia Tx: is produced in the skin after exposure to UV irradiation.
- IV: calcium gluconate infused slowly to prevent arrythmias Vit D3 is converted to metabolites in the liver (25 hydroxy-D3)
- Oral: calcium carbonate (TUMS) and kidney (1,25 and 24, 25 dihydroxy D3).
- 1,25(OH)D for rapid effect. Raises serum calcium in 24-48 hrs 25 (OH)-D3 and 1,25 (OH)2-D3 (active metabolite) are
- Carefully monitor Ca and PO4 to avoid ectopic calcification available for clinical use.

361

362
363

364
Monitoring required the following: pregnancy test, CBC, liver tests,
lipid panel and psychiatric symptoms
G H
365

366

367

Benefits of Aerosol Delivery


1. The pathophysiology of asthma appears to involve the
respiratory tract alone. So, ideally, effective treatment could
be achieved if drug administration was restricted to the lungs.
2. Aerosol application of drugs to the lungs can produce a high
local concentration in the lungs with a low systemic
KEY FEATURES OF ASTHMA absorption, thereby significantly improving the therapeutic
1. Mast cell activation associated with early bronchospasm ratio by minimizing side effects. 3. Both 2-agonists and
2. Inflammatory cell infiltration with subsequently mediator cortocosteroids have potentially serious side effects when
release delivered systemically.
3. Epithelial cell damage 4. Probably more than 90% of asthmatic patients who are
368 4. Increased responsiveness of the airways to a variety of non capable of manipulating inhaler devices can be managed by
specific stimuli aerosol treatments alone.
The initial burst of mast cell activity leads to a generalized 5. Factors that determine effective deposition of drug in the
activation of leukocytes in the peripheral circulation. The release lung a. Particle size: >10 microm deposit in mouth and
of mediators from these activated cells contributes to the oropharynx; <0.5 microm are inhaled and then exhaled; 1-5
bronchoconstriction, mucosal edema, and increased mucus microm deposit in small airway and are most effective. b.
secretion associated with late phase responses. Enzyme release rate of breathing and breath holding c. recommendation is
from inflammatory cells can also contribute to bronchial that a slow, deep breath be taken and held for 5 - 10 sec. 6.
hyperresponsiveness by damaging the respiratory epithelium, Even under ideal conditions only 2 - 10 % of drug is deposited
enhancing neuropeptide release, and exposing afferent nerve in lungs; most of the remainder (90%) is swallowed.
endings that can evoke enhanced vagal responses. Other Therefore, to have minimal systemic side effects, an
iInflammatory cells other than mast cells implicated in the aerosolized drug should be either poorly absorbed from the GI
pathogenesis of asthma include eosinophils, neutrophils, tract or be rapidly inactivated by first-pass liver metabolism.
macrophages, lymphocytes, and platelets. Hint: Consider Ipratropium
Levalbuterol is the R-isomer of racemic (R+S) albuterol available
369
only as a nebulized solution.
370

371
Terbutaline can also be given orally, or as subcutaneous injection,
or IV infusion.
G H

Inhaled steroids are not effective with pts who have a


372 dramatically low FEV1, or FEV1/FVC, as their inhalation
Children appear to have more cholinergic receptors - more capacity is most likely inhibited as well (would have SE with no
responsive to parasympathetic stimualtion than adults theraputic effect)
Bitolterol may produce a longer period of useful
373 bronchodilation (3-6 hrs) than the 2 to 3 hours provided by the
other drugs, perhaps because it is a prodrug that must be
converted to colterol, the active compound, in the lung.

374
Over use may lead to tolerance, some data suggests overuse of
beta agonist may worsen condition, still debated

375

376

377

378
MAO breaks E down very rapidly, short acting
379

380

381
G H

Ipratropium bromide and tiotropium are quaternary amine


muscarinic receptor antagonists. If given parenterally, these
drugs would have peripheral effects similar to atropine
(tachycardia, bronchodilation, inhibition of salivary secretion),
382 but would lack significant CNS effects because the quaternary
ammonium structure precludes CNS access. By the
inhalation route, the effects are confined to the mouth and
airways. These drugs produces little or no change in
heart rate, blood pressure, bladder function, intraocular
pressure, or pupillary diameter. This selectivity results from
inefficient absorption from the lung or GI tract.

383 Tiotropium is supplied as dry powder capsules for inhalation with


an inhaler device.

384 Cellular Actions of Methylxanthines


a. Adenosine receptor antagonists
b. Inhibit cyclic nucleotide (cyclic AMP and cyclic GMP)
Methylxanthines are alkaloids that occur in plants widely phosphodiesterases and thereby elevate the cellular
distributed geographically and members of this group of agents concentrations of these second messengers. However, the
have been widely used for centuries. Important methylxanthines concentrations required to inhibit these enzymes is probably
include theophylline, caffeine, and theobromine. Tea, coffee, not achieved with therapeutic doses.
cocoa, chocolate, and cola-flavored drinks contain caffeine and/or b. Lower intracellular calcium ion concentrations.
other related alkaloids. c. Hyperpolarize cell membranes

385

386
G H

387
1. The development of aerosol formulations or aqueous
intranasal sprays significantly improved the safety of
corticosteroid treatment for moderate asthma or other respiratory
disease. 2. Asthmatics who require inhaled -adrenergic
agonists four or more times weekly are viewed as candidates
for inhaled corticosteroid. 3. Available preparations are viewed Asthmatic patients maintained on inhaled corticosteroids show
as being equivalent in efficacy and potential adverse effects, but improvement of symptoms and lowered requirements for
vary considerably in amount of drug aerosolized per inhaler rescue with -adrenergic agonists. Improvement may be
activation. Therefore, the dose of inhaled steroid must be seen within one week, may continue for up 2 years or longer,
empirically determined for each patient. and reductions in dose over time are often possible.

388

389 Inhaled steroids are the DOC for allergic rhinitis, especially
with nasal symptoms including nasal obstruction (mucosal edema)
from inflammed turbinantes (anti-histamines do not)

390

391 Inhaled steroids are the DOC for allergic rhinitis, especially
with nasal symptoms including nasal obstruction (mucosal edema) All inhaled glucocorticoids are effective give twice a day
from inflammed turbinantes (anti-histamines do not) (budesonide can be given once a day for mild asthma)

392

393
G H

Systemic (parenteral or oral) steroid therapy is used in severe


asthmatic attacks requiring hospitalization and sometimes in less
severe, acute exacerbations of asthma or in patients who fail to
respond to other therapies. Parenteral therapy is also used for
394 some COPD patients and to control other inflammatory pulmonary
disorders, e.g., infiltrative pulmonary diseases. For severe
asthma (hospital), prednisone or methylprednisolone is given
i.v., followed by oral doses and gradual tapering of doses. For
acute exacerbations, oral prednisone is administered for 1-2
weeks. Longer treatment requires gradual tapering of dose Longer treatments require tapering of the dose to account
because of hypothalamic-pituitary-adrenal axis suppression. for hypothalamic-pituitary-adrenal suppression.
395
396

397

398

399 Cromolyn and nedocromil are generally less effective than


inhaled glucocorticoids in controlling asthma. These agents
are useful in mild to moderate asthma as added therapy or as
an alternative to regularly administered oral or inhaled -agonists Seasonal allergic rhinitis (hay fever) is caused by deposition
and oral methylxanthines. Some studies suggest that nedocromil of allergens on the nasal mucosa resulting in immediate
used in combination with inhaled corticosteroids produces no hypersensitivity reactions. This reaction is different from
further benefit, but modest reduction in steroid doses may be asthma in that larger particles are usually involved that do not
possible. become inhaled into the lower airways.

400

401
G H

402
Stimulate vasoconstriction in the nasal mucosa, primarily
Nasal decongestants that are -adrenergic agonists that cause on venous sinusoids, resulting reduced edema, i.e.,
vasoconstriction via activation of 1-adrenergic receptors are decongestions; They are effective only for relief of nasal
found in many, many over-the-counter preparations. congestion and (not?) for sneezing, itching, or discharge.

403

404

1. Role of leukotrienes in airway inflammation: Considerable


evidence shows that the leukotriene (LT) autocoids are important
mediators of inflammatory reactions and anaphylaxis.
405 Leukotrienes are lipid mediators derived from arachidonic acid in Zafirlukast and montelukast are selective LTD4 receptor
the 5-lipoxogenase pathway. LTs are synthesized by eosinophils, antagonists and drugs have the advantage of being taken
mast cells, macrophages, and basophils. LTB4 is a potent orally. They are rapidly absorbed with peak plasma levels
neutrophil chemoattractant. LTC4 and LTD4 exert many obtained in 1-3 hours. The drugs are metabolized in the liver
effects known to occur in asthma including with metabolites excreted in the urine. Plasma t1/2 values are
bronchoconstriction, increased bronchial reactivity, mucosal approximately 2.5 hours. Thus, they must be taken QID
edema, and mucus hypersecretion. (montelukast BID).

406
Inhibits P450

407

Guaifenesin (Glyceryl Guaiacolate): is claimed to enhance


the output of respiratory tract fluid by reducing adhesiveness
408 and surface tension facilitating the removal of viscous mucus.
Therapeutic Rationale: Stimulation of secretion in the respiratory As a result, nonproductive coughs become more productive
tract is of theoretic value in the treatment of chronic irritating and less frequent. There is a lack of convincing studies to
cough. document efficacy.

Iodides enhance the secretion of respiratory fluids, thus


409 decreasing the mucus viscosity. In addition, iodides may stimulate
breakdown of fibrinoid material in inflammatory exudates.
Objective evidence of clinical efficacy is lacking. Because of the
potential for adverse effects, other agents are usually preferred.
G H

410 Therapeutic Rationale: Stimulation of secretion in the respiratory


tract is of theoretic value in the treatment of chronic irritating
cough.

Recombinant DNase available as a nebulizer solution for


treatment of cystic fibrosis. In CF, inspissated secretions
containing large numbers of inflammatory cells lodge in the smaller
airways, causing obstruction. A substantial portion of the purulent
411 material is due to the DNA from the nuclei of lysed cells. Inhaled
DNase has been shown to aid in clearing these secretions.
Clinical trials are underway to assess DNAse treatment in adult
COPD exacerbations, where purulent bronchial secretions also
contribute to airway obstruction.

Cough is a nonspecific sign of upper or lower airway irritation or


inflammation and is mediated through reflex vagal pathways.
412
Nonproductive cough that is irritating to the throat and self
perpetuating or exhausting to the patient is an indication for
antitussive therapy. Multiple factors may cause cough, such as
airway hyperactivity, smoking, infection, neoplasms, foreign
bodies, "postnasal drip", esophageal reflux, or irritation of the Opioids are orally active, metabolized in the liver and renally
sinuses, upper airway and eardrum. excreted.

413
Opioids are orally active, metabolized in the liver and renally
excreted.

414

415 Unlike in asthma, antihistamines (H1 histamine receptor


antagonists) produce considerable, though incomplete, symptom
relief of cough

416
G H
417
418

419

420

421 Chantix, prescription medication, tablet form. Generally prescribed


for 12 weeks. May prescribe Chantix for another 12 weeks to Researchers found Chantix to be more effective than a
enhance long-term success. placebo in helping people quit smoking.

422

Mycobacterium tuberculosis
Tuberculosis still the leading cause of death by infectious disease
throughout the world
Increasing incidence in USA, AIDS patients, homeless, immigrants
423 Difficult to stain & acid-fast
Grows slowly and are relatively resistant to most antibiotics,
therefore must treat for months - years
Lipid-rich cell wall impermeable to many agents
Substantial portion of organisms are intracellular, so inaccessible Treatment divided into:
to drugs which penetrate poorly 1. treatment of latent infection diagnosed by a positive PPD
Many resistant strains so use multiple drug therapy 2. treatment of active clinical TB

424 For patients who cannot tolerate rifampin: 9-12 months of INH
+ ethambutol + pyrazinamide +/- a fluoroquinolone (levofloxacin,
moxifloxacin, gatifloxacin)
Rifabutin has been substituted for rifampin in some patients who
could not take rifampin because of drug interactions (HIV patients Resistance to rifampin: isoniazid + ethambutol for 18mo or
on multiple drugs) isoniazid + pyrazinamide + streptomycin for 9mo

425
Do not use rifobutin with ritonavir or delaviridine (protease inhibitor
and NNRTI respectfully)
G H
426

427 MDRTB multi-drug resistant TB (Latent): regimens may


include two drugs, e.g., pyrazinamide + ethambutol or a
fluoroquinolone for 9-12 months but are poorly tolerated
Pyrazinamide bacteriacidal for slowly growing intracellular (in M0)
428
at acid pH

429
Other second line drugs include: Ethionamide, Aminosalicylic Acid, Streptomycin bacteriacidal for actively growing extracellular
Capreomycin, Cycloserine organism
430
431
432

433

434
Conventional amphotericin deoxycholate (Fungizone) older, non-
lipid formulation, least expensive - Better tolerated, new
formulations replacing this drug
Lipid Formulations: three lipid formulations are available; generally
better tolerated, nephrotoxicity is less severe than with
conventional Ampho B

435

436

437

438
G H
439

440

441
442

443
444

445

446

447

448

449

450

451
Resistance
Through alteration in viral thymidin kinase
Through alteration in viral DNA polymerase
Pharmacokinetics
Used orally or intravenously for treating genital herpes
Cleared by glomerular filtration
G H
452
453

454

455

456

457

458
H1 receptors activation results in:
bronchoconstriction
Storage location of Histamine: exocrine excretion (?)
1. mast cells major source of stored histamine in mammalian increase capillary permeability
tissues contraction of intestinal smooth muscle
2. basophils basophilic leucocytes of the blood contain stored stimulation of sensory nerve endings
histamine Cellular signaling mechanism
3. CNS and peripheral nerves - increase phosphoinositol hydrolysis, increase intracellular
Histamine Receptors- H1, H2, and (H3 not relevant clinically); all Ca++
are G protein-coupled receptors Distribution: smooth muscle, endothelial cells, brain

459

460

461
G H

462

Azelastine hydrochloride (Astelin), 0.1% nasal spray approved for


treatment of seasonal allergic rhinitis; Clinical trials indicate it is as
effective or more so than Seldane or Cetirizine in relieving
symptoms of seasonal or perennial allergic rhinitis; Metabolized to
463 desmethylazelastine, which is also active. Half-life of 22 and 54
hrs, respectively. Recommended dosing is 2 sprays per nostril
b.i.d.; Does not have effects on cardiac conduction, or dangerous
drug interactions seen with some others; Cost is comparable to
2nd generation anti-H1s.

464

465

466

Second-Generation Antihistamines: These drugs penetrate Allergic Conjunctivitis: the most common form of ocular allergy, is usually associated with allergi
poorly into the brain and are much less likely than 1st-gens to seasonal or perennial. An oral antihistamine, a 2nd generation, relatively non-sedating drug such as
have adverse effects on the CNS; The oral drugs loratadine fexofenadine, or loratadine is recommended to relieve the main symptom, itching. Antihistamines fo
(generic [$21.30], Claritin [$27.30], Alavert [$16.50]) and also available.
467 desloratadine Clarinex [$63.29] are non-sedating in recommended Topical decongestants reduce erythema, congestion, and eyelid edema; their adverse effects includ
doses; with higher doses, sedation may occur; Fexofenadine rebound hyperemia and conjunctivitis medicamentosa.
(Allegra [$84.62]) has been free of sedative effects; Cetirizine Antihistamine/decongestant combinations such as pheniramine/naphazoline (Visine A, and others)
(Zyrtec [$63.29]) is sedating in some patients but has a better antazoline/naphazoline (Vasocon-A) available OTC may be more effective than either agent alone, b
established safety record in young children than the other drugs; of action and may cause rebound vasodilation with continued use.
No well-controlled trials have convincingly established that any one Topical corticosteroids should only be used as a last resort because they are associated wit
of the 2nd-generation drugs is more effective than the others. pressure, cataract formation and complications with viral infections.

468

469

Cetirizine is sedating in some patients but has a better


470 established safety record in young children than the other
drugs;
G H

471

H2 receptor antagonists pharmacokinetics:


Cimetidine inhibits the P 450 oxidative drug metabolism system - elimination via kidney
monitor when coadministered with P-450 metabolized drugs t1/2 = 1-4 hr.

472

473

474
475

476

477
Alpha1 Receptor Distribution and Effects of Stimulation:
Arterioles/Veins Constricts
Eye (Radial Muscle of the Iris) - Contracts (leads to pupil dilation Alpha2 Receptor Distribution and Effects of Stimulation:
mydriasis) NE Nerve Terminals - Decreases NE outflow (autoreceptor)
Intestine- Constricts sphincters, Decreases motility CNS - Decreases sympathetic outflow
(hyperpolarization leads to relaxation), Also : Inhibit release of insulin
Prostate (note: this is an 1A receptor; vascular alpha receptors Relaxes intestinal smooth muscle
are likely 1B) - Contraction, Promotes tissue growth
Urinary bladder sphincters - Constricts
G H

478

Because E at low dose does not raise mean blood pressure, no


vagal reflexes are activated. Potency slightly greater for beta
than alpha receptors, but clinically (when given at pharmacologic Alpha1 Receptors Second Messenger Excitation:
doses) see alpha and beta stimulation simultaneously. The Gq second message is amplified by activation of
concept of net effect requires knowledge of which receptor phospholipase, which leads sequentially to:
response will prevail (what type of receptors does the tissue Increased levels of IP3
possess?) (if the dose of E is raised, only 1 agonist effects will be Increased levels of intracellular Ca++ (notice, Caffery's cell
seen because E has more efficacy at 1 than 2 receptors), Signaling shows Gp, not Gq)

479
Net effect: Positive inotropic effect, but reflex bradycardia
because of increased systolic and diastolic blood pressure.
G H

Direct Acting Non-Catecholamines (notice, isoproterenol


is a catecholamine): Synthetic agents, lacking the catechol
480 moiety. Analogues of NE or EPI.
Non-catecholamines are metabolized more slowly (they are
not acted upon as readily by monoamine oxidase [MAO],
notice that isoproterenol, a pure 1/2 agonist, has a greater and often they are not stored in vesicles). Therefore they
vasodilating effect than E are generally longer acting; some are effective p.o.

481
2 Selective Adrenergic Agonists: As a group, 5-10X more
potent at 2 than 1 adrenergic receptors.
Therefore more selective for smooth than cardiac muscle.
Longer acting than catecholamines.
COMBIVENT = albuterol + Ipratropium bromide Tolerance may develop.

482

483

The effect of tyramine and NE on BP is negated in the presence of


cocaine. Note that initially both drugs are given in doses to
produce approximately equal effect. Tyramine is an indirect agonist
485 (it releases NE). Following cocaine, the effect of tyramine is
abolished because tyramine cannot gain access to the inside of
the NE nerve terminal. The effect of NE is enhanced because it is
not removed into nerves.
G H

486 dopamine (DA) vs dobutamine (DB): both agents have positive


inotropic effects. At higher doses of DA, an increase in systemic
vascular resistance (SVR) limits cardiac output and worsens
congestion (PCP). The inotropic effect of DB occurs with little
change in heart rate (HR).

487

488
As non-catecholamines, they are metabolized slowly and are
effective p.o.; They are non-polar and penetrate the CNS;
Generally display a higher ratio of CNS to peripheral CV effects.
However, vasoconstriction and a positive inotropic effect are
present.

489
Relatively insensitive to degradation by MAO and COMT. Effective
p.o.

Note: psuedoephedrine is so polar it penetrates the CNS poorly


490 and thus has much less abuse potential). This drug is in the news
because it is a one-step synthesis to produce methamphetamine
from it. Still a very popular component of nasal decongestants.
G H

491

492

493

494

Central Adrenergic Agonists Clonidine:


Not first-line because of side-effects and withdrawal hypertension
(CNS upregulation?)
Give with diuretic (to reduce Na+ retention)
Useful in opioid withdrawal (calms sympathetic component of the Alpha-2 agonists directly inhibit the pancreas from releasing
withdrawal) insulin

495

496

497

Adrenergic neuronal depleting agents. These should only be of


historical interest, but they still show up on Boards.
G H

498
Adrenergic neuronal depleting agents. These should only be of Does NOT get into CNS (highly polar)
historical interest, but they still show up on Boards. Basis of Board questions concerning this agent vs. reserpine;

499

500

501

502

Alpha Adrenergic Blockers:


They block the effects of any compound acting at a receptors
(whether that compound acts directly or indirectly)
Blockade of 2 leads to even greater quantities of NE in the Endogenous agonists (epinephrine; norepinephrine). Note:
synapse. In the heart, 1 effects of NE are not blocked, so sympathetic tone explains why antagonists produce effects.
tachycardia is profound. Exogenously applied drugs (e.g. norepinephrine,
phenylephrine, tyramine)
G H

503
G H

Note: In the absence of reflexes, beta blocking effects should


lead to decreased BP. In reality, if CO falls, sympathetic tone
504 is increased. In the presence of a beta-blocker sympathetic
activation doesnt do much to cardiac function; however,
through alpha-receptors, peripheral resistance increases.
Propranolol is a competitive blocker of beta receptors. It shifts the Peripheral Resistance (complicated phenomena): block of
NE dose-effect curve to the right. It also shifts the Isoproterenol b2 can lead to increased in BP (usually does not); block of
dose-effect curve to the right. Note that the full effect NE or renin release decreases peripheral resistance (usual effect).
Isoproterenol can be re-obtained with higher NE or Isoproterenol Control of Renin release (beta1): under the control of cAMP
dose. (predominate control is exerted by sodium concentration);
Propranolol Sudden Withdrawl: May see rebound hypertension high Na+ inhibits renin release (adenosine, produced in
and/or anginal attacks. Example of receptor up-regulation. Beta macula densa, stimulates Gi second message, inhibits renin
blocker use leads to increased beta receptor synthesis. Sudden release from juxtaglomerular cells); low Na+ increases
termination of beta-blocker uncovers greater density of receptors prostaglandin synthesis, produced in macula densa cell, which
for endogenous agonists. then stimulates cAMP and thus renin release from
Propranolol is very lipid-soluble and is almost completely absorbed juxtaglomerular cells
from the GI tract after an oral dose. However, extensively Lesser control, but still important, is exerted by b1 receptor
metabolized by its first pass through the liver that only about 25% stimulation (stimulates cAMP production)
of the drug reaches the systemic circulation

505

506
G H

Dramatically decrease mortality in Class II and III CHF pts


507
(class IV is less clear may worsen)
Adverse effects All 1-selective drugs lose selectivity at high doses - use
Symptomatic hypotension common initially very cautiously if at all in patient