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Drug type Drug Mechanism Clinical Use Side Effects
Muscarinic receptors bind acetylcholine (ACh). Receptors M1-M5 not important to
know but M2/4 are inhibitory
CHOLINERGIC These are direct acting agonists (do not require nerve inervation).
AGONIST -Agonist of muscarine CV -Salivation, Miosis,
receptor (M>N) -Lowers BP & HR Lacrimation, Urination,
-Slows conduction thru AV node Defacation, Sweating, -
-Only used in dx of bronchial Bronchoconstriction,
reactivity Bradychardia
NOTE: Sweating is the only
Sympathetic action here
*Relaxation of blood vessel→
↓BP→ reflex ↑HR
Carbechol -Direct stimulant of RARE USE THERAPEUTICALLY same
muscarine & nicotinic
receptor -Potent & long duration
-NOT degraded by ACh- -Relieve glaucoma
esterase -After cataract surgery
Bethanechol -Muscarinic only GU same
-Not degraded by ACh- -Stimulate atonic bladder (urinate)
esterase GI
-Increase motility
-Esophageal reflux relief
-Post-op ileus tx

Pilocarpine -3’ amine, partial agonist at ** ↓Intraocular pressure in open

-Aggravates ulcers
M receptor angle glaucoma tx (DOC before
-Crosses the BBB timolol)
-Closed angle glaucoma (used w/
other drugs)
-Xerostomia tx – post radiation tx
-Selective for sweat, salivary,
lacrimal, bronchial glands & iris
smooth muscle (weak effects on GI
smmoth muscle and heart)
Cevimeline M1 & M3 agonist Tx of Sjogren syndrome Similar to pilocarpine
AChE- AChE Inhbitors are indirect acting cholinomimetics (requires nerve
innervation for effects→ so no effect on blood
INHIBITORS vessels). Since ACh is released onto nicotinic (N) and muscarinic (M)
receptors. You would see nicotinic sitmulation (unlike
bethanecol) and muscarinic stimulation. Increasing ACh in the synapse would compete
away competetive muscarinic

antagonists (e.g. atropine overdose) and competetive nicotinic antatonists

(curare). IF you have desensitized muscle
receptors causing paralysis, should you use an agonist to stimulate? If you use an
agonist, it will only make it worse by
further desensitization. Should you use an antagonist? No, the efficacy of a
blocker is zero.
Edrophonium -Similar to neostigmine, -Used in dx of myasthenia gravis -Generalized
ACh stimulation
duration of 2-10 min Cholinergic crisis – antidote is
-MG tests: better =MG crisis
worse= cholinergic crisis Atropine
Physostigmine -Indirect acting 3’ amine -↑ ↑ ↑ ↑GI/GU motility -CNS convulsion
-Periphery & INTO CNS -Miosis (constriction) -Paralysis of skeletal muscle
(lipid sol) -Tx of Glaucoma (↓ocular pressure) (too much ACh)
-Antidote for OD of muscarinic -Potentially fatal arrhythmias
-Reversible inhibition of antagonists (Atropine, from AV block
ACh-esterase phenothiazine, TCA) -Aggravation of asthma
Neostigmine -Reversibly inhibits ACh- -Stimulates GI/GU motility -Potentially fatal
esterase -Tx for myasthenia gravis (b/c no from AV block
-4’ amine; does NOT into CNS effects & long life) -aggravation of asthma
CNS -NO Pupil constriction
-Orally active -Antidote for tubocurarine
Pyridostigmine Same as neostigmine Tx. Myasthenia gravis
Demecarium Same as neostigmine Tx. glaucoma
Organophosphates “Irreversible” & lipid -Glaucoma only in very very dilute CNS
DFP/Echothiphaate soluble (CNS effects) solutions -Excessive muscarinic/
-Tounge Fasiculations nicotinic effects: confusion,
Slow Reversible Covalently binds to ACh- ataxia, slurred speech, loss of
Malathion, esterase Antidote → → → → Pralidoxime & reflexes, sweating, salivation,
parathion, soman, -Nerve gas & insecticides convulsions, coma, respiratory
tabun, sarin paralysis, death
-These compounds *CHRONIC toxicity is different -Organophosphates (except
phosphorylate the esteratic from acute toxicity, and causes echothiophate) are
site on AChE at serine demyelination→ motor/sensory distributed to all parts of the
hydroxyl groups impairment (think of a farmer) body including the CNS
Tacrine -Only used for the CNS Symptomatic Tx of Alzheimer’s -Many side effects of
↑Ach in
Donepezil muscarinic effects→ ↑ACh periphery on M and N
Rivastigmine in brain receptors (unwanted effects)
Galantamine -N receptor paralysis
Given Orally (desensitized muscle) may
cause respiratory paralysis of
-AV block in elderly
OXIMES Pralidoxime Binds to ACh-esterasee Antidote for acute -Only effective in
short time
(2-PAM) inhibitor to pull it from organophosphate exposure period after AchE
enzyme (breaks P-bond) NOT chronic exposure New nerve gases have very
(NO CNS effects) short window of opportunity.
DAM -Must use oxime before aging *DAM not available in USA
DAM has CNS effects (aging for serine is 2-3 min)
Antimuscarinic drugs are always contraindicated in patients with benign prostatic
hypertrophy because of aggravation of
symptoms. They are also contraindicated in glaucoma because of the mydriasis and
cycloplegia effects of the drug. Blocking
ciliary muscle contraction blocks the outflow of vitreous humor, may lead to
Atropine Competitive antagonist to Eye Low dose:
muscarinic receptor -Cycloplegic & myadriatic (near -Bradycardia
accommodation/dilation) -Sedation
Effects (in order of dose): -Antispasmodic in GI/GU Higher doses
• All secretions shut down -Antidote for organophosphates -Tachycardia (may →

• Mydriasis, cycloplegia -Tx of incontinence (must use ventricular arrhythmias)

• Hyperthermia (w/ ↑↑doses, & would see many SE, so -CNS hyperexcitation
resulting vasodilation) not really used) -Delerium
• Tachycardia -Antisecretory for surgery -Hallucinations
• Sedation -Tx ulcer (stops secretion of H+) -Seizures
• Urinary retention & Anesthetic – decreases secretions
constipation -Tx of parkinsons -Dry mouth (no salivation)
• Behavioral excitation & -Blurred vision (Pupil dilation +
hallucination loss of accommodation)
-Flushing of skin
-Hot (no sweat i.e. no

CI: glaucoma, BPH

Scopolamine -Competitive blocker of DOC- Motion Sickness
muscarin receptors
-Greater action in CNS,
longer duration
Tropicamide Competitive antagonist to Eye exam -SE only last a few hours
muscarinic receptor -Cycloplegic& myadriatic
-Topical use
Ipatropium Competitive antagonist to -Anti-asthmatic, esp. in COPD Generally
considered safer
Tiotropium muscarinic receptor w/ vagal componenets & elderly than giving a β-
agonist for
Thiotropium -Does not change mucous patients asthma b/c the agonist will
viscosity, ↓ ↓ ↓ ↓overal mucous -DOC in bronchospasms definitely have an effect
volume associated w/ β β β β-blockers in drugs elsewhere, antaonist has no
-Thio = inhalant w/ much used in asthmatics efficacy
longer half life
Pirenzepine Selective M1 receptor Ulcer tx Central effects not seen
Benztropine -Penetrates CNS Parkinson’s Disease (central
Trihexyphenidyl effects)…will Tx the tremor &
rigidity (caused by too much ACh)

CHOLINERGIC ANTAGOINIST (Classified by structure)

3’ Amines Atropine
Oxybutynin Anticholinergic, Tx of hyper-reflexic bladder
Homatropine -Opthamology (preferred to
Cyclopentolate atropine b/c shorter duration)
Benztropine -enter CNS -Tx parkinsonism
mesylate -Tx extrapyramidal effects of
antipsychotic drugs
-Tx irritable bowel syndrome
Solifenacin Selective M3 receptor
-Tx overactive bladder
Darifenacin antagonist
4’ Amines Ipratropium
Propantheline -Antispasmodic, rhinitis, urinary -Neuromuscular blocking b/c
incontinence, Tx of ulcers nicotinic effects (high doses)
Glycopyrrolate -used orally to inhibit GI motility
-used parenterally to prevent
bradycardia during surgical


Class Drug Mechanism Clincal Use Side Effects
Ganglionic The effects of ganglionic blockers will cause the dominant system (symp
or para) at the tissue to be blocked.
blockers • Arterioles (symp) → vasodilatoin; veins (Symp)→ dilation, ↓venous
return, ↓CO
• Heart (para)→ tachycardia. Does the tachycardia result from excess sympathetics
after blocking parasympathetic?
No, all autonomic output is blocked. The intrinsic heart rate is faster than normal
heart rate. If you put this person on
a treadmill, will their HR ↑? No, all autonomic output blocked.
• Iris (para)→ mydriasis. So is this do to excess sympathetic tone on the iris? No,
it is because the normal tone is
dilated (think of a person in a coma). If you flashed a pin light in the eye, would
you see miosis? No, fixed pupils.
• Ciliary muscle (para)→ cycloplegia
• GI tract (para)→ ↓tone and motility, constipation; Bladder (para)→urinary
• Salivary glands (para)→ xerostomia; Sweat glands (symp) → anhydrosis
These are important (only on board exams) for preventing baroreceptor reflex
changes in heart rate→ orthostatic hypotension
Trimetaphan (given -Short-acting blocker -Reduces HTN & -All effects listed above
IV) prevents reflex
-Good for treating a
HTN patient w/ acute
aortic dissecting
Mecamylamine (given 2’ amine, so better absorption from GI Same as trimetaphan
-WILL cross BBB (unlike
orally) trimetaphan)
-SE: sedation, tremor,
choreiform movements & mental
Tetraethyl- 1 ganglionic blocker No longer used
ammoniium (TEA) very short acting
4’ ammonium
Hexamethonium 4’ ammonium Experimental only,
Decamethonium Neuromuscular depolarizing blocking
Ganglionic Tetramethyl- Stimulation is not followed by Experimental only
stimulants ammonium ganglionic blockade

Partial agonist at N receptor -used to stop smoking
Ganglionic & Nicotine -Preferentially stimulate Nn Higher doses cause ganglionic
NMJ stimulants Lobeline (ganglionic) block
-3’ amines
NM BLOCKERS The nicotinic receptors have 2αβyd structures. ACh binds to the α
subunit, thus 2 ACh must bind to a receptor for activation.
There are no cardiac or smooth muscle side effects because those tissues do not
have the receptors. Make sure to add a CNS
depressant so that patient does not remember.
Tubocurarine Low dose: Competitive blocker by -Flaccid paralysis – 30- *Low dose
action can be
binding nicotinic Receptor 60 min overcome by increasing [Ach]
NONdepolarizing (AChE inhib)
-Progressive paralysis (face,
High dose: block ion channels of end limbs, respiratory muscles→
plate must intubate
-NO effects on cardiac & SM
-NO CNS effects (non-
responding, but still aware)
Mivacurium Very short duration, metabolized by -Emergency -Not short duration in
plasma cholinesterases (genotypically metabolizer (could antagonize
determined) long duration w/ AChE-I)
Atracurium Ester hydrolysis, Hofmann elimination; -Safe in hepatic or -HR/BP
Onset – 2-3min; moderate duration; renal impairment (b/c -Bronchospasm
Rapid recovery not metab) -Laudanosine toxicity→ → → →
-Not metab→ spontaneous inactivation -Not used seizures
to laudanosine
CisAtracurium 1 of 10 stereoisomers -People like it -No CV or Autonomic SE
Hofmann Elimination -Predictable elimination
Stable BP w/ dosing
Onset in 2-3min Moderate duration
Succinylcholine -Nicotinic receptor agonist (analog of -Initial fasciculations
-Malignant hyperthermia (due
ACh→has efficacy) -Short acting: to excessive release of Ca from
-DEPOLARIZING, noncompetitive deactivated by butyryl the SR) Tx = dantrolene
-IV b/c very short duration ChE in serum release of Ca from SR)
-Rapidly hydrolyzed by -Useful for rapid -NO ganglionic block unless in
pseudocholinesterase endotracheal intubation ↑doses
and during ECT -No antidotes b/c AChE-I would
Two phases: worsen b/c no breakdown, and
1. Phase I: depolarization, agonist would only worsen depol
fasciculation, prolong block
depolarization, flaccid paralysis CI: atypical
2. Phase II: desensitization (thus no pseudocholinesterase,
impulses through) hyperkalemia (↑risk of prolonged
depolarization of tissue)

NM Blockers Short acting Intermediate acting Long Acting AE: autonomic effects,
NON-depolarizing Mivacurium Atracurium Tubocurarine (pancuronium) block M
Cisatracurium Metocurine receptors;
Rocuronium* Doxacurium Histamine Release-
(*Steroid derivatives) Vecuronium* Pancuronium* tubocurarine and metocurine;
and possibly with atracurium
and mivacurium
Neuromuscular Blockers:
Two Types:
I. Non-depolarizing-Competitively inhibits the NMJ receptors by binding without
activation of pre and postsynaptic sites. These cannot enter CNS due the charge of
the ammonium ions.
a. Presynaptic inhibition- Release of Ach diminishes and contraction “fades”
b. Postsynaptic inhibition- Blocks Ach at receptor. This is a competitive block
therefore increased Ach can reverse this.
II. Depolarizing-Competitive agonist that binds to and activates the NMJ receptor
inactivates it by keeping the ion channel open (IE the receptor is prevented from
cycling back to it’s closed state).

Beta-receptors are usually more sensitive to activators. So, beta responses are
dominant at low doses. At higher doses, the alpha responses
will predominate. (pp=pulse pressure, later)
α α1
α α
• Radial muscle of eye→ mydriasis
• Arterioles & veins→ vasoconstriction
• Liver→ ↑glycogenolysis
• Kidney→ ↓renin
α α α α2
• Autoregulation (presynaptic inhibition)
• Pancreas→ ↓insulin (remember that insulin is regulated by cAMP, that’s why it
can’t be α1 receptor mediated, which causes ↑Ca++)
• Platelets→ aggregation (since platelets are not innervated, this effect is caused
by circulating epinephrine)
β β β β1
• Heart→ ↑contractility, ↑HR, ↑conduction velocity
• Kidney→ ↑renin
β β2 (mostly not innervated)
β β
• Vasodilation
• Uterus→ Relaxation
• Liver→ ↑gluconeogenesis, ↑glycogenolysis, ↑ lipolysis (& in adipose)
• Skeletal muscle→ ↑glycogenolysis (for muscle contraction)
• Pancreas→ ↑insulin secretion (if you are running away from the alligator, you
have to be able to use the glucose)→ ↑lipoprotein lipase
• Lung→ bronchodilation
Drug type Drug Mechanism Clinical Use Side Effects
Epinephrine (α1, β1, β2) DOC – bronchospasm & -CNS – anxiety, fear, tension,
*Note: only epinephrine interacts w/ β2 anaphylaxis (β β2) h/a, tremor
β β
receptors -Glaucoma – ↓pressure via -Cerebral hemorrhage via
-Since β receptors are more sensivitve, these vasoconstriction of ciliary blood ↑BP
effects would be seen at low dose epinephrine vessels -Pulmonary edema
-↑Duration of local anesthetics
LOW dose: (like isoproterenol) via vasoconstriction (α1) to limit -Cardiac
arrhythmia – esp. in
• β1: ↑HR, ↑SV, ↑CO, ↑pp abs & distribution digitalis pt.
• β2: ↓TPR, ↓BP, ↑pp -Tx cardiac arrest
→Slightly lower BP, ↑systolic BP, ↓diastolic BP
HINTS (Is it Epi or NE):
MEDIUM dose: →β2 effects = epi
• β β β β1: ↑ ↑ ↑ ↑HR, ↑ ↑ ↑ ↑SV, ↑ ↑ ↑ ↑CO, ↑ ↑ ↑ ↑pp →If bronchodilate = Epi
• β β2:↓ ↓TPR, ↓ ↓BP, ↑ ↑pp →If prevent premature labor= Epi
β β ↓ ↓ ↓ ↓ ↑ ↑
• α1: ↑TPR, ↑BP →If metabolic effects = Epi
→So, maintains BP, while ↑CO & ↑perfusion
pressure **At ↑↑dose epinephrine: if give
an α1 blocker, only have β1, β2
HIGH dose: (like NE) effects and the previous
hypertension (α1) → hypotension
• α α α α1: ↑ ↑ ↑ ↑TPR, ↑ ↑ ↑ ↑BP, potential reflex ↓ ↓ ↓ ↓HR
• β1: ↑HR, ↑SV, ↑CO, ↑pp b/c unmasked β2 = EPINEPHRINE
→ ↑BP, ↑vasoconstrict & in shock this would *Clinically, if titrating ↑doses of
↓perfusion→ more hypoxia, infarction, necrosis epi into emergency patient in
→↓HR via reflex→ ↓perfusion even more shock, and pt goes into
hypertension, giving α1 blocker
can be lifesaving
Norepinephrine (α1, β1) Shock –powerful vasoconstrictor
-Less pulmonary action than w/ epi -Not good enough for
NE can NEVER drop BP (no β2 activty) bronchodilation
β AGONIST These will cause a decrease in blood pressure (β2) and an increase in
heart rate (β1). Pulse pressure also increases.
nonselective Isoproterenol β2 > β1 >>>a -Tx bronchospasms (bronchodilat) -Flushing
(vasodilat) (β2)
-Tx heart block & -↑HR→ arrhythmias (β1)
bradyarrhythmias (by ↑conduct)
Decreases peripheral resistance -Discontinued from due to
b/c no association w/ alpha deaths from CV involvement
β1 AGONIST Dobutamine B1 selective agonist -Tx acute CHF → ↑CO w/ little Use w/
caution in A-fib
(β1 > β2) change in HR
-Shock/resucitation – increases Dobutamine - Tx
force more than rate NORMOTENSIVE
*Chronic CHF would have
desensitization of those Dopamine – Tx
receptors, so cannot use dobutam HYPOTENSIVE
These will cause a decrease in blood pressure (β2) and a reflexive increase in
heart rate (causing palpitations). These
are not anti-inflammatory, so you would need to address the inflammatory effects if
you were treating asthma. Common

complaints of those using β2 agonists are anxiety & insomnia (think that β2 is part
of fight/fright, so CNS stimulating).
Short acting (4hrs)
Also, β2 prepares muscles for fight/flight (↑glycogenolysis, ↑perfusion), so may
see muscle tremors. Glucose levels
would also increase because liver gluconeogenesis and glycogenolysis are
stimulated. So don’t give to diabetics.
Metaproterenol -Little effect on heart -Acute Bronchodilator – asthma β2-Muscle
Terbutaline -Resistant to COMT -Relaxes uterus to prevent restlessness, ↑death rate
methylation/degradation childbirth asthmatics
β1- tachycardia, arrhythmia,

pulmonary edema in
Long acting (>12hr)
pregnancy, high dose
continuous use →hypokalemia
Terbutaline -More selective for β2 than SAME
Albuterol metaproterenol -Prevent premature labor (give IV
Salmeterol -Slow PK, onset in 30-45min -Only used for prophylaxis, may
↓nighttime attacks
Same -Primarily against premature labor -Hyperglycemia in mother &
reactive hypoglycemia in
-Risky – CV effects
Blocking β β2 may precipitate (not cause) bronchospasms and vasospastic diseases.
Also, since β2 increases lipolysis,
β β
glycogenolysis, then with a blocker you may expect hyperlipidemia and fasting
hypoglycemia. β2 typically increase
insulin, so blocking insulin release would not cause fasting hypoglycemia (insulin
has little role between meals), but
rather it would cause HYPERglycemia after a meal, when insulin is required for
glucose uptake. So obviously, B-
blockers would always be bad to diabetics (epinephrine’s effects are good via β1
and β2 to help alert to hypoglycemia, &
if blocked they would not know they are hypoglycemic)
Propanolol Don’t give B-blockers: MAJOR USE: -CI in acute CHF b/c
1. Diabetics -Essential Hypertension, cannot give drug to ↑ ↑ ↑ ↑CO
2. CHF arrhythmia, -Rebound tachycardia if
3. Asthmatics -Migraines – blocks catechlamine suddenly removed
induced vasodilation in brain CNS depressive!!!!
-Anxiety CI: ASTHMA
-Hypethyroidism – decrese -Exercise intolerance – can’t
sympathetic stimulation & blocks increase CO
periphera conversin of T4 to T3 -Decreased HR
-Angina pectoris – reduction of -Exacerbate CHF
O2 requirement of heart -Conduction slowing
-MI-reinfarct protection -Incease TAGS (LDL)
-Glaucoma -Sexual dysfxn
-Delays response to
Naldol Longer acting pure
-No CNS involvement
Timolol Glaucoma – reduced ciliary -Watch for systemic effects
epithelial humour production -Sedating
Pindolol Partial agonist (have No effect on blood lipids
intrinsic symp activity) (due to ISA)
Sotalol K+ channel blocker & B- -Antiarrhythmic (class III)
In the heart, β1 block would case a decrease in CO, SV, and HR. In the kidney, β1
block would allow α1 predominance,
leading to a suppressed rennin release. In general, a drop in blood pressure would
cause a reflex tachycardia (β1) and in
a few days an increase in rennin (β1). Both of these effects are blocked. β1
blocker also decreases aqueous humor
production. Blockers A → M are β1 selective, N→Z are nonselective
Anti hypertension/ sympathetic Atenolol does not cause
cardiac overstimulation sedation (too water soluble
-Pt. on antidepressants w/ HTN, to cross BBB)
atenolol good b/c no sedation
Partial agonist (have
Acebutolol No effect on blood lipids
intrinsic symp activity) (due to ISA)
-Very short t1/2 -Use in ill pt.s where risk of
hypotension or heart failure is
-If they start to die, fine…. just
stop giving the med
Metaprolol Used in pregnancy
β1/β2 BLOCKER β1/β2 BLOCKER Hypertension – peripheral Orthostatic hypotension
nonselective & Carvediolol nonselective & vasodilator. Decrease BP w/o Dizziness
α1 Blocker α1 Blocker altering TAG or glucose
-Antihypertensive w/o reflex
DA Dopamine Precursor ofr NE Tx of shock –↑CO (β1 on heart), -Same SE as
DA > β1 > α1 enhances perfusion to renal (D1), -DA metabolized (MOA or
splanchnic & coronary arteries COMT)→ HVA→ Nausea,
*DA = NE w/out the OH -But at ↑↑DA→ ↑TPR (bad)→ hypertension, arrhythmia
group aggravating the ischemic/necrosis
potential and possible reflex ↓HR
*Think about DA w/ α1 blocker!
Phenylephrine Tx of mydriasis & hypotension
α1 > α2
Methoxamine -Nasal decongestant
-Slow metabolism w/ little
Metaraminol -Eye drops – ↓ redness via
CNS penetratin
-Likely to be used topically
-End paroxysmal atrial
to cuase vasoconstriction
tachycardia (via vagal reflex)
Midorine α1 agonist Tx of postural hypotension
Prodrug→ desglymidodrine
In gerneral, antagonists have zero efficacy. so blocking α does not CAUSE
vasodilation. Blocking α prevents
vasoconstriction. Lowering blood pressure can cause reflex tachycardias (via β1),
but you can block with B-blockers.
Phenoxybenzamine -IRREVERSIBLY blocks α1 Decrease BP Only mechanism to overcome
& α2 (slightly α1 selective) -Tx for pheochromocytoma- is by making new adreno-
induced hypertension. recptors, which takes approx
-Also blocks H1, muscarinic -Dx of pheochromocytoma 24 hrs
& 5HT receptors, & inhibits -Frostbite -↓MPR →reflex tachycardia
NE reuptake -Clonidine w/drawal -Reflex ↑CO from blocked
-Raynaud’s phenomena α2→ β1 system overrides
-Preoperative tx to help control -Postural hypotension, nasal
hypertension & sweating stuffiness, nausea, vomiting
-Ejaculation problems
(shooting blanks)
Phentolamine Nonselective, REVERSIBLE -Same as Phenox but reversible -Can trigger
arrhythmias and
-Blocks α1 & α2 -Prevention of dermal necrosis anginal pain
-Blocks 5HT after the inadvertent
-Agonist at muscarinic, H1, extravasation ofNE CI: patients w/ ↓coronary
H2 receptors perfusion
α1 BLOCKER Prazosin Highly α1 selective Decreases BP w/ no reflex Orthostatic
hypotension (u’ll
tachycardia get suPRAZed when u stand
Antihypertensive up)
-Nasal congestion
Terazosin α1 selective Tx of BPH-associated urinary
-Relaxes SM of prostate
Tamsulosin α-1a selective antagonist Tx BPH ↓ Incidence of orthostatic
(GU sm musc) hypotension
The effect of an α2 agonist is never immediate because enzyme activity (tyrosine
hydroxylase) is changed by
decreased synthesis. So, these are not likely to have effects on the blood pressure
tracings seen on board exams. You
may see a transient hypertension initially.
-Decreases central NE -Tx of mild hypertension Sedation
-Minimize sx from w/d from -Orthostatic hypotension
opiates, cigarettes & BDZ’s w/d sx include hi BP, h/a,
-Rx’s heroin’s anti-adrenergic tremors, sweating,
effects tachycardia
-Decreases sympathetic activity
Methyldopa Prodrug
α2 BLOCKER Yohimbine Increased release of NE, -Erectile dysfunction Replaced by PDE
5 inhibitors
stimulating cardiac β1 & -Reverse Clonidine effects
vascular α1
Since these drugs are indirect, the de-inervated tissues will be nonresponsive.
Indirect acting agonists will displace
norepinephrine from mobile pool. Drug interactions include MOA-a inhibitors.
1. MOA-a→ breaks down catecholamines (ACh, NE, serotonin), but NOT dopamine
2. MOA-b→ breaks down dopamine
Tyramine -Released from cheese and red wine, normally oral bioavailability CI: MAO-
a inibitors
is limited by MOA-a metabolism of tyramine in the gut & liver.
With MOA-a inhibition, there is ↑bioavailability
Amphetamine -Promote NE release (DA, Used to be used for ADHD CI: MAO-a inibitors
Ritaline 5HT release also)
-CNS target
Ephedrine -Same as above -Included in many cold medicines CI: MAO-a inibitors
-CNS is side effect
REUPTAKE -Prevents cytosolic -Reduces reuptake of NE -Side effects limited by
INHIBITORS reuptake of NE into vesicles -Effective, cheap using low dose
Cocaine Block reuptake of NE -Used socially
-Amplifies any adrenergic
peripheral or central

There are two types of glaucoma. The angel refers to the irido-corneal angel, where
the aqueous humor drains
1. Open Angel glaucoma – degenerative changes in the canal of Schlemm to drain
causes slowly increasing pressure, pressing the back of the
eye. GOAL: decrease production of aqueous humor by blocking β β1
β β
2. Closed Angel glaucoma – the angel is narrowed. It could be because the iris is
obstructing the canal of Schlemm, or it could be from
genetics. A drug that causes constriction of the radial muscle may cause a
mechanical blockage of the canal (α1 agonist drugs). GOAL:
stretch the iris via miosis, or constrict the ciliary muscles to allow the iris to
bow backwards and allow drainage
Class Drug Mechanism Clincal Use Side Effects
Cholinomimetic Pilocarpine M agonist DOC for emergency closed
angel or open angel glaucoma
Echothiophate AChE inhibitor (organophosphate) Same, longer duration
β-Blocker Timolol Block actions of NE at ciliary
nonselective epithelium and ↓ aqueous humor
Carbonic anhydrase

Class Drug Mechanism Clinical Use Side Effects
Histamine H1 receptor:
(H1) BLOCKER → Gq coupled
→Found on the endothelium→ ↑Ca→ NO synthesis→ diffuses to smooth muscle→
→ Increases capillary permeability (associated w/ contraction of endothelial

→ Found on bronchioles→ bronchoconstriction

→ Increases activation of peripheral nociceptors (PAIN & pruritus)
→ Involved in inflammatory and allegic reactions
→ Via Gi coupling, will decrease AV nodal conduction
H2 receptor:
→Gs coupled (↑cAMP)
→In stomach, causes increased gastric acid secretion from parietal cells→ ulcers
→In the heart, causes increased SA nodal conduction
→Also found on mast cells & in the CNS
Diphenhydramine -Competetive blockers at -Allergic rhinitis/urticaria -Sedation,
Chlorpheniramine H1 receptors -Motion sickness antagonize serotonin
Hydroxyzine (scopolamine is better) -Dry mouth
Meclizine 1 Generation -Sedation (side effect) -Drug induced parkinson’s
Promethazine -Also antagonize ACh, -Sleep induction Potentiates effects of other
NE, Serotonin in CNS -Parkinson’s disease (b/c depressants (alcohol etc)
**Not used in antimuscarinic) Loss of appetite, nausea, distress,
bronchospasm** -Diphyd – also good local constipation or diarrhea
anesthetic that reverses
effect of phenothiazines
Fexofenadine -Competetive blockers at Allergic rhinitis (daytime PVC’s –
Larotidine H1 receptors benefits)→ “non sedative” Prolonged QT interval
Liver dysfxn
2 generation Substrates for P-glycoprotein
(*Taken off market)
-No sedation (do NOT transp.
cross BBB)
Histamine Cimetidine -Inhibit gastric acid -Gastric ulcer Mainly Cimetidine:
(H2) secretion -Zollinger-ellison syndrome -Inhibits P450**
BLOCKER -See GI drugs -GERD (PPI are better) Anti-androgenic→ Gynecomastia,
-Hiatal hernia low sperm count, galactorrhea
Ranitidine -Do NOT inhibit P450 - -Same -VERY safe drugs
Longer acting -Headache, dizzy, diarrhea,
Nizatidine Less side effects than cimetidine
Serotonin Methysergide -Congener of LSD which -Migraine – prophylactically -Toxic
effects limit use
antagonist antagonizes 5-HT Carcinoid sndrome -Leads to fatal pulmonary/cardiac
Nonselective receptor fibrosis if used chronically
HT2 BLOCKER HT2 (a-c):
• Gq coupled→ ↑IP3/DAG
• In CNS→ excitatory
• In PERIPHERY → vasodilation, GI contraction, bronchial contraction, uterine SM
contract, platelet aggregation
Cyproheptidine -Also blocks H1 -Post gastric dumping Sedating due to H1 Block
-Vasospastic disease- trials
-May be used as
-Allergic rhinitis, vasomotor
-Tx of smooth muscle
manifest of carcinoid synd.
Olanzapine Blocks HT-2a receptors in -Tx of schizophrenia
CNS (atypical antipsychotic)
Ketanserin -Highly selective Hypertension – trials
-Also blocks α1 receptors Vasospastic disease – trials
• Found in area postrema, peripheral sensory and enteric nerves
• Opens ion channels (only 5HT ion channel)
Ondansetron Adjunct in cancer
Granisetron chemotherapy:
Palonosetron -Anti-emetic
Dolasetron -Prevents nausea/vomiting
(esp from cisplatin)
HT4 HT4:
AGONIST • Coupled through Gs→ ↑cAMP
• Found in GI SM
Cisapride HT4 agonist in GI→ → → → Tx constipation in IBS Serious cardiac effects,
no longer
Tegaserod prokinetic GERD? used in USA
Metoclopramide HT4 agonist in GI Prokinetic (aka constipation)
HT1 HT1 (a-f):
AGONIST • Usually coupled through Gi→ ↓cAMP (sometimes Gs coupled)
• Found in CNS
Busipirone HT-1a partial agonist, Anxiolytic Non-addicting
DA2, HT2 blocker No cross tolerance w/ alcohol
HT1d agonist Migraine acute tx (b/c -Tingling/flushing @ injection site
(“triptan”) vasoconstriction effect) -Chest tightness, angina in CAD
Cost -CI patients at risk for coronary
-More effective than ergots heart disease b/c of the drug’s
(ergonovine, vasoconstriction
methylergonivine, ergotamine
–used in postpartum

SSRI Fluoxetime Inhibits reuptake of 5HT Depression Weight loss

(Prozac) → ↑5HT levels Insomnia
Flushing, sweating
GI disturbances
Ergot Ergotamine Partial agonist at α and Tx of acute migraine -GI distress
Alkaloids 5HT-2 receptors in the attacks -Prolonged vasoconstriction→
vasculature & maybe CNS ischemia & gangrene, abortion
near term
dihydroergotamine Bind α-adrenoceptors, Tx of acute migraine Avoid over use
(rebound migraine)
dopamine recpt, 5-HT attacks
Bromocriptine Tx of hyperprolactinemia
Cabergoline (Cabergoline more potent)
Ergonovine Same -Tx of postpartum
maleate IM -Uterine SM hemorrhage (usually use
contraction→can stimulate oxytocin)
labor -Diagnosis of variant angina
-Causes constriction of by inducing coronary
vascular smooth muscle by vasospasm
stimulating both adrenergic
and serotonergic receptors

Adenosine Adenosine Inhibits all excitable cells Paroxysmal Supraventricular

-Receptors through out body
-Esp. AV node tachycardia -Anginal pain – vasodilation
-Involved in autoregulation -DOC after failure of -Asystole (watch dose)
valsalva type maneuvers --Luckily short acting drug
-Diagnostic & curative -Contraindicated in pt. on
Adenosine stress test – for dipyridamol – potentiates affects
those unable to jump on the (theophylline is antidote)
Adenosine Methylxanthines -Intereferes w/ Ca++ CNS Stimulant Anxiety, agitation
Antagonists (Theophylline, binding by SR ↑ ↑ ↑ ↑HR & ↑CO Insomnia
caffeine, -Inhibits -CVS: catecholamine release,
theobromine) phosphodiesterase→ Arrhythmias
prevents ↑cAMP & cGMP
Theophylline -Bronchodilation via Asthma –(controversial) -Many PK drug
inhibition of PDE→ ↑cAMP -CVS: catecholamine release,
& also by antagonism of Arrhythmias
adenosine (a
-Induction of histone
deacetylases to suppress
inflammatory gene
-Promotes corticoid action
Adenosine Dipyramidole -Blocks adensine reuptake -Tx angina pectoris Do not give
adenosine while on
agonists -i.e. increases levels -Inhibit emboli from this drug b/c pt. may arrest
-Vasodilator (increases prosthetic valve
Prostaglandins Misoprostol PGE1 analog – ↑mucosal -GI protection from NSAID-
-Diarrhea, cramping abdominal
resistance to injury induce ulcers only in high risk pain
-Inhibits secretion of HCl patients b/c of high adverse -Stimulates uterine
in stomach & inhibit SE and need for multiple
gastric acid & gastrin dosing (give PPI instead) CI: pregnancy
secretion -Opens Ductus arteriosus
-Ripen cervix before
induction of labor
-Used w/ methotrexate (or
mifepristone) in terminating
pregnancy in 1 trimester
Alprostadil PGE1 -Keeps open ductus
Given IV arteriosus
-Male impotence (old use)
Dinoprostone PGE2→ causes uterine -Ripen cervix before
contraction induction of labor w/
Epoprostenol Analog of PGI2→ -Used in severe pulmonary
↓peripheral, pulmonary & hypertension
coronary resistance -Prevents platelet
aggregation in dialysis
Latanoprost PGF2α α (↓aqueous humor -Glaucoma
α α
Bimatoprost production)
Leukotriene Zileuton Inhibits 5-lipoxygenase Asthma Tx
inhibitor (inhibits leuktn snth) -Cold, NSAID, exercise
Zafirlukast Blocks receptor for LTD4 Same
Corticosteroid Inhalants: Inhibit phospholipase A2 ASTHMA Inhalants: Local-
*Inhalants: tx of asthma candidiasis, hoarseness;
Budesonide (mild-moderate), decrease Systemic-minor AE b/c little
Fluticasone hyperreactivity, improve bioavailability
epithelial function;
Systemic: *Oral: used w/ long acting β2
Prednisone agonist (and theophylline) in
severe persistent asthma
Cortisol Same -Tx of adrenal crises -Na retention, EC volume
Prednisone -Immunosuppres, antinflamm expansion, hypokalemia, alkalosis
-Withdraw drug slowly -Preterm labor to stimulate -Iatrogenic cushings
Betamethasone fetal lung maturation -Osteoporosis
Dexamethasone *Avoid in diabetics→ -↑GI acid & pepsin release
↑plasma glucose *Lack of cortisol associated -↑Glaucoma, ↑cataracts (via
(Listed in w/ hypotension b/c sorbitol)
increasing potency) *Avoid in CHF b/c Na permissive effects -↓Wound healing,
retention DRUG toxicities:
-Cardiac glycoside→hypokalemia
-Loop diuretics, thiazides→ ↑K
-NSAIDs – peptic ulcers, ↑ GI
-ACE-I - ↑risk of blood dyscrasias
-Chloroquine/mefloquine- risk of
myopathy, cardiomyopathy
-Anticholinergics - ↑intraoc Pres
Aldosterone Stimulates -Fludro= also has some anti-
mineralocorticoid R inflamm
Cortisol Metyrapone Blocks 11-OH, inhibit -Diagnose adrenal
Blocker synthesis of adrenal deficiencies
steroids (Cortisol) -Tx Cushings
Mast cell Cromolyn Inhibit early/late mast cell Topical aerosol for Cough & airway
stabilizers Nedocromil histamine release prophylaxis in asthma CI: acute episodes
(prevents degranulation)
Anti-IgE Omalizumab Inhibits IgE binding to Tx asthma
antibodies FceR
Mucolytic Acetylcysteine Disrupts S-S bonds in -Asthma (Facilitate -Mechanical
airway irritation, GI
mucoproteins expectoration) disturbances
CAUTION: in severe asthma or
gastric ulcer patients (mucous is
Progestin Mifepristone Blocks glucocorticoid & -Abortion (esp. when given w/
Uterine bleeding, malaise, GI, skin
Antagonist progestin recptrs PGE1 or PGF or misoprostol) rashes
-Give during mid-luteal -Postcoital contraception CI: ectopic preg; COPD,
phase when progesterone (w/in 72 hours) renal/hepatic dysfunction, adrenal
is normally high -Interferes w/ failure, steroid therapy
glucocorticoid for Cushing
-Tx of progesterone dep
Drug Mechanism Clinical Use Side Effects
Nonselective Aspirin Irreversible acetylation of -Analgesia– not visceral pain, -GI
COX Inhibitor COX prevents sensitization of pain -↑Risk of gout, competes w/
-Prevents formation of receptrs to mechanical & chemical excretion/reabs of uric

PGE, TXA2, Prostacyclin stimuli (blocks PGE2) -Reyes syndrome

-Deacetylation # salicylate -Reduce fever -Liver toxicity

which is anti-inflammatory -Reduce inflammation -Acute Interstitial Nephritis –

-Analgesic at low doses and -Anti-platelet coagulation (more type 1 HS rxn→ acute
anti-inflamm at ↑↑doses later) failure
(45mg/kg/day) -↑ Survival post-MI -Analgesic Nephropathy→ renal
PK: Elimination follows 1 -Some evidence that aspirin papillary necrosis aftr many
order kinetics at low doses ↓incidence of colon cancer -Bronchoconstriction (b/c
(half life=3.5 hr); 0 order COX → leukotrienes)
kinetics at ↑↑doses -Salicylism (at chronic↑↑ doses)–
Overdose stimulate resp centr→
reversible tinnitus, dizziness, h/a,
hyperventilation→ → → → Respiratory
-↓PGE2 (normally renal vasodilator
Ketoprofen* → →Metabolic acidosis
→ →
that maintains renal perfusion)
Ketorolac 1. Salicylates are a weak acids
can ↑Na and water retention
Meclofenamate 2. Impairs renal function→
-↓PGI2 (normal renal vasodil) may
Mefenamic acid accumult of sulfuric and
→ hyperkalemia, acute renal
Nabumetone phosphor acid
Naproxen 3. Uncoupled oxidat phosph→
↑ ↑ ↑ ↑BT (antiplatelet at low dose)
Oxaprozin ↑CO2 product→ ↑glycolysis
↑ ↑ ↑ ↑PT (anticoagulant at high dose)
Phenylbutazone →↑glycogenolysis, gluconeo,

Piroxicam* lipolysis, FA ox→ ketones

Overdose tx --- fluid, glucose,
Sulindac 4. Inhibited dehydrogenases in
HCO3-, K+, cooling, diuresis
Tenoxicam Krebs cycle→ lactic acidosis
(enhance renal excretion by
*Patient presents w/ mixed resp
alkaline urine – CAI), lavage,
Tolmetin alk & metab acid →but after
↑↑doses/prolonged exposure→

depress medulla→resp paralysis

*High risk of GI side effects

→resp acidosis→ mixed acidosis
resp & met (↓bicarb, ↓Pco )
Ibuprofen -Same potency as aspirin Inflammatory diseases GI disturbances
-hi analgesia & antipyretic Dysmenorrhea Tinnitus
properties Rashes
-Reversible inhibition of H/a
cyclo-oxygenase Interstitial nephritis
Naproxen Longer-acting derivative of
Indomethacin More potent cyclo- Serious hematologic rxns
Closes ductus arteriosis
oxygenase inhibitor
Only effective in Hodgkin’s fever
-No ↑ ↑ ↑ ↑bleeding time Aplastic anemia
Acute renal failure
Ankylosing spondylitis
N/V h/a
Gouty arthritis
Acute pancreatitis
Pre-term uterine-contraction
Phenylbutazone No longer used Bad SE (aplastic anemia)
More potent than aspirin <than aspirin
Tolmetin Long t ½
Sulindac Pro-drug (hepatic Gouty arthritis Agranulocytosis
activation) Pre-term labor
Decreases adenomas w/ FAP
Ankylosing spondylitis
Keterolac Injectible form Same as other NSAIDS
Post-op pain –visceral
Like opiates w/o CNS side
Allergic conjunctivitis
COX-2 -Fewer GI SE than nonselective
Celecoxib -Coxibs used primarily for
Selective inflammatory disorders COX inhibitors
Inhibitor -Renal toxicities similar to
nonselective COX inhib
-HS rxns (it is a sulfonamide)
-COX-1 not blocked → plateltes
make TXA2 →thrombotic state
Rofecoxib Withdrawn from US market Associated w/ thrombotic events
Etoricoxib 2 generation, highest Not approved in US
Meloxicam Preferentially inhibits COX-
2, but not as selective as
Non-NSAID Accetominophen NO anti-inflammatory Analgesia -Does not affect uric acid
NO antiplatlet Fever -Hepatotoxic @ ↑↑doses
-Weak COX-1,2 inibitor in Good for pt. on probenecid &
peripheral tissues uricosuric for gout b/c no X- ANTIDOTE: Acetylcystein is
-May inhibits COX-3 in CNS tolerence antidote (sometimes cimetidine)
Phenacetin Toxic prodrug is metabolized Still available in some countries
to acetaminophen

GI Drugs
Drug Mechanism Clinical Use Side Effects
H2 Receptor Cimetidine MOA: Blocks gastric mucosal -Tx of Zollinger-Ellison -Many
drug interactions
Antagonist histamine (H2) receptor→ syndrome -Decrease hepatic blood flow
↓gastric acid production (by -Tx GERD -Inhibit P450
90%) & decrease pepsin -Tx peptic ulcers & prevent -Anti-androgenic effects
formation recurrence (gynecomastia in males and
-Must take before eating -Prophylaxis in ICU against galactorrhea)
stress ulcers -Infertility, ↓libido
PK: usually given PO, in -Preoperative→ prevents -Skin rash
emergencies give IV aspiration pneumonia -Immunosuppression
-Tx of Tylenol O.D. -↑IV dose→ hallucination,
-Hiatal hernia delirium, restlessness,
dizziness, somnolence
-↓ ↓ ↓ ↓Absorption of weak acids
CI: pregnancy
Ranitidine More potent than cimetidine, same -No anti-androgen effects
Famotidine longer duration -No CNS effects
Nizatidine -No P450 inhibition
-↓Absorption of weak acids
Muscarinic Prienzepine -Selective M3 receptor -Adjuncts to histamine receptor -Same
as atropine
Antagonists blocker blocker tx -Dryness of mouth, blurred
-Atropine-like compound have -Tx peptic ulcer vision, tachycardia, urinary
only small ability to decrease -Not currently used retention, constipatin (higher
gastric acid doses)
-Little ability to cross CNS -More side effects than benefit
Dicyclomine -Inhibits vagal stimulation of -Tx of IBS same
acid secretion
PROTON Omeprazole -Prodrug→sulfenamide DOC→ Z-E Syndrome (or MEN) -Very safe at low
PUMP Lansoprazole MOA: Covalently DOC→ → → → peptic ulcers -H/a, dizzy, nausea
INHIBITOR Esomeprazole (irreversibly) binds H/K -Tx histamine resistant ulcers
-Abdominal Pain
S (PPI) ATPase on mucosal side of -Tx GERD -Long term use may be
Rabeprazole parietal cell→ suppresses H+ -H. pylori infection carcinogenic due to
hi gastrin
secretion (18hrs); they -Tx of hemorrhagic ulcers levels
support platelet aggregation -Tx systemic mastocytosis -Hyperplasia of oxyntic
maintain clot integrity (↑mast cells→ ↑histamine) cells
PK: effects in 1 hour -↓ ↓ ↓ ↓Absorption of weak acids
-Acid environment is required
H. pylori triple therapy (7-14
days): for absorption of Ketoconazole/
→ →PPI + Clarithromycin + itraconazole (impairs abs)
→ →
→ → → →PPI + Clarithromycin +
Metronidazole (give if penicillin
→PPI + Tetracycline +
Metronidazole + bismuth
*But continue PPI or H2-R block
for 4-6 weeks
MUCOSAL Misoprostol PGE1 receptor agonist→ -Prevent NSAID-induced ulcer -Diarrhea
PROTECTIVE inhibits basal & stimulated only in high risk patients b/c of -Uterine
AGENTS gastric acid secrtion (Gi→ high adverse SE and need for -Abdominal pain
↓cAMP) multiple dosing (give PPI
-Enhances mucosal barrier by instead) CI: pregnancy
increasing mucus & NaHCO3 -Abortiion w/ (MTX)
Sucralfate -At pH < 4 →extensive -GI ulcers & erosions No major side effects
polymyerization→sticky gel -Stimulate PGE production -Alterss bioavailability of
→adheres strongly to base -Promotes healing (increase drugs
of ulcer crater (physical cell#) -“Large Pill” compliance
barrier ( -Constipation
-Coats for >5 hrs CI: other anti-ulcer meds (b/c
this drug needs an acid pH)
Bismuth e.g. peptobismol -Said to have some antibacterial
-Not a prodrug action against H. pylori →
-Forms into white precipitate combined w/ metronidazole +
at pH <3.5→ coats ulcer tetracyclines
crater & acts as a diffusion
barrier to H+/pepsin
ANTACIDS The carbonanates will alkalinize (remember carbonate is an endogenous
buffer). The hydroxides work as a bze to
neutralize the acid. Antacids will increase oral absorption of weak bases (e.g.
quinidine), decrease oral absorption of
weak acid (e.g. warfarin), and decrease absorption of tetracyclines (via
Na-bicarbonate Immediate onset -ANTACIDS→ Symptomatic -Belching
-Short duration (not curative) relief of
-May increase gastric pH to dyspepsia associated w/ GERD, -Alkalosis
alkaline level which increases gastritis, peptic ulcers -Sodium retention
HCl secretion
Ca Carbonate Rapid onset -Same -Nephrolithiasis
-Think: carbonates alkalinize -Can be given as an adjuvant in -Hypercalcemia
osteoporosis -Alkalosis
-Gastric acid rebound
-Dense stools (→constipation)
-chleated by tetracylcines
Mg hydroxide Mg(OH)2 – milk of magnesia Same -Osmotic diarrhea
Relatively insoluble (poorly -Hypermagnesemia
abs) # slows removal from -Belching
stomach -↓Abs of digoxin & tetracyclins
-Gastric acid rebound
↑Mg→loss of DTR & respiratory
Least potent Used in combo w/ other antacids -Reacts w/ HCl→ AlCl →
Al Hydroxide 3
Think: hydroxides neutralize constipation
-Long term use→ hypophosphat
-NO Gastric acid rebound
PRO-EMETIC Ipecac Stimulate CTZ/gastric Tx of accidental poisonings
Apomorphine mucosal irritation
The sources of afferent input to the Chemotactic Trigger Zone (CTZ):
EMETIC 1. CTZ has D2 receptors, 5HT-3 receptors, neurokinin1 (NK1) receptors, and
opiod receptors →→stimuli = emesis
2. Vestibular system (CN VIII)→ motion sickness → emesis
3. Irritation of the pharynx, innervated by the vagus (CN X)→ gag reflex
(note: vagus = muscarinic R)
4. Vagal and spinal afferent nerves from the GI tract are rich in 5HT-3 receptors
→ irritation of GI mucosa from
chemo, radiation, or distention→ release of serotonin→vagus stimulation→emesis
5. CNS→ psychological → emesis (e.g. vomiting prior to chemo)
Ondansetron 5HT-3 receptor blocker - Tx nausea/vomiting Well tolerated & very
5HT-3 Recptor
Granisetron centrally at CTZ and -H/a, dizziness, constipation,
Dolasetron peripherally at GI Diarrhea

Palonosetron PK: PO, IV; Palon→newer

drug, more specific for -Small prolongation of QT

5HT-3 & longer ½ life (40 interval


-Others have short ½ life


-Hepatic metabolism

Dexamethasone Unknown mechanism for -Enhance efficacy of 5HT-3

Methylprednisolone antiemesis recptr blockers
Aprepitant NK1 receptor blocker (this -Used w/ 5HT-3 blocker for -Fatigue,
dizziness, diarrhea
NK1 Recptor
is the receptor to prevention of acut/delayed n/v -Metab by CPY3A4 & would
substance P) inhibit other drugs from metab

Dopamine receptors (D1) are also found on the lower esophageal shpincter, causing
it to contract better

D2 receptor Phenothiazines -Blocks DA receptors in Cisplatin induced N/V Sedation

Prochlorperazine chemoreceptor zone Poisons & visceral afferent pain Extrapyramidal

Promethazine -Blocks muscarinic (dystonias)


-Antihistamine→ sedation

Metoclopramide D2-receptor blocker -Anti-emetic -Fatigue

HT3-receptor blocker -GERD -Insomnia

HT4-receptor agonist -Uremia -Hyperprolactinemia, infertility

-ACh agonist w/in GI→ -Diabetic gastroperesis -Extrapyramidal symptoms

↑GI motility (dystonias, restlessness,


Diphenhydramine -Antihistamine (Blocks H1) Motion sickness Sedation

See antihistamines Allergic rhinits/urticaria Don’t give w/ other CNS

H1 blocker
Sedation depressants

Dimenhydrinate -Antihistamine (Blocks H1) Motion sickness (inner ear) Sedation

Meclizine -Blocks muscarinic receptrs Vestibular inflammation

(Remember 1 generation

H1 blockers)

Hyoscine -Antimuscarinic
M blocker

Nabilone Canabanoids (THC) -Tx n/v associated w/ chemo Hi abuse potential

Dronabinol Unknown mechanism -Tx wasting syndrome in AIDs & Drowsiness
-Works in higher centers in certain cancers Ataxia
brain -Tx glaucoma Inability to concentrate
Dronabinol→ not really used Anxiety
b/c ↓bioavailability Psychosis
Laughter (that horrible stuff….)
Lorazepam Benzodiazepines→reduce
Diazepam anticipatory vomiting
Cisapride -Release Ach in myenteric -Long QT syndrome
-Tx diabetic gastroparesis (predisposes to arrhythmias w/
-↑ ↑ ↑ ↑Muscle tone in the erythromycin or ketoconazole)
esophageal sphincter -Diarrhea
-↑ ↑ ↑ ↑Gastric empyting in
people w/ diabetic
Metoclopramide See above See above See above
The prokinetic is via
muscarinic activity
LAXATIVES Bran BULK FORMING AGENTS -Tx Constipation Virtually safe & effective
Agar -Pre-op or pre-radiological exam
Methylcellulose -Indigestible, hydrophilic, -Maintain insulin control -If not taken
w/ H2O, then may
Psyllium absorb water→ form bulky -↓Cholesterol cause obstruction/impaction
gel→distends colon, -↓Colon cancer risk -Dehydration, electrolyte
promotes peristalsis imbalance
-Cramping, constipation
-Nutritional def of calories,
Lactulose OSMOTIC LAXATIVE -Tx constipation vitamins, & minerals
Sorbitol Soluble, non-abs salts → -Tx systemic encephalopathy
Mg oxide hold water in stool by -Tx IBS-constipation (lac/sorb)
CI: bowel obstruction,
osmosis -Don’t use -Mg oxide for long
undiagnosed acute abdomen
-Lactulose also a substrate time in renal disease b/c hyper-
*Stimulants avoided in
for gut bacteria→ ↑↑lactic Mg
acid→ ↓pH of gut→ (NH → pregnancy
NH +, now not absorbed -Flatulence & gas & cramping w/
from gut) lactulose
Polyethylene Glycol OSMOTIC LAXATIVE -Preop GI cleaning
(PEG) Nonabs sugar w/ other -IBS-constipation
salts→no signif fluid or
electrolyte shifts NO bowel cramps
-Tx painful defecation or
-Soften stool, permitting constipation
water and lipids to
-Prevent/Tx fecal impaction in
Lubricates fecal material, young children and debilitated
retarding water absorption -Used for constipat of morphine
Caster oil→potent (seldom used) -May develop cathartic colon?
Bisacodyl -Induce bowel movement Fluid/electrolyte deficit
Phenolphthalein Ex-lax→ removed from market Allergic rxn

(Ex-Lax) (carcinogenic) Turns urine/feces pink

Aloe STIMULANT LAXATIVES Produce bowel movement in 6-12 Chronic use→ brown
Senna Occur naturally in plants hrs pigmentation of the colon
Cascara (melanosis coli)
-May turn urine red?
ANTI- Diphenoxylate OPIATE w/ little CNS -General diarrhea -Habit forming
DIARRHEAL action -AIDS associated diarrhea -Not too addicting b/c they are
-Produces bowel relaxation -Tx IBS-diarrhea relatively insoluble
& ↓peristalsis -Promotes ulcer formation
-Onset in 1hr -Antimusc→dry skin, dry mouth,
-Atropine is added to tachycardia, arrhythmias
discourage abuse. Atrope is
an antispasmodic & would CI: don’t give to kids
help in the constipating
Loperamide OPIATE, much lower abuse -Much more effective on GI
(Imodium) potential b/c ↓ability to -Tx IBS-diarrhea
cross CNS -Over the counter
Hyoscyamine Block ACh receptors to Diarrhea Only produce the atropine-like
Dicyclomine decrease parasympathetic side effects @ hi doses
tone & motility of GI tract
-Antispasmodic action
Bismuth- Coats intestinal epithelium H. pylori diarrhea
subsalicylate & ↓irritation
(Pepto Bismol)
Octreotide -Somatostatin derivative -Tx diarrhea associat w/
(Somatostn normally used in metastatic carcinoid &
Tx acromegally→inhib GH) VIPomas

Sulfasalazine Have anti-inflamm effect -Used in ulcerative colitis &

crohn’s disease
Monoclonal antibody to TNF -Tx IBS & RA
Tegaserod Selective 5HT-4 agonist Relieve Irritable Bowel
Syndrome – constipation
Alosetron Selective 5HT-3 blocker Relieve Irritable Bowel
Cilansetron Syndrome – diarrhea
SSRIs Serotonergic effect Would seem to help IBS
Kaolin Adsorbants→ absorb water
Pectin to form better stools

Acute Colchicine Binds to tubulin→ ↓microtubul Acute attach of gout
episodes polymerization, ↓LTB4, ↓ (rarely used anwymore,
give NSAIDS)
Prophylaxis Allopurinol Prodrug→ converted by Prevents the synthesis GI distress,
peripheral neuropathy
xanthine oxidase→ inhibit the -Rash, vasculitis
enzmze→ ↓purine metab→ -Stone formation
↓uric acid -Inhibits 6-mercaptopurine
Probenecid Inhibits PCT reabsorption of -Do urinanalysis, and if -Crystallization
if high excretion of
uric acid see high concentration of uric acid
uric acid crystals (do -Inhibits the secrtion of many acidic
NOT use probenecid , drugs (e.g. penicillins,
give allopurinol if patient cephalosporins)
is a high excretor)

“Diuretic should be interpreted as “loss of salt”, not lose of fluids. Many of
these drugs have sulfa allergies associated with
them. A quick screening is that many white wines have sulfites in them, so ask if
patient can drink white wines.
Class Drug Mechanisms Side Effects
Clincal Use
Carbonic Intracellular carbonic anhydrase generates H+ and HCO3-. The H+ leaves via
the NHE. The H+ combines with
anhydrase filtered HC03 to form H2C03, which is broken down by luminal membrane CA
into water and CO2 (both
inhibitor permeable).
Acetazolamide -Related to -Short term tx of -Bicarbonaturia
Dorzolamide dichlorphenamide glaucoma→ ↓aqueous hum -Hyperchloremic
(“-zolamide”) (dorzol topical, acetazol in -ACIDOSIS
MOA: emergency) -HYPOKALEMIA
1. ↓H+ formed in PCT by CA -Urinary alkalinisation→ → -Renal stones (b/c
→ →
(Carb Anhydrase blocked) excretion of weak acids ↑bicarb in urine, Ca++,
2. ↓Na+/H+ antiport (NHE) (e.g. ASA Overdose) Phophate precipitate)
3. ↑Na & bicarb in lumen -↓CSF production -Sulfa allergies
4. ↑Diuresis -Tx of metabolic alkalosis
-Acute mountain sickness CI – cirrhosis → NH4+
-↑K+ secretion distally in (↑altitude→ hypervent usually trapped in acidic
exchange for Na →resp alk, which is compens urine but reversed on
-↑Cl b/c ↑Na absorbed in by metab acidosis; also drug alkaliniztion → hepatic
DCT via NCCT prevents hypoxic vasoconstr encephalopathy (NH4+)
ACIDazolamide = ACIDosis in lung→edema)
Osmotic Mannitol -Excreted in glomerular -Acute diuresis -H/a, n/v
diuretic filtrate w/in 30 min -Maintain tubular flow/flush -Acute hypovolemia
-Mannitol is not debris -Dehydration,
reabsorbed→ Retains H2O -↓Intracranial/intraocular hypernatremia
in tubule pressure (mannitol 1 causes
*Work on entire tubule, but -Tx of Rhabdomyolysis ↑fluid retention in
considered to have greatest vascular b/for kidney→
action at PCT b/c PCT = ↑preload = bad)
most active CI: anuric states, CHF
Loop diuretic Furosemide -Duration 2-3 hours -Tx acute pulmonary -Ototoxic → esp.
Bumetanide -Given IV, instant onset edema aminoglycoside
Torsemide -Direct effects on blood -Fored diuresis esp. in acute -Hypokalemic
flow (renal/ pulmonary) renal failure -ALKALOSIS
-Tx anion overdose -HYPOCALCEMIA
1. Block NKCC of TAL -Tx hypercalcemia, -Hypomagnesemia
2. ↓Intracell K in TAL hyperkalemia -Hyperuricemia (loops =
3. ↓Back diffusion of K into -Tx of HTN weak acids, which would
lumen compete w/ uric acid for
4. Lose (+) lumen potential HTN, CHF – 2 line tx secrtion)
5. ↓Mg, Ca reabsporption (thiazides #1) -Nephritis
6. ↓Reabsorption of Na+
7. ↑ Diuresis -Patient w/ sulpha allergies Drug interactions: digoxin
use ethacrynic acid (NOT (from the hypo-Mg)
*Loops = potent vasodilators furosemide)
by ↑prostaglandins (prostag CI: GOUT,
blocked by NSAIDS)
-Pt w/ sulfa allergies
Ethacrynic acid NO sulfa allergy
Thiazide There is a basolateral Na/Ca pump (Na in, Ca out). So if the NCCT blocked,
then there is less Na inside the cell,
so more will be pumped in via the Na/Ca (thus, more Ca exported into blood). The
only way the Ca gets into the
tubule cell is via a Ca channel, which is PTH regulated. The effect of
hypercalcemia has never proven beneficial
for osteoporosis because the calcium entery can only occur if PTH is there (which
is only stimulated by low Ca).
There is NO change in blood/urine Ca or phosphate in osteoporosis anyways.
Hydrochlorothiazide -Excreted by organic acid -HTN Hypokalemic metabolic
secretory system -CHF alkalosis
1. Block NCCT in DCT -Tx of kidney stones (if Ca Hyperglycemia*
2.↑ Luminal Na & Cl stones) due to idiopathic Hyperlipidemia *
3.↑ Diuresis hypercalciuria→ Ca does not Hyperuricemia
*Hypocalcemia (+) PTH, (Gs build up in renal tubule HYPERCALCEMIA
coupled)→ phorylates lumen -DOC in nephrogenic ALKALOSIS
Ca+ channel to ↑Ca uptake diabetes insipidus→ loss of *From ↓insulin release
Na at DCL will cause (↑K channel open→
*Thiazides = potent Na/water at CD hyperpol of islets)
vasodilators via ATP dep-K+ -Avoid use in diabetics or
channel opening (remember *Note “thio” means sulfur in hyperlipidemias
minoxidil or dizoxide) the drug (think sulfa Drug interactions: digoxin
allergy) (↑toxicity from
electrolyte disturb)
Indapamide Same Same No hyperlipidemia
Similar to thiazides BUT unlike thiazides, also
effective at GFR < 30mL
K+ sparing K+ sparing diuretics will not enhance diuresis much because they act at
the very end of the system, after most
of Na reabsorption has already occurred. Aldosterone inserts ENaC into the luminal
membrane, causing passive
Na diffusion on luminal side. For each Na coming in, a K+ leaves the cell into the
Triamterene Triamterene→ hepatic -Adjunct to K+ wasting HYPERKALEMIA esp w/
Amiloride metab & renal excretion diuretics B-blockers, ACE-I
Amiloride→ only renal -ACIDOSIS
-Lithium induced DI
Triamterene – acute renal
*Block Na/K or Na/H failure (+indomethacin),
antiporters in principle cells kidney stones
of CD
Spironolactone Aldosterone receptor -Adjunct to K+ wasting -Same
antagonist diuretics -Antiandrogen: Female
-Only used in ↑ ↑ ↑ ↑aldosterone hirsuitism, male
states (remember blockers gynecomastia
have zero efficacy)→ so no
effect in Addison’s disease
(b/c no aldosterone)
Eplerenone Aldosterone receptor Same -Same
antagonist (Kidney specific) -NO antiandrogen
Natriuretic Nesirtide 1. Activates guanylyl -CHF
peptide cyclase→vascular SM B-type natriuretic peptide
relaxation in cardiac ventricles
2.↓tubular Na reabs & ↑GFR released b/c of distension

Drug type Drug Mechanism Clinical Use Side Effects
Mifeprestone -PGE-1 analog -Induction of labor upto 7wk.s Uterine bleeding,
-The morning after (72 hr) rash
(RU 486)

CI: ectopic, COPD,

renal/hepatic, adrenal
failure, steroid therapy
PGE2/PGF2a Cause uterine contractions Induce abortion/labor -GI-nausea, vomiting,
Topical – ripen cervix diarrhea

CI: asthma, COPD, CAVD

Oxytocin -Milk ejection -Lactation – nasal spray Rare
-Contraction in gravid uterus – -Induce/maintain labor
efficacy increases near term Antidote: fenoterol CI:
-Weak antidiuretic -Control hemorrhage -Fetal distress
(contraction) -Premature
-Test fetoplacental circulatory -Cephalopelvic
reserve misproportion
Engonovine -a-adrenergic, dopaminergic, DOC: induce p.p. contraction N/ abd pain
serotoninergic (hemorrhage control) H/a
-Lo dose – contract gravid uterus -Prophylaxis Dizziness
(promote labor/stop -Uterine atony (prolonged Tinnitus
hemorrhage) labor/big uterus) Hypertension
Ergotism – necrosis of
Tocolytics Tocolytics inhibit uterine contraction.
Ritodrine B2 agonist-high cAMP to relax -Prevention of premature labor -Maternal
smooth muscle of the uterus -Relaxes SM in uterus/resp. -h/a, vertigo
-3-6 hr. onset tract -Constipation
-Fetal tachycardia
Tocolytic indication: uterine -Hypoglycemia in fetus
bleeding, cramping (<20wk.), CI:
premature labor w/ dilation (36 -
Mg++ sulfate -Prolonged distribution in deep -Tx pre-eclampsia seizure
-Bradycardia, delayed AV
compartments -Hypomagnesemia – prevent fetal conduction
-Similar efficacy to B- hypotrophy -Hypotension
sympathomimetics -Adjunct tx of MI -Must monitor, BP, fetal
-Mg++ antagonizes Ca++ -Osmotic laxative HR, reflexes
Ca++ gluconate - antidote
Toxicity: ECG changes # resp.
depression # loss of corneal CI:
reflex -Renal failure,
myasthenia, AV block,
before delivery

Any drug that lowers blood pressure will cause a reflex tachycardia. Over a few
days, the kideys will retain fluids via rennin secretion, which
may lead to edema. These side effects must be addressed when trying to treat
hypertension. Also, any of the drugs affecting the
sympathetics will causes CNS depression and as well as many parasympathetic side
Drug type Drug Mechanism Clinical Use Side Effects
Diuretics Thiazides See diuretic section -1 line against -Hyper-GLUC
hypertension -Hypokalemia – add K+ sparing if this is
-CHF –shows the greatest a problem
effect to dec. ventricular
hypertrophy, morbidity, and
-GFR < 30mL use
Loop & K Sparing See diuretic section -K+- sparing is 2 line
-GFR < 30mL use loops
Presynaptic Reserpine Destroys vesicles→ ↓CO, -Not used clinically anymore
Denervation of sympathetics
blocking ↓TPR (b/c ↓NE in -60-80% # nasal congestion
periphery) (inhibit -Hypersecretion
VMAT?) -Bronchoconstriction
↑GI secretion, incontinence
-Mental depression, may promote
-Parkinsonism, ulcers

Guanethidine Accumulated into nerve Drug interactions: TCA or cocaine

ending by reuptake pump, (TCA block reuptake pump→ block

binds vesicles, preventing action of guanethedine)
release of NE from -Diarrhea, edema

Stimulation of α2 causes a decrease of sympathetics outflow. This means there is a

decrease TPR (↓symp on α1) and
also a decrease HR (less NE on β1). No reflex tachycardias.

Clonidine Central acting -2 line tx for HTN -Dry mouth

-↓CO -Tx withdrawl symptoms in -Sedation
-↓ Peripheral resistance alcohol/heroin/benzodiazepi -Orthostatic Hypotension
w/ maintanence of renal en -Bradycardia
blood flow -Alcoholic delirium -AV block
-Relaxation of veins -Postmenopausal syndrome -Would never see rebound tachycardia
-Refractory diarrhea b/c ↓sympath outflow
-w/drawal symptoms: Rebound
(High BP, headache, tremor, sweathing,
Methyldopa -Similar to clonidine -Tx of HTN in pregnancy -Coombs test (+) receptors
-Centrally acting b/c highly protein pound antigenic when bound to methyldopa
-Prodrug→methylNE (b/c similar to endogenous compnds)
-↓Perfusion pressure of kidney→
↑renin → edema, so give w/ diuretic
Drug interactions: TCA (block re-
uptake, ↑NE)
α1 BLOCKER Prazosin -Competitively bocks a1 -Mild HTN -1 -dose Phenomenon→ weakness
(t½ 3-4hr) receptors w/out a reflex -Low TPR syncope w/in 1hr. after 1 dose.
tachycardia -Low BP by relaxing arterial -Postural hypotension
Terazosin -No effect on A2 and venous smooth muscle -Dizziness, h/a
(t½ 12hr) -HTN -Reflex tachycardia
*Good effect on lipid -BPH -Tests for antinuclear factor (ANF)

Doxazosin profile: ↓LDL & ↑HDL may turn (+)

(t½ 22hr) -Urinary incontinence under strain
b/c relaxed sphincters
β-BLOCKER Propanolol -↑LDL, ↑TAGs, & ↓HDL -Do not use in asthma, CI of nonselective
BB: pregnancy,
Atenolol COPD, CHF, SA or AV node IDDM, (Blocks sympathetic response
Metoprolol abnormalities to hypoglycemia therefore pt could
Pindolol drop dead due to hypoglycemia with no
Esmolol symptoms)
*β-Blockers also suppres renin
VASODILATORS These drugs work by the Nitric Oxide (NO) pathway
(Direct acting) Hydralazine ↓TPR via arteriole -Use in moderate to severe -Edema
dilation HTN Reflex tachycardia
-Blacks respond well -Drug induced SLE-like syndrome
Nitroprusside ↓TPR via dilation of -Use in HTN emergencies -Cyanide toxicity
BOTH arterioles & (only use acutely, 12-24h) thiosulfate)
These drugs act by opening potassium channels, causing hyperpolarization of smooth
muscle and dilation.
-Opens K-channels→ -Tx of SEVERE HTN Hyperglycemia (↓insulin release)
arteriolar vasodilation -Topical minoxidil used to
-NO? Tx baldness
Diazoxide -Given IV HTN emergencies -Hyperglycemia (from ↓insulin)
-Opens K channels→
arteriolar vasodilation
Ca Channel Blockers CCBs block the L-type of Ca channel (found in Heart & blood
vessels). All CCBs vasodilate arterioles, but not all go into
the heart and decrease CO. All CCBs will be used for angina and hypertension
Verapamil Cause ↓ ↓ ↓ ↓CO & vasodilate -Antiarrhythmic due to -No reflex
Diltiazem arterioles ↓nodal conductivity -Constipation (Verapamil)
-Verapamil most potent
on heart.
“--dipines” Vasodilate (especially -Hypotension→ reflex tachycardia
coronary) → ↓TPR -Gingival hyperplasia (remember…
-very little effect on AV phenytoin & cyclosporin)
Fast onset/short Long acting, slow onset Long acting & ↑ vascular ↑ potency:
Verapamil Amlodipine selectivity: Isradipine
Diltiazem Felodipine Nisoldipine
Diuretics Thiazides See diuretic section -1 line for HTN -Hyper-GLUC
-CHF –shows the greatest -Hypokalemia – add K+ sparing if this is
effect to ↓ventricular a problem
hypertrophy, morbidity, and
-GFR < 30mL use
Loop & K Sparing See diuretic section -K+- sparing is 2 line
-GFR < 30mL use loops
Angiotensin-II (AT-II) has two receptors, AT-1 and AT-2. The AT-1 receptors are
found on blood vessels and are sitmulated through Gq
coupling, causing vasoconstriction. AT-1 receptors are also found the zona
glomerulosa of the adrenal cortex and their stimulation results in
aldosterone secretion. The vasoconstriction raises TPR and increases the blood
pressure back to normal. Angiotensin II causes EFFERENT
vasoconstriction at renal arterioles. Aldosterone causes the DCT or collecting duct
to retain Na and water. These drugs will not need the
coadministration of diuretics
ACE-I Captopril See CHF -Protective of diabetic -Dry cough (↑bradykinin)
-Blocks formation of AT- nephropathy -Hyperkalemia (due to ↓aldosterone)
II, -CHF -Angioedema
-Acute renal failure in renal art sten
ARB Losartan AT-1 receptor antagonist Same No cough
*NOT approved for CHF
Pulmonary Hypertension may result from left heart failure or may be a consequence
of fibrousing diseases of the lungs. Conversely, it may be
a consequence of shunts, or it may simply be idiopathic.
ET-A BLOCKER Bosentan Endothelin (ET-1) is a Tx of pulmonary HTN CI: pregnancy
powerful vasoconstrictor
through ET-A and ET-B
-Bosentan blocks ET-A
PGI analogs Epoprostenol Anolog of prostacyclin Tx of pulmonary HTN CI: pregnancy
(promotes aborption &
(PGI ), contraction of myometrium)
-Given via infusion pump
PDE-5 inhibitor Sildenafil Inhibit PDE-5→ ↑cGMP→ CI: nitrates
pulmon artery vasodilat

What if HTN and a comorbidity?

Angina Beta blocker, CCB
Diabetes ACE-I, ARB (avoid B-blocker + thiazide→ hyperglycemia)
Heart Failure ACE-I, ARB (or B-blocker)
Post-MI Beta blocker
BPH Alpha blocker
Dyslipidemia Alpha blockers, CCB, ACE-I, ARB (basically avoid B-blockers &

Angina is an ischemic heart disease. There are two basic categories: angina of
exertion (coronary atherosclerosis) and Prinzmetal angina
(vasospastic). Angina and heart attack only differ at the histological level. In
heart attack, the tissue has infracted and died. Effective
treatment of angina must address the development of atherosclerosis. Risk factors
for angina: hypertension, diabetes, hyperlipidemia, and
smoking. Vasospastic angina does not typically involve hyperlipidemias.
The strategy of treatment:
1. Increase oxygen delivery to the heart by dilation of the coronaies. This should
reduce vasospasms. (Nitrates and CCBs)
2. Decrease oxygen requirement of the heart by ↓TPR, ↓CO, or both (Nitrates, CCBs,
and Beta blockers)
Drug type Drug Mechanism Clinical Use Side Effects
B-blockers Propranolol -Decrease severity/freq of -Cardioprotective post-MI CI:
vasospastic angina
Atenolol exertional angina (keep on for 2-3 yr.s)
Metoprolol -Ineffective in unstable Remember other CI:
-(-) Inotropic effect Angina associated w/: -Astham/COPD
-(-) Chronotropic effect -Exertional -CHF
-Decreased sys BP w/ exercise -Diabetes
NET EFFECT: decrease heart
O2 demand
Ca Channel blockers Nifedipine Binds serum proteins -DOC for vasospastic angina
(dihydropyridine) -Hepatic metabolism, renal (Nifedipine) -Dizzy, h/a, flush,
secretion dyasthesia, peripheral
Verapamil -Blocks L-type Ca++ receptors – All CCBs can be used for edema,
constipation, reflex
Diltiazem cardiopressant & vasodilation angina, only nifed for vasosp tachy
-Decrease afterload
-↑ risk of MI in HTN patient Verapamil, diltiazem –
bradycardia, slow SA & AV
Nitrates In an endothelial cell, there is Nitric Oxide synthase, which is turned on
by phosphorylating reactions when bradykinin,
serotonin, and ACh bind. Nitric Oxide synthase will produce NO, which will diffuse
into the vascular smooth muscle.
Nitric Oxide will stimulate the production of cGMP leading to dephosphorylation of
the myosin light chain (i.e.
relaxation). Nitroglycerin (R-O-N=O) require cellular cysteine to be metabolized
to a nitrosothiol, which will donote
NO. Note: people with angina may have atherosclerosis and diabetes, both of which
may decrease penile function. A
side effect of nitrates also causes some dysfunction, BUT sildenafil is
*Review the mechanism of smooth muscle contraction and relaxation and drugs
affecting them (Kaplan 2008 p.109).
VERY complicated
Nitroglycerin -Relax coronary arteries -Tx of acute angina -Flush, headache
-Venodilate → ↓preload of -Orthostatic hypotension
heart→ less contractility needed -↑Doses→ arterial vasodil
→ less work done by heart →reflex tachy & edema

*(Some arteriolar dilation at -Methemoglobinemia

↑↑doses) -Tachphylaxis (repeated
-Decreased myocardial demand use→ uses sulfhydryl groups)
PK: Buccal, IV, transdermal, -Dizziness, weakness,
sublingual cerebral ischemia
-Decrease preload
CI: Sildenafil
(cardiovascular toxicity)
Isosorbide PK: only PO, extended release Chronic management of
angina (preventive)
(& mononitrate)
Amyl Nitrites Extremely volatile at room temp No longer used for angina
-Tx of CN- poisoning Abuse


DIURETICS Tx CHF→↓associated backward
failure & pulmonary edema
Spirinolactone ↑Improves survival ↓Remodeling in CHF
ANF analog Nesiritide Recombinant ANF (recombinant human Tx acutely decompensated
B-type natriuretic peptide (rh BNP)→
↑ ↑ ↑ ↑cGMP→ → → → vasodilation
ACE-inhibitors Captopril -Renal elmination -1 line drug—Hypertension -Hypotension
-Angiotensin II Antagonist -CHF – decrease sudden death, -Dry cough/bronchospasm
-Decreased vasoconstriction, NE, progression, morbidity, (bradykinin)
aldosterone -MI – if started in preinfarct -Angioedema
↑ Bradykinin → vasodilation period -Hyperkalemia
-No, Reflex tachy, no change in CO, No -Progressive renal disease -Proteinuria
Na/H2O retention -Dysgeusia (taste)
↓ sympathetic tone -Less efficacious in Black -Hypercalcemia
Vasodilates venous blood vessels to Patients. CI – renal artery stenosis, renal
decreased pre-load and aterioles to failure, pregnancy fetal
lower TPR. Decreased Na/fluid -1 DOC-first line of choice in hypoperfusino→
retention the Rx of CHF w/ diuretics hx of angioedema (COPD)
Toxicity – hypotension w/o
Interactions: NSAID (bradykinin
pthway), K+ spare/waste diuretic,
↑digoxin, lithium levels
Enalapril -Enalapril is prodrug (hepatic -More potent than captopril,
(enalaprilat) conversion) slower onset, longer action
Fosinopril -Enalaprilat – IV for HPT emergency
Moexipril -Fosinopril, moexipril – only hepatic
INOTROPES Diuretics are often on board in a patient with CHF. All diuretics will
distrurb electrolytes. All diuretics (except K+ sparing) will
decrease K+, which increases digoxin toxicity. Loop diuretics can cause
hypomagnesemia. Thiazides may cause hyper-Ca. Low Mg and
high Ca cause increased contractility, which may precipitate arrhythmias if on
-CHF -Arrhythmia (any type)
Digitalis Inhibits cardiac Na/K ATPase→
(Digoxin) ↑intracell Na+, ↓Na/Ca exchange→ -Tx arrythmias: supraventricul -GI
distress: anorexia, vomiting,
↑intracell Ca→↑Ca release from SR→ tachycardia (↓ AV conduction) diarrhea (abs of
nutrients follows
↑contraction force *Do NOT use in Wolf Parkinson Na+ gradient, which is now

White syndrome -Neurologic- seizures (also due to

Indirect effect: Na+ block), “digitalis delirium”

-Inhibits neuronal Na/K ATPase→ Non-indicated (headache, fatigue, neuralgia,

results in ↑vagal and ↑sympath -Myocarditis, cor pulmonale hallucinations, and
mental sx)
stimulation -Uncontrolled HTN -Visual disturbances → halo’s,
-Decrease AV conduction (prolong -Bradyarrhythmias particularly everything yellow

ERP) -Gynecomastia – rare

Tx of Digoxin toxicity:

*Long half life→ need loading dose -↓ or withdraw drug Precipitating factors for

-Monitor dig & K+ levels, EKG -Hypokalemia

ECG -Correct electrolyte -Hypo Mg++, or hyper Ca++
Atria- P changes -Arrhythmias→ lidocaine -Quinidine & verapamil displace

AV – PR prolonged (heart is more depol than digoxin from binding sites

Ventricles – short QT, depressed ST, normal, & lidocain binds depol),
-Sympathomimetics may

T ↑contractility→ arrythmias

-Mg++, K+(take to normal hi), -Resp. disease – increase digoxin

↓ Morbidity but no effect on mortality -Temporary pacemaker response
-Digitalis Ab ->65, skinny, fever
-Acid base imbalance

Amrinone (AKA Phosphodiesterase inhibitors→ → → →↑cAMP -Like coffee it relaxes

vascular Milrinone has actually shown to

inamrinone) which ↑Ca current→ ↑contractility… and bronchial smooth muscle have an

(Remember that NE on β1 causes -Never actually proved beneficial

Milrinone ↑cAMP)

Sympathomimetics→ →↑ cAMP→ PKA -Acute CHF→ b/c chronic CHF See autonomics
Dopamine → →

Dobutamine phosphorylates Ca-channels→↑Ca β recepters are desensitized -Use with

caution in atrial fib.
current into heart→ ↑ ↑ ↑ ↑contractility. -Shock
Also has some vasodilating effects -BP up with ↑perfusion to
ARB (AT-II Losartan Like ACE-I: decrease -Hypertension NO COUGH b/c there is no
Receptr Blckr) vasoconstriction, NE release, ↑ ↑ ↑ ↑levels of bradykinin
aldosterone secretion -It may be fetotoxic

Unlike ACE-I: no affect on

degradation of bradykinin
Antiarrhythmic Drugs
NOTE: these are some of the harder arrhythmias to understand:
• Atrial tachycardias are divided into those originating from the node and those
that do not. If it comes from the
node, use B-blocker or CCB to slow nodal conduction. If not from the node, use
something that slows AV nodal
conduction (e.g. adensine). Atrial tachycardias not from the SA node (but at other
sites in atria) can be caused by
CAD, COPD, increased catecholamines, alcohol and digoxin.
• Supraventricular tachycardias (PSVT) refer to those SVT that have a sudden almost
immediate onset. A person
experiencing PSVT may see their heart rate go from 90 to 180 beats per minute
instantaneously. Because sinus
tachycardias have a gradual (i.e. non-immediate) onset, they are excluded from the
PSVT category. PSVTs are usually
AV nodal reentrant tachycardias.
• AV nodal reentrant tachycardia (AVNRT) is also sometimes referred to as a
junctional reciprocating tachycardia. It
involves a reentry circuit forming just next to or within the AV node itself. The
circuit most often involves two tiny
pathways one faster than the other, within the AV node. Because the AV node is
immediately between the atria and
the ventricle the re-entry circuit often stimulates both, meaning that a
retrogradely conducted p-wave is buried
within or occurs just after the regular, narrow QRS complexes.
• Atrioventricular reentrant tachycardia also results from a reentry circuit,
although one physically much larger than
the AVNRT. One portion of the circuit is usually the AV node, and the other, an
abnormal accessory pathway from the
atria to the ventricle (e.g. Wolff-Parkinson-White syndrome with the Bundle of
Class Drug Mechanism Indications Adverse Effects

Ia Quinidine -Binds to open, activated *Tx of Atrial fib, need Toxicity
Na-channels to prevent Na prior digitalization -Cinchonism (blurred vision,
influx & prolong APD (digoxin slows AV nodal ringing in ears, headache,
(prolong phase 0) conduction counteracting altered color perception, nausea,
-Block K+ channel (prolong the antimuscarinic vomiting, diarrhea→→all referr
AP & ERP) effects of quinidine) to the drug’s autonomic effects)
-Antimuscarinic– (low doses) -↓Contractility
paradoxical ↑AV conduction -Supraventricular -Proarrhthmic: block M→ → → → symp
b/c ↑ sympathetic control arrhythmia control of heart→ → → → ↑ ↑ ↑ ↑HR
-α Blocker (high -DOC for Chronic
concentration)→ hypotens→ Ventricular Tachycardia ***Toxicity, wide QRS***
reflex tachycardia (arrhth) -Wide QRS (b/c anti-M & more
-Depress automaticity cells depolarized at a period of
*Quinidine = weak base, & (ectopic pacemakers) time)
antacids ↑abs→ ↑↑toxcity -Depress conduction & -Long QT & changed T
excitability (esp. -Prolong PR interval→→torsade
*ANY DRUG prolonging depolarized tissue) d’pointes
depolarization will be a risk
for torsade d’pointes (this -Antimalarial Drug interactions: hyperkalemia,
includes all anti-M drugs) quinidine displace digoxin from
tissue binding sites
Procainamide Similar to Quinidine Procainamide – 2 line Procainamide
Dysopyramide -Ischemic tissue is more acute MI-associated -Drug induced SLE
depolarized than normal vent. Arrhythmias -Agranulocytosis,
tissue & closer to threshold (lidocaine – 1 ) -Antimuscarinic: aggravate
-Prolongs the refractory glaucoma, urinary retention
period -Mental confusion/ psychosis
-Block active Na+ channel
-Less antimuscarinic Disopyramide
-α1 block? (Kaplan says no) -Negative inotropy,
-Acetylated # (NAPA) -Cardiac failure w/o existing
(blocks K+ channels) myocardial dysfxn
-Atropine-like systemic AE
Ib Lidocaine -Block inactive/refractory Suppression of arrhyth -Exacerbation of
Na+ channels & shorten assosociated w/ -SA stands still in pt. w/ MI
APD (↓ ↓phase 0) due to depolarization: -CNS toxicity @ high dose
↓ ↓
block “window” Na current -DOC Post-MI
-Inactive channels more -Open heart surgery Interactions
likely to be found in -Digoxin toxicity -Agents enterfering w/ hepatic
ischemic tissue (since partly -CNS toxicity perfusion or P450-
depolarized)→ drug -DOC for ventricular
preferentially goes to tachycardia & fibrillation Least cardiotoxic
ischemic tissue after cardio-conversion
-Not for long-term
EXTENSIVE 1 PASS prophylactic post MI
METABOLISM due to *Not useful in atrial
metabolism by amidases arrhythmias
(So only given IV)
Tocainamide Similar to lidocaine Same as lidocaine -Frequent @ therapeutic dose
Mexilitine Orally active (used in -Neurologic: N, tremor, blurred
chronic dosing) vision
-Allergic: rash, fever,
Ic Flecainide -Acts on ALL Na channels -Life threatening *MOST pro-arrhythmogenic
Propafenone conformations refractory ventricular (15% of patients die)
Moricizine -NO effect on APD arrhythmias ONLY -Visual disturbances
-NO ANS effects -Use only orally for atrial -Increases mortality post-MI tx
-Slow dissociation from Na+ arrhythmias of PVC
channel in recovery -Pretreat w/AVN blocker
II β β β β-BLOCKERS: They are used to control supraventricular tachychardias like
atrial fib and atrial flutter. Their
mode of action is on NODAL tisussue.

Propranolol Decrease Phase 4 -Recovery from MI → Hypotension

Acebutol (β1) -Depresses SA-node freq → prevent sudden death Aggravation of CHF
Esmolol (β1) sinus bradycardia (post -MI prophylaxis) Asystole
Satolol (β1,β2) -↓ Automaticity of purkinje Propanolol= very lipid soluble →
-↓ Conduction AV-node -Control SVT & A-fib CNS depression
-Negative ionotrope→ the (b/c class II affects
reason β-blockers are good nodal tissue, the atrial CI – diabetes, vasospastic
prophylaxis post-MI, beats must go thru AV) disorders (e.g asthma,
prevent heart working too -Exercise/stress induced prinzmetal angina)
hard vent. Arrhythmias
-Suppress ectopic -Ischemic HD/ angina
ventricular depolarization -In ICU give esmolol
-Hemodynamic activity (short t ½ IV)
Metoprolol DOC in pregnancy
III K+ BLOCKERS: Used only with life threatening ventricular arrhythmias (i.e. wide
QRS) that don’t respond well
to class I, but all of this is debatable and changes often.

Amiodarone -Blocks K+ channels→ ↑APD -CHF w/ <30% EF -Pulmonary Fibrosis up to 45%

-Low dose for atrial fib of pts
-Blocks Na-channels (Ia) -Supraventricular -Photosensitivity
Arrhythmia -“Grey man syndrome”
-Mostly effects -IV for acute ventricular -Blue skin discolor (“smurf
purkinje/ventricular (long tachycardia skin”) b/c of iodine rxn w/
plateau) -Anti-anginal starches in skin
t½ = 30-120 days→ steady -Corneal depositis
state @ 8-10mo (use *Amiodarone is a class Ia, -Hepatotoxicity
loading doses) II, III, IV, so no -Hyperthyroidism
matter what arrhythmia ↑ ↑QT (but Torsade rare)
↑ ↑
“iod” in amiodarone means it it should have an effect
has iodine Drug interaction – digoxin,
warfarin, quinidine, theophylline
Ibutilide Used for emergencies ↑ ↑QT (↑risk of Torsade)
↑ ↑
CI: if ↓K or ↑QT
Sotalol Prolongs repol (phase 3) Tx/prophylaxis severe -Postural Hypotension
Nonselective β1-blocker ventricular arrhythmias -Proarrhythmic
(class II) esp those not responding -Torsades des pointes
-Renal excretion to class Ib -CNS depression
(unchanged) -Atrial arrhythmias *Before starting sotolol, must
hospitalz for 72 hrs & make sure
patient not a fast responder
IV Ca+ CHANNEL BLOCKERS: The main clinical use will be that of supraventricular
tachycardias (like B-blockers).
Their mode of action is on NODAL tissue (the depolarization in nodal tissue is due
to Ca entry).
Verapamil -Blocks L-type Ca++ DOC in atrial -Well tolerated
Diltiazem channels fibrillation/flutter -Constipation
Bepridil -Lg effect on AV conduction -AV block (esp w/ added AV
due to ↓phase O of nodal -Re-entry SVT block of B-block & digoxin)
conduction (also some -SVT -Verapamil displaces digoxin
effect on phase 4) -Ischemic heart disease from tissue binding sites→more
& HTN dig toxicity
-Negative inotropic effect

-CI: depressed cardiac function.

Other These are not classified as antiarrhythmics, but they have a role in
Adenosine Adenosine receptors in -DOC for Tx of -Flushing
heart nodal tissue are Gi paroxysmal ventricular -Bronchoconstriction (Gq)→
coupled (↓cAMP)→↓SA/AV tachycardia (90% dyspnea
nodal conduction effective) → stops heart
-Enhance K+ conductance for a second -A-fib, V-fib
-Inhibits cAMP-mediated -Potent vasodilator
influx ## hyperpolarization
## -Emergency management -Adenosine is antagonized by
(esp. AV node) theophyline (so theophyline
-Degraded in seconds by would ↑ nodal conduction)
adenosine deaminase
Atropine Muscarinic antagonist Brady-arrhythmias to
↓vagal tone
Magnesium -Functional Ca++ antagonist Tx for torsades des
-K+ channel block
-Tx for digitalis induced
-prophylaxis for
arrhythmias in acute MI
Treatment of Torsades des pointes: Drugs causing Torsades:
• Correct hypokalemia • K+ channel blockers (class
• Correct hypomagnesemia IA & III)
• Discontinue drugs that prolong the QT interval • Antipsychotics
• Attempt to shorten APD with drugs (e.g. isoproterenol) or electrical pacing
• TCA’s

Things u shouldn’t do

Disease Contraindicated Reason

COPD, asthma B-blockers Induction of bronchospasm
ACE-I Induction of cough, use AT1
Bradycardia Clonidine Aggravation, risk of Adams-Stokes
B-blocker syndrome
Diabetes Thiazides Reduced glucose tolerance
B-blockers Blunt sx of hypoglycemia
Gout Thiazides Reduced excrfetion of uric acid
CAD Hydralazine Provocation of angina (reflex
Prazosin tachycardia)
Peripheral artery occlusive disease B-blockers Aggravation/manifestation
CHF Ca++ antagonist Negative inotrope
Renal failure Amiloride, Triamterene May cause hyperkalemia
ACE-I Plasma concentration up, side effects

Sx/problem Approach
Fatigue Rest, + intotrope
Edema Salt restriction
Digitalis (+ inotropre)
Dyspnea Diuretic (thiazide, loop)
Congestion Nitrovasodilator
Poor cardiac + Inotrope, digitalis
↑ preload/afterload ACE-I
Cardiac tissue ACE-I
remodeling Ang-block
Irreversible heart Transplant
Cell wall damage/syntheisis Penicillin
inhibited Cephalosporins
Cytoplasmic membrane damage Polymyxins
or sythesis inhibited Polyene antibiotics
Inhibit synthesis/metabolism Quinolones (DNA Gyrase)
of nucleic acids Rifmapin
Inhibit protein synthesis 30S
Aminoglycosides (e.g. Neomycin)

Macrolides (e.g. Chloramphenicol, Erythromycin)
Modify energy metabolism Sulfonamide
Nucleic acid analogs Zidovudine

General principles:
• For seriously ill patients, use bactericidal drugs because their immune system
cannot clear the organism
• For drugs that act by concentration dependent killing (aminoglycosides,
fluoroquinolones, and carbapenems), once daily dosing can achieve
the high levels.
• For drugs that act by time dependent killing (B-lactams, glycopeptides,
macrolides, clindamycin, and linezolid), treatment should be via
continuous infusion or multiple daily dosing.
• Note: bacteriostatic vs. bacteriocidal is a little outdated, but listed anyways.
Many bacteriostatic become bacteriocidal at higher doses
Class Drug Mechanism Clincal Use Side Effects
SULFONAMIDES Sulfonamides were the 1 drugs used to cure or prevent systemic
infections, but since the penicillins they have become less
useful. Sulfonamides are derivates of PABA. They are bacteriostatic. Sulfonamides
are acetylated by the liver (actually
become less water soluble) and then excreted by the kidneys. Drink a lot of water
to avoid renal stones. Sulfonamdies inhibit
RAPIDLY dihydropteroate synthase. Generally, sulphonamides are DOC for PCP
infections of AIDS. Sulfonamides inhibit gram (+) and (-),
ABSORBED: nocardia, chlamydia, and some protozoa. Ricketsiae are NOT inhibited but
are actually stiulated in their growth.

PABA→(Dihydropteroate synthase)→ DIHYDROFOLIC ACID →(dihydrofolate reductase)→ THF

→ → → → purines/DNA

Dont give sulphonamides to neonates (no conjugating rxns) & the drugs will displace
bilirubin from albumin. Sulphonamides are

used for E. coli and are soluble enough to cross BBB → but don’t give for neonatal
E. coli meningitis.

Sulfisoxazole -Short acting (4-8h), rapidly -Nocardia (immunocompromised)

Short acting
absorbed Pneumonia/brain abcess (Stevens-johnson)

-Trachoma -Crystalluria, hematuria

-Lympphogranuloma venereum -Hemolytic anemia (in G6PD

-Tx of UTI (sulfisoxazole +
phenazopyridein) -Kernicterus
-1 line Tx against Toxoplasma -High protein binding→

(sulfisoxazole + pyrimethamine) displacement of drugs from

binding sites (warfarin,


-Drug interaction (292


Sulfadiazine -Short acting, rapidly Above

absorbed - Tx of toxoplasma (sulfadiazine +

Sulfamethoxoazole -Intermediate acting (12- Above + resp. infection in combo

(SMX) 18h) -Neisseria

-Gram (–)
SMX + trimethroprim = BACTRIM’s spectrum:
Bactrim for UTI/resp. tract -DOC & prophylaxis of

Pneumocystis carini

-DOC for nocardia


- Complicated UTI
-TB (part of tx)
Sulfadoxine -Long acting (7-9 days) Prophylaxis for malaria
-Used w/ pyrimethamine

Sulfasalazine -In the GI →broken down to -Tx IBD & RA -Reversible infertility
5-aminosalicylate (anti- Derivatives of 5-ASA: -Crystalluria (esp at acid pH)

inflam) & sulfapyridine 1. Pentasa – controlled relase

formulation delivering to entire

POORLY absorbed GI tract including small bowel

2. Asacol – delayed delivery to

terminal ileum & beyond

3. Olsalazine – new prodrug, coupled

5-ASA split by intestinal bacteria

4. Rowasa – Rectal enema and

suppositories, used for

Sulfacetamide -Opthalmic infxns (e.g. trachoma)

Mafenide Carbonic anhydrase -Burns (topical) use for short -Irritation

Inhibitor period & only localized area -Pain
-Acidosis (w/ extensive use)
Silver sulfadiazine -Prevents infection of burnt -Well tolerated (minimal SE)
surfaces and chronic ulcers -Rash, itch, allergy
Trimethoprim Inhibits DHF reductase in Used w/ sulfamethoxazole BMS &
bacteria -Megaloblastic anemia
TMP-SMX oral -PCP, most community acquired
MRSA, toxoplasma
Pyrimethamine Inhibits DHF reductase in BMS & enterocolitis

FLUORO- Inhibit replication by inhibiting topoisomerase II & IV (block A subunit of
DNA gyrase). DNA gyrase normally introduces
QUINOLONES negative supercoiles. Quinolones enter cells easily via porins and are
used to treat INTRACELLULAR pathogens (e.g. legionella
or mycoplasma). Good against S.pneumo + atypicals so, great for pneumonia
-Fe and Ca limit absorption due -UTI -Articular damage (children)
to chelation –Gram (–)’s -Tendonitis/tendon rupture
-STD’s/PID -Photosensitivity
-Cutaneous, soft tissue (except -GI irritation
nalidixic acid) & bone infections -Rash
(osteomyelitis) -Convlsions, N/V
-Respiratory –) except nalidixic -All quiniolones ↑QT interval
acid) -May cause increase
-Bacterial enteritis intracranial pressure in kids
-Diarrhea -↑ [plasma] of theophylline
CI: pregnancy, kids
Nalixic acid Narrow spectrum UTI
Ciprofloxacin -Pseudomonas assoc. w/ cystic
Ofloxacin fibrosis
-Enterobacteriacea & other

gram (–) bacilli

-Synergistic w/ penicillins
-Acute diarrrheal enteric
pathogens (grm – rods)
-Gonorrhea (2 line after
-UTI’s comp/uncomp
Lomefloxacin -More gram (+)
-Some strains of MRSA &
-Fewer gram (-)
Moxifloxacin -Broadest spectrum *Elminated via biliary -Moxiflox ↑↑risk of long QT

OTHERS Methenamine -Liberates formaldehyde w/ UTI -Gastritis

mandelate urinary pH <5.5 -Chemical cystitis
(Methenamine + -No affect at alkaline pH -Hematuria
mandelic acid) -Metabolite caustic to bugs in -Painful/frequent micturition
urinary system. -DO NOT GIVE W/
SULFONAMIDES – insoluble
complex (crystaluria)
Nitrofurantoin -Bacteriostatic UTI’s – E. Coli -Interstitial pulmon fibrosis
-U/k mechanism (reactive -Hemolytic anemia G6PD
intermediates damage DNA) def.
-Turns urine brown -Peripheral neuritis
-Cholestatic jaundice
-GI irritation
Phenazopyridine -Used along w/ urinary -Urinary analgesic (takes care of
-Red/Orange urine
antiseptics burning piss) -Overdosage can produce
-No antibacterial effects methemaglobinemia
CELL WALL Penicillins are BACTERICIDAL drugs that inhibit cell wall synthesis. They
bind to penicillin binding proteins (PBP), which
INHIBITORS inhibits transpeptidase enzymes (responsible for the linking/cross
linking of peptidoglycans). This causes the activation of
autolytic enzymes. Penicillins are effective against actively growing microbes,
but ineffective against microbes that do not
have a cell wall (e.g. mycoplasma). Betalactamase enzymes are bacterial enzymes
that break the betalactam ring. Penicillins
cause TIME DEPENDENT killing, where drug is directly related to the time above
MIC. B-lactams are synergistic with

Generally, all penicillins are water soluble (exceptions: nafcillin, ampicillin),

thus renal excretion and need dose reduction in
renal disease. Tubular secretion can be blocked by probenecid so that high
concentrations can be achieved. Aquired
resistance to penicillins by plasmid transfer has become a serious problem. Most
of the penicillins are incompletely absorbed

after oral administration, and they reach the intestine in sufficient amounts to
affect the composition of the intestinal
flora. However, amoxicillin is almost completely absorbed. So, amoxicillin is NOT
appropriate therapy for the treatment of
(for example) shigella or salmonella derived enteritis. Also, penetration for
penicillins is generally good, although no
penetration into the CNS, unless inflammation has opened pores in the BBB.

Penicillin G -Acid labile, so give IV or IM Serious life threatening disease

Jarisch Herxheimer rxn
1 generation

-Poor CNS effects (unless -Strep pneumo (although

meningitis) ↑resistance)

-90% excreted by renal -Strep pyogenes

secretion, 10% by glomerular -Strep viridans
-Bacillus anthracis
-Corynebacterium diptheriae
-Syphillus (1’ and 2’)
-Neisseria gonorrhoeae
-Neisseria meningitides
-Clostridium perfringens
Penicillin V Given PO b/c acid stable Prophylaxis/mild infections -Not used for Tx
bacteremia b/c of its
↑minimum bactericidal


Procaine penicillin Slo abs. Lasts 12-24 hr.s Gonococcal infections

Abs. Very slow lasts 2 wk.s

Benzathine penicillin

Usually suppository form

2 generation
Cloxacillin Penicillinase resistant -Very narrow spectrum Interstitial nephritis

Oxacillin -Tx penicillinase producing Staph (Methicillin)

Nafcillin is elimited primarily via


Dicloxacillin the biliary route. “Naf for Staph”

3 generation
-Commonly given w/ Beta -Broad spectrum
Amoxicillin -Pt. w/ mono will develop

Ampicillin lactamase inhibitors (sulbactam (Similar spectrum to penicillin G, rash

when given Ampicillin

& clavulinic acid) but includes some gram -) -Inactivation a problem b/c

-Widely used in Tx of of plasmid mediated

Not water soluble respiratory diseases penicilliniase (typically E.coli

-Amoxicillin is completely and H.influenza)

absorbed from GI, so don’t tx GI


Active against:




-Salmonella typhi

DOC for Listeria (Ampicillin)

4 generation
Piperacillin -Tx Pseudomonas infxn Carbenicillin & Ticarcillin

Mezlocillin -Effective against many gram (-), causes platelet dysfxn

Carbenicillin but NOT Klebsiella

(constituative penicillinase)…add

Ticarcillin clavulanic acid

5 generation

Most cephalosporins are eliminated through the kidney (a few exceptions).

Cephalosporins have ADVERSE EFFECTS:
been divided into 4 generations. As the generations progress, there is: -Cross
sensitivity w/

• ↓ Gram (+) coverage penicillin in 10%

• ↑Gram (-) coverage -Cefamandole, cefotetan,

• ↑ CNS penetration cefoperazone cause
• ↑ Resistance to β-lactamase hypoprothrombinemia

(inhibit Vit K dep factors)

Cephalosporins are INEFFECTIVE against LAME: & disulfiram-like rxn (due

L= Listeria monocytogenes to MTT side chain (“azol”)

A= Atypicals (mycoplasma, legionella, C. pneumonia) -Nephrotoxicity (↑doses)

M= MRSA -Hemolytic anemia (rare)

E= Enterococci

PARENTERAL Water soluble→ Don’t cross -Good activity against gram (+)

Cefazolin into CSF -Modest activity against Gram (-)
1 generation

Cephapirin Active against PEcK:

Cephradine *Note: ”ph” in name = 1 Proteus

generation E. Coli

ORAL Klebsiella

Cephalexin Cefazolin – long half life, used Moraxella

Cefadroxil in surgery prophylaxis


PARENTERAL ↑gram (-), ↓gram (+) Active against HEN-PEcKS

Cefamandole* -H. influenza

Cefotetan None enter CSF EXCEPT: -Enterobacter aerogenes
2 generation
Cefonicid -Cefuroxime -Neisseria

Cefuroxime sodium -Cefaclor -Proteus mirabilis

Cefoxitin -E. coli

Ceforanide *Eliminated via biliary (for pts -Klebsiella

w/ renal problems) -Strep pneumo & pyogenes

ORAL -Tx B. fragilis (Cefoxitin, but has

Cefaclor little activity against H. influenza)

Cefuroxime axetil

PARENTERAL *Eliminated via biliary (for pts -Often used w/ a macrolide to cover
-All penetrate CNS

w/ renal problems), i.e. NOT atypicals in community aquired EXCEPT cefoperazone

Ceftriaxone* water soluble pneumonia (does not cross enough to

Ceftazidime -DOC for Gonorrhea (IM fight meningitis)

rd Cefotaxime CNS→ → → → cefotAXime, Ceftriaxone single dose)

3 generation
Ceftizoxime ceftriAXone -DOC in meningitis (Cefotaxime,

Moxalactam --Think of an AX to the head Ceftriaxone)

that chops meningitis. - Tx B. fragilis (Cetizoxime)

ORAL -Ceftazidime has pseudomonas
Cefiximne coverage

Cefepine -Extended spetrum -Tx gram (–) resistant bacilli to

-↑ Stability to beta-
3 generation cephalo’s

lactamases -Effective against pseudomonas

4 Generation
OTHER CELL WALL Cycloserine -Structural analog of D- -Tx TB resistant to
streptomycin, -Psychoses
SYNTHESIS alanine→ competitively isoniazid, PAS -Delirium
INHIBITORS inhibits conversion of L- -Atypical mycobacterium (MAC, -Confusion
alanine to D-form and linkage kansasii) often sensitive -H/a
(stage 1 of cell wall synth) -2 line in TB & CNS nocardia -Convulsions
(1 = sulfa) -Tremors
-Topical use only (ointment & drops) -Toxic for systemic use
Bacitracin Inhibitor of the isoprenyl
phosphate (stage 2 of cell wall -Tx furunculosis, impetigo, -Nephrotoxicity
synth) pyoderma, carbuncle, abscesses

-Tx suppurative/infected corneal


Vancomycin -Inhibits transglycosylase by -Tx MRSA (IV Vanco) -Must be given


interfering w/ D-alanyl-D- -Tx Enterococci -Red man syndrome (type-

alanine cell wall precursor -Backup for C. difficile 1 HS causing vasodilation

units (stage 3 of cell wall (pseudomembranous colitis)→ give from histamine→ i.e.

synth) Flagyl 1 extreme flushing)

-SERIOUS staph infections -Pain, chills, rash, fever

-Does NOT enter CNS -Hypotension

-Water soluble Resistance: -Nephrotoxic

1. Cytoplasmic protein that reduces

-Systemic effects only when the access of the drug to the FONT

given IV site of its action Flushing

-Oral form is not absorbed 2. VRE→ use D-alanyl-D-lactate

from GI as a precursor Nephrotoxic

→Resistant VRSA & VRE→ give Thrombophlebitis

Daptomycin &/or quinopristin/

dafopristin & linezolid

Teicoplanin -Inhibits bacterial cell wall -Similar spectrum to Vanco

synthesis -Tx MRSA & E. Fecalis

MOA: same as penicillins; Tx of gram (-) rods only (give IV) No cross-allergenicity
resistant to β-lactamases penicillins or cephalosporin

Carbapenems are resistant to β-lactamases, active against most gram (-) and (+)
including anaerobes (except MRSA and VRE).
They are NOT active against intracellular bacteria. They have a structure very
similar to the penicillins, but they have sulfur

in the structure. Carbapenems are thus far the only antibiotic capable of
inhibiting the L,D-Transpeptidases. They are
administered IV in the hospital for SEVERE infections.
Imipenem Cilastatin is not an antibiotic Seizures (50% of pts)
(+ Cilastatin) but a peptidase inhibitor that
protects imipenem from renal
MEMBRANE Polymyxin B -Competively replace Mg++ and
INHIBITORS Polymyxin E Ca++ from negatively charged
P groups on membrane lipids→
disrupts cell membrane


AMINOGLYCOSIDE Aminoglycosides are bactericidal, accumulated intracellularly via an
oxygen-dependent uptake (do not work against
anaerobics). Use aminoglycosides to kill GRAM NEGATIVE RODS.
• Concentration dependent killing & are bacteriocidal.
• Inhibit the formation of initiation complex (30S)
• Water-soluble (no surprise w/ glycoside, ie sugar), and they are excreted
unchanged in the urine→ thus,
↑↑[aminoglycoside] in renal disease
• Synergistic with β-lactams
• Poorly absorbed from the GI tract.
• Limited penetration into CSF
• Ototoxicity (esp when used w/ loop diuretics) & nephrotoxicity (esp when used w/
cephalosporins). Other side effects
include: 1) neuromuscular blockade from inhibiting the release of ACh (reverse w/
infusion of calcium gluconate or
neostigmine) and 2) contact dermatitis. Toxcity may be enhanced by loop diuretics
• There is some partial cross-resistance among them. The main mode of resistance
is the production of conjugating
Streptomycin -Not very effective against gram (-) -Optic nerve dysfunction
-Tx of TB (chronic use)
-Tx of Enterococcal infections
(Penicillin G + streptomycin)
-DOC for bubonic plague &
Neomycin Used topically (very toxic); Adjunct in hepatic encephalopathy -Contact
can be used orally sometimes to kill off gut bacteria→ ↓systemic -Found over the
counter in
→not absorbed to kill gut ammonia the triple antibiotic
flora ointment (e.g. Neosporin)

Amikacin -Resistant to aminoglycoside -Pseudomonas coverage

inactivating enzymes
-Resistant to aminoglycoside
Netilmicin -Reserved for organisms resistant
inactivating enzymes to other aminoglycosides
Tobramycin -Pseudomonas coverage
Gentamicin - NEVER use for respiratory
Daptomycin Distinct MOA, disrupts -Skin and soft tissue infections
multiple aspects of bacterial caused by Gram (+) infections
cell membrane function & -Staph aureus bacteraemia and
appears to bind to the right-sided S. aureus endocarditis.
membrane & cause rapid -Binds avidly to pulmonary
depolarization→ loss of surfactant, and therefore cannot be
membrane potential → used in the treatment of pneumonia.
inhibition of protein, DNA and -Good against mutidrug resistant
RNA synthesis, →bacterial staph (e.g. MRSA)
cell death
Spectinomycin Tx of resistant gonococcal infection
TETRACYLCINE -Broad spectrum (same spectrum as macrolide) VACUUM THe Bed Room
-Fanconi-like syndrome
-Bacteriostatic -Vibrio cholerae -GI irritaton
-30s at A site→ prevents elongation -Acne (propionibacter) -Pain & phlebitis
-Impaired abs w/ milk & food -Chlamydia -Hepatotoxic (esp in
-Chelation w/ cations -Ureaplasma Urealyticum pregnant)
-Concentrate in liver, spleen, skin, teeth -Mycoplasma (erythromycin also
-Gram + resistant DOC) -Superinfection
-Gonococci/meningococci respond -Tularemia -Hypersensitivity
-Resistance b/c of of pumping drug out of cell -H. pylori -Brown mottled teeth (Ca
-Binds Ca in body in teeth and bone (so don’t give kids) -Borellia burgdorferi
-Rickettsia -Leucocytosis, thromboct
*Cannot be used for bone CI: pregnant,& kids (<8yrs)
-Tx traveler’s diarrhea from -Vestibular toxicity (balance
Doxycycline -Lipid sol→ biliary excretion
(Good for renal problems) ETEC not hearing, reversible)
-Good penetration into tissues -Good CNS penetration -Food does not interfere w/
-No food interruption -DOC for Lyme’s disease abs & poor Ca++ chelation
-DOC for prostatitis
Minocycline -Water sol→ distributes in -Tx of asymptomatic -Vestibular toxicity
body fluids (↑↑ in saliva/tears) meningococcal carrier state -Food does not
interfere w/
-Enters CSF w/o inflamed (rifampin same use) abs & poor Ca++ chelation
meninges -Tx nocardiosis (better combined
-No food interruption w/ sulfonamides)
Demeclocycline Tx of SIADH Photosensitivity (also seen
w/ sulphonamides, quinolones)
Diabetes insipidus
Tigecycline Derivatve of minocylcine Active against gram (-) and (+), -Don’t use in
anaerobes, chlamydiae, infections
mycobacteria, MRSA, VRE

Chloramphenicol -Lipid soluble -Meningitis (H. influenzae, N. -Aplastic anemia

-Broad spectrum, binds 50S meningitides, S. pneumo)→ used in -Gray baby syndrome
-Inhibits peptide bond babies in past before vaccinat lacks UDP glucuronly trans)
formation -Backup for Salmonella typhi, B. -Superinfection
-Inhibit peptidyl transferase fragilis, Rickettsia -Hypersensitivity
-DOC for Rickettsia in pregnancy -Very toxic, not used often
-Inhibits CYP 450
or in child
MACROLIDES Macrolides inhibit protein synthesis by blocking transloctation (50S).
They inhibit CYP450. They are probably safe in
pregnancy, and may cause reversible deafness at high doses. Since macrolides are
bacteriostatic and are used in HIV patients,
you must use huge doses→ pay attention to the side effects. Resistance is usually
by the production of methyltransferases.
Macrolides increase serum concentrations of theophyllines & oral contraceptives.
Erythromycin -Metabolized by liver & -Gram (+), not MRSA -GI distress (from
excreted in bile -Atypicals stimulating motilin receptors)
-Legionella -Erythromycin estolate→
-Campylobacter cholestasis & obstructive
Azithromycin -Metabolized by liver & -Similar spectrum, more active in -GI distress
excreted in bile respiratory infections stimulating motilin receptors)
-DOES NOT inhibit CYP450 -Best macrolide to use in pregnant
-Mycobacterium avium
Clarithromycin ↑Activity against M. avium & LEAST GI distressing
-NOT a macrolide, same MOA -Gram (+) (except enterococcus) -1 known drug
associated w/
-Distributes to bone & stays -Some ANAEROBES pseudomembranous colitis
-Does not cross CNS, -Osteomyelitis
eliminated via biliary
Linezolid Inhibits the formation of the -Tx VRSA & VRE (enterococcus -BMS
initiation complex (50S) faecium NOT faecalis) & other
-No cross resistance w/ other drug resistant Gram (+) cocci
protein synthesis inhibit
STREPTOGRAMINS -Given together 30:70
Quinupristin + -VRSA
Dalfopristin -Binds 50S preventing AA -VRE (enterococus faecium AND
incorporation at A site fecalis)

Disulfiram-like Effects

Tx of MRSA










Class Drug Mechanism Clinical Use Side Effects
NRTI Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are components of most
combination drug regimens. Commonly two NRTIs are
used together with a protease inhibitor. They all lack a 3’ OH group, and once
phosphorylated by cellular enzymes they are
incorporated into viral DNA by reverse transcriptase. They inhibit elongation
because cannot form a phosphodiester bond. The
NRTIs are mostly renally excreted. Also, do not give the same nucleoside analogue.
All the drugs put on the market after AZT are
less BMS.
Zidovudine The 1 drug for HIV infection→ -Tx and prophylaxis of HIV -BMS (esp at
(AZT) lots of different resistances -Headache → don’t forget the added
Resistance: toxicities from taking an antiinflamm (e.g.
MOA: thymine analogue, requires -Mutations in the genes aspirin)
triphosphorylation to be activated that code for RT -Hematotoxicity (dose limit)→
PK: well abs PO (less w/ food), require blood transfusion on starting tx
crosses CNS, ½ life (1 hrs), -Myalgia and myopathy (don’t take aspirin
intracell ½ life (3 hrs) family drugs→ kidney toxicity)
-Peripheral neuropathy
Rare, but potentially fatal lactic acidosis

Drug Interact:
-Azole antifungals, cimetidine inhibit
CYP450s→ ↑AZT (worse toxicity)
-Indomethacin & probenecid→ they
affect renal clearance
-TMP-SMX→ additive BMS (used in
pneumocystis carini)
-Rifampin (induces P450)→ ↓AZT
-Stavudine & rivavirin activated by the
same pathways
Abacavir -Analog of guanosine Resistance: GI, h/a, dizziness
PK: NOT renally excreted, but -May be cross-resistance 5% hypersensitivity rxn (1
or more: rash,
metab by alcohol dehydrogenase w/ strains resistant to AZT GI, malaise, respiratory
and glucuronyl transferase & 3TC 0sensitized individuals should never be
rechallenged (can be genetically screened)
Didanosine (DDI) Inosine analogue (precursor for Greater affinity for mito DNA
guanosine/adenosine)→ ddATP in polymerase→ peripheral neuropathy,
cell lipoatrophy, pancreatitis (…remember
PK: Abs best in fasting state or valproate)
w/ antacid, crosses CNS (less -Less BMS than AZT
than AZT) CI: Zalcitabine, stavudine (similar
Lamivudine (3TC) MOA: Cytosine analog that -Tx of HIV -Least toxic of NRTIs (least
terminates synthesis of proviral -Acitive in hepatitis B -Few significant SE
DNA chain & inhibits HIV & HBV -Never used alone→ too
RT (does not affect mito DNA weak (should not be used w/
synth or BM precursor cells other cytosine analogs
-Mutation at viral codon 184
(but restores sensitivity to
AZT & tenofovir)
Emtricitabine -Fluoro-derivative of analog of -Inhibits HIV and HBV RT -Does not
affect CYP450s, no significant
3TC interactions w/ other drugs
-Taken once a day -Diarrhea, h/a, rash
-Hyperpigmentation of the soles/palms
-Lactic acidosis, fatty liver,
Stavudine (D4T) AZT analogue (thymidine alalog)→ Tx HIV Greater affinity for mito
binds same site polymerase→ peripheral neuropathy,
-Strong inhibitor of β and y DNA pancreatitis, lipoatrophy
polymerases -Less BMS than AZT
PK: completely abs PO not -DO NOT USE W/ AZT
affected by food, crosses CNS
Zalcitabine 1 cytosine analog developed, but Tx HIV -Peripheral neuropathy (dose
(DDC) removed from the market b/c of -GI distress
toxicity -Pancreatitis, neutropenia, rash
CI: Didanosine (similar toxicities)
Tenofovir MOA: nucleoTIDE (AMP) analog Tx HIV GI (n/v/d, flatulence)
PK: take w/ food, long half life→
once daily dosing CI: only NRTI w/ sig drug interactions
(↑DDI, no longer recommended combined
use & ↓atazanavir→so ↑ by boosting w/

NNRTI Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) are highly

selective, noncompetitive inhibitors of HIV-1 RT do not
require metabolic activation. They inhibit reverse transcriptase at a different
site from the NRTIs. Since they can be added to
the NRTIs, they are synergistic with NRTIs. They lack cross-resistance with NRTIs.
These drugs have cross-resistance WITHIN
the NNRTI class, drug interactions, and a high incidence of hypersensitivity rxns.
These drugs are NOT myelosuppressive.
Nevirapine PK: well abs PO (not affected by Used in combination -Potential severe
hepatotoxicity (don’t use
(NVP) food), crosses to CNS, excreted in with other antiretroviral in women w/ CD4
< 250, male CD4 < 400)
the urine as metabolites (CYP3A4 + drugs for HIV-1 tx in
CYP2B6) adults and children CI: induces CYP3A4→ → → → ↑ ↑ ↑ ↑metab of PI’s (no
dosage adjust needed), oral
Resistance: contraceptives, ketoconazole,
-Target site is HIV-1 methadone, metronidazole, quinidine,
specific, not essential to
theophyline, warfarin
enzyme→ rapid resist
Efavirenz (EFV) Preferred NNRTI -Mostly CNS (50%)→ dizziness, h/a, vivid
PK: ↑bioavail w/ fatty meal; well dreams, loss of concentration→resolves
distrib after PO, 99% plasma after few weeks
albumin bound, half life -Rash (25%)
(>40hrs)→once-a-day dosing
CI: Pregnancy; potent inducer of CYP450
Adefovir Does not require phosphorylation
Protease Aspartate protease (pol gene encoded) is a viral enzyme that cleaves
precursor polypeptides in HIV buds to form the proteins of the
Inhibitors mature virus core. The enzyme contains a dipeptide structure not seen in
mammalian proteins (important for selectivity). PIs bind to
this dipeptide, inhibiting the enzyme. Resistance occurs via specific point
mutations in the pol gene, such that there is not complete
cross-resistance b/w different PIs. Since PIs have nothing to do with DNA
replication, they will NOT cause BMS→thus, good for
adding these drugs to the regimen!. Since they have a different MOA, they can only
be synergistic with those drugs blocking
replication. Most have poor bioavailablity. However, the biggest problem is the
inhibition of CYP450s. They also cause disorded lipid
and carbohydrate metabolism.
Saquinavir Given w/ low dose RTV; high fat meals H/A, fatigue, nausea, GI
enhance absorption CI: drugs that enhance metabolism
Half life = 7-12 hours
(e.g. rifampin, rifabutin, nevirapine)
Indinavir Given w/ RTV to increase absorption, -Nephrolithiasis
permit twice daily dosing -Hyperbilirubinemia
-Least protein bound, absorption decreaed -Fat redistribuation
when taken w/ meals -GI distress
-Half life = 1.8hours -Thrombocytopenia
-Inhibition of CYP3A4
CI: dosage should be reduced w/
hepatic insufficiency
Ritonavir PK enhancer/ booster of other PI’s -GI distress
-Potent inhibitor of CYP3A4 -Asthenia & circumoral paresthesias
-Half life = 3-5 hours -Major drug interactions: induces
CYP 1A2 & inhibit the major P450s
(3A4 & 2D6)→ thus limited use
Nelfinavir (NFV) Canot be boosted y RTV; metabol by several Diarrhea (controlled
by loperamide),
CYPS; major metabolite (CYP2C19) has nausea, flatulence
antiviral activity equal to parent compound

-half life = 5h CI: can inhibit metabolism of other

Given w/ RTV; prodrug→ amprenavir H/A, fatigue, nausea, vomiting,
(fAPV) paresthesias
CI: can inhibit metab of other drugs
One of the preferred PIs; given with RTV GI, hypertriglyceridemia, insulin
Lopinavir (LPVr)
-Poor intrinsic bioavailability resistance
-half life =1.8 hours CI: enzyme inducers (avoid St Johns
Wort), Oral solution contains EtOH
(ovoid disulfiram or metroniadazole)
Atazanavir ATV + RTV = only once daily preferred PI; -Competitive inhibitor of
(ATZ) structurally unrelated to other PIs; well transferase (benign
absorbed orally (increased by food) + jaundice)
-Highly protein bound (86%) -Prolongs PR intervale + slows HR
-Half life = 7h CI: Metabolized by & inhibits
CYP3A4, proton pump inhibitors;
administration must by more than
12h apart from H2 blockers &
Tipranavir (TPV) Inhibits HIV protease resistant to other Same as other PIs +
severe and fatal
PIs hepatitis
-Twice daily w/ RTV -Fatal/nonfatal intracranial
-Well absorbed when taken with food; half hemorrhags
life = 6h
CI:Inducer of CYP 450
Darunavir Inhibits HIV protease resistant to other Same as other PIs + RASH
PIs; well absorbed when taken w/ food
Half life = 15 h (w/ RTV) CI: metabolized by & inhibits
VIRAL Enfurvitide -Fusion inhibitor; structurally resembles -Use for tx-
-Injection-related (3% discontinue)
ATTACHMENT gp41 experienced adults w/ $$$ (estimated at $20,000)
MOA: Binds gp41 (recognizes chemokine evidence of HIV
receptrs) and inhibits fusion of HIV-1 to replication
(note: gp120 → recognizes CD4+)
-Has to be administered parenterally (twice
daily subQ injections)
VIRAL ENTRY Maraviroc Blocks CCR5 coreceptor that works w/ -Well tolerated
gp41 to facilitate HIV entry through cell
membrane (only CCR5 expressing virus can
be treated w/ maraviroc
INTEGRASE Raltegravir Specifically inhibts final step in integration -Give w/ other
Well tolerated
INHIBITOR of viral DNA into host cell DNA retrovirals for tx- Nausea, h/a
-Half life = 9h→ twice daily dose experienced patients Diarrha
-Metabol via UGT1A1-mediated w/ evidenc of viral
glucuronidation→ no interactions w/ replication
CYP450 inducers, inhibitors

Respiratory Virus Oseltamivir -Inhibits viral neuraminidase by acting as -Effective
against both -GI discomfot & vomiting, so take
infections Zanamivir a sialic aicd analog Influenza A and B the drug w/ food
-Does not interfere w/ the immune -Prevent infection (if -Airway irritation (zana)
response to influenza A given prior to exposure)
-Oseltamivir (oral) -Modest effect if given CI: severe reactive asthma (zana)
-Zanamivir (inhaled/nasal spray) w/in first 24-48h of
Blocks the viral membrane matrix protein (M2), which functions as a channel for H+
(required for fusion of viral membrane w/ host
cell membrane). Does not impair immune response to Influenza A vaccine. Viral
Uncoating Inhibitors
Amantadine PK: Distributes well and penetrates CNS; -Tx & prevention of -Livedo
NOT extensively metabolized, but Influenza A infxns -Nose/throat irrriation
excreted in urine & may accumulate in -Atropine-like SE
renal failure -Parkinson’s
-Also antimuscarinic action
Rimantadine Does NOT cross CNS; extensively
metabolized by liver; metabolites and
drug eliminated by kidney
Ribavirin Synthetic guanosine analog→ → → → Effective against a broad Dose-
dependent transient anemia
phoshorylat→ → → → then inhibits IMP spectrum of RNA and (hematotoxic)

dehydrogenase→→ as a triphosphate DNA viruses (RSV, -Upper airway irritation

inhibits viral mRNA capping Influenza A & B, Lassa

fever, Hanta viruses) CI: Pregnancy

-Adjunct to α INF in HCV

Palivizumab Monoclonal antibody against RSV -Given in premature
infants before start of
RSV season if <12mo old
Anti-Herpes Acyclovir Guanosine analog that is 1 phosphorylated -Tx HSV-1,2 & VZV
-Will NOT cause BMS
Drugs by viral thimidine kinase→ incorporates -Minor SE w/ oral use
into DNA & causes chain termination Resistance: change or -Crystaluria
absence (TK- strains) in
the thymidine kinase -Cannot be used for CMV b/c
virus lacks thymidine kinase
Valacyclovir Prodrug→ → → → acyclovir; longer half life than
acyclovir and more bioavail
Pencyclovir Acivated by viral thymidine kinase &
inhibits DNA pol, but does not cause chain
Famcyclovir Prodrug→ → → →pencyclovir -Gential herpes & herpes
-Given Orally zoster
Docosanol Aliphatic alcohol that inhibits fusion -Shortens healing time
between HSV envelope and plasma
membranes, preventing viral entry &
subsequent replication
-Used toppically
Guanine derivative that is -Prophylaxis & Tx of Dose limiting BMS (a problem with
phosphor→GTP→ inhibits DNA pol of CMV CMV retinitis and over those already
and HSV & causes chain termination; CMV infections
usually given IV; penetrates into CNS
-Any kinase can turn on ganciclovir
Foscarnet Not an antimetabolite; but still inhibits -CMV Dose-limiting
nephrotoxicity with
DNA & RNA pol. Requires an IV infusion -HSV resistant strains acute tubular
necrosis, electrolyte
pump (so must be hospitalized) (e.g. TK- strains) imbalance with hypocalcemia
(tremors & seizures)
-NOT hematotoxic (so no BMS)
-Avoid pentamidine IV (used for
pneumocystis when bactrim not
working→ also nephrotoxicity)

Drug type Drug Mechanism Clinical Use Side Effects
Drugs that are cell cycle specific are more effective against actively growing
tumors with high growth fractions (leukemias, lymphomas).
Cell cycle specific (S phase) are easy to recognize because typically they have
some type of nucleotide analog.
5-Fluorouracil MOA: 5-FU→ 5’ FUMP→5- -Topical for basal cell -BMS, alopecia,
anorexia, n/v/d
1. Pyrimidine
FUDP→ 5-FdUMP, which cancer and keratoses -Severe ulceration of oral & GI
Antagonists inhibits thymidylate mucosa
-Tx slowly growing solid
synthetase (dUMP→dTMP) tumors (e.g. colorectal, -Hand/foot syndrome
PK: IV, topical; rapidly metab breast, ovarian, pancreatic, (erythmatous
desquamation of
in liver, lug, kidney→fluoro-β- gastric) palms & soles after extended
alanine (urine) + CO (exhaled) infusions)

-Elevated levels of *Usually given w/

dihydropyrimidine Leucovorin→ → → →

dehydrogenase (DPD) = ↑5-FU ↑effectiveness of 5-FU


Capecitabine MOA: Oral prodrug→5-FU, -Metastatic breast cancer Similar to 5-FU


but the final step is thymidine (resistant to 1 line) -GI toxicity

phosphorylase (found in -Colorectal cancer -Carefully used in patients w/

tumors)→ →TUMOR SPECIFIC renal or hepatic impairment

→ →

PK: PO, well absorbed CI: pregnancy, lactation,

patients on coumarin

anticoagulants or phenytoin

Cytarabine Analog of 2’deoxy-cytidine -AML 1 line (Cytarabine + -N/V/D

(ara-C) (arabinose instead of ribose) 6-TG + daunorubicin) -Severe BMS

MOA: Ara-c enters -Hepatic dysfunction

cell→phosph by deoxycytidine -High doses or IT injection→

kinase & other kinases→ ara- leukoencephalopathy
CTP (cytotoxic) →inhibits
DNA polymerase
→Inhibits DNA elongation
PK: not effective orally
(deaminated in intestine,
liver); does NOT go into CNS

Gemcitabine MOA: Analog of Locally advanced or BMS (dose limited)

deoxycytidine→ metastatic adenocarcinoma -N/V, alopecia, rash, flu-like

(deoxycytidine kinase)→ 2’,2’- of pancreas (1 line) syndrome
difluorodeoxycytidine -Non small cell lung cancer -Transient elevation of serum
triphosphate, which: transaminases, proteinuria,
→Inhibits DNA synth hematuria

→Inhibits ribonucleotide


PK: IV, eaminated to non-toxic


6-Mercaptopurine MOA: 6-MP → 6-thioinosinic -Acute lymphocytic -BMS

(6-MP) acid (TIMP, a thio analog of leukemia (ALL) -Hepatotox (jaundice, necrosis)
2. Purine
hypoxanthine) by HGPRT, -Immunosuppression -
which adds a ribose-P:

→ → → →Blocks 1 step of de novo Resistance:

purine ring biosynth (via 1. Inability to

glutamine phosphoribosyl biotransform 6-MP to

pyrophasphate the corresponding

amidotransferase) nucelodite b/c of When taking Allopurinol (inhibits

→ → → →Blocks IMP →AMP & XMP ↓HGPRT (e.g. lesch xanthine oxidase)→ reduce 6-MP

→ → → →TIMP→TGMP to inhibit nyhan syndrome) dose by 75% to avoid toxicities

RNA 2. ↑Dephos

PK: PO, erratic abs; metab in 3. ↑ Metab of the drug to

liver→ 6-methyl-MP or to thiouric acid

thiouric acid via xanthine


Cladribine -Similar rxns to fludarabine -Hairy cell leukemia Severe BMS

-Incorporated At 3’ end of -Non-hodgkin lymphoma Fever

DNA→blocks elongation Peripheral neuropathy

-Also, blocks DNA repair and Teratogenic

inhibits ribonucleotide reducts

PK: single continuous 7-day

infusion; well distributes &

into CNS

Fludarabine 5’ phosphate of 2- -CLL* -BMS (dose limiting)

fluoroadenine arabinoside -Hairy cell leukemia -Diarrhea, n/v

MOA: prodrug loses Phos→ 2- -Indolent Non-Hodgk Lymph -Fever

F-araA→ taken into cells & -Edema,

phosph→ incorporated into *May replace chlorambucil -Severe neuro toxicity -

DNA & RNA (S-phase) Progressive encephalopathy,

PK: IV (if oral→intest bacter blindess & death at ↑ ↑ ↑ ↑↑ ↑ ↑ ↑doses

split off the sugar→ toxic)

Pentostatin MOA: potent inhibitor of -Hairy Cell Leukemia (good BMS

adenosine deaminase (ADA) at causing complete GI symptoms

→Blocks DNA synth remission) Skin rashes

→Blocks ribnucleotide -CLL, CML, promyelocytic Abnormal liver function results

reductase leukemia cutaneous T cell Immunosuppression (long lasting)

lymphoma, non-Hodgkin Renal/neuro complications

lymphoma, Langerhans cell (↑↑doses)


-No sig affect on solid

tumors or multiple myeloma CI: given w/ fludarabine → →
→ →
severe/fatal pulmonary toxicity

6-Thioguanine 6-TG→ TGMP (6-thioguanylic -AML (6-TG + BMS (dose dependent)

(6-TG) acid) via HGPRT→TGDP→ Daunorubicin + Cytarabine) Liver toxicity
→Blocks purine synth *Not recommended for *Breakdown via thiopurine
→Blocks phosphorylation of maintainance therapy or methyltransferase (TPMT), must

GMP→GDP continuous for long term screen patients before therapy

→TGTP incorporated into (liver tox) (3% of whites/blacks have a

DNA, blocking cell cycle homozygous deletion of TPMT)

PK: PO, abs erratic & *Can give w/ Allopurinal w/out
incomplete ↓ ↓ ↓ ↓dose b/c 6-TG requires
deamination before it is

metabolize by xanthine oxidase

(so if XO is inhib, already


Methotrexate MOA: Folate analogue→ -ALL -Diarrhea, n/v, stomatitis, rash,

enters cell via active -Burkitt’s lymphoma erythema, urticaria, alopecia

transpor→ inhibits DHF -Breast cancer -Crystalluria

reductase (S phase) -Choriocarcinoma -Long use→ liver cirrhosis

-Head and neck carcinomas -Pulmonary toxicity (rare)

Antidote = Leucovorin -RA, psoriasis -Neurotoxicity

3. Folate
rescue (N5, N10-methylene --Abortion when used w/ -BMS,
FH → DHFR not needed) b/c misoprostol in 3 term CI: pregnancy
healthy cells pick up the
folate better than the
cancer cells (can give before

Pemetrexed -Folate analogue, transported -Mesthelioma (+ cisplatin) -BMS

into cell same as MTX -Second line therapy of non- -Skin rash, mucositis, diarrhea,
-Inhibits DHFR & small cell lung cancer fatigue
thymidylate synthase
ANTI-TUMOR Bleomycin G2 phose -Testicular cancers -Pulmonary fibrosis
ANTIBIOTICS Copper/Fe chelating (Bleomycin + etoposide + -Pneumonitis
(CCS) Complexes w/ Fe and O2→ → → → cisplatin or vinblastine) -Mucocutaneous rxns
Dna strand breaks -Squamous cell carcinomas -Alopecia
PK: bleomycin inactivating -Lymphomas -Hypersensitivity
enzyme is high in some -BMS IS RARE
tissues (liver, spleen), low in
others (lung, skin)

MOA: effective in S & G2 Broad spectrum:
Doxorubicin -Irreversible cardiotxicity→

phases -Hematologic malignancies dilated cardiomyopathy (co-

→Inibits topoisomerase II -Solid tumors (e.g. lung, admin w/ iron chelator

→Intercalation into DNA→ ovarian, breat) dextrazone to ↓toxicity)

inhibition of synth & DNA -Transient BMS, stomatitis, GI

strand breaks *One of the most widely used disturbances

→Bind to cellular membranes, -Severe Alopecia

altering the fluidity/ion -Increased skin pigmentation


→Generation of semiquinone *Drugs are dark red→ veins may

& oxygen free radicals become visible and red urine

(→cardiotoxicity) by CYP450 *Extravasation of drug is a

PK: IV, metab by liver serious proglem→ tissue necrosis

Daunorubicin Same -Tx AML Same
Mitoxantrone MOA: resembles -Advanced, hormone -BMS (dose limiting)
anthracycline ring→ binds refractory prostate cancer -Blue discoloration of
DNA→ strand breaks→ -Low grade non-Hodgkin’s fingernails, sclera & urine
synth inhbiited lymphoma -Mild nausea, vomiting, mucositis,
-Breast cancer alopecia
Plicamycin MOA: ↓plasma calcium thu -Testicular cancer
actions on osteoclasts indep -Hypercalcemia associated
of action on tumors w/ neoplasms
ANTI-TUMOR Dactinomycin MOA: -Wilm’s tumor (Surgury + Highly toxic, older drug
ANTIBIOTICS (Actinomycin D) → Intercalates into double Dactinomycin + vincristine)
-BMS (dose limiting)
(CCNS) helix→ stable complex -Stomatitis, n/v/d, alopecia
→Also blocks RNA -Gestationl choriocarcinoma -Sensitizes to radiation
polymerase elongation & (Dactinomycin + MTX)
causes strand breaks
Mitomycin MOA: Generates alkylating -Squamous cell cancer of -Hemolytic Uremic
agents (via reduction) that the anus (Mitomycin + 5-FU
cross link DNA + radiation)
-Targets hypoxic tumor stem -Squamous cell carcinomas
cells (as environment is more -Pancreatic cancer
conducive to reduction) -Superficial bladder cancer
(intravesical tx)
EPIPODO- Etoposide Cell cycle specific -Germ cell cancer (testicul) Leukopenia
(dose limiting)
PHYLLOTOXINS MOA: inibit late S-G2 -Gastic cancer
phase; inhibits -Lung cancer Note: “topo” = topoisomerase
topoisomerase II -Lymphomas
PK: water insoluble
Teniposide -Same as etoposide ALL Leukopenia (dose limiting)
-Semisynthetic derivative of
podophyllotoxin (mayapple
MICROTUBULE Microtubule inhibitors are effective because the mitotic spindle is
part of the cytoskeleton and is essential for equal
INHIBITORS: partitioning of DNA. These compounds are NATURAL products that are cell
cycle specific (CCS) at the M phase.
Paclitaxel -From European Yew -Ovarian cancer -Neutropenia
-Stabilize microtubules -Metastatic breast cancer -Hypersensitivity (premedicate

PK: IV (not into CNS) -Non small cell lung cancer w/ dexamethasone +

(Paclitaxel + cisplatin) diphenhydramine)

CI: patients w/ cardiac disease

Docetaxel -Same as paclitaxel -Fewer SE than paclitaxel

-Semisynthetic -Neutropenia

CI: patients w/ cardiac disease

Vinblastine -Block microtubule -Metastatic testicular BMS (dose limiting)
synth→ → → →prevents cell prolif cancer (Bleomycin + GI, alopecia
PK: rapid cytotoxicity Cisplatin + Vinblastine)
Vincristine Same -ALL Peripheral neuropathy
-Wilm’s tumor
-Ewing’s sarcoma
Vinrelbine Same Non-small cell lung cancer Granulocytopenia (dlose limiting)
CAMPTOTHECINS Irinotecan -Semisynthetic -Colon or rectal cancer (1 -BMS (dose
-Inhibit topoisomerase I line) (Irinotecan + 5-FU + -Thrombocytopenia
leucovorin) -Anemia
Topotecan Same as Irinotecan -Ovarian Cancer (when Same
primary therapy fails)
ALKYLATING Alkylating agents are Cell Cycle Non-Specific (CCNS) and do not
differentiate b/w cycling and resting cells, although
AGENTS they are most toxic to rapidly dividing cells. In addition to being
cytotoxic, they are mutagenic and carcinogenic and can
lead to 2’ malignacies, such as acute leukemia.

Mechlorethamine -Alkylation of N7 Guanine on -Lymphatic cancers (mainly -Severe n/v

(can premedicate w/
both strands of DNA used for Hodgkin’s) dexamethasone)
(“bifunctional agent”) -Solid tumors -Severe BMS

-Cross-linkage between -Latent viral infxn

chains & depurination→ -Extravasation is serious (give

strand breaks, miscoding -Developed as a nitrogen sodium thiosulfite to inactivate

mutations mustard during WWII drug)

PK: very unstable, must be

made just before using;

powerful blistering agent

(vesicant)→ so give IV

Cyclophosphamide -Similar to mustard agents -Many cancers (e.g. Burkitt’s, -BMS

Pro-Drug→ → hydroxylation via breast) -Mucositis

→ →
CYP450→ breaks down into -HEMORHAGIC CYSTITIS → →
→ →

phosphoramide mustard + -Nephrotic syndrome Antidote = mesna

acrolein (acrolein→hem cy) -Intractable RA -Hepatotoxicity (↑dose)
-Phosph mustard rxn w/ DNA -Veno-oclusive disease of the
is cytotoxic, attaks DNA at liver

N7 guanine -Amenorrhea, testicular atrophy,

PK: Oral (unlike most sterility

alkylating agents)
Ifosfamide Similar to cyclophosphamide -Neurotoxicity → probably

related to the metabolite,


Carmustine MOA: Alkylation that inhibits Brain tumors (glioblastoma -Delayed

replication, RNA, protein multiforme) depression
Nitrosureas Lomustine
synthesis, target dividing -Aplastic BM (prolonged use)
cells -Renal toxicity
PK: crosses CNS -Pulmonary fibrosis

Carmustine = IV
Lomustine = oral

Streptozocin MOA: Alkylation that inhibits Insulinomas -Diabetogenic

replication, RNA, protein -Minimal BM toxicity
synthesis, target dividing

-Specifically toxic to β-cells

of pancreas

Dacarbazine Prodrug→ MTIC via CYP450 Melanoma -BMS, n/v

→forms methylcarbonium -Hepatotoxicity

ions that attack nucleophilic Hepatic vascular occlusion

gropus, cytotoxic by DNA
Temozolomide MOA: prodrug→MTIC (NOT -Resistant gliomas -BMS
via CYP450)→ forms methyl- -Anaplastic astrocytomas -n/v
carbonium ions that attack
nucleophilic groups, cytotoxic
via DNA methylatation
-Also inhibits DNA repair
enzyme 06-guanine DNA
PK: PO, crosses CNS (but to
lesser extent than
Melphalan -Bifunctional alkylating agent -Multiple myeloma Hematologic toxicities
PK: PO -GI upset
Chlorambucil CLL -Leukemogenic
Busulfan CML -BMS & pulmonary fibrosis in old
HORMONAL Glucocorticoids: Bind to receptor to induce -Induce remission in ALL
AGENTS: Dexamethazone production of specific -Lymphomas -Hyperglycemia
Prednisone proteins -Cataracts
Glucocorticoids Hydrocortisone -Glaucoma
-Mood changes
SERMs interact at estrogen receptors but have different effects on different
tissues. Tamoxifen is an estrogen
antagonist in breast cancer tissue, but can cause endometrial hyperplasia by
acting as a partial agonist in the uterus
Estrogen antagonist (SERM) -Estrogen receptor positive -Similar to estrogen (hot
Selective Estrogen
→ binds to estrogen breast cancer flashes, n/v, rash, vaginal
recepotors→ depletes *Note: estrogen competes w/ bleeding)
Modulators (SERM)
estrogen, estrogen receptrs, tamoxifen, use w/ a GnRH -Hypercalcemia

& growth factors analog (e.g. leuprolide) in -Endometrial cancer


Toremifene SERM, Similar to tamoxifen -Advanced breast cancer


-Prophylaxis in high risk


AIs block aromatase in liver, fat, muscle, skin and breast tissue. Peripheral
aromatization is an important estrogen

source postmenopausally
Aminoglutethemide -AI Metastatic breast cancer *Newer AI’s developed due to
inhibitors (AI’s)
-Inhibits adrenal synth of SE

pregnenolone (precursor of → Usually taken w/

estrogen) hydrocortisone

-Inhibits hydrocortisone

synth→ compensatory

↑ACTH→ overrides drug

Exemestane -Steroidal AI Breast cancer -Hot flashes, n/v

-Metab by CYP450 -Androgenic SE (acne, hair

Anastrozole -Non-steroidal AI -Breast cancer (2 line to -Do not predispose to

-More potent & selective tamoxifen) endometrial cancer


than aminoglutethemdie →Do not need to be given w/ -Do not have androgenic SE


Prostate cancer is dependent upon hormonal stimulation with androgens

Leuprolide GnRH agonist→ ↓androgens Prostate cancer -Impotence

& estrogens (castration level) -Hot flashes

PK: sustained release prep, -Tumor flare (minimal compared

SC, depot IM to estrogen tx)

Goserelin GnRH agonist Prostate cancer Same


Flutamide Synthetic, non-steroidal Prostate cancer Liver failure

antiandrogen → competes w/ -Since it blocks inhibitory

natural hormone for recetpor effects of testosterone on

binding, preventing GnRH→ ↑LH, ↑testosterone,

translocation to nucleus it is always given w/

PK: PO leuprolide or goserelin

Nilutamide Same Prostate cancer Visual problems

Ethinyl estradiol Synthetic estrogens →Block Postatic cancer Thromboemboli, MI,


Diethylstilbesterol production of LH→ *Replaced by GnRH (↓SE) hypercalcemia,


↓androgen synthesis in impotence

Megesterol- -Progestins Breast
Acetate *Replaced by AIs Endometrial cancer
PLATINUM Cisplatin -Similar to alkylating agents, -Solid tumors (e.g. -Severe
persistent vomiting
COORDINATION bind to DNA→ cross links→ testicular cancer) (Cisplatin (1hr-5days)
(use ondansetron)
COMPLEXES inhibit synthesis + Bleomycin + etoposide) -Nephrotoxicity (dose
-Cell cycle nonspecific tx w/ amifostine, also requires
(CCNS) -Ovarian cancer aggressive hydration
(Cyclophosphamide + -Hypomagnesemia
PK: IV, intraperitoneally for Cisplatin) -Hypocalcemia
ovarian cancer -Ototoxicity, tinnitus
-Bladder cancer -NO BMS
-Neurotoxicity (deafness)
Carboplatin Same -When patients cannot be -Mild n/v
vigorously hydrated -NO nephrotox
-Switch to carboplatin when -NO ototoxicity
nephrotox on cisplatin -NO neurotox
-BMS (dose limiting)
Oxaliplatin Same Advanced Colorectal Cancer
MONOCLONAL Binds to HER2 sites in Breast cancer CHF, fever, chills, h/a, dizziness,
ANTIBODIES breast cancer tissue n/v
Rituximab Binds to CD20 antigen on B -Posttransplant lymphoma -Hypotension,
cells -CLL -Angioedema
PK: infuse slowly (fast can be -Cardiac arrythmias,
fatal) -Tumor lysis syndrome
Inhibits angiogenesis
Bevacizumab Bevacizumab + 5-FU →
colorectal cancer
Cetuximab Targets EGF & interferes w/ Colorectal cancer Difficulty breathing, low
cancer cell growth interstitial lung disease, rash,
fever, constipation
Gemtuzumab- AML
Alemtuzumab B-cell CLL
I131-tositumonab Relapsed non-Hodgkin’s
SIGNAL Imatinib Deregulates BCR-ABL -CML in blast crisis -Fluid retention, edema
TRANSDUCTION kinase→ prevents tyrosine -GI stromal tumor -Hepatotoxicity
INHIBITORS phosph→ inhibits proliferat -Thrombocytopenia
Gefitinib Targets EGF Non-small cell lung cancer Acne, nausea, diarrhea,
(when other therapy fails) interstitial lung disease (rare)
Proteasome inhibitor, Few adverse SE
induces growth inhibition &
Sunitinib Inhibits VEGFR-1, VEGFR-2,
Sorafenib Inhibits B-RAF, VEGFR-1,
Vatalanaib Inhibits VEGFR-1, VEGFR-2
Thalidomide -Immunomodulatory drug
-Inhibits angiogenesis,
stimulates T-cells
Lenalidomide Analogue of thalidomide
Procarbazine Undergoes oxidative rxn→ Hodgkin’s disease -BMS, n/v/d
cytotoxic *Inhibits MOA→ avoid -Neurotoxic
tyramine -Mutagenic & teratogenic
L-Asparaginase Breaks down asparagine -ALL (L-asparginase +
(tumor cells cannot Vincristine + prednisone)
synthesize asparagine)
INTERFERONS Interferon 2α α α α -Hiary cell Leukemia
-Aids relatd Kaposi sarcoma
Interferon 2β β β β -Hiary cell Leukemia
-Aids relatd Kaposi sarcoma
-Follicular lymphoma
Urea analog→ inhibits -BMS (dose limiting)
Hydroxyurea -CML
-Mucositis, diarrhea, h/a,
ribonucleotide reductase→ -Tx of blast crisis of AML
inhibit DNA synth -Adjunct therapy w/ ↑lethargy
-S phase radiation for head + neck ca -Maculopapular rash
(Also ↑synth of HbF→use fo
tx of sickle cell)
Tretinoin All trans-retinoic acid -Acute promyelocytic Vitamin A toxicity (h/a,
(tretinoin) induces remission leukmia dry skin & mucous membranes,
through induction of terminal skin rash, pruritis,
differentiation, in which conjunctivitis), CNS toxicity,
leukemic promyelocytes lose weight gain
ability to proliferate -Teratogenic
Arsenic Trioxide Induces differentation & -Acute promyelocytic -Fatigue
apoptosis leukemia (induces remission -QT elongation
in those w/ the t(15:17) -Arrthymias

Immune activation cascade SIGNALS:
1. T-cell triggering at CD3-APC
2. Co-stimulation (CD80/86 of APC engage CD28 on T cell)
• Signals 1 and 2 activate several intracellular signal transduction pathways, one
of which is the
calcium-calcineurin pathway, which is targeted by cyclosporine and tacrolimus
3. Stimulus for T cell proliferation: IL-2 binds to CD25 (aka IL-2 receptor) on the
surface of other T
cells to activate mammalian target of rapamycin (mTOR)
Drug type Drug Mechanism Clinical Use Side Effects
CORTICOSTEROID Prednisone MOA: unclear, but Tcells -Suppress acute rejection of
Methylprednisolon affected most organ allografts -Hypercholesterolemia
-Tx chronic GVHD -Cataracts
-Tx autoimmune conditions -Osteoporosis
ANTIMETABOLITE Azathioprine Pro-drug interacts w/ sulfhydral -Immunosuppression
after N/V,
(OLD) compounds (e.g. glutathione) → → → → transplantation Skin rash
6-mercaptopurine→ → → →thioinosinic -Inflammatory bowel disease Hypersensitivity
acid (immunosupprssive *Antimetabolites usually used BMS
nucleotide) w/ corticosteroids + calcineurin Gi irritation
-Lymphocytes mostly affected inhibitors (CsA, TAC)
by cytotoxicity due to their *Little effect suppressing a CI: pregnancy
rapid proliferation & dependence chronic immune response *Allopurinol significantly
on de novo synthesis of purines *Has been replaced by MMF ↓metab of azathioprine
Methotrexate MOA: Unknown -Tx rheumatoid arthritis, Hepatic
Particularly active against psoriasis fibrosis/cirrhosis (not
lymphoid cells -Prevent GVHD BM suppression)
-See cancer chemotherapy Abortion w/ misoprostol
-Antinflamm but not cytotoxic (PGE1 analog)
ANTIMETABOLITE Mycophenolate- MOA: inhibit purine synth; -Heart, liver, kidney
transplant -Diarrhea, n/v,
(NEW) mofetil (MMF) MMF→mycophenolic acid (MPA), -Abdominal pain
a potent reversible inhib of IMP -Leucopenia
dehydrogenase (block the de -Anemia
novo formation of GMP b/c
lymphocytes lack the salvage CI: pregnancy
PK: extensively bound to albumin,
long ½ life (14-18days);
-Prodrug→active metabolite
-Antacids ↓absorption
Leflunomide -Blocks dihydroorotate→orotate Rheumatoid Arthritis CI: pregnancy
(drug inhibits dihydroorotate
ALKYLATING Cyclophosphamide -2 line to azothioprine -Tx disorders of humoral
AGENTS -Hi dose # tolerance to new immunity (SLE) Cardiotoxicity
antigen Alopecia
PK: PO, Prodrug→ hydroxylatd- ↑Risk of bladder cancer
intermed→active phosphoramide -RBC hemolysis, Ab RBC b/c of mutagenicity
mustard & acrolein (phos must→ dyscrasia, BM suppression (acrolein)
cytotoxic) BM transplant @ hi doses BM suppression
-Hemorrhagic cystitis
(antidote = mesna)

-Doesn’t cause side

effects of steroids/anti
ca drugs
CYTOKINE Cyclosporin A -Complexes w/ cyclophilin (an -Organ transplants
INHIBITORS (CsA) immunophilin)→ binds calcineurin -Severe RA (alternative to
→ →inhibits dephos of NFATc→ methotrexate) -Viral infection common
→ →
NFATc cannot enter nucleus to -Recalcitrant psoriasis not (CMV, herpes)
promote rxns for cytokine synth responding to other therapies -Hypertension,
→ ↓ ↓ ↓ ↓IL-2 synthesis *Most effective w/ -Hyperlipidemia
PK: PO or IV, metab by CYP3A4 cortisteroids + antimetabolite -Hyperkalemia, tremor
-Glucose intolerance
-Gum hyperplasia
Tacrolimus (TAC) MOA: same as CsA (but binds -Liver, kidney transplants (give
-Similar to Cyclosporin A
immunophilin-FKBP-12 instead) w/ corticostrds &/or antimetab) (NO gingival
-Higher potency & fewer side -Ointment prep for mod-severe NO hirsutism)
effects than CsA atopic dermatitis -Nephrotox, neurotox
PK: PO or IV, oral abs variable, *Preferred to CsA b/c ↓ ↓ ↓ ↓doses more common
than CsA
abs ↓ w/ fatty meal, long half of corticosteroids required -Post transplant insulin
life, metab by CYP3A4 dependent diabetes (esp
Black & Hispanic patients)
-Avoid use w/ NSAID –
interferes w/ renal blood
MOA: forms complex w/ FKBP- -Prevent reject of renal -CsA + SRL→ more
Rapamycin (SRL) 12→binds MTOR (serine- transplnt nephrotoxic than CsA
threonine kinase)→block -SRL + CsA + corticosteroids -Nausea, diarrhea, h/a
progression of activated T cells (allows lower doses) -Leucopenia
from G1→S phase→ inhibit cell -SRL-coated stents inhibit -Thrombocytopenia
proliferat→inhibit cell response restenosis of blood vessels -Impaired wound
(↓endothelial cell proliferation) (esp diabetics & obese→
to IL2 (NOT ↓ ↓ ↓ ↓IL-2 synthesis)
PK: Oral only, ↓Abs w/ fatty problem for transplantng)
meal, long ½ life, metab by -Hyperlipidemia
*SRL → ↑[CsA], so don’t give at
same time (separate 1-2 hrs)
TNFα Inhibitors Etanercept TNF-receptor dimmer binds -RA ↑ ↑ ↑ ↑Risk of
both TNFα α α α and TNFβ β β β -Chron’s disease latent TB→ → → → must screen
Infliximab Ab against TNFα α -Psoriasis
α α
*Will improve symptoms but not
Adalimumab IgG1 against TNFα α α α
reverse pathophys
IL-1 Inhibitors Anakinra Recombinant form of IL-1ra -RA Neutropenia
(receptor antagonist) -Modest effects on pain, ↑Susceptibility to
swelling, but ↓ ↓ ↓ ↓↓ ↓ ↓ ↓bony erosions infeciton
ANTIBODIES Antithymocyte- Rxn against T-cell precursors -Give at time of
transplant to Chills
Globulins (ATG) (thymocytes); polyclonal prevent early allograph Fever
PK: IV (very slow infusion, 1- rejection Leukopenia
2wk), half life 3-9 days -Tx severe rejection episodes of Thrombocytopenia
corticosteroid resist acute Infections
reject Skin rashes
Note: Muro→ murine -Acute reject of renal allograph
Muromonab-CD3 Monoclonal antibody against -Anaphylactic rxns
antibodies (OKT3) CD3 of mature T-cell -Corticosteroid resist acute -Cytokine
storm (initial
-Depletes Tcells for 48 hrs allograft reject (heart, liver) binding of OKT3→

PK: IV -Depletes T-cells from donor BM activation of Tcell)

prior to transplant *Prevent cyto storm w/


diphenhydramine +

Note: Chimeric
Basiliximab Monoclonal anti-IL-2 receptor -Acute rejection of renal Well tolerated
antibodies→ “xi”
Daclizumab (Anti-CD25) transplant (give w/ CsA +
PK: IV, Corticosteroids)

Dacilizumab: long ½ life

(20days); give 5 doses (1@ 24hr

before, 4@14 day intervals)
*Basiliximab ½ life only 7 days,
only 2 doses given (1@ 2hrs
prior, 1@4days after
Note: Humanized Alemtuzumab Monoclonal Anti-CD52 (depletes -Refractory B-cell CLL
-Cytokine storm
antibodies → “zu” T cells -Neutropenia

-Pancytopenia (rare)
Note: anything
Alefacept Anti-CD2 (inhibits T cells) Chronic plaque psoriasis CI: HIV patients
binding to a receptor
depletes CD4, CD8 cells
→ ends in “cept”
→ ↑risk of infection)
Abataccept Anti-B7 (down regulates Tcells) Rheumatoid Arthritis -Exacerbations of
-↑Risk of infection
Efalizumab Anti-LFA-1 (limits Tcell Chronic plaque psoriasis Immune-mediated
adhesion, activation, & migration) thrombocytopenia
-Hemolytic anemia
↑risk of infection
STEROIDS Prednisone CANCER: Lymphomas Adrenal suppression
General anti-lymphocytic effect DOC for: Growth inhibition
-Triggers apoptosis -ITP Decreased muscle tone
IMMUNOSUPPRESSION: -Autoimmune hemolytic anemia Osteoporosis
Toxic to some T-cell lines -Acute glomerulonephritis Cushing’s syndrome
-Suppress immunity & inhibits G vs. H disease Immune suppression
production of mediators
-Ameliorate drug

Hypercholesterolemia is associated with atherosclerosis. Liver synthesizes
cholesterol-esters and package with TAGs to make a VLDL (B-100).
Loss of TAG via lipoprotein lipase (requires C2) from the VLDL produces IDL (mainly
Chol-ester). The IDL collects more chol-esters from HDL.
The IDL becomes LDL. HDL picks up extra cholesterol from tissues (via LCAT & A2).
Drug type Drug Mechanism Clinical Use Side Effects
STATIN Lovastatin ALL statins -Tx for hypercholesterolemia Grapefruit juice
inhibits CYP450
Simvastatin 1. Inhibit HMG CoA (↑LDL-c) 3A4→ aggravating statin toxicity→
Atorvastatin reductase→ → → → block -Tx for hypertrigleridemias (esp.
cholesterol synthesis mixed ↑LDL, ↑TAG diseases)
↓Liver cholesterol, ALL STATINS:
↑LDL-R expression Rule of 6’s = 2x dose of statin → -Myalgia→ check CK regularly
↓Plasma LDL ↓6% cholesterol (use drug combos -Rhabdomyolysis (↑risk w/
2. ↓ ↓ ↓ ↓VLDL synthesis → instead) gemfibrozil)→ relased myoglobin→
↓triglyceridemia ATN→ kidney failure (give
mannitol→enhance mg excret)
-PK: metabolized on P450 -Hepatotoxicity (check liver function
3A4 tests)
*Don’t give to homozyogos familial
Fluvastatin PK: metabolized by -Same
alternative P450’s hypercholest. → No LDL recptrs
CI: pregnancy, breast feeding, active
Pravastatin PK: NOT metabolized by -Same
liver disease, & may cause problems in
Rosuvastatin P450’s -Good for people on other drugs
Niacin Niacin -Inhibits lipolysis in adipose -Increases HDL -Cutaneous Flush (b/c
(Nicotinic Acid) tissue→ ↓TAG synthesis prostaglandins→ tx w/ aspirin)
Vitamin B3 requird for VLDL →→Blocks -Hepatotoxicity (fatty liver b/c liver
synthesis of VLDL is forced to keep its fat)
-Impaired insulin sensitivity
↑ ↑ ↑ ↑HDL, ↓VLDL, ↓LDL -Myopathy (if given w/ statin→just
↓ApoA1 Clearnce (↑HDL) monitor closely)
-Acute gouty attack
Fibrates Fenofibrate Activate PPARα α α α→ activates Tx of hypertriglyceridemia
-Mild GI (less common w/ fenofibr)
Gemfibrozil lipoprotein lipase→ ↑FA -Gall stones (↑risk b/c more free
uptake→ ↓plasma TAG fatty acids being excreted)
-Myositis (renal patients at risk)
↓VLDL, ↓IDL -More breakdown of VLDL can cause
Modest ↓LDL ↑production of LDL in some
↑HDL in most
Drug interacts: compete w/ warfarin
for plasma binding sites
CI: Statins; safety in pregnancy not
Bile acid Cholestyramine Prevents reabsorption of -Tx of hypercholesterolemia (esp.
-Steatorrhea, constipation,
Sequestrant Colestipol bile acid→ synthsis uses in young and pregnant women)
bloating, flatulence, nausea
Colesvelam cholest. → ↑LDL-Recpt→ -DOC for type IIa/b -Malabsorption of fat sol
vitamins &
LDL clearance hyperlipidemias oral lipid soluble drugs (digoxin,
-Tx of pruritus (only warfain, & thiazides)
-IF ↓LDL the liver tries to Cholestyramine) caused by -Colesvelam has fewer GI SE
make more→ → → → ↑ ↑ ↑ ↑VLDL and accumulation of bile acid in -↑VLDL & TAG
TAG synthesis→ hyper-TAG patients w/ biliary obstruction (e.g.
in pancreatic cancer) CI: hypertriglyceridemia
Cholesterol Ezetimibe -Inhibits uptake of dietary -Hypercholesterolemia (when
-Diarrhea, abdominal pain
Absorption Plant sterols cholesterol by blocking statin CI) -Used w/ statins
Inhibitors transporter (NPC1L1 -Rash & angioedema (rare)
receptr) in GI → forces liver
to synth more cholesterol→ CI: Breast feeding
-Inhibit VLDL prodct→ ↓ ↓ ↓ ↓LDL
PK: metabolized in SI & liver
w/ biliary & renal exretion
Omega 3-FA ↓ ↓TAG biosynthesis & ↑ ↑FA -Used if TAG >500mg/dL
↓ ↓ ↑ ↑
(fish oils) oxidation

Drug Mechanism Clinical Use Side Effects
THROMBOLYTIC Streptokinase -Acts on both bound & free - IV in short term emergency
-Excessive bleeding, possible
AGENTS plasminogen→ plasmin→ not clot management of coronary intracerebral
specific→ deplete circulating thrombus in MI, DVT, PE -Hypersensitivity rxns &
fibrinogen, & factors V, VIII -EARLY ADMINISTRATION!! hypotension
-used in situations angioplasty is -antigenic, s trep antibodies
not readily available may ↓activity
Antidote: aminocaproic &
tranexainic acids
Urokinase Human kidney cells Same
Generates plasmin
Alteplase (tPA) Recombinant Same, but also used in ischemic -No allergy problems
Reteplase -Clot specific, acting mainly on fibrin stroke human recombinant
bound plasminogen→ plasmin -Very $$ ($500/dose)
Aspirin -Irreversible acetylation of COX -Prophylactic treatment of
-Inhibits TXA2 (normally TXA2→ transient cerebral ischemia

platelets to degranulate & aggregate) -↓Incidence of recurrent-MI

-Increases bleeding time -↓Mortality in post-MI
-Vascular COX is less sensitive to
aspirin than platelet COX
Clopidogrel -ADP Receptor Blocker - ↓ ↓ ↓ ↓Ischemic events in patients Clopi→fewer
Ticlopidine -Irreversible inhibitors of P2Y12 (ADP with ischemic stroke, MI, or
-Hemorrhage, leucopenia,
receptor subtype on platelet peripheral vascular disease thrombocytopenic purpura
surface)→interfering w/ aggregation (alternative to aspirin) (making aspirin safer)
and activation by preventing ADP- -Used as antiplatetlet (instead
induced expression of platelet GP2b/3a of aspirin) if patient also has
gastric ulceration
Dipyridamole -Phosphodiesterase inhibitor→ ↑cAMP -Little effect by self
(Percantine) (which ↓platelet sensitivity to - Dipyridamole + warfarin→
activating stimuli) prevent thromboemboli in

patients w/ artificial valves

-and block uptake of adenosine (acts at -Prophlaxis tx in angina
A2 receptors to activate platelet -Coronary vasodilator
adenylyl cyclase)??? -Aspirin + dipyridamole (extend
release)→ 2’ prophylaxis of
cerebrovascular disease
Cilostazol -Phosphodiesterase inhibitor -Tx of intermittent claudication
-Promotes vasodiation and inhibition
of platelet aggregation
Abciximab -Monoclonal antibody against human -Acute coronary syndromes
GP IIb/IIIa receptor -Post-angioplasty
-↓ platelet aggregation by preventing
the cross linking rxn
Eptifibatide -cyclic peptide reversible antagonist -Acute coronary syndromes
of GP IIb/IIIa receptor -Post-angioplasty
Tirofiban -Nonpeptide reversible antagonist of -Acute coronary syndromes
GP IIb/IIIa receptor -Post-angioplasty
ANTICOAGULANT Renal excretion -Good for emergency situations -Bleeding # 1 sign
Structure: large polysaccharide, water -DOC for anticoagulation in
-Hypersensitivity rxns
soluble pregnancy -High doses→ ↓AT-III
-Kinetics: give parenterally (IV, SC), (sequestration)→ ↓inactivat
hepatic & RES elimination; no placental of coagul fact→thrombosis
access, half life = 2 hrs -Heparin induced
-Mechanism: binds antithrombin III→ thrombocytopenia (HIT)
↑ serine protease-inhibiting activity→ type II (antibodies to
fast inactivation of IIa, IXa, Xa, XIa, complex of heparin and a
XIIa (binding of heparin to ATIII platelet protein, Platelet
allows it to rapidly inhibt thrombin Factor 4)→ platelet
except that already bound to fibrin); aggregation & degranulation
works on active form of factors, →discontinue heparin & give
inactivating intrinsic/common pathway a DTI or fondaparinux
(i.e. works in plasma & works fast) -LMWH have longer half
LMWH inhibit activated factor X but lives, less thrombocytopenia
have less effect on thrombin (II) Antagonist: Protamine
sulfate →chemical
than UFH
Monitoring: PTT (no LMWH monitor) antagonism, fast

Enoxaparin LMWH DOC for unstable Angina

(Lovenox) DOC for MI

Danaparoid -Mainly inhibits factor Xa, less -Prophylaxis of deep vein -Less
immunogenic, safer in

inhibition of thrombin thrombosis in hip replacement hypersens rxns to heparin

-LMWH-like from porcine gut mucosa surgery

-Contains heparin sulfate, dermatan -Tx of HIT

sulfate, chondroitin sulfate

Fondaparinux -Factor Xa inhibitor -Prevention & tx of DVT

-Synthetic pentasaccharide, binds

antithrombin III which leads to

inhibiting of Xa;

-Once daily SC injection

Direct Factor Xa
Rivaroxaban Direct Factor Xa inhibitor
Apixaban Direct Factor Xa inhibitor

Lepirudin Direct Thrombin Inhibitors (DTIs) Bivalirudin + aspirin→ tx of -No


Desirudin -Recombinant forms of hirudin (from unstable angina when undergoing

Direct Thrombin
Bivalirudin leech) percutaneous transluminal
Argatroban -Directly bind to active site of coronary angioplasty (PTCA)
thrombin (independent of AT-III, thus
can reach and inactivate fibrin-bound
thrombin in thrombi)
-Monitored by PTT, given parenterally
Dabigatran Direct Thrombin Inhibitor
Structure: small, lipid soluble Prophylaxis use -Hemorrhage
(coumarins) -Kinetics: lipid soluble →ORAL, 98% -Bleeding of fetus
protein bound, half life = 30+ hours; Drug interactions: -Petechiae
placenta access, slow hepatic metab -Inhibitors of P450’s ↑warfarin -Adrenal
Dicumarol -Mechanism: inhibits Vit K epoxide activity (cimetidine macrolide, -Low
Therapeutic index
reductase→ prevents γ-carboxy→ azole antifungal) -Protein C deficiency→
↓liver synthesis of vit. K-dep. clotting -Inducers of P450’s: ↓warfarin
procoagulant effect in 1
factors (II, VII, IX, X, protein C); No activity (barbituates, few days & thus
effect on factors already present (i.e. carbamazine, rifampin) heparinization of
works on inactive forms of clot factors -Warfarin is an acidic molecule always
before warfarin
in liver), effect takes 8-12 hours, →abs↓ by cholestyramine →Cutaneous necrosis
inhibit extrinsic/common pathway -Displacement from plasma ↓protein C)
Monitoring: PT (need close monitoring) proteins by other drugs→ ↑free
Antagonist: Vit K (slow onset), fresh fraction→ ↑anticoagulat
CI: pregnancy
flozen plasma
Phytonadione Cofactor for synthesis of clotting Give for all coagulopathy as CI:
Synthetic analogs
(Vit K) factors adjuctive.
Hemolysis – G6PD
Kernicterus – newborn
-decrease prothrombin/
clotting factors
-ecchymoses, bleeding
From dried human plasma Hemophilia B (Christmas)
Has several Vit. K-dep. factors
PCC Trivalent:

Plasminogen Tranexamic Inhibit conversion of plasminogen to
Activation Inhibitors acid plasmin
Aminocaproic Same Post-tPA, urokinase,
acid streptokinase
i.e. bleeding due to fibrinolysis
Clots fibrinogen Topical hemostat (capillary
OTHER Protamine Heparin antagonist Anaphylaxis in some
From fish sperm vasectomy patients

Drug Mechanism Clincal Use Side Effects
MALARIA Liver forms of malaria are common in plasmodium vivax and ovale.
Chloroquine MOA: Drug is concentrated in -DOC for Tx of all malaria Very well
tolerated even w/
organism’s food vacuole→in the food (except resistant falciparum) long use
vacule, the organism digets the host’s -Chloroquine + primaquine→
1. Short term – GI
Hb→release of toxic heme→organism Prophylaxis for all malaria disturbance
protects itself by polymerizing the -Chloroquine + primaquine→ Tx 2. Long-term –
heme to hemozoin→BUT chloroquine of persistent liver stage HEARING DAMAGE
binds to heme, preventing its -Chloroquine + emetine→ Toxicity: dizziness, blurred
polymerization to hemozin→ ↑pH, Amebic liver abcess vision, retinal damage,
↑heme = oxidative damage to -Collagen disorders/autoimmune headache, diarrhea, GI
membrane→death of parasite and cell like lupus & RA due to the anti- irritation,
epigastric pain,
PK: given PO rapidly, completely abs; inflammatory effect exfoliative dermatitis,
concentrates in erythrocytes, liver, myocardia depression
spleen, kidney, lung, crosses CNS -Chloroquine resistant species *Long term high
dose for
can expel the drug via a rheumatologic disease→
BLOOD SCHIZONTICIDE membrane P-glycoprotein pump irreversible ototoxicity,
(Erythrocytic phase) retinopathy, myopathy,
Safe in pregnancy if traveling neuropathy
-Gametocidal except for falciparum *Causes EKG changes (b/c
quinidine like effect)
CI: psoriasis, porphyria
Primaquine 8-aminoquinolone -Tx exoerythrocytic forms of -GI irritation, H/A
-Liver phase of infxn recurring malarias (P. vivax and -Agranulocytosis
-Extensive metabolism (oxidation/ ovale) -Pruritis
demethylation) -Methemaglobinemia
Gametocidal (primaquine is a cell oxidant)
Pyrimethamine ANTIFOLATES! -Proguanil + Atorvaquone -↑ ↑↑ ↑Pyrimethamine→ →
↑ ↑↑ ↑ → →
Proguanil -Pyrimeth, proguan→ cycloguanil→ (malarone)→ prophylxis of megaloblastic
anemia (tx w/
Sulfadoxine* inhibits DHF reductase of parasite (at resist falciparum leucovorin)
Dapsone* low concentrations) -Pyrimethamine + sulfadoxine -GI distress
*Oral route, urinary elimination (fansidar)→ prophylaxis in -Sulfas →crystalluria,
chloroquine sensitive regions hemolysis, Steven-Johnson
Blood schizonticide & sporontocide-(in syndrome
mosquito’s gut)
Quinine -MOA: unknown…interfere w/ heme -Reserved for the serious -Cinchonism
(h/a, tinnitus,
polymerization→ death of erythrocytic infections (IV dose) vertigo blurred vision,
form of parasite? Prevent DNA strand -Tx chloroquine-resistant distress)
separation? falciparum (1 line therapy) -Cardiac conduction
-Relieve leg cramps disturbances & hypotension w/
-Quinidine can be used in place of -Myotonia congenital overdose
quinine -Sclerosing agent - Black water fever,
-Quinine + doxycycline or (intravascular hemolysis)
BLOOD SCHIZONTICDE -Hemolysis in G6PD patients
clindamycin or pyrimethamine
→ limits toxicity & shortens -Avoid in psoriasis
therapy CI: pregnancy (X)
Mefloquine -MOA: unknown -1 line for prophylaxis (Use -Cardiac conduction
-PK: Long half life (6 days)→b/c of doxycline instead??)
enterohepatic circulaiton; ONLY given -Tx for chloroquine resist -Avoid in
orally b/c IM causes irritation; highly falciparum (alternative) disorders &
protein bound; 20% excreted -Safe for pregnancies if -Neurological abnormalities
unchanged, traveling to chloroquine- (people becoming vegetables)
BLOOD SCHIZONTICDE resistant areas
-Not available on USA market
Amiodaquine Similar to cloroquine Often used b/c of low cost, -Agranulocytosis
limited toxicity, and sometimes -Aplastic anemia
BLOOD SCHIZONTICDE effective against falciparum -Hepatotoxicity
Amiodaquine + artesunate→tx -Photosensitivity
falciparum (as an alternative) -Dermatitis
-GI disturbances, H/A
MOA: unknown -Tx all malarias (even resistant) -Cardiotoxicity→ long QT
-Effective in erythrocytic phases -Not available in USA, but -Embryotoxicity
approved by FDA -Limited use b/c of irregular
abs & cardiotoxicity
Doxycycline ANTIBIOTIC Prophylaxis for chloroquine-
Often used w/ quinine resistant & mefloquine-
resistant falcip
Artemether MOA: metabolized in food vacuole -Tx multi-drug resistant Nausea,
vomiting, diarrhea
Artesunate PK: short half life (thus, not good falciparum (acts very rapidly)
prophylaxis), lipid soluble -Only drugs reliably effective Very $$, limited
BLOOD SCHIZONTICDE against quinine resistant strains (Not available in USA)
Atorvaquone -Inhibits electron transport/ATP No resistance seen
Asymptomatic Intestinal Amebic Colitis→ metronidazole + luminal amebicide
Extraintestinal Infection→ metronidazole + luminal
infection → give luminal amebicide
amebicide →TC + erythromycin (alternative) for moderate colitis *10 day course of
metronidazole cures 95% of
→Dehydroemetine or emetine (alternative) for severe uncomplicated liver abscesses
(can follow w/ choloroquine)
infection, but usually avoided due to toxicities
Metronidazole MOA: prodrug→ bioactivation -DOC for all tissue infxns from
AMEBIASIS Tinidazole (pyruvate:oxidoreducase – present in E. histolytica -Ataxia
anerobic bacteria) → forms a -DOC for Tx giardiasis -Disulfiram-like effects
cytotoxic product which binds to -DOC for Tx urogenital -N/V, diarrhea
protein and DNA→kills parasite trichomoniasis→ → → →tx both partnr -Dry
PK: PO, parenteral -Gardnerella vaginalis -Insomnia
-Anaerobic infxn “below the -Weakness
diaphragm”→ esp B. fragilis & -Potentiates coumarin drugs
*It is elminated via hepatic C. difficile (DOC for -Urethral burning
metabolism. Thus, any ↑P450→ Pseudomembranous colitis) -Metallic taste
↓drug -Acute ulcerative gingivitis
Safety in pregnancy not
-Cancrum oris
established, teratogenic/
TISSUE AMEBICIDAL -Ulcerative colitis
carcinogenic in animals
-Cutaneous leishmania
-Decubitis ulcers
-Alternative for Tx H. pylori
(metronidazole + TC + PPI/H X)
Emetine MOA: Blocks ribosomal movement→ → → → -Severe intestinal & extra- VERY
Dehydroemetine inhibting protein synthesis intestinal amebiasis Heart→ → → →cloudy
swelling &
Only given to hospital patients *Almost completely replaced by necrosis,
hypotension, CHF,
Narrow therapeutic range metronidazole arrhythmia, retrosternal pain
PK: subcutaneously or IM, -Urticaria/ pruritic eruption
concentrated in liver, spleen, -Balantidium coli -N/V, diarrhea
kidney heart; eliminated through -Fasciiola hepatica -Muscular weakness, pain,
kidney -Pargonimus westermani abscess @ injxn site
TISSUE AMEBICIAL -Fatigue, h/a, dizziness
MOA: unknown Mild, mainly GI
Diloxanide- DOC→ → → → asymptomatic carriers
furoate PK Oral→ → → →hydrolyzed in gut→ of cysts -N/V, abdominal cramps
diloxanide (amebicidal) & furoate -Tx moderate/severe -Esophagitis
(abs from the gut, conjugated in intestinal amebiasis -Dry mouth
liver & excreted in urine) *Kills amebiasis in 80-90% of -Pruritus
-Oral, 90% absorbed, conjugated patients w/ single course of -Urticaria
in liver, urine excretion therapy -Proteinuria
Iodoquinol MOA: unknown -Alternate for tx asymptomatic Infrequent SE:
carriers -Diarrhea, anorexia, N/V
LUMINAL AMEBICDE -Alternate for Tx mild to High doses→systemic:
severe intestinal amebiasis -Nephrotoxicity
-Optic atrophy
-Peripheral neuropathy
-Thyroid enlargement
CI: thyroid, renal disease
Paramomycin LUMINAL AMEBICDE -Some efficacy against
cryptosporidiosis in AIDs
Tetracycline MOA: eliminates normal intestinal *Ineffective used alone CI: children
under 8yrs &
flora (ameba’s main food source) pregnancy
-Chelates Ca, Mg, Al forms into non-
absorbable compounds
Chloroquine Tissue amebicidal Used in combo for hepatic absc See malaria
TRYPANOSOMIASIS Nifurtimox Tx of trypanosma cruzi (Chagas
Arsenicals Tx of African trypanosma

(rhondiense, gambiense)
LEISHMANIASIS Stibogluconate
TOXOPLASMOSIS Pyrimethamine +
GIARDIASIS Metronidazole
Pentamidine Backups CI: foscarnet
Atovaquone Interferes w/ electron transport Backups Very toxic

Typically, the treatment will be one large dose. So, the side effects generally are
mild or not an issue.
FOR Mebendazole -Inhibits microtubule synthesis DOC: Nematodes GI irritation
NEMATODES -Depletes helminth energy stores 1. Whip worm (trichuris
(“roundworms”) by decreasing glucose uptake trichuria); prolapsed Use w/ caution:
in cirrhosis, in
-Affected parasites are expelled w/ rectum children under 2yrs
feces 2. Pin worm (enterobius
-Rapid metabolization, reduced abs vermicularis) CI: pregnancy
w/ high fat meal 3. Hookworms (Necator
americanus & Ancyclostoma
4. Roundworm (Ascaris
Thiabendazole -Inhibits microtubules synthesis 1. Threadworm TOXIC
Larvicidal & ovicidal (strongyloides)→ → → →alternat -CNS distorbances, n/v,
Inactivated by liver hydroxylation to ivermectin dizziness, anorexia
-Excreted urine/liver 2. Trichinella (early stages) - Rarely, Steven-Johnson
3. Cutaneous larva migrans syndrome, erythema
(Ancyclostoma caninum, A. multiforme, fatalities
braziliense)→ alternative
to ivermectin CI: pregnancy, kidney/liver
*Much more toxic than other
benzimidazoles/ivermectin, so
other drugs are preferred
Ivermectin MOA: GABA agonist, chloride influx DOC: -Mazotti rxn: killing of
is enhanced→ hyperpolarization→ 1. Onchocerca volvulus microfilaria (oncocerca)→
paralysis of worm 2. Strongloidiasis fever, h/a, dizziness,
PK: doesn’t cross BBB somnolence, hypotension→ if
-Tx scabies, lice, cutaneous severe, given corticoids
larva migrans w/ external use CI: pregnancy, patients w/
Diethylcarbamazine MOA: not known DOC: Lacks serious toxicity
1. Lymphatic filariasis
PK: Take after meals 2. Loa loa
3. Tropical eosinophilia
*Replaced by ivermectin for tx
of onchocerca
Depolarizing NM block## spastic Mild: n/v, diarrhea
Pyrantel-pamoate ## Broad spectrum antihelmintic
paralysis of worm# expelled from
-Tx pinworm & Ascaris
GI tract (roundworm)
-Moderately effective for Tx
PK: poorly abs orally, exerts effects of hookworm
in GI
Doxycylcine -Tetracycline Tx Wuchereria bancrofti
MOA: indirectly acting by killing -Also onchocerca
Wolbachia (intracell symbiont of
filarial parasites)
FOR Praziquantel MOA: ↑ ↑ ↑ ↑permeability of cell DOC: -Drowsiness, dizziness,
TREMATODES membrane to Ca→ paralysis of 1. ALL schistosomiasis malaise, anorexia,
GI upset
(flukes) parasite 2. Most trematodes -Not recommended in
3. Most Cestode pregnancy
PK: rapidly abs orally, goes into CSF, *Cysticercosis→ albendazole CI: ocular
short ½ life preferred but prazi has similar worm would blow up in
efficacy eye→blindness (tx surgical)
Drug interact→ phenytoin,
carbamazepine, cimetidine
(↑prazi b/c inhibit P450s)
Bithionol MOA: inihibit helminth’s electron DOC for Tx of fasciolia Common/mild,
can be severe
transport chain hepatica (sheep liver fluke) -Diarrhea, abdominal cramps,
-Tx pulmonary paragonimas anorexia, n/v, dizziness, h/a,
-Not available in USA westermani (alternate) skin rashes
FOR CESTODES Albendazole MOA: Similar to mebendazole DOC: -Few SE w/ 1-3 day use
(tapeworm) 1. Neurocystercosis (Taenia -Long term use (hydatid
PK: erratically absorbed after PO, solium)→ controversial disease)→GI distress,
abs enhanced by high fat meal; rapid 2. Hydatid disease fever, fatigue, alopecia,
first pass (Echinococcus) pancytopenia
3. Pinworm -Neurocyster tx→
*Give on empty stomach for luminal Also: Hookworm, strongyloides, inflammatory
parasites trichuris *Follow blood count & liver
*Give w/ fatty meal for use against *Glucocorticoids usually given enzyms for long
tissue parasites gefore therapy to ↓SE from CI: pregnancy, kids <2yrs
dying cysticerci
Niclosamide -Salicylamide derivate 2 line Tx of most cestodes Nausea
MOA: Inhibits parasit mitochondrial -T. Solium (followed by purge) Abd pain
anaerobic phosphorylation of ADP in -T. saginata Pruruitis
-Lethal for cestode’s scolex & -Diphyllobothrium (fish tape Fever
segments of cestodes, but not worm, B12 def)
*Avoid alcohol w/in 1 day of
against ova present in segments
-Give laxative prior→ purge bowl of NO longer used in USA Tx
all dead segments to prevent
digestion and liberation of the ova,
which could lead to cysticercosis.

Drug Mechanism Clincal Use Side Effects
SUBCUTANEOUS Amphotericin B MOA: Binds ergosterol→ → pores in Broad spectrum
→ →
& SYSTEMIC membrane (increases permeability) Cumulative toxicity:
INFECTIONS -Low therapeutic index -DOC –for life threatening -Nephrotoxic (dose
-Fungicidal or fungistatic depending systemic mycoses dependent)→ tubular
on organism (Candida, Histoplasma, ↓GFR, anemia
Cocidioides, Blastomyces, -Neurologic (intrathec→ neural
PK: Slow IV infusion; extensively Aspergillus, cryptococcus) damage/seizures)
bound to plasma proteins; little -Anemia (from ↓EPO)
goes into CSF→ give intrathecal in -Fungal mening (Intrathecal)
meningitis (no inflamm effect on -GI mycosis (Oral) Infusion releated:
meninges) -Tx of mucormycosis -Fever, chills, vomiting, h/a,
-Poorly absorbed from the GI, so hypotension (sometime ↓K+)
oral effective only on fngi within -Histamine release
the lumen of the tract (not Resistance: -Alleviated partly by pre-tx w/
systemic) -Fungi w/ low ergosterol in NSAIDs, antihistamines
-Half life is > 2 weeks their membranes
-Hepatic impairment, renal
impairment, and dialysis have little
impact on drug concentrations

Amphotec® New lipid formulations Used for those who cannot ↓Nephrotoxicity

Abelcet® tolerate Amphotericin B -$$$

Flucytosine MOA: Pro-Drug→ → → →(fungal cytosine -Tx systemic mycoses & 5-FU is an
antineoplastic, so

deaminase)→ 5-fluorouracil (5-FU) Cryptococcus meningitis would see those side

1. 5-FU→5fdUMP→inhibits (Flucytosine + Ampho B) which ar significant b/c tx
thymidylate synthase→ -Tx Chromoblastomycosis lasts 6-9 months
inhibits DNA synthesis (Flucytosine + itraconazole) -BM depression (dose-
2. 5-FU→FUTP→ -Synergistic (Ampho B depend)

incorporates into RNA→ ↑flucytosine penetrance) -Hepatic dysfunction

inhibit protein synthesis -GI disturbances

PK: well absorb orally, enters CSF -Severe enterocolitis

Azoles *Flucytosine NOT used along
b/c ↑synthesis of cytosine→

Imidazoles have two nitrogens on azol ring (ketoconazole, miconazole,

clotrimazole). Triazoles have three nitrogens on the azol

ring (intraconazole, fluconazole, voriconazole, posaconazole). They all block 14α α

α α-sterol demethylase(CYP 450)→block

demethylation of lanosterol to ergosterol (blocks ergosterol synth). Generally, the

imidazoles are less specific than the

triazoles. Effective orally & will have problems with absorption. Absorption is
decreased by food and antacids. Resistance via


Ketoconazole -Less selective for fungalP450 -Rarely used to Tx systemic -N/V,


than newer azoles) mycoses b/c narrow spectrum & -Allergic rash

-Disrupts membrane, adverse effects→ replaced by -Inhibits steroid synthesis→

↑permeability itraconazole ↓ ↓ ↓ ↓cortisol, ↓ ↓ ↓ ↓testosterone→

-Also inhibits gonadal/adrenal -Active against Histo, Blasto, Antiandrogen effects→

→ → →

Candida, and Coccidiodies, but not

steroid synthesis ↓ ↓ ↓ ↓libido, gynecomastia

PK: PO only; azoles = weak aspergillus species. -Liver dysfxn (rare)

acids→ ↓abs w/ food or -Still used for Tx of -Nephrotoxic

antacids, (e.g. give w/ coke), mucocutaneous candidiasis

DOES NOT ENTER CNS -Tx Cushings Syndrome, INHIBTS CYP450’s → Many

Testicular Ca (anti-androgen) drug interactions

Resistance seen esp in protracted CI: pregnancy

therapy w/ advanced HIV infxn

Itraconazole PK: PO, metab in liver Broad spectrum -N/V, rash, hypokalemia, h/a,

(CYP3A4)→ major metabolite edema, hypertension

-Azole of choice (DOC) for Tx:

also antifungal 1. Blastomycosis

-Strong inhibitor of CYP3A4 2. Sporotrichosis

-Does NOT enter CSF 3. Paracoccidiomycosis

4. AIDs-Histoplasmosis

Fluconazole -Enters CSF -Broad spectrum Least toxic azole

-Slow metabolism, renal -Azole of choice for Tx of -NO endocrine effects

excretion systemic funal infxn→ less toxic

-No endocrine side effects than amphoB and distributes to CNS -Least effect of all

-High oral bioavailability, wide -Tx & prophyalxis (azole of on hepatic microsomal

therapeutic index, NOT

choice, DOC?) enzymes

dependent on gastric acidity 1. Cryptococal meningitis

-Poorly metabolized 2. Candidiasis

3. Coccidoides

-Prophylactic in bone marrow

transplants & AIDs

Voriconazole PK: PO, IV preps; metabolized Broad spectrum *Many drug interactions

by multiple CYP450’s Tx serious infections from metab by multiple P450’s

scedosporium, apiospermum,
-Goes into CSF -Transiet visual

fusarium species
disturbances, resolves in

-DOC invasive aspergillosis (seems 30min-1hr (>30% of users)

to have replaced ampho B)

PK: Oral only, CYP3A4 inhibitor -Broad spectrum, similar to

-Administer w/ full meal itraconazole

-Goes into CSF -Tx Mucor and other zygomycetes
Caspofungin MOA: inhibit β β(1,3) glucan -Tx Aspergillus & Candida (2 line -Fever,
rash, nausea,
β β
Micafungin synthesis→ → → →interfere w/ fungal after ampho B phlebitis, flushing
Anidulafungin cell wall synthesis→ cell lysis release)
PK: only IV, not CYP450’s
CUTANEOUS Terbinafine Inhibits squalene epoxidase→ DOC for dermatophytoses (esp -GI
disturbances, h/a, rash
INFECTIONS ↓synthesesis of ergosterol in onychomycoses) -Taste & visual
dermatophytes -Tx candida (rare)
PK: PO, but for topical fungal -Possilbe hepatotoxicity
infxn; deposited in skin, nails,
fat; long ½ life (200-400hrs)
-Does NOT affect CYP450
Griseofulvin -Accumulates in keratin Tx Dermatophytes only (Replaced -Barbiturates
↓ ↓ ↓ ↓absorption
containing tissues (keratin is in by terbinafine) -Hepatotoxic→ ↑ metab of
hair, skin, nails)→ Disrupts -Microsporum warfarin, contraceptives
mitotic spindles→inhibits fungal -Epidermophyton -H/a post-discontinuation
mitosis -Trichophyton -Peripheral neuritis
PK: PO, but for topical fungal -Teratogenic /carcinogenic
infxn active, must given w/ -Can be given IV to tx Candidas if -Potentiates effects
fatty meal, allergic to ampho B alcohol
-Induces CYP450 (so avoid
w/ history of porphyrias)
-Tx for 6-12mo
Nystatin (topical) MOA: Similar to Ampho B Candidiasis Rare SE
-Not well-absorbed from GI -Vaginal –Lack of absorption
-Too toxic for IV -Skin -N/V
-Never used parenterally, only -Oral for topical tx of GI fungi
given PO (thrush)
MOA: same as ketoconazole -DOC – topical Tx of candida Rare SE
Clotrimazole Topical only -Micocon→potent inhib of
Butoconazole warfarin metabolism

Headaches or mild/moderate pain is usually treated with an NSAID. Neurogenic pain
responds best to anticonvulsants, TCA, or SSRI. However, for
severe or chroinic malignant pain, opiods are the drug of choice. Opiods interact
with μ (mu), κ (kappa), and δ (delta) receptors. The analgesic
properties are mainly mediated by the μ receptors, but the with κ receptors in the
dorsal horn also contribute. The enkephalins interact more
selectively with the δ receptors in the periphery. All the opiod receptors are Gi
protein linked (↓ ↓cAMP). The respiratory depression of opiods is due
↓ ↓
to suppression of the respiratory drive in response to high CO2 (opiods do NOT
affect respiratory drive in response to low O2). The distribution of
1. Brainstem→ receptors influence respiration, cough, nausea, vomiting, blood
pressure, papillary diameter, and control of stomach secretions
2. Medial Thalamus→ → → → receptors mediate deep pain that is poorly localized and
emotionally influenced
3. Spinal cord→ → → → Receptors in the substantia gelantinosa receive incoming
sensory information, leading to the attenuation of painful afferent
4. Hypothalamus→ → receptors affect neuroendocrine function
→ →
5. Limbic system→ → → → greatest concentration of opiate receptors in the limbic
system is in the amygdala. These do not exert analgesic action, but
may influene mood.
6. Periphery → → → → Opiods bind to peripheral sensory nerve fibers and their
terminals. As in the CNS, they inhibit calcium-dependent release of
excitatory proinflammatory substances (e.g. substance P) from these nerve endings.
• Longitudinal smooth muscle tends to relax
• Circular smooth muscle tends to constrict
7. Immune cells→ → → → have a role in nociception (response to painful stimuli)

Tolerance is pharacodynamic (aka functional) because of a change in receptor

sensitivity to drugs. Opiate receptors are Gi coupled, and tolerance
causes an ↑cAMP production, escaping effects of opiates. Tolerance occurs in all
CNS effects, but there is no tolerance in peripheral effects such as
miosis and constipation. Dependence is both physical and psychological.
Withdrawl syndrome→ (physical) yawning, lacrimation, rhinorrhea, salivation, t
anxiety, sweating, goose bumps, muscle cramps, spasms, CNS originating
pain (mostly b/c excessive sympathetic response) (clonidine can be given for many
symptoms, but the pain management must be centrally acting,
methadone is used because of its longer half life). Withdrawl lasts several weeks
and is very PAINFUL. Withdrawl is also psychological, and craving
may be seen.

Why are opiods contraindicated in pregnancy? They are lipid soluble and would cross
the placenta into the baby, causing respiratory depression.
Most likely the baby would be stillborn. Don’t forget that the baby cannat do
glucuronidation. (Exception, you can give meperidine, not glucuronidated).
Class Drug Mechanism Clincal Use Side Effects
STRONG These drugs show a high affinity for μ μ μ μ receptors and varying
affinities for the other receptors.
Morphine MOA: -Analgesia -Respiratory depression (most
-Act at CNS receptors→ -Tx diarrhea common cause of death in OD)
hyperpolarize nerve→ inhibit -Relief of cough (codeine or -Pin point pupils
(morphine excites
firing dextromethorphan used now) the Edinger-Westphal nucleus of the
-Acts at k recptors in Lamina I/II -Tx acute pulmonary edema oculomotor nerve →↑
parasymp to
of the dorsal horn→ ↓release of eye)
substance P (modulates pain -Emesis (morphine directly stimulates
percept) the CTZ)
-Inhibits the release of many -GI symptoms (↑ circular SM tone,
excitatory transmitters from longitudinal SM relax→ constipat,
noceceptive nerves cramping, ↑biliary pressure,
-No major cardiovasc effects
-Inhibits release of GnRH, CRH, -Histamine release→urticaria,
LH, FSH, ACTH, β-endorphin sweating, vasodilation, & sometimes
-↑GH, ↑prolactin, ↑ADH (causes bronchoconstrict
urinary retention) -Hormonal (can ↑urinary retention,
but inhibit voiding, so may need a
PK: abs slow, erratic; significant catheter)
st nd
1 pass in liver, only small amount -Labor – may prolong the 2 stage of
crosses CNS, duration of 3-5hrs labor b/c ↓uterine contractions
-Liver conjugation→ → → → morphine- -Enhances cerebral and spinal
6-glucuronide (100X more potent) ischemia
-Little effect on the heart

Drug interact: depressant actions

enhanced by phenothiazines, MOA-I,
TCA. Low doses of amphetamine or
hydroxyzine enhance analgesia
Caution: renal dysfunction→
metabolite build up→respiratory
CI: Asthmatics, pregnancy (no
glucuronidation in newborn→ death
Meperidine -Antimuscarinic -Analgesia -NO miosis (pupil dilation)
MOA: 1. Biliary colic -Tachycardia
-IV→Dilates blood vessels, 2. Analgesia in pregnancy -NO GI/GU/gallbladder spasm
including cerebral vessels→ ↑CSF (Baby’s have CYP450s, -Seizures (from ↑serotonin)
pressure but main potential SE is -Respiratory depression similar to
-Contracts SM (lesser extent still respiratory morphine
than morphine) depression) -Antimuscarinic (e.g. dry mouth)
PK: short acting; metabolized by
CYP450→normeperidine (SSRI) Drug interactions: SSRI (too much
Duration of 2-4hrs ↑↑serotonin)
Methadone Causes less euphoria -Withdrawl maintenenance of -↑Biliary pressure
PK: PO good abs, longer duration opiate addicts -Constipation
(25hrs), -Physical dependence
Fentanyl PK: IV, epideral, intrathecal, rapid -Anesthesia -Respiratory depression
onset, short duration (15- -Tx of cancer patients w/ CI: fentanyl patch in the
30min)→ but half life terminal breathrough pain who are management of acute &
postop pain
(9hrs); tolerant to opiods (Fentanyl (due to hypoventilation)
100X potent as morphine; metab patch→ used in chronic pain
by CYP3A4 managemnt)

Transdermal half life (17hrs)

Alfentanil An ultra-short acting (5-10 min) -Analgesia Stronger respiratory
depression than
derivative of fentanyl, but less fentanyl
Sufentanil A more potent (5-10X) derivative -Heart surgury
of fentanyl
Remifentanil The shortest acting opiod w/ -Anesthesia
rapid offset, even after prolonged
Carfentanil Derivative of fentanyl, but -Veterinary medicine to
10,000X more potent immobilize large animals
Heroin Produced by diacetylation of morphine→ 3x more potent and ↑lipid -Not used
clinically in USA
solubility→ crosses CNS→ exaggerated euphoria -Used in the UK
Heroin is converted to morphine in body, but lasts half as long -most abused
Oxycodone -Semisynthetic morphine Tx. Severe pain -Abuse→ death
MIXED k Agonist→ spinal cord analgesia, -Little abuse potential
AGONIST- Pentazocine dysphoria (as opposed to
ANTAGONIST euphoria)
μ μ μ μ Antagonist→ precipitate
PARTIAL Partial agonists can precipitate withdrawl if the patient is taking a full
agonist (e.g. heroin or methadone). The ceiling effect is
AGONIST seen with the partial agonists. At some point after continuing to up the
dose, there is no further analgesic effect, only further
side effects. However, if you were using a full agonist (e.g. morphine) you cannot
saturate the receptors and can continue to
increase dosing with increasing analgesia
Codeine Lower doses→ antitussive w/ -Cough suppressant (replaced by -Rarely
produces dependence
little analgesic dextromethorphan)
-Analgesia (due to conversion to
-Used w/ NSAIDS
Tramadol MOA: unknown, partial agonist?? Ceiling effect for respiratory
-Centrally acting, binds μ depression
-Weakly inhibts reuptake of
serotonin & NE
Buprenorphine -Partial agonist at μ μ μ μ receptors -Opiate detox→ less severe
-Little sedation
withdrawl symptom compared to -Little respiratory depression
-Antagonist at k recptors
PK: sublingual, parenteral, long methadone (ceiling effect)
half life (37hrs), OD hard to
reverse b/c high binding affinity
ANTAGONIST Naloxone PK: IV, PO; duration (60-100min) -Reversal for respiratory
depression (IV)…can give for a relative
Competitive antagonist at at μ μ μ μ, overdose and the patient can walk out of the
room…will drift back into
k, δ δ δ δ receptors intox like an hour later
Naltrexone Much longer acting (48hrs), PO -↓ ↓Craving for alcohol (PO)
↓ ↓
-Tx of opiate addiction (PO) for “painless withdrawl”→rich kid put
on general anesthesia and muscle relaxants and given naltrexone to
mediate the biochemical withdrawl within 48 hours instead of a
week…and without seizures.
Alvimopan Peripherally acting antagonist at -Relief constipation from analgesic
μ μ receptors, basically the “anti- therapy w/ chronic tx w/ opiods
μ μ
ANTIDIARRHEA Loperamide Peripheral opiate receptor Tx diarrhea
L agonist, not abs→ stays in the gut
Tinctura opii Basically pure opium -Given if loperamide isn’t enough, so
this would stimulate all the opiate
ANTITUSSIVE Dextrometorphane -no analgesia Tx of cough
Other Apomorphine -Dopaminergic agonist (D1, -Adjunct tx of Parkinsons
D2)→ → centrally acting -Powerful emetic (Used to be used
→ →
-Morphine derivative, but does for intoxications to cause emesis,
not contain morphine or bind to μ now used in torture)
receptors -Alternative medicine, tx of
addiction, “vomiting therapy” for 2-
3weeks…low relapse rates


1st line for TB The treatment of TB is always multiple drugs, at minimum two drugs
(both bacteriocidal). Most of these drugs will be used for
6mo-1yr for tx. Treatment is divided into two phases. The intensive phase lasts 2
months, and the Continuation phase is the
final four months of treatment. For example, the intial short course therapy for TB
includes rifampin, isoniazid,
pyrazinamide, and ethambutol (RIPE) for 2 months. Then isoniazid and rifampin are
given for the next 4 months.
Isoniazid and Rifampin will cure 95-98% in 9 mo. The other drugs are added to
shorten duration of treatment.
Isoniazid (INH) MOA: INH = prodrug, needs -DOC in latent TB -Peripheral neuritis
bacterial catalase (KatG) to be →Given 1 yr for PPD+ kids from ↑B6 exretion (give
turned on→ inhibits synthesis of (<3yr) restlessness, muscle
mycolic acid & cell wall→ effective -Prophylaxis: twitching, insomnia
1. Immunosuppressed -Hepatotoxicity (<2%) in
against intracell and extracellular
organisms 2. Infants of highly infx elderly due to conversion of
PK: well abs (not w/ antacids), Goes parents (used for 6 weeks) INH in the liver to
into CNS 3. Close contacts of active TB (toxic metabolit)→ take
-INH is acetylated (genetic *INH is specific for TB, baseline hepatic enzyme level
variable), excreted through renal effective against intracellular -Sideroblastic
anemia (no B6
bacteria → used in transaminase rxn
*INH is the most potent of TB to detox amino groups from
drugs, but never given alone. Resistance: INH)
-Deletion of KatG gene -SLE in slow acetylators
*Bactericidal for rapidly growing, -Deletion of inhA (codes for
but bacteriostatic for bacilli in the “target”→ low Resistance) Drug Interact:
stationary phase; -Inhibits phenytoin &
warfarin metab
-MAO-I→ tyramine rxn
Rifampin MOA: Inhibits RNA polymerase -Broader spectrum; -Hepatitis
(Rifabutin) (by inhibiting rho factor) -Rash, n/v
-Rifabutin = DOC for TB
(Rifapentine) -Bactericidal against intracell & infected HIV patients b/c less
-Induces many P450’s
extracell mycobacterial strains interaction w/ HAART drugs, (↑elimination of
steroid Oral
(and other gram +/-) also better aginst MAC contracept)
-Enhances effect of -Red-orange metabolites
-Rifapentine- longer half life, amphotericin B in systemic (desmethyl?) → → → →all
permits weekly dosing; fungal infexn fluid turns red
-Tx of Brucellosis (Doxy + -Flu-like syndrome
Rifampin) -Take baseline hepatic
*Resistance via change in enzymes & CBC count
Ethambutol Inhibits synthesis of -Bacteriostatic, specific for TB Dose-dep
retrobulbar (optic)
arabinogalactan (cell wall and M. kansasii neuritis→ → → → ↓ ↓ ↓ ↓visual acuity
component) red/green discrimination
-Restistance: mutation of emb (Don’t give kids <5)
gene -Interferes w/ excretion of
uric acid
-Establish baseline visual
acuity and color vision
Streptomcin -May be included as 2 line, see -One of the first drugs used to
Deafness, vestibular
aminoglycosides tx TB, dysfunction, nephrotoxicity
Pyrazinamide MOA: unknown, but metabolically -Bactericidal to actively Hepatitis,
activated by bacteria (pncA dividing TB myalgia, rash, hyperuricemia,
gene)→ strains lacking the photosensitivity, ↑ ↑ ↑ ↑porphyrin
bioactivating enzyme are resistanc Resistance → lack of pncA gene synthesis
-Take baseline hepatic
enzymes and uric acid
2nd line for TB The 2 line drugs are either less effective, more toxic, or have not
been studied as extensively. They are useful in patients who
cannot tolerate the first line drugs or who are infected with mycobacteria that
are reistant to the 1 line agents.
Capreomycin Inhibits protein synthesis -Reserved for tx of multidrug
resistant TB -Ototoxicity
Ethionamide Structural analog of Capreomycin, -Gastric irritation
but different MOA -Hepatotoxicity
MOA: inhibits acetylation of -Peripheral neuropathies
isoniazid -Optic neuritis
-Mental disturub, impotence
Cycloserine Bacteriostatic, inhibits bacterial -CNS disturbances
cell wall synthesis involving D- (psychosis)
alanine (alanine racemase) -Peripheral neuropathy
CI: Epileptic patients
Para-Amino- -Blocks dinhdropteroate -Alternative for ethabutol in -Hypersensitivity
Salicylic Acid (PAS) synthase) kids < 5 yrs -Renal, thyroid, liver
-Does not go into CNS dysfunctions
Ciprofloxacin Fluoroquinolones Tx of multidrug resistant TB &
Ofloxacin some atypical strains
Azithromycin Macrolides, use ↑↑doses -Azith→ → → →good prophylactic for
Clarithromycin M. avium in AIDs
Azithromycin – long ½ life (4 days) -Part of the regimen that
Clarithromycin – short ½ life includes ethambutol and
-Tx of M. avium intracellulare
LEPROSY DRUGS Mycobacterium leprae (leprosy) does not grow on artificial media
(obligate intracellular). Droplets from sneezes and nasal
mucosa are heavily infected. M. Leprae shows a predilection for peripheral nerves,
skin, and mucosa of upper respiratory tract,
and it appears to grow in cooler areas of the body. Severeity depends on host
immunity. Primary resistance is due to acquiring
infection from patients harboring resistant organisms. Secondary resistance
develops during treatment from noncompliant or
subtherapeutic dosing.
TUBERCULOUS LEPROSY: Rifampin + Dapsone (for 6 months)
LEPROMATOUS LEPROSY: Rifampin + Dapsone + clofazimine (for 12 months)
Dapsone -Structurally & MOA like to -DOC for leprosy (daspone + -Hemolysis (esp in
sulfonamides & inhibits folate rifampin) -Methemoglobinemia
synthesis -Tx pnuemocystis jiroveci -Peripheral neuropathy
-Short acting pneumonia -Drug induced SLE
-Bacteriostatic for M. leprae -Lepra Rxn→ Erythemia
nodosum leprosum (like
Jarisch Herxheimer rxn)→
tx w/ clofazimine
Acedapsone Repository from of dapsone; longer
Clofazimine -Structurally related to dapsone, -Tx of dapsone-resist leprosy
-Eosinophilic enteritis, GI
but no cross resistance↓ -Tx of Lepra Rxn irritation
-Tx of leprosy in those not -Skin discoloration (red-
tolerating dapsone brown)
Amithiozone -Alternative to dapsone
-Used in combination

Disease Modifying Anti-Rheumatid Drugs (DMARD)

Rheumatoid arthritis appears to be an autoimmune disease driven primaryily by
activated T cells (IL-1, TNF). NSAIDS offer mainly symptomatic
relief. They reduce inflammation and the pain it causes and often preserve
function, but they have little effect on the progression of bone and
cartilage destruction. . The DMARDs have the potential to reduce or prevent joint
damage, but the effects of therapy may take 6 weeks to 6 months
to become evident. You can start the patient on an NSAID in this window period.
Combination therapy generally more effective: give weekly MTX and
add other agents (note: leflunomide + MTX increases the risk of hepatotoxicity, so
monitor closely; Anakinra & TNF inhibitors increase the risk of
neutropenia and infections, so don’t use)
Class Drug Mechanism Clincal Use Side Effects
Methotrexate MOA: competitively inhibits AICAR -DOC for Tx of RA -Nausea
transformylase (the last step in de -Mucosal ulcers
novo purine synthesis→IMP), causes -Hepatotoxicity (dose related)
↑AICAR levels which inhbits ADA -Hypersensitivty (rare)
andd AMP deaminase (no degradation -Pseudolymphomatous rxn
of AMP→IMP). AMP is extracell (rare)
converted to adenosine by the ecto-
5’nucleotidase Antidote = leucovorin
-Adenosine is a potent anti- (↓toxicity)
inflammatory mediator (acts on A2b
receptors)→suppresses NFkB
activation induced by TNF
Gold -IM formulations contain 50% -Used infrequently b/c of
Aurothiomalate elemental -gold; PO contain 29% gold toxicity
(IM) MOA: gold salts taken up by
Aurothioglucose macrophages and suppress
(IM) phaocytosis and lysosomal enzyme
Auranofin(PO) activity
CYTOTOXIC Chlorambucil -Probably phenylacetic acid mustard
AGENTS: (a metabolite) cross links
Alkylating agents DNA→preventing cell replication
Cyclophosphamide -Phosphoramide mustard cross links -PO for tx of RA (not
-Infertility (dose limiting)
DNA→prevents cell replication effective IV) -BMS

-Suppresses T/B cell function by 30- -Tx SLE -Hemorrhagic cystitis

Azathioprine Purine antimetabolite→ 6- -BMS
MP→suppresses B/T cell function -GI disturbances
-Xanthine oxidase degrades it →6- -↑infexns & malignancies
thiouric acid prior to excretion via -↓Dose if given w/ allopurinol
Leflunomide -Undergoes rpaid conversion to active -Patients not responding to
-Diarrhea & elevation of liver
metabolite A77-1726→inhibits MTX, give MTX + enzymes
dihydroorotate dehydrogenase→ ↓de leflunomide
novo orate synth→ ↓UMP→ p53
translocates to nucleus
-Lymphocytes arrested in G1 phase
Mycophenolate See immunosuppress; IMP
mofetil dehydrogenase inhibitor (isoform 2,
the one expressed in lymphocytes)
IMMUNOPHILIN MOA: see immunosuppress; also
LIGANDS increases expression of TGF-B, a
potent inhibitor of IL-2 stimulated T
cell proliferation and generation of
CTL lymphs
ANTIMALARIAL Chloroquine MOA: mechanism of anti-inflamm -Often used as adjuvants to
-Irreversible retinal damage
DRUGS Hydrochloroquine unclear NSAIDs (never gonna see the malaria
-Often given to those who comin’)→ less w/
have not responded hydrochloroquine
optimally to salicylates and
D-penicillamine Analog of AA cysteine -Tx RA (after use of gold -Dermatologic
MOA: unknown salts has failed but before -Nephritis
use of corticosteroids) -Aplastic anemia
Sulfasalzine drug→ 5-aminosalicylic (5-ASA) + -Tx ulcerative colitis -Rash
sulfapyridine; metabolized by GI -Tx RA (5-ASA) -Dizziness, n/v & h/a
bacteria -Tx juvenil arthritis -Occasionally leukopenia
-TX ankylosing spondylitis
ANTI-CYTOKINE Adalimumab Human IgG1 anti-TNF antibody→
DRUGS binds TNF-α→prevents interaction
w/ p55 & p75 cell surface
receptors→ downregulation of
macrophage & T cell function
Infliximab Chimeric monoclonal antibody that -Tx RA, ankylosing -B/c it is a
chimeric therapy,
binds w/ ↑affinity/specificity to spondylitis, Crohn’s disease, can → formation of
TNFα psoriatic arthritis antichimeric antibodies
-Given IV (HACA)→ give MTX to ↓
-ANA antibodies & anti-double
stranded DNA found, but only
very rarely→ drug induce SLE
Etanercept Recombinant fusion receptor; has two -Injection site reactions→
soluble TNF p75 receptor moieties erythema, local pain, swelling,
linked to the Fc portion of human itching (20-40% of patients)
IgG1→ binds TNFα and also inhibits -ANA antibodies & anti-double
lymphotoxin-α stranded DNA found, but not
“cept” = receptor analog documented SLE
ANTI-INTERLEUKIN Anakinra IL-1 receptor antagonist
INHIBITORS OF Abatacept -Fusion protein composed of an
COSTIMULATION immunoglobulin fused to the extracell
domain of CTLA-4 (can bind B7)
-Inhibits activation of T-cells
Rituximab -Chimeric monoclonal antibody -Targets CD20 positive B
-Anti-CD20 lymphocytes
GLUCOCORTICOIDS -Inhibit phospholipase A2 -Can slow down the -Fractures,

-Also selectively inhibit expression of appearance of new bone cataracts

COX-2 erosions -Diabetes, hypertension,
-Alleviate pain (intra- accelerated atherosclerotic
articular glucocort) heart disease
Class Drug Mechanism Clincal Use Side Effects
INSULIN Insulins may be in suspensions, the thicker the suspension (i.e more
complexing agent), the slower the kinetic. Insulin will be
ANALOGS used to treat type 1 DM, life-threatening hyperkalemias, and stress induced

Lispro Not suspension, IV solution

Rapid Acting
Onset: 0.3-0.5h

Peak effect: 1-2h

Duration: 3-4h

Aspart Rapid & short acting


Regular Insulin Not suspension, IV solution

Short Acting
(Regular Humulin) Onset: 0.5-1h

Peak effect: 2-4h

Duration: 5-7h

Short acting, soluble, crystalline zinc insulin, usually given SC

Lente Suspension (30% semilente, 70% ultralente), given only SC

Onset: 2-4h
Peak effect: 8-12h

Duration: 18-24h

Amorphous precipitate of insulin with zinc ion in acetate buffer;

Semilente Insulin

not suitable for IV (only SC)


Neutral protamine -Suspension of crystalline zinc insuoin combined at neutral pH

with protamine (positively charged polypeptide) (only given SC)

Hagedorn (NPH)

(AKA isophane insulin


Ultralente Suspension -Used to have a baseline

Long Acting
Onset: 3-4h insulin level in a diabetic

Peak effect: 8-16h (LONG ACTING) patient

Duration: 18-24h


ORAL Tachyphylaxis is a term describing a rapid decrease in response to the drug
after repeated doses over a short period of time.
SECRETOGOGUES This may be due to change in drug metabolism, progression of B cell
failure, change in dietary compliance, misdiagnosis of slow
onset type 1 DM. Most of these patients will eventually require insulin. Since
some of these drugs are cleared by liver or
kidney, drug interactions will cause hypoglycemia. Cimetidine (inhibit p450) for
the liver metab or acetylacetates (kidney).
Long term administration of oral secretogogues reduces serum glucagon levels,
which may contribute to the hypoglycemic effect
of the drugs.

SULFONYLUREAS MOA: Block (bind SUR1 subunit) the -Used in Type 2 -Hypoglycemia

ATP-dep K+ channels on B-cells (like diabetics -Weight gain

↑ATP) → ↑insulin release, ↓glucagon -Hypersensitivity (possible cross-
release, ↑insulin receptor sensitivity allergy w/ sulfonamides

Drug interactions:

-Mainly w/ first generation

drugs→ ↑hypoglycemia w/
1 generation cimetidine insulin, salicylates,
Sulfonylureas sulfonamides

Tobutamide -Short duration of action, rapidly Appropriate in renal

metabolized by the liver dysfunction
-Safest sulfonylurea
for use in elderly
Chlorpropamide Long acting, slowly metabolized by -SIADH (drug potentiates action
the liver of ADH)
-Transient hematologic toxicity
(leucopenia, thrombocytopenia)

-Disulfiram rxns

CI: elderly patients

Acetohexamide Active metabolites, cleared by kidney

↓dose in renal dysfunction

Second generation sulfonlyreas have increased potency by weight compared to the

first generation. They have decreased side
2 generation
effects and are more expensive. They should be used with caution in patients with
cardiovascular disease.
Shortest half life (2-4h), metaboliz
Glipizide -Safe to use in elderly CI: hepatic impairment & renal

by liver (little hypoglycemia) insufficiency

-Absoption delayed w/ food (take

30min before breakfast)

Glyburide Metabolized in liver, longer acting -Causes hypoglycemia in 20-30%

CI: hepatic impairment & renal


Glimepiride Long duration & most potent→ once -Hypoglycemia in only 2-4%

daily dosing & improves compliance;

metabolized by liver

-Sometimes called 3 generation

Repaglinide MOA: like sulfonlyureas, stimulate -Postprandial glucose -Do not use w/

insulin release by binding to SUR1 and regulators (b/c so rapid) -No sulfur in the
Meglitinide analogs
inhibiting ATP-dep K+ channel -Used in Type 2
PK: rapid onset (peak at 1hr), short diabetics w/ sulfa Drugs interactions:
duration (5-8hr), metab by CYP3A4 allergy -Drugs that inhibit CYP3A4
-Take just before each meal enhance glucose lowering effect
*Not as effective as sulfonlyureas in -Drugs that induce CYP3A4 lower
reducing FPG and HbA1c levels effects
-Newer drug, SAME as repaglinide SAME SAME
-Also partially restores initial insulin -Safe in patients w/
release in response to glucose (lost in ↓ ↓↓ ↓renal function
↓ ↓↓ ↓
type 2 DM -In contrast to other
-Cleared by CYP2C9 and 3A4 oral secretogogues, dose
-Duration is less than 4 hrs titration not required
INSULIN Two classes of agents, the biguanides and thiazolidinediones, improve
insulin action. These agents lower blood sugar by improving
SENSITIZERS target cell response to insulin (thus require insulin for action)
without increasing pancreatic insulin secretion. These drugs are
Biguanides Metformin MOA: Inhibits hepatic -Newly diagnosed Type -Risk for
hypoglycemia is very low
gluconeogenesis→ ↓hepatic glucose 2 DM (1 line) -GI distress (anorexia, n/v/d)

output; also slows intestinal abs of -Tx of polycystic ovary -Small risk of
potentially fatal

sugars & improves peripheral glucose disease lactic acidosis (impairment of

uptake & utilization -Decreases body weight liver gluconeo→blocks liver
-NOT metabolized, excreted as an -Only hypoglycemia metabolism of lactic acid)
active compound by kidneys agent shown to -↓Absorption of B12 (long term
-↓Hyperlipidemia (LDL & VLDL) ↓macrovascular events use)→ annually screen B12
cholesterol &↑HDL, (↓plasma TAGs by in Type 2 DM

15-20%) CI: Renal or hepatic disease,

*Equivalent efficacy to sulfonylureas alcoholism, acute MI, severe

in ↓FPG and HBA1c infection, or diabetic

ketoacidosis→ →due to ↑risk of
lactic acidosis

Thiazolidinediones have “thio” in the name, noting that they have sulfur in their
structure and may cause hypersensitivity. Since
another thiazolidinedione (troglitazone) was withdrawn from the market because of
hepatic toxicity, liver function enzymes are

routinely monitored.

Pioglitazone MOA: ligand of PPARy, a nuclear ↓Mortality & -Hepatotoxicity (watch

liver enz)
receptor (promotes glucose macrovascular events -Less hypoglycemia than
uptake/use, modulates synthesis of sulfonylureas
lipid hormones or cytokines, -Prevention of Type 2 -Weight gain
↑adiponectin?, ↓adiopcyte production diabetes -Fluid retention (presents as mild
& secretion of FA)→ ↑insulin anemia w/ peripheral edema)
sensitivity/↓resistance in adipose
tissue, liver, & skeletal muscle Drug interactions: oral
-Also has PPAR-α α effects contraceptives
α α
-Metabolized by 2C8 & 3A4 to active -CI: pregnancy, heart failure, liver
metabolites disease
Rosiglitazone Ligand of PPARy, less ↓TAG effects Same, but no significant drug
-Metabolized mainly by 2C8 and 2C9 interactions
to active metabolites
α-GLUCOSIDASE Competitive e inhibitors of the Used as monotherapy in -Gas,
diarrhea, abdominal pain
INHIBITOR intestinal α glucosidases→ type 2 DM or in -Hypoglycemia if combined w/
↓postprandial hyperglycemia combinations sulphonureas →must tx w/ glucose
Same effects, different structure, (dextrose) NOT sucrose
much more potent (breakdown blocked
CI: renal impairment or IBD
DPP-4 INHIBITOR Sitagliptin Inhibitor of dipeptidyl peptidase-4 -Potentiation of
(DPP-4), the enzyme that degrades mediated insulin
GLP-1 and other GLP-1-like secretion, suppression
of postprandial glucagon
INCRETIN Exenatide Synthetic analog of GLP-1 N/V/D
AMYLIN ANALOG Pramlintide Amyli is a small polypeptide released by the β-cells of
pancreas at
the same time as insulin. Amylin is also deficient in diabetics. It
slows gastric emptying and promotes satiety→→ ↓glucose in
blood. It is used as an ajunct in both type 1 & 2 DM


Drugs that mimic or block the effects of hypothalamic and pituitary hormones have
three primary applications:
1. Replacement therapy for hormone deficiency states
2. Antagonists for diseases that result from excess production of pituitary
3. Diagnostic tools for identifying endocrine abnormalities
Class Drug Mechanism Clincal Use Side Effects
GROWTH GH (somatotropin) secretion varies throughout life. Secretion is high in
childhood, reaches maximum levels during adolexcence &
HORMONE (GH) decreases as the age advances. Amplitude of GH secretory pulses is
maximal at night, shortly after the onset of deep sleep. GH
release is stimulated by 5HT, clonidine, & HYPOGLYCEMIA. GH release is suppressed
by IGF-1, free fatty acids, &
-Tx of GH-dep growth retardation KIDS:
Somatropin Recombinant human GH
Somatrem (rhGH) (symmetrical pituitary dwarfism) -Intracranial hypertension
PK: given SC or IM 3X/week, -Improves muscle or bone strength (rare)
onset=2-4h, duration =36h -Tx AIDs associated wasting -Scoliosis from rapid growth
syndrome -Hypothyroidism
-Tx of growth failure in Prader Willi ADULTS:
Syndrome -Tend to have more AE
-Tx of Turner syndrome (increase -Peripheral edema, myalgias,
height) arthralgias (esp hands/wrist)
CI: patients w/ malignancies
Recombinant IGF-1 (& IGF -Tx of GH insensitivity (Laron -Hypoglycemia (eat a snack
binding protein-3) dwarfism) 20min before or after drug)
-GH deficiency & anti-GH antibodies
GH ANTAGONIST Octreotide Somatostatin analog (45X -Tx small GH-secreting ademonas
Very $$$
Lanreotide more potent in inhibiting GH, (which→gigantism/acromegally) -Gall stones
& pancreatitis w/
2X potent in inhibiting insulin -Tx many hormone secreting long term use
secretion)→ reduces GH tumors (e.g. Carcinoid syndrome, -n/v/d, abdominal cramps,
product gastrinoma, glucagonoma) flatulence, steatorrhea
-Long duration
Bromocriptine Dopamine receptor agonist Tx acromegally
→reduces GH production
Pegvisomant Prevents GH from activating Tx acromegally
its receptor
GHRH -Used to test for GH secretion
Sermorelin GHRH analog
-Stimulate GH (for short people)
GONADOTROPINS are used to induce ovulation in women with anovulation due to
hypogonadotropic hypogonadism, polycystic ovarian syndrome,
obesity, & other causes. Because of the high cost of gonadotropins and the need for
close monitoring during their administration, gonadotropins are
generally reserved for anovulatory women who fail to respond to other less
complicated forms of treatment (e.g. clomiphene, AI, metformin). The two
most serious complications in women treated with gonadotropins and hCG are the
ovarian hyperstimulation syndrome (0.5% of pateints→ ovarian
enlargement, ascites, hydrothorax, hypovolemia, sometimes shock) and multiple
pregnancies (risk at 15-20%).
Menotropins (hMG) Extracted from the urine of -Used in hypogonadal states of men
postmenopausal women (FSH- & women
like and LH-like & hCG?)
FSH Urofolitropin Purified preparation of human -Stimulates gametogenesis &
(uFSH) FSH extraceted from the development in women &
urine of post-menopuasal spermatogenesis in men
women -Tx infertility
-Tx hypogonadotropic hypogonadism
& associated oligospermia
Folitropin alfa Recombinant forms of FSH
Folitropin beta (rFSH), shorter half life than
ones from urine
LH LH is a major stimulant of gonadal steroid production. It regulates follicular
development and ovulation. No pure preparation of
LH is available for use. Drugs may produce ovarian hyperstimulation or familial
ovarian hyperstimulation, causing multiple
pregnancies (Rx. Ganirelix)
Lutropin Recombinant hman LH (rLH), -Stimulates follicular development in
given SC, half life of 10h infertile women w/ profound LH def
(Lutropin + Folitropin alfa)
hCG -Purified hCG from the urine -Used in infertility
-LH agonist
Choriogonadotropin Recombinant hCG (rhCG)
GnRH Leuprolide -Given in pulsatile doses, Long acting agonists -Gonadotroph
Histrelin resembling physiological -Tx prostate cancer does not occur immediately
cycling -Endometriosis (tx up to 6mo) (transient flare up initially)
-Continuous dosing would ↓LH -Precocious puberty -Less likely than gonadotropins
& ↓FSH -Uterine leiomyoma (tx 3-6mo) to cause multiple pregnancies
-First 7-10 days causes “flare” & ovarian hyperstimulation
& afterwards suppresses Pulsatile: syndrome
PK: injected once daily -Amenorrhea, infertility
Goserelin PK: depot injection 1x/mo
Nafarelin PK: Nasal spray, longer lasting
GnRH When gonadotropins are used -Used in controlled ovarian -These produce an
ANTAGONIST Cetrorelix to stimulate follicle develop→ hyperstimulation until the
effect (as opposed to GnRH
risk of premature endogenous apprapriate follicular maturation has agonists), so
don’t need to use
surge in LH b/c of rapidly occurred, then drug discontinued until day 6-7 of cycle
changing hormones→ the LH -Lower risk of ovarian
surge could prematurely hyperstimulation syndrome
stimulate ovulation -Adherence is critical b/c
effects reverse very quickly
Abarelix Palliative prostate cancer
PROLACTIN Prolactin is responsible for lactation (milk production).
Hyperprolactinemia inhibits GnRH release causing hypogonadism and
infertility. Also seen with high prolactin levels are amenorrhea, galactorrhea in
women, & loss of libido & infertility in men.
Prolactin -No therapeutic value
PROLACTIN Bromocriptine Dopamine agonist, ↑affinity -Suppresses prolactin release
-Light headedness, h/a, nausea
ANTAGONIST Cabergoline for D2 receptor -Shrink pituitary prolactin secretg
-Orthostatic hypotension
Pergolide -Bromocriptine ½ life = 7h tumors & restore ovulation in many -Fatigue
-Pergolide ½ life = 20h -Acromegally -Psychiatric manifestations
-Cabergoline ½ life = 65h -Erythromelalgia (rare)
CORTISOL is bound to plasma Corticosteroid binding globulin (CBG), an α2 globulin
synthesized by the liver that binds about 90% of the circulating
hormone. The remainder is free (5-10%) or loosely bound to albumin (5%). CBG is ↑in
pregnancy due to estrogen and hypothyroidism
CRH CRH CRH stimulates the release of -CRH can be used in the diagnosis of
ACTH from the anterior pituit ACTH secretion by pituitary
adenoma, adrenal & ectopic tumors
ACTH ACTH -Only used in diagnostic purposes in
adrenal insufficiency
Cosyntropin Synthetic analog of ACTH -DOC in infantile spasms

Signs of hyperthyroidism: 1) Marie’s sign- tremors of the body or extremity seen

especially in outstretched hands, 2) Dalrymaple sign– staring look, 3)
Ballet sign– loss of voluntary movements of the eye, 4) Stellwag’s sign– infrequent

Steps in synthesis of THYROID hormones:

1. TSH stimulates the thyroid to uptake Iodide (I-) via the sodium/iodide symporter
(NIS). This can be inhibited by thiocyanate (SCN-),
pertechnetate and perchlorate & radioactive iodide.
2. Oxidation to iodine (I ) by thyroid peroxidase at the apical membrane. Thyroidal
peroxidase is transiently blocked by high levels of
intrathyroidal iodide and blocked more persistently by thioamide drugs
3. Then tyrosine residues on the thyroglobulin molecule are rapidly iodinated to
form MIT & DIT in a process called iodide organification (occurs
in the colloid)…blocked by thioamide drugs
4. Condensation of two DITs produces T4 (still attached to thyroglobulin)…blocked
by thioamide drugs.
5. Thyroglobulin is endocytosed back into the cell
6. T3 & T4 are cleaved from thyroglobulin via the lysosome and secreted into the
plasma. Inhibited by Ipodate
7. Peripheral deiodination of T4 produces T3. Deiodination may occur in the inner
ring, producing rT3, which is metabolically inactive.
Amiodarone, iodinated contrast media, B-blockers, corticosteroids, severe illness,
or starvation inhibit the 5’ deiodinase necessary for
the conversion of T4 to T3, resulting in low T3 and high rT3 in the serum.

Goitrogenic: cabbage (contain thiocyanate), sulfodimethoxine, & cassave (contains

carbohydrates and thiocyanate)

Severeal drugs may provoke autoimmune or destructive inflammatory thyroiditis→

1. Amiodarone, structurally similar to thyroid hormone
2. Lithium, increased levels in thyroid gland inhibit release of hormones
3. Interferon Alfa & interleukin-2
TRH Protirelin -TRH stimulates TSH and -Test the anterior pituitary’s
prolactin secretion ability to secrete TSH
THYROID T3 & T4 T3 is fast acting, has short -Tx Myxedema -T4 sensitizes myocardium
to the
HORMONES half life and more $$$ effects of sympathetics→
-Borderline adrenal insuff
patient→ adrenal insufficiency
THIOAMIDES Methimazole -Block thyroid peroxidase -Tx of thyrotoxicosis -Nausea, GI
-Block iodination of tyrosine (preferred drug b/c less serious -Altered sense of
taste or smell
residue on TG SE) (only methim)
-Block coupling rxns -Maculopapular pruritic rash
-Methimazole does not *Note, since the synthesis rather -Arthralgia
inhibit conversion from T4 to than the release of hormones is Rare:
affected, the onset of these
T3 (& antagonizes PTU) -Agranulocytosis
-Methimazole is 10X as agents is slow, often requiring 3-4
potent as PTU weeks before stores of T4 are -Vasculitis (manifests as lupus)
PK: given 1x/day, PO depleted.
-Cross placental barrier and are
concentrated by the fetal thyroid
(Category D in preg→ risk of fetal
Propylthiouracil Same, but also blocks -Tx of thyrotoxicosis -Same AE as Meth, but
is more
5’deiodinase in peripheral -Preferable in pregnancy highly protein bound→less cross
tissue -Preferred in thyroid storm due placenta, so preferable in
PK: given 3x/day, PO to ability to block T4 to T3 pregnancy
-More serous AE
IODIDES Wolff-Chaikoff effect - large doses of iodides initially causes
hypothyroidism for 10-14 days, but they the effect “escapes”
and thyroid hormone production resumes.
Iodine/Iodide salts -Inhibit organification -Used prior to introduction of
-Jodbase-dow phenomenon
-Block hormone release thioamides in 1940’s, now rarely (→hyperthyroidism in
-↓The size & vascularity of used as sole therapy people)
the hyperplastic gland -Improvement in thyrotoxic in 2- -↑Intraglandular stores of
7d (valuable in thyroid storm) (may delay onset of thioamide tx or
*Do NOT use alone b/c gland - Useful in preoperative prep prevent use of
radioactive iodine)
will escape from iodide block -Thyrotoxic crisis (Iodides + -Avoid chronic use in
preg (fetal
in 2-8 wks→may exacerbate PTU + B-blockers) goiter)
thyrotoxicosis -Iodide intoxication (iodism)
-Anaphylactoid rxn (angioedem)
-Brassy taste, burning of
Lugols solution A mixture of iodine &
-Enlargement of parotid and
potassium iodide
maxillary glands
Saturated solution Potassium iodide
ANION Competitive block of iodide -Patients w/ iodide induced Aplastic anemia
K+ Perchlorate
INHIBITORS Pertechnetate uptake hyperthyroidism
Thiocyanate *Effects can be overcome by *Rarely used today b/c of SE
large doses of iodides, so
effectiveness is somewhat
Iodinated Contrast Diatrizoate MOA: Rapidly inhibit -Tx of hyperthyroidism
(offlabel Relatively nontoxic
Media converstion of T4→T3 use)

Ipodate MOA: same, may also inhibit

hormone release from
thyroid gland
Iohexol MOA: same same
RADIOACTIVE 131-Iodine Emits β rays that destroy -Only isotope used in Tx of No
risk of cancer
IODINE thyroid after a few weeks thyrotoxicosis NO pain
-Tx of refractory Grave’s disease Hypothyroidism
CI: pregnancy, nursing
B-Blockers Esmolol Improve symptoms, but do -Tx tachycardia, tremors,
not alter thyroid hormone sweating from thyrotoxicosis
Synthetic androgens -Replacement therapy in -Over-masculinization
Stanozolol hypogonadism, osteoporosis, and -Hirsutism (in women)
Fluoxymesterone could be used in growth -Depression of menses
Oxymetholone stimulation (↑muscle mass, ↑RBC) -Acne
Nandrolone -Clitoral enlargment
Phenpropionate -Rarely causes hepatic adenomas
and carcinomas
-Cholestatic jaundice & prostatic
-Premature closure of epiphysis
-May lead to dependence
CI: pregnancy
ANDROGEN Leuprolide GnRH analog @ continuous -Tx of prostatic cancer
ANTAGONIST Gonadorelin dose
Flutamide Receptor inhibitors -Tx of hirsuitism (cypro or
Cyproterone spironolac)
Ketoconazole Steroid synthesis inhibitors -Tx of Cushing’s disease
Metyrapone Synthesis inhibitor (blocks
Finasteride 5-α reductase inhibitor→ -Tx of benign prostatic
reduces production of DHT hyperplasia
Mifepristone Blocks Glucocorticoid & -Abortion
progestin receptors
ESTROGENS Estradiol is the major natural estrogen. Conjugated equine estrogen is
purified from pregnant mare’s urine. The most common
synthetic froms are ethinyl estradiol and mestranol. Diethylstilbestrol is a
nonsteroidal estrogen.
ESTROGEN • Regulates growth & -Tx of hypogonadism in girls -Hypertension
maturation of reprod -Oral Contraceptive Pills (+ -Thromboembolism
tract Progestins) -Hepatic adenoma
• Stimulates endomet -Postmenopausal HRT -Breast & endometrial cancer
growth -Tx prostate cancer, acne, -Procoagulant (↓ATIII, & @
• ↓Bone resorption & dysmenorrheal, DUB ↑doses→↑factors II, VII, IX, X)
maintain normal structure -Endometrial hyperplasia, breast
of the skin & blood tenderness, migraine,
vessels cholestastasis
• ↑Thyroxin binding globulin CI: Hx of thromboembol,
• ↑HDL and TAG levels
Pregnancy, Liver disease, Breast
• ↓LDL levels cancer
• Promotes coagulation

Ethinyl estradiol
Clomiphene -Estrogen antagonist Multiple births, ovarian
(hypothal & anterior pit) enlargment, hot flashes, visual
-Estrogen Agonist (ovary) disturbances
PROGESTIN Progestin is normally not used, only the synthetic compounds.
Progesterone is a progestin, but also androgenic and
ne acetate

Desogestrel -NO androgenic effects
-NO anti-estrogenic effects
PROGESTIN Mifepristone
Other Danazol Partial agonist at -Used to tx endometriosis (anti- -Weight gain
progesterone, glucocorticoid proliferative effect by negative -Edema
and androgen receptors feedback) -Acne
-↓HDL levels
Oxytocin Synthesized in 1. A uterine stimulant, used to -Hypertensive epidosdes
(b/c of
(Pitocin) paraventricular nuclei of the induce or enhance labor contraction of
blood vessels)
(Syntocinon) hypothalamus 2. Contracts myoepithelial cells of -Uterine rupture
breast & cuase milk letdown
3. Can control postpartal and
postabortal bleeding
ADH ANALOGS ADH is Synthesized in the supraoptic nuclei of the hypothalamus.
Adverse effects generally include: hypertension, headache,
abdominal cramps, and nausea. Too much ADH→ think SIADH → hyponatremia, dizziness,
volume contraction
ADH Receptors:
1. V1 in the arterioles→ vasoconstriction
2. V2→ insertion of aquaporin channels in kidney
Desmopressin -Synthetic, long acting ADH -Tx diabetes insipidus from No effect on
V1, →so will not
analog at V2 only, not V1 surgery or trauma or cranial affect blood pressure (no
-Nasal spray radiotherapy for lymphocytic hypertension)
Vasopressin Boosts factor VIII -Used in mild to moderate
-Used in bleeding from varices,
prior to definitive tx of portal
PTH Teriparatide PTH analog, use once daily -Promotes osteoblastic activity→
-Continuous PTH promotes new bone formation
osteoclastic activity

Calcium Salts Ca chloride IV preparations -Used in severe cases of -Peripheral

Ca gluconate hypocalcemia -Transient tingling
-Cardiac arrhythmias (if rapid
Ca carbonate Oral preparations -Preventive measures against
Ca citrate osteoporosis
Ca phosphate -Tx mild cases of hypocalcemia
Ca Lactate
Vitamin D Calcitriol Active form of Vit D Used in: -Vascular calcification
-Osteoporosis -Nephrocalcinosis
Cholecalciferol Vitamin D3
-Chronic renal failure -Soft tissue calcification
Ergocalciferol Vitamin D2
-Nutritional rickets -HYPERCALCEMIA (typically
Calcifediol 25-(OH) Vit D
Bisphosphonates Etidronate (IV, PO) Inhibit osteoclastic activity -Tx malignancy
associated -Erosive esophagitis (alendronate)
Pamidronate (IV) by disrupting mevalonate hypercalcemia -GI distress (gas)
Alendronate pathway (↓ osteoclast H+ -Tx paget’s disease of bone
ATPase) -Tx osteoporosis (esp -Osteomalacia if taken > 12 mo
“-dronate” -Reduce resorption and helps corticosteroid induced) (etidronate &
formation of hydroxyapatite
-Structural analog of
pyrophosphate Patient should stand for 30 min
-Very poorly absorbed (<1%) afterwards (reflux = caustic to
after oral administration, so esophagus)
must be given in fasting
state with

Class Drug Mechanism Clincal Use Side Effects

IFN B-1a Flu-like symptoms,

Glatiramer Ac

Class Drug Mechanism Clincal Use Side Effects

Class Drug Mechanism Clincal Use Side Effects
General principles:
1. Select AED that is most efficacious for seizure type
2. Consider other comorbidities that may also be treated w/ AED (e.g depression,
headache) or other special considerations (pregnancy)
3. Consider side effect profile
a. Inducers vs. inhibitors
b. There is decreased efficacy of oral contraceptives via induction of cytochrome
P450. A person with seizures may want to avoid
pregnancy since many of the drugs cannot be taken, but remind patients that oral
contraceptives are metabolized quicker
potentially causing an unwanted pregnancy.
c. Safe for pregnancy: f
4. Consider conviencence and dosing
5. Consider cost

The mechanisms of action:

1. Decrease axonal conduction by preventing Na influx through fast Na channels
(blocks the propagation of seizures, does not prevent)
2. Increasing inhibitory tone by facilitation of GABA-mediated hyperpolarization
3. Decrease the excitatory effects of glutamate
4. Decrease the presynaptic Ca influx through type T channels in the thalamic

Inducers: Phenytoin, carbamazepine, oxcarbazepine, phenobarbitol

Inhibitors: valporic acid

Approach to Status Epilepictus:

1 generation Carbamazepine Same as phenytoin Same -CNS depression
-CYP450 inducer -DOC for trigeminal -Exfoliative dermatitis (SJS)
neuralgia -Osteomalacia (↓Vit D)
-↑ ↑ ↑ ↑ADH secretion
-Megaloblastic anemia (↓folate)
-Aplastic anemia rare
-Teratogenic (cleft lip/palate/
spina bifida)

Ethosuximide Blocks T-type Ca channels mainly in DOC for Absence Blood toxicities
thalamus seizures
Phenobarbitol Act POSTsynaptically Block Sedation
glutamate receptors (and also help Dizziness
↑GABA) Impaired ognitive function
BM suppression
Frozen shoulder
Dupuytren contracture
Reduced libido
Phenytoin Blocks axonal Na channels in their -Blocks the propagation of -Induction
of CYP 450
inactivated state seizures -CNS depression
-Non-linear kinetics (↑[blood] faster -Tx of any seizure except -Gingival
than expected) absence seizures (…remember dihydropyridines)
-Zero order elimination kinetics -Hirsutism
-Osteomalacia (↓Vit D)
-Megaloblastic anemia (↓folate)
-Aplastic anemia (check CBCs)
-Teratogenic (cleft lip/palate)
-Cerebellar degeneration
Valproate -Like phenytoin (block Na channel) -Any seizure state (even -Inhibits CYP
-Inhibits GABA transaminase (blocks absence seizure) -Hepatotoxicity
degradation of GABA→ ↑GABA) -Tx of mania in bipolar -Thrombocytopenia
-Block T-Type Ca Channels (thalamus) -Tx of migraines -Pancreatitis (rare)
-Teratogenic (spina bifida)
2 Generation Felbamate -Block Na channels -Hepatotoxicity
-Block glutamate receptor (NMDA) -Aplastic anemia
Lamotrigine -Block Na channels -SJS rashes
-Block glutamate receptor (AMPA)
Oxcarbazepine CYP450 inducer -Drowsiness
Tiagabine Act PREsynaptically, inhibit
reuptake of GABA
Topiramate Act POSTsynaptically Block
glutamate receptors (and also help
Viagabatrin Act PREsynaptically, inhibit
degradation of GABA (inhibits
GABA aminotransferase)
Zonisamide Same as phenytoin

3 generation

Partial seizure (simple or complex) Valproate, phenytoin,
General-tonic clonic Valproate, phenytoin,
General- Absence Ethosuximide
Status epilepticus Lorazepam (IV), diazepam,
phenytoin, or fosphenytoin


GABA GABA-A INHIBITORY: When two molecules of GABA Muscimol Picrotoxin
bind receptor, the ion gate is opened and influx Bucuculline
of Cl. Found throughout CNS, generates fast
GABA-B INHIBITORY: GABA binds receptor and elicits
action through AC pathway (↓cAMP levels +
opens a K+ channel so that K+ flows out of the
cell→ hyperpolarization + closes Ca channel) →
slow IPSP
Glutamate NMDA STIMULATORY: When Glutamate + glycine Amantadine
(cofactor) bind NMDA receptor, the ion gate Memantine
opens with influx of Na and Ca and efflux of K. Ketamine
Stimulatory. A voltage dependent membrane PCP
depolarization is also required to open the gate Dizocilpine
b/c NMDA is plugged by extracellular Mg.
AMPA STIMULATORY: When Glutamate bind AMPA
receptor, the ion gate opens with influx of Na
and Ca and efflux of K. May play a role in
excitotoxicity in neuronal cell death
Glycine Glycine INHIBITORY: Glycine binds receptors found in
Receptors spinal cord causing ion channel to open and influx
of Cl
Dopamine D1 STIMULATORY: dopamine binds D1 receptor→ Pergolide
activates AC pathway (↑cAMP) and PLc pathway
(↑IP3 + DAG). Found in the CNS
D2 INHIBITORY: dopamine binds D2 receptor→ Bromocriptine
AC pathway (↓cAMP + opens K channel so efflux Pergolide
of K) → hyperpolarization Pramipexole
Histamine H1 PLC pathway
H2 AC pathway Diphenhydramine

The stages of anesthesia (1-4):
1. Stage of analgesia: The patient initially experiences analgesia without amnesia.
Later in Stage I, both analgesia and amnesia are produced
2. Stage of excitement: During this stage, the patient often appears to be
delirious and may vocalize but is definitely amnesic. Respiration is
irregular both in volume and rate, and retching and vomiting may occur if the
patient is stimulated. For these reasons, efforts mre made to
limit the duration and severity of this stage, which ends with the reestablishment
of regular breathing.
3. Stage of surgical anesthesia: This stage begins with the recurrence of regular
respiration and extends to complete cessation of
spontaneous respiration (apnea). The most reliable indication that stage III has
been achieved is loss of responsiveness to noxious stimuli
and reestablishment of a regular respiratory pattern.
4. Stage of medullary depression: This deep stage of anesthesia includes severe
depression of the vasomotor center in the medulla, as well as
the respiratory center. Without circulatory and respiratory support, death rapidly

Class Drug Mechanism Clincal Use Side Effects

IV ANESTHETICS Many IV drugs have an onset of anesthetic action faster than the
most rapid inhaled agents (desflurane, sevoflurane).
Adjunctive use of potent opiods (fentanyl) contributes cardiovascular stability,
enhanced sedation, and profound perioperative
analgesia. Benzodiazepines have a slower onset and slower recovery than the
barbiturates or propofol and are rarely used for
induction of anesthesia. However, preanesthetic administration of benzodiazepines
can be used to provide anxiolysis, sedation,
and amnesia when used in conjunction with other anesthetic agents
Hypnotics Short acting hypnotic -Induction & -Patients feel better in the
(Diprivan) -Alkylphenol/10% lipid (made from mantainance anesthesia immediate
post-op b/c ↓post-op n/v
”milk of amnesia” soy/egg) (most popular) -Cardiovas/resp depression

MOA: GABA & NMDA -DOC for ambulatory -Hypertriglyceridemia

surgery -Severe acidosis in kids w/

PK: half life = 15-20min; rapid -Given w/ adjuvant respiratory infection

hepatic clearance (10x faster than antimicrobials (infections Drug of abuse
thiopental) from bacterial -Burning at injection site (90%) b/c
↓↓Blood pressure during induction contamination of drug is a direct irritant to
through ↓peripheral arterial emulsion) vessel (↑pain if ↓lipids in emulsion)

resistance -Antiemetic ↓Cerebral metabolic rate

↓Cerebral blood flow, ↓ ICP

Etomidate -Short acting hypnotic Cardiovascular stability -Less Cardiovas/resp


-Imidazole (only dextro isomer w/ (NO histamine release)

anesthetic properties) -Burning at injection site

MOA: GABA? -↓Cerebral metab rate

Half life = 3-6 min; hepatic -↓Cerebral blood flow

clearance -↓ICP

-Myoclonic jerks

-Inhibition of adrenocortical
synthesis (8-24h)


Ketamine -Moderately rapid action hypnotic -Bronchodilator -↑ ↑ ↑ ↑Oral secretions

(“Special K”) -Dissociative anesthetic -Good in elderly w/ CV -Night terrors

-Acrylcyclohexilamine (PCP-like, S- disase -CVS stable (slight stimulant), slight

isomer >>>> R) -Induction ↓BP

-↑ ↑ ↑ ↑ICP, ↑ ↑ ↑ ↑cerebral blood flow,

PK: Half life = 5 min; liver clearance ↑ ↑cerebral metabolic rate

↑ ↑

(hepatic active metabolite 30%- -Seizure activation

norketamine) -Emergent delirium, hallucinations

(emergent rxns impair recovery)

CI: intracranial surgery

Barbiturates reduce hepatic blood flow and glomerular filtration rate, but these
drugs produce no adverse effects on hepatic or

renal function. Barbiturates can exacerbate acute intermittent porphyria by

inducing the production of hepatic ALA synthase.

Thiopental -Moderate duration thiobarbituarte -Tx seizure -People complain of


-Rapid onset and rapid recovery -Given when operating on -Cardiovas/resp depression

(bolus dose); slow recovery following aortic arch to lower -↓ ↓ ↓ ↓Cerebral metab
rate (55% w/

infusion cerebral meatab rate isoelectric EEG)

-Rapidly diffuses out of brain & is while blood flow is -Bronchoconstriction


redistributed to muscle/fat stopped -Precipitation & porphyria

MOA: GABA agonist -Standard induction

Half life = 11min; hepatic clearance, agent CI: porphyrias

long elmination time -Used on patients w/

-30% ↓dose in elderly cerebral swelling (b/c no

↑ICP from drug)

Methohexital Short duration oxybarbiturate -Used for ECT sedation -Mild

cardiovas/resp depression

MOA: GABA (poor antiseizure med) -Can ↓ ↓ ↓ ↓Cerebral metab rate (55%

PK: half life = 4 min, hepatic -Neurosurg ablation of w/ isoelectric EEG→ → → →but

clearance (faster than thiopental) sezure foci (b/c drug can change the seizure
cause central excitatory -Hiccoughing
activity) Non-malignant hypertherm trigger
Fentanyl -Analgesia -Significant depression of
Hydromorphone -Blunt sympathetics hypercarbic respiratory drive

Benzodiazepines are primarily used as premediation before anesthesia b/c of

sedative, anxiolytic, amnestic properties.
Compared with the IV barbiturates, benzodiazepines produce a slower onset of
central nervous system depressant effects
which reach a plateau at a depth of sedation that is inadequate for surgical

Midazolam PK: more rapid, shorter elimination -Used in balanced -AMNESIA

half life (2-4h); steep dose response anesthesia & conscious Flumazenil reversal

curve; sedation, cardiovascular

-Water soluble stability

-DOC for parenteral


Not water soluble


Diazepam Not water soluble

Dexmedetomidate -α2 agonist (central > peripheral) -Atypical sedative -Little RR


PK: half life = 6min, but ↑ w/ renal & (cardiac surgical -Twilight state
α2 Agonist
hepatic dysfunction indication, ↑ICU & OR -Hypertension & bradycardia

use)’ -Low BP & bradycardia

-Used for people on

INHALED Volatile anesthetic = liquid at room temp, but evaporate easily↑

(Halothane, Isoflurane, Desflurane, Enflurane, Sevoflurane)
Uptake & Distribution of Inhaled anesthetics
1. Solubility – The blood:gas partition coefficient is a useful index of solubility
and defines the relative affinity of an
anesthetic for the blood compared with that of inspired gas. So, low coefficients
mean a relatively insoluble drug in the
blood (desflurane, nitrous oxide). When an anesthetic with low blood solubility
diffuses from the lung into the arterial blood,
relatively few molecules are required to raise its partial pressure, and so
arterial tension rises rapidly. If high arterial
tensions are reached rapidly, then there is a rapid equilibration with the brain
and a fast onset of action. Conversely, for
anesthetics with moderate to high solubility (halothane, isoflurane), more
molecules dissolve before partial pressure changes
2. Anesthetic concentration in the inspired air – has direct effects on both the
maximum tension that can be achieved in the
alveoli and the rate of increase in its tension in arterial blood. Increases in the
inspired anesthetic concentration increase
the rate of induction of anesthesia by increasing the rate of transfer into the
3. Pulmonary ventilation – the rate of rise of anesthetic gas tension in arterial
blood is directly dependent on both the rate
and depth of ventilation (magnitude of effect related to the blood:gas partition
coefficient). An increase in pulmonary
ventilation is accompanied by only a slight increase in arterial tension of an
anesthetic with low blood solubility or low
coefficient but can significantly increase tension of agents with moderate to high
blood solubility. THUS, hyperventilation
increases the speed of induction of anesthesia with inhaled anesthetics that would
normally have a slow onset.
4. Pulmonary blood flow – An increase in pulmonary blood flow (ie increased CO)
slows the rate of rise in arterial tension,
particularly for those anesthetics with moderate to high blood solubility.
Increased pulmonary blood flow exposes a larger
volume of blood to the anesthetic. In persons with circulatory shock, the combined
effects of decreased cardiac output
(resulting in decreased pulmonary flow) and increased ventilation will accelerate
induction of anesthesia with halothane.
5. AV concentration gradient – dependent mainly on uptake of the anesthetic by the


• All inhaled anesthetics tend to increase right atrial pressure in a dose-related
fashion, which reflects depression of
myocardial function. (Enflurane, Halothane more so)
• Inhaled anesthetics decrease the metabolic rate of the brain.
• The more soluble volatile agents increase cerebral blood flow because they
decrease cerebral vascular resistance.
The increase in cerebral blood flow (thus ↑ ↑ ↑ ↑ICP) is not wanted in patients who
already have increased intracranial
pressure. At low concentrations, all of the halogenated agents increase cerebral
blood fow, but at higher
concentrations, the increase in cerebral blood flow is less with the more insoluble
• All volatile anesthetics are respiratory depressants and also depress mucociliary
function in the airway. Prolonged
anesthesia may lead to pooling of mucus and then result in atelactasis and
postoperative respiratory infections.
• Solubility: Halothane > Enflurane > Isoflurane > Nitrous Oxide
• Nitrous oxide has little effect on uterine muscle, but the halogenated
anesthetics are potent uterine muscle relaxants
(concentration dependent)
• Minimum Alveolar Concentration (MAC) = concentration (as a % of inspired gas) to
prevent movement in 50% of
people to a surgical incision
• Malignant Hyperthermia – hypermetabolic state in muscle tissue & dysfunctional
Ryr1 receptor; seen in 1:15000 kids &
1 in 40000 adults; triggers include inhalation anesthetics and succinylcholine. The
signs of MH include increased
ETCO2, trunk or total body rigidity, masseter spasm or trismus, tachycardia,
tachypnea, acidosis, increased
temperature may be a late sign
Nitrous oxide PK; true gas, not metab (no -May be a better inducer -B12
(“Laughing gas”) hetapotox), sweet smelling for those w/ CV disease -Spontaneous
LOW SOLUBILITY than halothane -PostOperative Nausea Vomiting
-MAC = 104, low potency (30%)
-↑ ↑Cerebral metab rate -Minimal CV effects
↑ ↑
-Least likely to ↑ ↑ ↑ ↑cerebral blood flow
Note: of inhaled anesthetics
Nitric Oxide = NO -Expanding gas (75% N20 for 10 min
Nitrous Oxide = N O = 2X size of pneumothorax b/c N20
is 20X more soluble than N2?)
-Diffusional hypoxia
Desflurane Fluorinated methyl ethyl ether -Ambulatory patients -Expensive
-Isoflurane w/ a F- instead of Cl- (rapid anesthesia, rapid -Caustic smell (too
much too quickly
PK: off) causes bronchospasms/coughing &
MAC = 6.1, low potency sympathomimetic SE)
LOW SOLUBILITY -Carbon Monoxide production
-↓MAP in direct proportion to their -Little hepatitis risk
alveolar concentration due to ↓ ↓ ↓ ↓ -Low volatility → need special
systemic vascular resistance vaporizer
Sevoflurane Fluorinated methyl isopropyl ethyl Cardiac stable: -↑ ↑ ↑ ↑[Compound
A]→ → → → renal damage
PK: degraded by contact with the -Ischemic preconditioning -Expensive
carbond dioxide absorbent in (via K-ATP channels) -NO hepatitis risk
anesthesia machines→ to vinyl ether
called “Compound A” -Pediatric anesthesia
MAC = 2.1, medium potency -Ambulatory patients
LOW SOLUBILITY (rapid anesthesia, rapid
-↓MAP in direct proportion to their off)
alveolar concentration due to ↓ ↓ ↓ ↓
systemic vascular resistance
Isoflurane -Halogenated methyl ethyl ether -Mainstay anesthetic -↑ ↑ ↑ ↑Respiratory
-MAC = 1.2, medium potency -Possible coronary steal
Medium solubility Cardiac stable:
-↓MAP in direct proportion to their -Ischemic preconditioning
alveolar concentration due to ↓ ↓ (via K-ATP channels, ↓ w/
↓ ↓
systemic vascular resistance sulfonylurea &
-Depressant effect on the EEG hyperglycemia)
Halogenated methyl ethyl ether -precursor to Isoflurane -Mild generalized muscle
-↓MAP in direct proportion to their (myoclonic) @ ↑doses
alveolar concentration due to ↓ ↓ ↓ ↓CO -↑ ↑Respiratory depression
↑ ↑
-Depressant effect on the EEG -Seizures
-Renal complications
Halothane Halogenated ethane -One of the most widely -Halothane hepatitis
(cumulative, so
PK: 40% metab by liver (highest), used internationally, not if used halothane in
past, ↑risk)
-HIGH SOLUBILITY used in the USA -↑Intracranial pressure (ICP)
-↓MAP in direct proportion to their -Cheap -Sensitizes the myocardium to
alveolar concentration due to ↓ ↓CO -Still used in pediatric
↓ ↓ circulating catecholamines
(bradycardia w/ kids) anesthesia (being (epinephrine)→ may cause ventricular
MAC = 0.75, High potency replaced by sevoflurane) arrhythmias
-Depressant effect on the EEG -Malignant hyperthermia (give
-Bronchodilation dantrolene)
-Pleasant smell
Methoxyflurane 70% metab by liver→ release -Nephrotoxicity
fluoride ions→ nephrotox -VERY slow onset and recovery
Xenon Inert gas, “ideal agent” -CV stable EXTREMELY EXPENSIVE
MAC: High 70 -non-smelly

GABA-A receptor activation opens Cl- channels. GABA-B receptors allow K+ effux.
Both receptors cause hyperpolarization. Benzodiazepines and
barbiturates act only on the GABA-A receptors. Benzodiazepines use the y (gamma)
binding site. Barbiturates bind at the β site.
Class Drug Mechanism Clincal Use Side Effects
Benzodiazepines Benzodiazepines are used in insomnia, anxiety, and as
anticonvulsants. Benzodiazepines potentiate the action of GABA. They
have zero efficacy. Most of the benzodiazepines are very similar and really only
differ in their pharmacokinetics. These drugs
are liver metabolized to active compounds (except for oxazepam, temazepam, and
lorazepam). Because of all the active
metabolites, half-life of the drug does not correspond to duration of action. The
onset of action is related to the relative
degree of lipid solubility. BZs that are highly lipid soluble (midazolam,
triazolam, diazepam, flurazepam) have a more rapid
onset of action. Longer acting drugs will be used for anxiety, while the short
acting will be used for insomnia. Just a few points
to remember…Do not treat pain with a benzodiazepine & benzodiazepines are NOT
Midazolam Ultra-short acting (3-8h) -Use for uncomfortable -Drowsiness, sedation,
Triazolam procedures (Preop sedation, -Ataxis (vertigo, slurr speech)
Anesthesia) -Resp depression (very ↑dose)
-Amnesia (retrograde &
Temazepam Short acting, No active metabolites Sleep disorder
Oxazepam Anxiety (oxazepam) anterograde)
-Floppy infant syndrome if taken
Alprazolam Short duration of action Anxiety, panic attacks,
in the perinatal period
(Xanex) phobias
-↓ Libido
Lorazepam Short-medium duration (10-20h) Anxiety, preop sedation,
-Enhanced sedation w/ many
IV, no active metabolites status epilepticus (IV)
other drugs
Diazepam -Very long duration (1-3 days) due to Anxiety, preop sedation,

many active metabolites muscle relaxation, withdrawl

Long term:
-Given IV states
-Sleep disturbances (REM is

Clonazepam Very long duration (1-3 days) Tx of epilepsy
-Withdrawl syndrome (rebound
insomnia, anxiety)
Flurazaepam Short onset, long duration Acute Tx of insominia ↑risk of falls in
Flumazenil BZ receptor antagonist (BZ-1 & BZ- -Reverse the CNS -Will NOT reverse
2) depressant effect of BZ depression of barbiturates or
overdose alcohols
Barbiturates Barbiturates increase the duration of Cl channel opening (allow GABA
to stay on there longer), but they also have GAGAmimetic
activity at high doses. Barbiturates also inhbit complex 1 of the electron
transport chain. Barbiturates are general inducers of
CYP450. Barbiturates induce metabolism of most lipid-soluble drugs, such as oral
contraceptives, carbamazepine, phenytoin,
warfarin, ect.
Thiopental Ultra-short acting; extremely lipid Induce anesthesia (IV) -Sulfa
allergies (thiopent)
soluble (half life = 3-10h) -Withdrawl (anxiety, agitation,
Pentobarbital Half life = 15-50 hours ER management of seizures life threatening
CI: porphyrias
Phenobarbital Long acting (half life = 80-120 h) Tx seizures
Non-BZ drugs Zolpidem These are NOT benzodiazepines. They do not share the
benzodiazepine stucture, but they bind to the
Zaleplon BZ-1 receptor specifically
BZ-1 receptor agonist Tx of insomnia -Less tolerance & abuse potential
-OD reversed by flumazenil
Buspirone No effect on GABA, Used for generalized anxiety -Nonsedative anxiolytic
5HT-1a portial agonist (modulates disorders opposed to BZ)
serotonin transmission) -Pupillary constriction
-Takes 1-2 weeks to have an effect -Nervousness, restlessness,
dysphoria, tachycardia
Class Drug Mechanism Clincal Use Side Effects

DOPAMINE: Parkinson’s & Psychosis

Dopamine receptors are classifed into D1 and D2:
• D1→Gs coupled
• D2→Gi coupled. These receptors are the most sensitive (by about 1000x compared to
o D2A = nigrostriatal pathway (cell bodies in substantia nigra project to the
striatum, where they release DA, which inhibits
GABAergic neurons. In Parkinson disease, the loss of DA neurons in this tract leads
to excessive ACh activity → extrapyramidal
o D2C= mesolimbic pathway (cell bodies in the midbrain project to the
cerebrocortical and limbic structures → functions include
regulation of affect, reinforcement (addiction), cognitive functions, and sensory
perception. Psychotic disorders and addition are
partly explained by ↑DA in these pathways… and drugs that ↑DA functions→
↑reinforcemtn and at high doses may cause psychoses
o Tuberoinfundibular (Cell bodies in hypothalamus project to anterior pituitary and
release DA→ ↓prolactin
o Chemotactic trigger zone (activation of DA receptors → emesis
Class Drug Mechanism Clincal Use Side Effects
DA PRECURSORS Levodopa Prodrug→dopamine: via aromatic -Symptomatic relief
amino acid decarboxlase (aka dopa -“On-off” effects
decarboxylase) in periphery & CNS -Psychosis
-Take on an empty stomach, don’t -In the periphery/GI tract→ n/v
take w/ B6 (↑DA metabolism) cardiac arrhythmias, hypotension,
-↓Response after 3-5yrs (tolerance flushing
+ sensitization) CI: history of melanoma, concomitant
use of MOA inhibitor
Carbidopa Inhibits DOPA decarboxylase→ -Blocks peripheral L-dopa + carbidopa:
↑CNS availability of L-dopa effects of L-dopa -Brown urine & saliva
-Does not cross into CNS -Always give L-dopa + CI: B6 (↑Breakdown of L-dopa),
carbidopa psychotic patients, glaucoma,
COMT Increased L-DOPA causes a compensatory increase in COMT degradation of
dopamine to 3-O-methyldopa, which competes w/ L-
INHIBITORS DOPA for active transport into CNS (decreasing L-DOPA in brain). 3-O-
methyldopa is a partial agonist. So, in the presence of a
full agonist, it acts like an antagonist
Tolcapone COMT inhibitor, crosses into CNS -Use when other -Fulminating hepatic
therapies fail
Entacapone COMT inhibitor, acts only in -Largely replaced
periphery tolcapone
DA AGONIST Bromocriptine Ergot derivative No longer available in -Dyskinesias
USA -Psychosis
-Pulmonary & retroperitoneal fibrosis
Pramipexole Depends on good renal function
Apomorphine Injectible -Acute management of -Powerful emetic drug
“off phenomenon”
Ropinirole Not an ergot derivative Tx. of parkinsons Lower incidence of postural
hypotension, dyskinesia, vomiting and
hallucination, unlike most DA agonists
Rotigotine Available in transdermal
formulation (once a day)
ANTI- Benztropine ↓ ↓ ↓ ↓Tremor and rigidity but have -Many side effects similar
MUSCARINIC Trihexyphenidyl little effect on bradykinesia atropine
Diphenhydramine CI: glaucoma, prostatic hyperplasia,
pyloric stenosis
MAO-B MAO-A breaks down NE and serotonin. MOA-B breaks down dopamine. Since MAO-B
does not interfere with tyramine
INHIBITORS breakdown there is no “cheese” effect.
Selegiline Inhibitor of MAO-B (not MAO-A -Insomnia
at recommended doses) -Severe HTN (@ ↑↑doses)
-Selegiline is metabolized in body
to amphetamine
Rasagiline -Irreversible inhibitor of MAO-B
-5X more potent than selegiline
-Not metabolized to amphetamine
OTHERS Amantadine -MORE effective than -Antiviral Livedo Reticularis (skin
anticholinergics against rigidity & -Tx of parkinson’s purplic meshwork of blood
generally around ankles)
Schizophrenia is a mixture of positive and negative symptoms. To fight the positive
symptoms, you need a depressant, but that would worsen the
negative symptoms. Also, to fight the negative symptoms you need an antidepressant
(i.e. stimulant), which would worsen the positive symptoms. The
main mechanism by which drugs will fight psychosis is by a blockade of dopamine D2
receptors and block of 5HT-2 receptors.
If you block dopamine, side effects may include:
1. Acute EPS from acute block of DA in the nigrostriatal
a. Presents like a pseudoparkinsonism, dystonia, akathisia
b. Management: antimuscarinics
2. Chronic EPS (aka tardive dyskinesia) from chronic block of DA receptors in the
nigrostriatal, which may be irreversible
a. The brain may either upregulate the number or sensitivity of DA receptors, and
the little DA around will cause hyperkinetic
b. Management: discontinue drug (may cause a tremendous epidosde of psychosis) &
switch to an atypical psychotic
3. Dysphoria, making compliance an issue
4. Endocrine dysfunction
a. Temperature regulation
b. ↑prolactin
c. ↑Eating (weight gain)
5. Antimuscarinic effects (tachycardia, ↓seizure threshold)
6. α-blocking (hypotension)
TYPICAL Ocular deposits in the lens
Thioridazine Such a strong antimuscarinic that -Little EPS
(Phenothiazines) it autotreats its EPS effects -Quinidine toxicity
-Strong α α block -Retinal deposits
α α
-Low potency ↑↑↑Sedation

Fluphenazine High potency

Can give as depot form

Haloperidol Can give as depot form -Most likely cause of neuroleptic
malignant syndrome and TD
ATYPICAL Atypicals lack the tardive dyskinesias side effects. The newer
antipsychotics also block the 5HT2 receptors, which are found
ANTIPSYCHOTICS presynaptically → increased release and synthesis of serotonin. This
will address the negative symptoms of schizophrenia.
Clozapine -Block D2C receptors (found 5-10% of pts suffer agranulocytosis
mesolimbic, mesocortical) (need weekly blood testing)
-Blocks 5HT-2
-Moderate antimuscarinic
-Strong α-blocker
Olanzapine -Block D2C receptor (not as well)
-Blocks 5HT-2
Risperidone Some tardive dyskinesia
Aripiprazole Partial agonist at D2 receptors -Not for severe psychosis
Blocks 5HT-2 b/c of ceiling effect

Class Drug Mechanism Clincal Use Side Effects
TCA TCA have a number of SE:
1. Anti-cholinergic
2. Anti-adrenergic
3. Anti-histaminic
4. Other
Amitriptyline Tertiary amines block the reuptake of -Major depression COMA,
Imipramine 5-HT > NE -Phobia CARDIOTOXICITY (the 3 C’s)
-OCD -Prevent antihypertensive action of
-Neuropathic pain α2 agonist & guanethidine
CI: MAO-I + TCA (if switching
Nortriptyline Secondary amines block the re-uptake
b/w give washout period of 2-3
Desipramine of NE > 5-HT

SSRI Fluoxetine Selectively block serotonin reuptake -Major depression -Sexual

dysfunction (anorgasmisa)
Fluvoxamine -Bulimia
Sertraline -Anxiety disorder Withdrawl: (“finish”)
Paroxetine F = flu-like symptoms
Citalopram I = insomnia
Escitalopram N = nausea
I = imbalance
S = sensory stuff (e.g. itchy teeth)
H = headache/hyperarousal
SNRI Duloxetine 5HT & NE reuptake inhibitor at all
relevant doses
MAO-I Phenelzine Irreversible, nonselective inhibitor of “Cheese effect” (HTN
Tranylcypromine MAOs -Serotonin syndrome (if SSRI +
Molobemide Reversible, selelctive for MAO-A
OTHER -Smoking cessation Minimal sexual SE (b/c does not
Bupropion Weak reuptake blocker of DA and
NE -WAS an antidepress enhance 5HT)
Mirtazapine α α α α2 antagonist→ ↑NE -HTN, tachycardia
-Weight gain
Trazodone ↑5HT by interfering w/ metabolism Antidepressant Cardiac arrhthmias
-Metabolized → serotonin agonist -Priapism
-α Block
Venlafaxine Non-selective reuptake blocker devoid
of ANS sideffects (like a TCA, but no

Rapid cycling Bipolar – at least 4 epidosdes of mood disturbances within the last
12 months
Class Drug Mechanism Clincal Use Side Effects
Lithium -Prevent the recycling of PIP2→ → → → -DOC for Bipolar -Tremor & life
↓ ↓Ca seizures (dose depend)
↓ ↓
-Inhibit cAMP signaling -Hypothyroidism w/ goiter
-Therapeutic index = 1-2 -For Toxicity (give amiloride) -Nephrogenic Diabetes
-Lithium “looks like” Na+ -Chronic doses of diuretics Insipidus
will ↓clearance of lithium

Valproate Rapid cycling

Carbamezepine Pure and mixed mania

Methylphenidate Amphetamine derivative (a

Atomoxetine Selective NE reuptake inhibitor