by Seetal K Dhaliwal H.

Section III

Flash cards by Seetal K. Dhaliwal H. S

Fast response Fibers: Cardiac Muscle, His-Purkinje

2

Ventricular AP:
During phases 0
3, slow Na+ influx
(window
current) occurs
helps prolong
duration of AP.

Phase 0: Na+ channels open Na enters cell down conc. gradient depolarization.
Phase 1: Na+ channels inactivated outward K+ & inward Cl- notch & overshoot.

Phase 2: slow influx Ca2+ with late outward K+ plateau.

Phase 3: continued outflux K+ as Ca2+ influx repolarization.

Phase 4: return to resting potential (RP) by Na+/K+-ATPase.

by Seetal K Dhaliwal H. S

Slow response Fibers: SA & AV nodes, Specialized cells

3

Phase 0: Ca2+ channels open slow conduction velocity AV node prolong transmission from
atria to ventricles.

Phase 2: missing plateau.

Phase 3: inactivation of Ca2+ channels & activation of K+ channels K+ efflux.
Phase 4: spontaneous MP depolarization due to Na+ conductance this slope in SA node
determines HR.

by Seetal K Dhaliwal H. S

Anti-arrhythmic Summary:
4

Class I blocks Na+ influx (in phase 0 fast fibers)

Class IA blocks K+ efflux (phase 3)

Class II blocks pacemaker current (phase 4) & slows

phase 0 fast fibers (depolarization)
Class III blocks K+ efflux (phase 3)
Class IV blocks slow fibers Ca2+ influx (phase 0) &
pacemaker current (phase 4)
by Seetal K Dhaliwal H. S

Anti-arrhythmic Drugs:
5

Class I (Na+ channel blockers):

Class IA (blocks fast Na+ channels & also K+ channels):

Quinidine also causes muscarinic block ( HR & AV conduction). Toxicity include

cinchonism, hypotension, prolonged QRS & Torsades ( QT interval with syncope).
Hyperkalemia enhances effects & vice-versa. Displaces digoxin enhancing toxicity.
Quinidine is a weak base antacids enhances its absorption causing toxicity.

Procainamide Metabolized via N-acetyltransferase to NAPA (active metabolite).

Toxicity include SLE-like syndrome, thrombocytopenia, agranulocytosis & Torsades.

Class IB (blocks fast Na+ channels & AP duration):

Lidocaine used as IV for post-MI, open heart surgery, digoxin toxicity. Toxicity
include seizures.

Mexiletine & tocainide same as Lidocaine but used orally.

Class IC (blocks fast Na+ channels, no effect on AP duration & ANS):

Flecainide has proarrhythmic effects in sudden death post-MI & when used
in VTs as prophylaxis.

by Seetal K Dhaliwal H. S

Anti-arrhythmic Drugs:
6

Class II (-blockers):

SA & AV nodal activity, & phase 4 slope (slow fibers).

Propanolol, Acebutolol & Esmolol.

Used for prophylaxis post-MI and SVTs.

Esmolol (IV) is used in acute SVTs.

Class III (K+ channel blockers):

AP duration & ERP

Amiodarone used in any arrhythmia. Toxicity include pulm. fibrosis, smurf

skin, phototoxicity, corneal deposits, hepatic necrosis, thyroid dysfunction.

Sotalol 1-blockade leading to HR & AV conduction. Used in lifethreatening ventricular tachycardia.

by Seetal K Dhaliwal H. S

Anti-arrhythmic Drugs:
7

Class IV (Ca2+ channel blockers):

SA & AV nodal activity, & phase 4 and phase 0 (slow fibers).

Verapamil & Diltiazem used in SVTs. Toxicity include constipation

(verapamil), dizziness, flushing, hypotension, AV block. Has additive action with
blockers & digoxin (verapamil displaces digoxin).

Unclassified:

Adenosine in cAMP, SA & AV nodal activity. DOC for paroxysmal SVTs

& AV nodal arrhythmias. Antagonized by theophylline (PDE inhibitor). Causes
flushing, sedation & dyspnea.

Magnesium Used in Torsades (familial risk of ventricular arrhythmias). To

correct torsades correct hypokalemia & hypomagnesemia, shorten AD
duration with drugs (isoproterenol) or electrical pacing.
by Seetal K Dhaliwal H. S

Antihypertensive Drugs:
8

2-agonists: Clonidine & Methyldopa (prodrug):

TPR & HR. Used in mild-moderate HTN, opiate withdrawal (clonidine),

pregnancy HTN (methyldopa).

Toxicity include positive Coombs test (methyldopa), CNS depression &

edema.

Tricyclic Antidepressants (TCAs) antihypertensive effects.

1-blockers: Prazosin, doxazosin, terazosin:

arteriolar & venous resistance. Causes reflex tachycardia.

Used in HTN & BPH (to ease urination).

Toxicity include first-dose syncope, orthostatic hypotension & urinary

incontinence.

Advantage: HDL, LDL

by Seetal K Dhaliwal H. S

Antihypertensive Drugs:

-blockers:

Toxicity include CVS depression, fatigue, sexual dysfunction, LDL & TG. Used
cautiously in asthma (exacerbation), vasospastic disorders, diabetics (causes
hypoglycemia)

Drugs that interfere with storage vesicles:

Reserpine destroys vesicles. CO & TPR, and NE (also in periphery), DA,

5-HT in CNS. Causes depression (often severe), edema & GI secretions.
Exacerbates HTN in pheochromocytoma ( release of amines).

Guanethidine inhibits NE release. Causes diarrhea & edema. TCAs blocks

action of Guanethidine.

Drugs acting through NO (causing arteriolar dilation):

Hydralazine TPR. Used in moderate-severe HTN.

Nitroprusside TPR. Used in hypertensive emergencies. Causes cyanide
toxicity (treat with sodium thiosulfate)
by Seetal K Dhaliwal H. S

Antihypertensive Drugs:
10

Drugs open K+ channels (cause hyperpolarization of smooth muscle):

Minoxidil & Diazoxide Used in Hypertensive emergencies (diazoxide),

severe HTN & baldness (minoxidil). Side effects are hypertrichosis

(minoxidil), hyperglycemia (insulin release [diazoxide]), edema & reflex

tachycardia.

Calcium-channel blockers (CCB):

Intracellular Ca2+ in heart & blood vessels causing CO (Verapamil &

Diltiazem), TPR (all CCBs, including dipines [Nifedipine])

Used in HTN (all CCBs) & as an antiarryhthmia (Verapamil & Diltiazem).

by Seetal K Dhaliwal H. S

Antihypertensive Drugs:
11

ACEIs & ARBs:

ACEIs (captopril) Blocks formation of Angiotensin (AT) II Aldosterone &

vasodilation. Also prevents bradykinin degradation (causes dry caugh). Slows
progression of diabetic nephropathy. Contraindicated in pregnancy.

ARBs (lorsatan) TPR. Blocks AT-1 receptors. Same effects as ACEIs but do

not interfere with bradykinin degradation. Contraindicated in pregnancy.

Treatment of Pulmonary HTN:

Bosentan Endothelin receptor antagonist. Administered orally.

Contraindicated in pregnancy.

Sildenafil (VIAGRA) Inhibits PDE5 cGMP pulmonary artery

relaxed pulmonary HTN.

by Seetal K Dhaliwal H. S

Use of Antihypertensive drugs in Comorbid

Conditions:
12

Indication

Suitable Drug(s)

Angina

Beta blockers, CCBs

Diabetes

ACEIs, ARBs

Heart Failure (HF)

ACEIs, ARBs

Post-MI

Beta blockers

BPH

Alpha blockers

Dyslipidemia

Alpha blockers, CCBs, ACEIs, ARBs

by Seetal K Dhaliwal H. S

Drugs for Heart Failure:

13

Drugs for Acute CHF inotropes

Drugs for Chronic CHF ACEIs & ARBs

Preload: diuretics, ACEIs, ARBs, & venodilators (A2V)

Afterload: ACEIs, ARBs, & arteriodilators (A3)

Contractility: Digoxin & -agonists (D)

Remodeling of cardiac muscle: ACEIs, ARBs & Spironolactone

(A2S)
by Seetal K Dhaliwal H. S

Drugs for Heart Failure:

14

Digoxin inhibit cardiac Na+/K+-ATPase intracell Na+ Na+/Ca2+

exchange Ca2+ intracell Ca2+ release from SR contraction. Indirect
inhibition of neuronal Na+/K+-ATPase vagal & sympathetic stimulation.

PDE inhibitors (Inamrinone & Milrinone) cAMP in heart muscle (inotropy) &
smooth muscle (TPR).

Sympathomimetics : Dobutamine & Dopamine

Diuretics

Metoprolol (1-blocker with membrane stabilizing activity [local anesthetic

activity]) HR, AV nodal, BP, CO, O2 demand. Used in HTN, angina
pectoris & Acute MI (AMI).

Carvedilol (1- & -blockers) causes vasodilation, HR & BP in HTN patients,

CO in HF patients. Used in HTN & HF.

Nesitride rhBNP. Causes cGMP, hence vasodilation. Used in acutely

decompensated CHF.

by Seetal K Dhaliwal H. S

Antianginal drugs:
15

Drugs strategies in classic & vasospastic angina:

Oxygen delivery by vasospasm (nitrates & CCBs)

Oxygen demand by TPR, CO, or both (nitrates, CCBs, & beta blockers)

Nitrates:

Venodilation preload cardiac work oxygen requirement

Nitroglycerin: subligual, transdermal & IV

Isosorbid: oral extended release for chronic use.

CCBs:

All CCBs can be used.

Nifedipine important for vasospastic angina.

Beta Blockers & Carvedilol:

Used in angina of effort (classic).

-blockers contraindicated in vasospastic angina.

by Seetal K Dhaliwal H. S

Diuretics (drugs site of action):

16

by Seetal K Dhaliwal H. S

Diuretics:
17

1.

CA inhibitors:

2.

Acetazolamide & Dorzolamide

Causes self-limited NaHCO3 diuresis & reduction in total body HCO3stores.
Use: glaucoma, metabolic acidosis, urinary alkalinization & mountain
sickness.
Toxicity: hyperchloremic metabolic acidosis, neuropathy, NH3 toxicity, sulfa
allergy.

Osmotic diuresis:

Mannitol (IV)
Tubular fluid osmolarity by inhibiting water reabsorption, producing
urine flow.
Use: shock, drug overdose, to IOP (glaucoma) & ICP.
Toxicity: pulmonary edema, hypokalemia, dehydration & acidosis.
Contraindicated in anuria & CHF.

by Seetal K Dhaliwal H. S

Diuretics:
18

Loop diuretics:

3.

Furosemide & Ethacrynic acid

Inhibits co-transport system (Na+/K+/2Cl-) of TAL. Abolishes
hypertonicity of medulla, preventing concentration of urine.
Ca2+ excretion.
.
Use: edematous state (CHF, cirrhosis, nephrotic syndrome, pulm.
edema), HTN & hypercalcemia.
Toxicity: Ototoxicity, Hypokalemia, Dehydration, Allergy (sulfaexcept Ethacrynic), Nephritis (interstitial), Gout. (OH DANG !)
NOTE: ethacrynic acid causes acute gout!!
by Seetal K Dhaliwal H. S

19

Diuretics:
Thiazides:

4.

19

Hydrochlorothiazide & Indapamide

Inhibits NaCl reabsorption in early DCT, reducing diluting

capacity of the nephron. Ca2+ excretion.

Use: HTN, CHF, nephrogenic DI, idiopathic hypercalciuria.

Toxicity:
, hyponatremia,
hyperGlycemia, hyperLipidemia, hyperUricemia &
hyperCalcemia

5.

(hyperGLUC). Sulfa allergy.

K+ sparing:

Spironolactone (aldosterone-receptor antagonist),

Amiloride & Triamterene (Na+ channel blockers) &
Eplerenone:

Use: hyperaldosteronism, K+ depletion, CHF

Toxicity: Hyperkalemia (can lead to arrhythmias),

endocrine-antiandrogen effects with aldosterone
antagonist (except Eplerenone).

Collecting Duct

by Seetal K Dhaliwal H. S

Antihyperlipidemics:
risk of atherosclerosis, CVS & cerebrovascular
diseases. Treatment goal includes lowering LDL & atheroma plaque formation.

20

HMG-CoA reductase inhibitors:

-statins; liver cholesterol, LDL-receptor expression, plasma LDL, VLDL

synthesis TG & small in HDL.

Side effects: myalgia, myopathy, rhabdomyolysis, hepatotoxicity.

Gemfibrozil (rhabdomyolysis), CYP450 toxicity.

Bile acid sequestrants:

Cholestyramine & Colestipol; enterohepatic recirculatioin of bile salts,

synthesis of new bile salts, liver cholesterol, LDL-receptor expression,
blood LDL.

Side effects: VLDL & TG, GI disturbances, malabsorption of lipid-soluble

vitamins

DO NOT USE IN HYPERTRIGLYCERIDEMIA.

by Seetal K Dhaliwal H. S

21

Antihyperlipidemics:

21

Nicotinic acid (Niacin, Vitamin B3):

Inhibit VLDL synthesis in liver; plasma VLDL, LDL, TG & plasma HDL.

Side effects: flushing, pruritus, rashes (use aspirin), hepatotoxicity.

Gemfibrozil:

Activate Lipoprotein Lipase; VLDL, slight LDL, TG,HDL.

Side effects: gallstones, myositis.

Ezetimibe:

Prevents intestinal absorption of cholesterol LDL.

Side effects: GI distress.

Lab findings

Drug(s) treatment

Cholesterol

Cholestyramine, colestipol, Ezetimibe

Triglycerides

Gemfibrozil

Cholesterol & Triglycerides

Statins & Niacin, Ezetimibe

by Seetal K Dhaliwal H. S

by Seetal K Dhaliwal H. S

Section IV

Flash cards by Seetal K. Dhaliwal H. S

22

23

Sedative Hypnotic Anxiolytic drugs

GABAA complex:

23

Cl-

GABA binding site

BZ binding site

GABAA activation Cl- influx Inhibitory effect

(membrane
GABAB activation K+ influx hyperpolarization)

Barbiturate binding site

Barbiturates:

Phenobarbital, pentobarbital, thiopental, secobarbital.

Prolong GABA activity (duration of Cl- channel opening).

Has GABA mimetic activity at high doses

Induces deep CNS depression at high doses & there is NO ANTIDOTE !

Uses: Phenobarbital for seizures; Thiopental for anesthetic induction.

Liver metabolized (sometimes to active compounds); inducers of CYP450;

contraindicated in porphyrias.

Withdrawal signs anxiety, agitation, life-threatening seizures (delirium

tremens with alcohol) treat with supportive and long-acting BZs.
by Seetal K Dhaliwal H. S

24

Benzodiazepines (BZs):

Potentiate GABAA by frequency of Cl- channel opening.

Mediates sedation (BZ1) , REM sleep, most have long half-lives and active
metabolites. Mediates antianxiety & cognitive impairment (BZ3).

Flumazenil nonspecific BZ receptor () antagonist. Used to reverse CNS

depression caused by BZs (used in Anesthesia & OD).

Uses of various BZs:

Alprazolam Anxiety, panic, phobias

Diazepam Anxiety, pre-op sedation, muscle relaxation, withdrawal states
Lorazepam Anxiety, pre-op sedation, status epilepticus (IV)
Midazolam Pre-op sedation, anesthesia (IV)
Temazepam Sleep disorders
Oxazepam Sleep disorders, anxiety

Liver metabolized to active compounds (except Temazepam, Oxazepam &

Lorazepam = non-active TOLl booths).

Variable t & duration of action: (MOTALD) mottled duration

24

Midazolam < Oxazepam < Temazepam < Alprazolam < Lorazepam < Diazepam

Withdrawal signs anxiety, seizures (when used in high doses or as

by Seetal K Dhaliwal H. S
antiepileptics) & rebound insomnia.

Sedative Hypnotic Anxiolytic drugs

25

Non-BZs drugs:
Zolpidem & Zaleplon:

BZ1 receptor agonist

Overdose reversed with Flumazenil
Used in sleep disorders

Buspirone:

NO effect on GABA
5-HT1A partial agonist
Used for Generalized Anxiety Disorder (GAD)
Non-sedative
Takes 1 2 weeks for effects
by Seetal K Dhaliwal H. S

Alcohols:

All alcohols can cause CNS depression (some via GABA mimetic) & met. acidosis.

26

Long acting inhibitor

of ADH

Inhibits acetaldehyde
DH, acetaldehyde
accumulates hangover !
by Seetal K Dhaliwal H. S

Alcohols:
27

Chronic alcoholism:

Hypoglycemia

Fatty liver & lipemia

Muscle wasting (long term alcoholic, poor food intake)

Gout (lactate competes with urate for excretion)

Fetal alcohol syndrome:

Leading cause of congenital malformations in the U.S:

Growth restrictions, holoprosencephaly (marked CNS dysfunction and mental

retardation), facial abnormalities, limb dislocation, and heart & lung fistulas.

Mechanism may include inhibition of cell migration.

by Seetal K Dhaliwal H. S

Anticonvulsants:
28

1.

2.
3.
4.

axonal conduction by preventing Na+ influx carbamezepine &

phenytoin
inhibitory GABA-mediated hyperpolarization barbiturates & BZs
excitatory glutamic acid lamotrigine, topiramate & felbamate
presynaptic Ca2+ influx (blocks T-type channels) Ethosuximide &
Valproic acid
Type of seizures

DOC

Partial-Simple / Complex

Valproic acid, carbamezepine & phenytoin

General tonic clonic

Valproic acid, carbamezepine & phenytoin

General absence

Ethosuximide

Status epilepticus

Lorazepam, Diazepam, phenytoin (or

fosphenytoin [>> water soluble I.V])
by Seetal K Dhaliwal H. S

29

Phenytoin:

29

Carbamazepine:

Induction of CYP450; zero-order kinetics of elimination

Side effects: CNS depression, gingival hyperplasia, hirsutism,
osteomalacia, megaloblastic anemia ( folate), SLE-like syndrome.
Teratogenic: cleft lip and palate, fetal hydantoin syndrome.
DOC for Trigeminal Neuralgia; induces CYP450 (including its OWN!)
Side effects: CNS depression, osteomalacia, megaloblastic anemia,
aplastic anemia, SIADH, Steven-Johnson syndrome, diplopia, ataxia, liver
toxicity
Teratogenic: cleft lip and palate, spina bifida

Valproic acid:

Used in mania/bipolar disporders & migraine; inhibits CYP450

Side effects: GI distress, rare hepatotoxicity, tremor, weight gain
Teratogenic: spina bifida (absolutely contraindicated in pregnancy)
by Seetal K Dhaliwal H. S

Anticonvulsants (additional information):

30

Anticonvulsants + CNS depressants:

Abrupt withdrawal:

ADDITIVE effect
SEIZURES !

Lamotrigine & Felbamate:

Used in seizure states (adjunct therapy)

Side effects: hepatotixicity (both); aplastic anemia (felbamate); Steven-Johnson

syndrome (lamotrigine)

Gabapentin:

GABA effects

Used in seizure states and neuropathic pain (post-herpetic neuralgia)

Phenobarbital is safest during pregnancy

by Seetal K Dhaliwal H. S

Anesthetics:
31

For a drug to cross the BBB, it has to be lipid soluble or actively transported

Drugs with solubility in blood ( blood-gas ratio) rapid onset & recovery

Drugs with solubility in lipid = potency = 1/MAC (where MAC/minimal

alveolar concentration is concentration of inhaled anesthetics at which 50%

patients do not respond to surgical stimulus)

N20 (nitrous oxide) has blood & lipid solubility rapid onset & recovery,
but low potency.

Halothane has blood & lipid solubility slow onset & recovery, but high
potency.
by Seetal K Dhaliwal H. S

32

Inhaled Anesthetics:

32

Halothane, enflurane (enthane), isoflurane, sevoflurane, methoxyflurane,

N2O.
Effects: causes myocardial & respiratory depression, nausea/emesis,
cerebral blood flow ( cerebral metabolic demand).
Toxicity: Hepatotoxicity (Halothane), nephrotoxicity (Methoxyflurane),
proconvulsant (enflurane avoid in seizure patients), malignant
hyperthermia (rare), expansion of trapped gas (N2O).

Dantrolene:

Used in the treatment of malignant hyperthermia, caused by concomitant

use of inhaled anesthetics (except N2O) and succinylcholine (depolarizing
muscle relaxant).

Also used to treat neuroleptic malignant syndrome (toxicity due to antipsychotic drugs).
MOA: prevents release of Ca2+ from sarcoplasmic reticulum
contractility
by Seetal K Dhaliwal H. S

33

Intravenous Anesthetics:
33

Benzodiazepines Midazolam most commonly for endoscopy; adjunct use with

gaseous anesthetics; pre-op sedation; anterograde amnesia.
May cause severe post-op resp. depression, BP (treat with
flumazenil) and amnesia.
Opiates

Morphine, fentanyl, used for induction and maintenance of

general anesthesia.

Propofol

Used for induction and maintenance of anesthesia (rapid onset).

Antiemetic.

Barbiturates

Thiopental high potency, high lipid solubility, rapid cross BBB.

Used for anesthesia induction. Short acting due to redistribution
from brain. Cerebral blood flow.

Ketamine

PCP analog a dissociative anesthetic. Stimulates CVS, causes

disporientation, hallucinations, bad dreams. Cerebral blood
flow (avoid in head injury patients)

Ben took Opiates and Proposed at Burger King! (I think we all know how that went)
by Seetal K Dhaliwal H. S

34

Local Anesthetics:

34

Esters (1 i in their names) procaine, cocaine, tetracaine

AmIdes (2 Is in their names) LIdocaIne, mepIvacaIne, bupIvacaIne
Uncharged penetrate membrane, then bind to ion channels as charged form block
Na+ channels from within axonal membrane.
In infected (acidic) tissue, anesthetics are charged, so more is needed.
The order of nerve blockade depends largely on size (also myelination):

The order of loss or nerve blockade (recovery) is the reverse:

B > C > A > A & A > A

B < C < A < A & A < A

Given with vasoconstrictors (Epi) to bleeding and anesthesia by systemic

circulation.
Toxicity: CNS excitation, CVS toxicity (bupivacaine), HTN, hypotension & arrhythmias
(cocaine).
Cocaine intrinsically causes vasoconstriction by blocking NE uptake.
Na+ channel toxins:
1.
2.

Na+ influx tetrodotoxin & saxitoxin

(prolong) Na+ influx ciguatoxin & batrachotoxin
by Seetal K Dhaliwal H. S

Skeletal muscle relaxants:

35

Selective for motor nicotinic receptor.

Depolarizing (non-competitive):

Succinlycholine (can cause severe hyperkalemia & malignant HTN (muscle rigidity,
hyperthermia, HTN, acidosis and hyperkalemia)

Phase I (prolonged depolarization): no antidote causes rigid paralysis

Phase II (desensitization/blocked repolarization): cholinesterase inhibitors (neostigmine) as

antidote causes flaccid paralysis.

Non-depolarizing (competitive):

Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rapacuronium

Competes with Ach for receptors.

For reversal of blockade use cholinesterase inhibitors neostigmine, edrophonium, etc.

by Seetal K Dhaliwal H. S

Opioid Analgesics:
36

Morphine, fentanyl, codeine, heroin, methadone, meperidine, dextromethorphan.

Act as agonist at opioid receptors (= morphine, = enkephalin, = dynorphin) to
modulate synaptic transmission. Inhibits release of ACh, NE, 5-HT, glutamate,
substance P.
Use: pain, cough suppression (dextromethorphan), diarrhea (loperamide &
diphenoxylate), acute pulmonary edema/congestion, maintenance programs for
addicts (methadone).

Toxicity: Addiction, respiratory depression, constipation, miosis (pinpoint pupils),

additive CNS depression with other drugs. Tolerance does not develop to miosis
& constipation. Treated with naloxone or naltrexone (opioid receptor antagonist).
Withdrawal: yawning, lacrimation, rhinorrhea, salivation, anxiety, sweating,
goosebumps, muscle cramps, spasms, CNS-originating pain. Treat with methadone
or clonidine.
by Seetal K Dhaliwal H. S

Contraindications & cautions for opioids:

37

37

Head injuries (possible increase in ICP)

Pulmonary dysfunction (except pulmonary edema)

Hepatic / renal dysfunction (possible accumulation)

Adrenal or thyroid deficiencies (exaggerated responses)

Pregnancy (possible neonatal depression or dependence), except meperidine.

Other opioids & analgesics:

Characteristics

Full agonists

Meperidine Antimuscarinic (tachycardia, pupil dilation), metabolized

by CYP450 to normeperidine, an SRI causes seizures.
Methadone Maintenance in opiate adicts.

Partial agonists

Codeine
Antitusive, analgesic, use with NSAIDs.
Buprenorphine Precipitation of withrawal.

Mixed agonists

Nalbuphine,
pentazocine

agonist (spinal analgesia, dysphoria);

agonist (precipitation of withrawal)

Naltrexone

PO, craving for alcohol & for opiate addicts

Antagonists

y Seetal K Dhaliwal H. S

Receptor Action Drug

Parkinsons disease drugs:

38

Parkinsonism: loss of DA and excess cholinergic activity.

DA agonists Bromocriptine, pergolide (ergot alkaloid & partial DA agonist),

pramipexole, ropinirole (non-ergot); non-ergots are preferred.
DA Amantidine (may DA release); antiviral for influenza A & Rubella;
toxicity = ataxia. L-dopa/carbidopa (converted to DA in CNS)
Prevent DA breakdown Selegiline (MAOB inhibitor); entacapone, tolcapone
(COMT inhibitors prevent L-dopa degradation)

access ACh Benztropine, diphenhydramine & trihexyphenidyl (Antimuscarinic;

improves tremor & rigiditiy but has little effect on bradykinesia).
For essential or familial tremors, use blockers (propanolol)

BALSA Park

BENZ:

Bromocriptine; Amantidine, Levodopa (with carbidopa); Selegiline (& COMT

inhibitors); Antimuscarinics (Benztropine).

by Seetal K Dhaliwal H. S

39

Antipsychotic drugs (neuroleptics):

39

High potency (neurological side effects) Haloperidol, trifluoperazine,

fluphenazine; Low potency (non-neurological side effects) thioRidazine (Retinal
deposits), Chlorpromazine (Corneal deposits);
Block D2 receptors ( [cAMP]1); used in Schizophrenia, psychosis, acute mania,
Tourettes syndrome.
Toxicity:

High lipid soluble and stored in fat (slowly removed from body); EPS; Endocrine effects
(DA antagonist hyperprolactinemia galactorrhea); anti-muscarinic effects (dry
mouth, constipation); anti- effects (hypotension); anti-histamine effects (sedation).

Neuroleptic Malignant Syndrome (NMS) rigidity, myoglobinuria, autonomic instability,

hyperpyrexia. Treat with dantrolene, DA agonist (Bromocriptine).

Tardive dyskinesia stereotypic oral-facial movements due to long-term antipsychotic

use. Often irreversible.

Evolution of EPS side effects:

4 h acute dystonia; 4 d akinesia; 4 wk akathisia; 4 mo tardive dyskinesia.

For NMS think FEVER:

Fever, Encephalopathy, Vital instabilities, Elevated enzymes, Rigidity of muscles.

by Seetal K Dhaliwal H. S

Atypical antipsychotics:
40

Olanzepine, Clozapine, Quetiapine, Risperidone, Aripiprazole,

Ziprasidone.

Blocks 5-HT2, , H1, and DA receptors.

Used in schizophrenia. Olanzepine is also used for OCD, anxiety disoreder,

depression, mania, Tourettes syndrome.
Fewer EPS and anticholinergic symptoms than typical antipsychotics.
Olanzepine/Clozapine may cause significant weight gain. Clozapine may cause
agranulocytosis (requires weekly WBC monitoring).

Its atypical for Old Clothes to Quietly Risper from A to Z.

Parental formulations of fluphenazine, haloperidol are available for rapid initiation

of treatment & maintenance therapy in noncompliant patients.

by Seetal K Dhaliwal H. S

Antidepressants:
41

MAO inhibitors:

Phenelzine, tranylcypromine, isocarboxazid, selegiline (MAOB inhibitor)

Level of amine NTs.

Used in atypical depression, anxiety and hypochondriasis.

Toxicity: hypertensive crisis with tyramine ingestion (wine & cheese) & -agonists; CNS
stimulantion. Contraindicated with SSRIs or meperidine (to prevent serotonin
syndrome).

Atypical antidepressants:

Bupropion (Wellbutrin) also used in smoking cessation; NE & DA; toxicity causes
tachycardia, insomnia, headache, & seizures in bulimic patients. No sexual side effects.

Mirtazepine 2-agonist ( release NE & 5-HT) & potent 5-HT2 & 5-HT3 antagonist.
Toxicity causes sedation, dry mouth, appetite & weight gain.

Maprotiline blocks NE reuptake. Toxicity causes sedation, orthostatic hypotension.

Tazodone inhibits 5-HT reuptake. Used for insomnia, as high doses are needed for
antidepressants effects. Toxicity: sedation, nausea, priapism, postural hypotension.
Called TrazoBONE due to male-specific side effects.
by Seetal K Dhaliwal H. S

Antidepressants:
42

Tricyclic Antidepressants (TCAs):

Imipramine, amitriptyline, desipramine, nortriptyline, clomipramine, doxepin,

amoxapine.

Blocks NE and 5-HT reuptake.

Used for major depression, bedwetting (imipramine), OCD (clomipramine),

fibromyalgia.

Side effects: sedation, -blocking effects, atropine like (anticholinergic)

effects (tachycardia, urinary retention). 3 TCAs (amitriptyline) have >
anticholinergic effects than 2 TCAs (nortriptyline). Desipramine is the least
sedating and has lower seizure threshold.

Toxicity: Tri-Cs: Convulsions, Coma, Cardiotoxicity (arrhythmias); also

respiratory depression, hyperpyrexia. Confusion and hallucinations in elderly
due to anticholinergic side effects (use nortriptyline instead). Treatment:
NaHCO3 for CV toxicity.

by Seetal K Dhaliwal H. S

Antidepressants:
43

SSRIs:

Fluoxetine, paroxetine, sertraline, citalopram.

Used in depression, OCD, bulimia, social phobias.

Toxicities: fewer than TCAs. GI distress, sexual dysfunction (anorgasmia), weight loss,
agitation & jitters. Serotonin Syndrome with any drug that serotonin (MAOIs)
hyperthermia, muscle rigidity, cardiovascular collapse, flushing, diarrhea, seizures.
Treatment: cyproheptadine (5-HT2 antagonist).

It normally 2 3 weeks for effects to take place. Should take in the morning to avoid
insomnia.

SNRIs:

Venlafaxine, Duloxetine.

Inhibit serotonin & NE reuptake.

Used in depression. Venlafaxine is also used in GAD, while Duloxetine for diabetic
peripheral neuropathy. Duloxetine has greater effect on NE.

Toxicity: BP most common; also stimulant effects, sedation & nausea.

by Seetal K Dhaliwal H. S

Bipolar disorder drug

LITHIUM:

ADHD drugs:

44

Perhaps due to inhibition of

phosphoinositol cascade.
Used as a mood stabilizer in bipolar
disorder; blocks relapse and acute
manic events. Also SIADH.
Toxocity: tremor, acne, sedation,
edema, heart block, hypothyroidism,
polyuria (ADH antagonist causing
nephrogenic DI), teratogenesis. Narrow
therapeutic window requires close
monitoring of serum levels.
LMNOP:

Lithium side effects:

Movement (tremor);
Nephrogenic DI;
hypOthyroidism;
Pregnancy problems

Methyphenidate (Ritalin):

NE release from vesicles

Atomoxetine:

NE reuptake.

GAD drug:

Buspirone:

Stimulates 5-HT1A
receptors.

Used in GAD. Does not

cause sedation, addiction, or
tolerance. Does not interact
with alcohol (barbiturates,
benzodiazepines).

by Seetal K Dhaliwal H. S