anti-arrhythmic lecture 1

Question 1

how many phases does a myocardial action potential have ?

Answer 1

4 phases
phase 0–> upstroke caused by “Na” influx
Phase 1–> K open slightly
Phase 2–> Ca open and K efflux is balanced (leads to platue )
Phase 3–> rapid repolarization
Phase 4 –> rest

Question 2

How Many phases does pacemaker action potential have ?

Answer 2

3 !
missing phase 1 and 2
Phase 4 –> funny eddy currents start a spontaneous depolarization leading to the threshold
Phase 0 –> “Ca” influx leads to the upstroke and repolarization - slow conduction velocity (ca induced Ca influx ?)

Question 3

arrythmias can cause the heart to ?

Answer 3

(a) Beat too slowly (bradycardia)
(b) Beat too rapidly (tachycardia)
(c) Beat regularly (sinus tachycardia or sinus bradycardia)
(d) Beat irregularly (atrial fibrillation

Question 4

common causes of arrhythmia

Answer 4

Common causes of arrhythmias:\

•Abnormal automaticity •Re-entrant circuits •Afterdepolarizations •Accessory tract pathways

Question 5

abnormal automaticity treatment

Answer 5

•decrease slope of phase 4 depolarization, and/or, •raise threshold of dischargeto less negative voltage (decrease frequency of discharge)

Question 6

accessory tract pathway leading to arrythmias

Answer 6

Bundle of Kent

Question 7

Class I anti arrhytmic

Answer 7

•Class I -fast channel blockers (Na+) •(IA) Quinidine, procainamide, disopyramide •(IB) Lidocaine, mexiletine •(IC) Flecainide, propafenone

Question 8

Class II - anti arrythmic

Answer 8

b-blockers (Ca2+) • Propranolol, metoprolol, esmolol

Question 9

Class III )

Answer 9

-inhibitors of repolarization(K+) •Amiodarone, sotalol, dofetilide

Question 10

Class IV

Answer 10

calcium channel blockers (Ca2+) • Verapamil, diltiazem

Question 11

overview class I ? dependance ?

Answer 11

•Block fast inward Na+ channels •Decreased Na+ entry slows rate of rise of Phase 0 depolarization •Cause in excitability and conduction velocity •Different properties depending on their affinity for Na+ channel •Possess use / state-dependence

Basically: Use/state dependence = cells discharging at abnormally high frequency are preferentially blocked

Question 12

Class I act on what phases

Answer 12

• Slow rate of change of phase 0 •Slowing conduction, prolonging action potential & increasing ventricular effective refractory period
• Prolong phase 3 by an inhibiting K+ channels
• Intermediate speed of associationwith activated / inactivated Na+ channels & intermediate rate of dissociation

Question 13

Effect of Class I on QT and QRS ?

Answer 13

Increase both

Question 14

quindine overview and clinical uses

Answer 14

CLass 1A
•Concomitant Class III activity (block K+ channels) •Pro-arrhythmic •Due to toxicity is being replaced by Ca2+ antagonists
Clinical Applications •Suppression of supraventricular and ventricular arrhythmias
Replaced by more effective/safer antiarrhythmicagents

Question 15

PK for Quinidine

Answer 15

Pharmacokinetics • Quinidine sulfate = rapid oralabsorption • Forms active metabolites (CYP 3A4) •Inhibits CYP 2D6, 3A4 & P-glycoprotein

Question 16

Quinidine AE

Answer 16

•Arrhythmias (torsades de pointes) • SA & AV block or asystole • Nausea, vomiting & diarrhea (30-50%) •Thrombocytopenic purpura •Toxic doses – ventricular tachycardia (exacerbated by hyperkalemia) •Cinchonism(blurred vision, tinnitus, headache, psychosis) • Mixed a-adrenergic block & antimuscarinic properties • Can increase [digoxin] by decreasing renal clearance

Question 17

Qunidine AE

Answer 17

•Do not use in patients with: • Complete heart block •Use with extreme caution in patients with: • Prolonged QT interval • History of Torsades de Pointes • Incomplete heart block • Uncompensated heart failure • Myocarditis • Severe myocardial damage

Question 18

Procinamide MOA? clinical application ?

Answer 18

• Derivative of local anesthetic procaine • Similar actions to quinidine •Blockade of Na+ channels in activated state •Blockade of K+ channels •Antimuscarinic propertie

Clinical Applications •Suppression of supraventricular and ventricular arrhythmias Due to proarrhythmiceffects use should be reserved for life-threatening arrhythmias

Question 19

Procinamide PK ?`

Answer 19

•IV • Metabolized by CYP 2D6 •Partly acetylated to N-acetylprocainamide (NAPA) which prolongs duration of action potential (class III)

Question 20

Procinamide AE

Answer 20

Chronic use= high incidence of AE •Reversible lupus-like syndrome (25-30%) •Toxic doses: asystole, induction of ventricular arrhythmias • CNS effects (depression, hallucination, psychosis) • Weak anticholingeric effects • Hypotension

Question 21

Prcinamide contraindications

Answer 21

Hypersensitivity • Complete heart block • 2nd degree AV block • Systemic lupus erythematosus (SLE) •Torsades de Pointes • Heart failure & hypertension (use with caution)

Question 22

Dispyramide MOA ? clinical uses

Answer 22

•Strong negative inotropiceffect (> quinidine & procainamide) •Strong antimuscarinicproperties •Causes peripheral vasoconstriction • Blocks K+ channels

Clinical Applications • Suppression of supraventricular and ventricular arrhythmias

Question 23

disopyramide AE

Answer 23

•Pronounced negative inotropiceffects •Severe antimuscariniceffects (dry-mouth, urinary retention, blurred vision, constipation) •May induce hypotension & cardiac failure without preexisting myocardial dysfunction

Question 24

Class Ib anti arrythmics

Answer 24

Lidocaine / Mexiletine

Question 25

Class Ib anti arrythmics overview ? what phases are effected

Answer 25

•Slow Phase 0 & decrease slope of Phase 4 • Shorten Phase 3 repolarization •Little effect on depolarization phase of action potential in normal cells •Rapidly associate and dissociate with Na+ channels

Question 26

Class Ib effect on QRS and QT

Answer 26

QRS increases

QT decreases

Question 27

lidocaine MOA ? PK ?

Answer 27

• Local anesthetic • More effect on ischemic or diseased tissue • Particularly useful in treating ventricular arrhythmias • LITTLE EFFECT on K+ channels
Pharmacokinetics •IV only (extensive first-pass metabolism)

Question 28

clinical applications lidocaine

Answer 28

•Acute treatment of ventricular arrhythmias from myocardial infarction or cardiac manipulation (eg, cardiac surgery) •Treatment of digitalis-induced arrhythmias •Lidocaine’s use for VT has declined as a consequence of trials showing IV amiodarone to be superior • Little effect on atrial or AV junction arrhythmias

Question 29

lidocaine AE

Answer 29

•Wide toxic-therapeutic ratio • CNS effects (drowsiness, slurred speech, agitation etc.) • Little impairment of left ventricular function •NOnegative inotropic effect •Cardiac arrhythmias (<10%) •Toxic doses: convulsions, coma

Question 30

mixilitine MOA ?PK? AE

Answer 30

•Orally activederivative of lidocaine • Can be used both orally and IV

Clinical Applications Management of severe ventricular arrhythmias

Adverse Effects Mainly CNS & GI