Antiarrhythmic 1

Question 1

What is the function of Class 1 Antiarrhythmics?

Na+ channel blockers

Answer 1

Na+ channel blockers

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

Question 2

What are the Use/ State - dependence for Class 1 Antiarrhythmics?

Answer 2

• Drugs bind more rapidly to open or inactivated Na+channels
• Drugs have greater effect in tissues more freq. depolarizing

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

Question 3

Class 1A Antiarrhytmics

Answer 3

Quinidine / Procainamide / Disopyramide

Sodium channel blockers;

• 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 association with activated / inactivated Na+ channels & intermediate rate of dissociation

Question 4

Quinidine / Procainamide / Disopyramide

Class 1A Antiarrhythmics

Answer 4

• Sodium channel blocker shifts phase 0 to the right
• Less sodium channels open = increase QRS
• potassium blocker: prolonged depolarizatipn = exteded QT

Question 5

Quinidine

Answer 5

• Ca2+ channel blocker

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 antiarrhythmic agents

Question 6

Quinidine Adverse Effects?

Answer 6

• 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 7

Quinidine Contraindications?

Answer 7

• 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 8

Procainamide Mechanism of Action?

Answer 8

• Similar actions to quinidine
• Blockade of Na+ channels in activated state
• Blockade of K+ channels
• Antimuscarinic properties

Clinical Applications:

• Suppression of supraventricular and ventricular arrhythmias

Due to proarrhythmic effects use should be reserved for life-threatening arrhythmias

Question 9

Procainamide PK?

Answer 9

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

Question 10

Procainamide adverse effects?

Answer 10

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 11

Procainamide Contraindications?

Answer 11

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

Question 12

Disopyramide Mechanism of Action

Class 1A

Answer 12

• Strong negative inotropic effect (> quinidine & procainamide)

• Strong antimuscarinic properties
• Causes peripheral vasoconstriction

• Blocks K+ channels

Clinical Applications

• Suppression of supraventricular and ventricular arrhythmias

Question 13

DIsopyramide adverse effects?

Answer 13

• Pronounced negative inotropic effects
• Severe antimuscarinic effects (dry-mouth, urinary retention, blurred vision, constipation)

• May induce hypotension & cardiac failure without pre- existing myocardial dysfunction

Question 14

What are thee effects of Class 1B Antiarrhythmics?

Answer 14

Lidocaine / Mexiletine

• 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 15

Class 1B drugs map

Lidocaine / Mexiletine

Answer 15

• Sodium channel blocker
• sodium channels midly blocked in phase 0 = mild increase in QRS
• shortening on Qt repolarizing pahse 4

Question 16

Lidocaine Mechanism of Action and class

Answer 16

• Class 1B
• 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 17

Lidocaine Clinical Application

Answer 17

• 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 18

Lidocaine Adverse Effects?

Answer 18

• Wide toxic-therapeutic ratio
• CNS effects (drowsiness, slurred speech, agitation etc.)
• Little impairment of left ventricular function
• NO negative inotropic effect
• Cardiac arrhythmias (<10%)
• Toxic doses: convulsions, coma

Question 19

Mexiletine effects and clinical use?

Answer 19

Class 1B

• Orally active derivative of lidocaine
• Can be used both orally and IV

Clinical Applications

Management of severe ventricular arrhythmias

Adverse Effects

Mainly CNS & GI