antiarrhythmics drug table

name the Group 1A antiarrhythmics

Procainamide; disopyramide; quinidine

Group 1A prototype MOA

Procainamide: use- and state-dependent Na+ channel block; some K+ channel block; slows conduction velocity and pacemaker activity; prolongs action potential duration and refractory period

Group 1A prototype clinical applications

Procainamide: atrial and ventricular arrhythmias, especially after myocardial infarction

Group 1A prototype pharmacokinetics

Procainamide: oral and parenteral; oral slow-release forms available; duration 2-3 h

Group 1A prototype toxicities & interactions

Procainamide: increased arrhythmias including torsades; hypotension; lupus-like syndrome

how is disopyramide different from procainamide?

Similar to procainamide but longer duration of action; toxicity includes antimuscarinic effects and heart failure

how is quinidine different from procainamide?

Similar to procainamide but greater toxicity, including cinchonism (tinnitus, vertigo, headache), gastrointestinal disturbance, and thrombocytopenia

name the Group 1B antiarrhythmics

Lidocaine; mexiletine

Group 1B prototype MOA

Lidocaine: highly selective use- and state-dependent Na+ block; minimal effect in normal tissue; no effect on K+ current

Group 1B prototype clinical applications

Lidocaine: ventricular arrhythmias postmyocardial infarction and digitalis-induced arrhythmias

Group 1B prototype pharmacokinetics

Lidocaine: IV and IM; duration 1-2 h

Group 1B prototype toxicities & interactions

Lidocaine: CNS sedation or excitation

how is mexiletine different from lidocaine?

Similar to lidocaine but oral activity and longer duration of action; also used in neuropathic pain

name the Group 1C antiarrhythmics

Flecainide; propafenone

Group 1C prototype MOA

Flecainide: selective use- and state-dependent Na+ block; slows conduction velocity and pacemaker activity

Group 1C prototype clinical application

Flecainide: refractory arrhythmias

Group 1C prototype pharmacokinetics

Flecainide: oral; half-life 20 h

Group 1C prototype toxicities & interactions

Flecainide: increased arrhythmias; CNS excitation

how is propafenone described?

Similar to flecainide

name the Group 2 antiarrhythmics

Propranolol; metoprolol; esmolol

Group 2 prototype MOA

Propranolol: blocks β receptors; slows pacemaker activity

Group 2 prototype clinical applications

Propranolol: postmyocardial infarction prophylaxis against sudden-death ventricular fibrillation; thyrotoxicosis

Group 2 prototype pharmacokinetics

Propranolol: oral, parenteral; duration 4-6 h

Group 2 prototype toxicities & interactions

Propranolol: bronchospasm; cardiac depression; AV block; hypotension

how is metoprolol different from propranolol?

Similar to propranolol but β1 selective

what is special about esmolol?

Selective β1-receptor blockade; IV only; 10-min duration; used in perioperative and thyrotoxicosis arrhythmias

name the Group 3 antiarrhythmics

Amiodarone; sotalol; ibutilide; dofetilide

amiodarone MOA

Strong K+ current block → marked prolongation of action potential and refractory period; also has Group 1, 2, and 4 activity

amiodarone clinical applications

Refractory arrhythmias; used off label in many arrhythmias (broad-spectrum antiarrhythmic action)

amiodarone pharmacokinetics

Oral, parenteral; half-life and duration of action 1-10 wk

amiodarone toxicities & interactions

Thyroid abnormalities; deposits in skin and cornea; pulmonary fibrosis; optic neuritis; torsades is rare

sotalol MOA

K+ current block and β-adrenoceptor block

sotalol clinical applications

Ventricular arrhythmias and atrial fibrillation

sotalol pharmacokinetics

Oral; duration 7 h

sotalol toxicities & interactions

Dose-related torsades de pointes; cardiac depression

ibutilide MOA

Selective K+ current block; prolonged action potential and QT interval

ibutilide clinical application

Treatment of acute atrial fibrillation

ibutilide pharmacokinetics

IV only; duration 6 h

ibutilide toxicity

Torsades de pointes

dofetilide MOA

Like ibutilide

dofetilide clinical applications

Treatment and prophylaxis of atrial fibrillation

dofetilide pharmacokinetics

Oral; duration 7 h

dofetilide toxicity

Torsades de pointes

name the Group 4 antiarrhythmics

Verapamil; diltiazem

verapamil MOA

State- and use-dependent Ca2+ current block; slows conduction in AV node and pacemaker activity; prolongs PR interval

verapamil clinical applications

AV nodal arrhythmias, especially in prophylaxis

verapamil pharmacokinetics

Oral, parenteral; duration 7 h

verapamil toxicities & interactions

Cardiac depression; constipation; hypotension

diltiazem MOA

Like verapamil

diltiazem clinical application

Rate control in atrial fibrillation

diltiazem pharmacokinetics

Oral, parenteral; duration 6 h

diltiazem toxicities & interactions

Like verapamil

what is important about dihydropyridines in arrhythmias?

Calcium channel blockers but not useful in arrhythmias; sometimes precipitate them

name the miscellaneous antiarrhythmics in the table

Adenosine; potassium ion; magnesium ion

adenosine MOA

Increases diastolic K+ current of AV node → marked hyperpolarization and conduction block; reduces Ca2+ current

adenosine clinical application

Acute nodal tachycardias

adenosine pharmacokinetics

IV only; duration 10-15 s

adenosine toxicities & interactions

Flushing; bronchospasm; chest pain; headache

potassium ion MOA

Increases all K+ currents; decreases automaticity; decreases digitalis toxicity

potassium ion clinical applications

Digitalis toxicity and other arrhythmias if serum K is low

potassium ion pharmacokinetics

Oral or IV

potassium ion toxicities & interactions

Both hypokalemia and hyperkalemia are associated with arrhythmogenesis; severe hyperkalemia causes cardiac arrest

magnesium ion MOA

Poorly understood; possible increase in Na+/K+ ATPase activity

magnesium ion clinical applications

Digitalis arrhythmias and other arrhythmias if serum Mg is low

magnesium ion pharmacokinetics

IV

magnesium ion toxicities & interactions

Muscle weakness; severe hypermagnesemia can cause respiratory paralysis