Antiarrhythmic Drugs Flashcards
Class I
Sodium Channel Blockers. Bind fast Na channels in the open and inactivated states and dissociate from channels during the resting state. This slows phase 0 depolarization and conduction velocity. There is a use-dependent blockade, which means the effect is potentiated at faster heart rates- when rapidly activated cardiac tissue Na channels spend more time in the open and inactivated states than in the resting state.
Class II
Beta-blockers. Inhibit sympathetic activation of cardiac automaticity and conduction, resulting in slowing of HR, decreased AV node conduction velocity, prolongation of AV node refractory period.
Side effects: bradycardia, hypotension, bronchospasms.
Beta blockade also prevents activation of adenylyl cyclase and the consequent increase in cAMP, thus having a negative inotropic effect.
Use: for all atrial arrhythmias, VT and VF. Does not prolong repolarization in ventricular tissues so is safe for patients with long QT syndrome.
Class III
Potassium Channel Blockers. Prolongs AP repolarization. Reverse-use dependence, which means the effect is better when the HR is slow. Mostly targets Ikr channels. The main common effect is an increase in ERP.
Class IV
Calcium Channel Blockers. Acts primarily on slow response cells (SA/AV nodal cells) which are dependent on Ca influx for AP depolarization. Increase threshold for AP firing in nodal cells. Increase nodal refractory period. Depress conduction velocity in the SA and AV node.
Use: paroxysmal SVT. Rarely used for VT.
Major side effect: Negative chronotropic effect, which decreases automaticity of the SA node. Negative inotropic effect due to a decrease in Ca influx during plateau phase of a ventricular action potential. Hypotension due to a decrease of Ca influx into vascular smooth muscle cells. Peripheral edema (nifedipine). Constipation due to a decrease of Ca influx in GI smooth muscle cells (verapamil). Interacts with digitalis to slow conduction velocity in the AV node resulting in heart block by increase levels of digitalis- competes for renal excretion (verapamil and diltiazem).
Drug interactions: Slows CYP3A4 metabolism of quinidine, digoxin, and simvastatin.
Class IA
Block voltage gates Na channels and delayed rectifier K channels. This results in slow phase 0 depolarization, slow conduction velocity and it prolongs AP and ERP duration. All are potentially proarrhythmic, limiting their use. Effective for treating reentrant and ectopic SVTs and VT.
Qunidine
Class IA. Increases AP duration, decreases conduction velocity, and increases ERP. Indirect effects are the blocking of K channels (delaying repolarization) causing EADs. Also has a vagolytic effect, which can be detrimental when an atrial flutter or AF is present (the slowing of conduction can be just enough to result in a 1:1 conduction through the AV node resulting in VT).
Side effects: severe GI effects (diarrhea, cramping), vagolytic effect, proarrhythmic.
Drug interactions: Slows CYP2D6 metabolism of narcotics and reduces the renal clearance of digitalis.
Class IB
Inhibits fast Na channels and typically shortens the duration of the AP and ERP. Is attributed to the blockade of small Na currents that continue through phase 2 of the AP. Act preferentially on diseased tissue (characterized by acidosis, faster rates of cell stimulation, increased extracellular K concentration- and thus a less negative maximum diastolic potential) because there are more Na channels in the inactivated state. There is a conduction blockade in ischemic tissue by reducing the slope of phase 0 depolarization and slowing the conduction velocity, thus inhibiting reentrant arrhythmias.
Lidocaine
Class IB. Increase AP threshold. There is an increased blockade of Na channels at a high HR because that is when Na channels spend more time in the inactivated state. This decreases conduction velocity. AP and ERP durations are also shortened.
Side effects: dizziness, seizures, nausea.
Use: VT, digitalis induced arrhythmias (slowed conduction velocities enhance the possibility of reentrant arrhythmias). Safe for patients with long QT syndrome.
Drug interactions: Slows CYP3A4 metabolism of cimetidine.
Class IC
Most potent blockade of fast Na channels. Slows conduction throughout the heart. There is less effect on K channels.
Flecainide
Class IC. Increases AP threshold, decreases conduction velocity, and has variable effects on ERP.
Side effects: proarrhythmic (CAST trial)
Use: Approved for use in life-threatening situations when SVT or VT are resistant to other drugs.
Drug interactions: Slows CYP2D6 metabolism.
Propranolol
Long acting beta blocker with oral administration
Esmolol
Short acting beta blocker with IV administration
Amiodarone
Class III. Potent K channel blocker (blocks Ikr and Iks channels). Is a modest Na, Ca and beta blocker.
Use: VT, VF. Prevention of paroxysmal atrial fibrillation or atrial flutter.
Side effects: EADs; but rarely associated with Torsades de Pointes. Altered thyroid function (inhibits conversion of T3 to T4)- hypothyroidism. Pulmonary fibrosis. Hepatotoxicity.
Drug interactions: Warfarin, digoxin, quinidine, felcainide, sildenafil, simvastatin.
Sotalol
Class III. Major Ikr blocker. Also has some beta blocking actions. Most serious side effect is triggered arrhythmias with Torsades de Pointes.
Side effects: fatigue and bradycardia
Use: VT, VF, SVT, AF.
Drug interactions: Administer with caution in conjunction with other drugs that prolong the QT interval like class IA, TCAs, quinolone antibiotics.
Dofetilide
Class III. Blocks Ikr channels.
Common side effects: headache, dizziness, chest pain
Serious side effects: triggered arrhythmias with Torsades de Pointes.
Use: AF, atrial flutter, safe for patients with left ventricular dysfunction.
Drug interactions: eliminated via kidneys. Drugs that interfere with renal secretion are contraindicated: cimetidine, verapamil, HCTZ, ketocanazole, trimethoprim.
