Page 265 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 14 Agents Used in Cardiac Arrhythmias 251

Mechanism Pharmacokinetics, Toxicities,
Subclass, Drug of Action Effects Clinical Applications Interactions
CLASS 1C
• Flecainide Sodium channel (I Na ) Dissociates from channel with slow Supraventricular arrhythmias Oral • hepatic and kidney metabolism
blockade kinetics • no change in action in patients with normal heart • half life ∼20 h • Toxicity: Proarrhythmic
potential duration • do not use in ischemic
conditions (post-myocardial
infarction)

• Propafenone: Orally active, weak β-blocking activity; supraventricular arrhythmias; hepatic metabolism
• Moricizine: Phenothiazine derivative, orally active; ventricular arrhythmias, proarrhythmic. Withdrawn in USA.
CLASS 2
• Propranolol β-Adrenoceptor Direct membrane effects (sodium Atrial arrhythmias and Oral, parenteral • duration 4–6 h
blockade channel block) and prolongation of prevention of recurrent • Toxicity: Asthma, AV blockade, acute
action potential duration • slows SA infarction and sudden death heart failure • Interactions: With other
node automaticity and AV nodal cardiac depressants and hypotensive
conduction velocity drugs
• Esmolol: Short-acting, IV only; used for intraoperative and other acute arrhythmias
CLASS 3
• Amiodarone Blocks I Kr , I Na , I Ca-L Prolongs action potential duration Serious ventricular Oral, IV • variable absorption and tissue
channels, β and QT interval • slows heart rate arrhythmias and accumulation • hepatic metabolism,
adrenoceptors and AV node conduction • low supraventricular elimination complex and slow • Toxicity:
incidence of torsades de pointes arrhythmias Bradycardia and heart block in diseased
heart, peripheral vasodilation,
pulmonary and hepatic toxicity • hyper-
or hypothyroidism. • Interactions: Many,
based on CYP metabolism
• Dofetilide I Kr block Prolongs action potential, effective Maintenance or restoration Oral • renal excretion • Toxicity: Torsades
refractory period of sinus rhythm in atrial de pointes (initiate in hospital with
fibrillation monitoring) • Interactions: Additive with
other QT-prolonging drugs
• Sotalol: β-Adrenergic and I Kr blocker, direct action potential prolongation properties, use for ventricular arrhythmias, atrial fibrillation
• Ibutilide: Potassium channel blocker, may activate inward current; IV use for conversion in atrial flutter and fibrillation
• Dronedarone: Amiodarone derivative; multichannel actions, reduces mortality in patients with atrial fibrillation
• Vernakalant: Investigational in the USA, multichannel actions in atria, prolongs atrial refractoriness, effective in atrial fibrillation
CLASS 4
• Verapamil Calcium channel Slows SA node automaticity and AV Supraventricular tachycardias, Oral, IV • hepatic metabolism • caution in
(I Ca-L type) blockade nodal conduction velocity • decreases hypertension, angina patients with hepatic dysfunction • Toxicity
cardiac contractility • reduces blood & Interactions: See Chapter 12
pressure
• Diltiazem: Equivalent to verapamil

MISCELLANEOUS
• Adenosine Activates inward Very brief, usually complete AV Paroxysmal supraventricular IV only • duration 10–15 s • Toxicity:
blockade tachycardias Flushing, chest tightness, dizziness
rectifier I K • blocks I Ca
• Interactions: Minimal
• Magnesium Poorly understood • Normalizes or increases Torsades de pointes • digitalis- IV • duration dependent on dosage
+
+
interacts with Na /K - plasma Mg 2+ induced arrhythmias • Toxicity: Muscle weakness in overdose
+
2+
ATPase, K , and Ca
channels
• Potassium Increases K + Slows ectopic pacemakers • slows Digitalis-induced arrhythmias Oral, IV • Toxicity: Reentrant arrhythmias,
permeability, K + conduction velocity in heart • arrhythmias associated with fibrillation or arrest in overdose
currents hypokalemia