anti-arrhythmic drugs Flashcards
The classification of anti-arrhythmic drugs (Vaughan Williams)
Class I - Sodium-channel blockers. Class II - Beta-blockers. Class III - Potassium-channel blockers. Class IV - Calcium-channel blockers. Others - adenosine. - electrolyte supplement (magnesium and potassium salts) - digitalis compounds (cardiac glycosides)
About Class I anti-arrhythmics : subclasses
- IA class : prolong action potential - Block fast Na+ channels (↓ INa), preferentially in the open or inactivated channels (‘state-dependent’ blockade) – tissues undergoing frequent depolarization are more susceptible to inhibition - Increased action potential duration (APD), increased effective refractory period (ERP) - Block K+ channels – prolong repolarization 2. IB class : shorten action potential - Block inactivated Na+ channels — preference for tissues partly depolarized (hypoxic and ischemic myocardial tissues) - Results in an increased threshold for excitation and suppressed excitability of hypoxic heart muscle 3. IC class : – no effect on action potential duration - Block fast Na+ channels (↓ INa); especially His-Purkinje tissue - No ANS effects
About Class IA anti-arrhythmics : 3 drugs (not in the list)
- Procainamide (not in the list), Disopyramide (not in the list) - Conduction velocity ↓, pacemaker rate ↓ - Oral, IV, IM - Hepatic metabolism to N-acetyl-procainamide (NAPA; active metabolite), and renal elimination - Most atrial and ventricular arrhythmias - 2nd line drug for most sustained ventricular arrhythmias associated with acute MI - Adverse effects: drug-induced lupus, hemototoxicity 2. Quinidine (not in the list) - Muscarinic receptor inhibition – HR and AV conduction ↑ - May cause vasodilation via α inhibition (potential reflex tachycardia) - Enhanced effects under hyperkalemia - Displaces digoxin from tissue binding sites (enhancing toxicity) - Weak base – antacids increase its absorption (increasing toxicity) - Oral - Wide clinical use in many arrhythmias - Malaria treatment - Adverse effects: cinchonism (GI, tinnitus, ocular dysfunction, CNS excitation), hypotension, prolongation of QRS and QT intervals associated with syncope
About Class IB anti-arrhythmics : 2 drugs (1 in the list)
- Lidocaine (B16) - IV or IM only (due to first-pass metabolism) - Ventricular arrhythmias (also post-MI) - Open-heart surgery - Digoxin toxicity - Side effects: CNS toxicity (seizures); least cardiotoxic of conventional anti-arrhythmics 2. Mexiletine (Not in the list) - Orally active lidocaine analogue - Ventricular arrhythmias - Chronic pain syndromes
About Class IC anti-arrhythmics : 2 drugs (1 in the list)
- Flecainide(not in the list), Propafenone(B16) - Oral - Limited use because of pro-arrhythmogenic effects (shown to increase sudden cardiac death post-MI)
About Class II anti-arrhythmics : Mode of Actions
Cardiac β-adrenoceptor inhibition and reduction of cAMP: - Reduction of both Na+ and Ca2+ currents – both responsible for the upstroke (phase 0) of action potential in nodal cells - Prolongation of action potential duration - SA node automaticity ↓, AV node conduction velocity ↓
About Class II anti-arrhythmics : 3 drugs (2 in the list)
- Cardio-selective β1-antagonists a. Acebutolol(not in the list) - Oral - Supraventricular arrhythmias - Post MI as prophylaxis b. Esmolol (B8, B16) - Short-acting (10 min’) - IV only - Intraoperative and other acute arrhythmias 2. Non-selective β-antagonists a. Propranolol (B8, B13) - Oral, parenteral - Duration of action 4-6 h’ - Supraventricular arrhythmias - Post MI as prophylaxis against sudden cardiac death (ventricular fibrillation) - Thyrotoxicosis arrhythmias - Side effects: heart blocks, brady-arrhythmias
About Class III anti-arrhythmics : Mode of Actions
Inhibition of K+ current (IK) – slows down phase 2 (plateau) and phase 3 (repolarization) of action potential: - Prolongation of action potential duration; prolongation of effective refractory period (especially Purkinje and ventricular fibers) - The heart is less responsive to tachy-arrhythmias (rhythm control)
About Class III anti-arrhythmics : 2 drugs (in the list)
- Amiodarone (B16) - Blocks IKr, INa, ICa-L channels, β-adrenoceptors - Heart rate ↓, AV node conduction ↓ - Elimination half-life (t1/2) 1-10 weeks - Binds extensively to tissues (Vd ↑) - Inhibition of cytochrome P450-mediated metabolism – increased systemic exposure to other drugs (warfarin, statins) - Broad-spectrum antiarrhythmic action - Side effects: thyroid abnormalities (high Iodine content), deposition in skin and cornea, pulmonary fibrosis, optic neuritis, photosensitivity, hepatic toxicity, heart blocks, neurotoxicity 2. Sotalol (B8, B16) - Blocks IKr + non-selective beta blocker (↓ HR, ↓ AV conduction) - Oral, duration of action 7 h’ - Ventricular arrhythmias, atrial fibrillation - Dose-dependent Torsade-de-Pointes
About Class IV anti-arrhythmics : Mode of Actions
Inhibition of Ca2+ current (ICa-L) – slows down phase 0 (upstroke) and phase 4 (pacemaker potential). - SA and AV nodal activity ↓ - rate control - Cardiac contractility and blood pressure ↓
About Class IV anti-arrhythmics : 2 drugs (1 in the list)
- Verapamil (B13, B16, B18), Diltiazem (not in the list) -Non-dihydropyridine - Oral, parenteral - Duration of action 5-7 h’ a. Verapamil (B13, B16, B18) - AV nodal arrhythmias (especially prophylaxis) - Side effects: constipation, dizziness, flushing, hypotension, AV block, gingival hypertrophy b. Diltiazem (not in the list) - Rate control in atrial fibrillation - Side effects: constipation, dizziness, flushing, hypotension, AV block, gingival hypertrophy
About Class V anti-arrhythmics(others) : 3 drugs ( 2 in the list)
- Adenosin (B16) - A1 receptors (Gi): K+ current ↑, Ca2+ current ↓ - hyperpolarization and suppression of Ca2+-dependent action potential - A2 receptors (Gs): vasodilation - IV only - Extremely short-acting agent (10-15 s’) - AV nodal arrhythmias - Paroxysmal supraventricular tachycardia - Side effects: flushing, sedation, dyspnea, hypotension, chest pain - Antagonized by methylxanthines (theophylline, caffeine) 2. K+ (not in the list) - Increases IK – depresses ectopic pacemakers - Oral, IV - Digitalis-induced arrhythmias - Hypokalemia is associated with increased incidence of arrhythmias (especially with digitalis treatment) - Hyperkalemia depress conduction – may lead to reentry arrhythmia, heart block 3. Mg2+(B16) - Interacts with Na+/K+ ATPase, Ca2+-channels (mechanism unknown) - IV - Torsade-de-Pointes - Digitalis-induced arrhythmias
Management strategies of atrial fibrillation – Rate control vs. Rhythm control
