Anti-arrhythmic Drugs PDF

Anti-arrhythmic Drugs Dr. Nabil Murghum Pharmacology Department Faculty of Medicine Tripoli University How the heart works ▪ The heart is a specialized muscle that contracts regularly and continuously, pumping blood to the body and the lungs ▪ The pumping action is caused b...

Anti-arrhythmic Drugs Dr. Nabil Murghum Pharmacology Department Faculty of Medicine Tripoli University How the heart works ▪ The heart is a specialized muscle that contracts regularly and continuously, pumping blood to the body and the lungs ▪ The pumping action is caused by a flow of regular electrical impulses through the heart that repeats itself in a cycle Conduction system of the heart Conduction system of the heart ▪ The heart’s natural pacemaker – the SA node – sends out regular electrical impulses from the atrium causing it to contract and pump blood into the ventricle ▪ The electrical impulse is then conducted to the ventricles through the AV node. The impulse spreads into the ventricles, causing the muscle to contract and to pump out the blood Normal sinus rhythm Arrhythmia ▪ Arrhythmia: An abnormal heart rhythm. Types of arrhythmia ▪ In an arrhythmia the heartbeats may be slow, rapid or irregular: Rapid arrhythmias (greater than 100 beats per minute) are called tachycardia Slow arrhythmias (slower than 60 beats per minute) are called bradycardia Irregular heart rhythms are called fibrillations (as in atrial fibrillation and ventricular fibrillation) Voughan William classification of anti-arrhythmic drugs ▪ According to their electrophysiological effects, they are classified into 4 classes: Class I → Na+ channel blockers Class II → β adrenoceptor blockers Class III → K+ channel blockers Class IV → Ca2+ channel blockers ▪ They restore normal rhythm through: Blocking Na+, K+ & Ca2+ channels ↓ sympathetic activity Class I ▪ They block Na+ channels ▪ According to their rate of dissociation from Na+ channels, they are classified into: Class Ia → they have moderate rate Class Ib → they have fast rate Class Ic → they have slow rate Class Ia Quinidine Procainamide Disopyramide ▪ They block Na+ channels & they have moderate rate of dissociation from Na+ channels ▪ They block K+ channels ▪ According to their actions, they produce: Prolong phase 0 Prolong phase 3 ↑ APD & ↑ ERP ↓ slope of phase 4 ↓ CV Class I anti-arrhythmic drug effects Quinidine ▪ It has anticholinergic effect [atropine like effect] ▪ It has ᾳ blocking effect ▪ Both actions ↑ HR, but antagonized by its depressed action on SAN & AVN ▪ It is anti-arrhythmic anti-malarial drug ▪ It is well absorbed orally & 90% is bound to plasma proteins ▪ It is metabolized in liver by hydroxylation ▪ Therapeutic uses: Supraventricular tachycardia Ventricular arrhythmia Malaria ▪ Side effects: Cardiotoxicity: 1. Ventricular tachycardia in patient with atrial flutter, because quinidine has atropine like action that ↑ AVN conduction. So digitalis is given to patient with AF before quinidine to block AVN conduction 2. Embolism in patient with atrial flutter, because in AF there is ↑atrial contractility → blood stagnation → intra atrial thrombi which becomes displaced by normal rhythm that is produced by quinidine. So anticoagulant is given to patient with AF as prophylaxis  GIT: Nausea, vomiting & diarrhea CNS: Cinchonism [headache, dizziness & tinnitus] Hepatitis Hypersensitivity ▪ Drug- drug interactions: Enzyme inducers like phenytoin → ↑ quinidine metabolism Enzyme inhibitors like cimetidine → ↓ quinidine metabolism Quinidine ↑ digoxin toxicity by displacement it from tissue binding site & ↓ its renal clearance Procainamide ▪ It has weak anticholinergic effect ▪ It has no ᾳ blocking effect ▪ It is well absorbed orally ▪ It is metabolized in liver by acetylation to form N- acetylprocainamide [NAPA] ▪ Therapeutic uses: Supraventricular arrhythmia Ventricular arrhythmia ▪ Side effects: Cardiotoxicity: similar to quinidine GIT: similar to quinidine CNS: depression & hallucination Hypersensitivity [common] SLE [with slow acetylation] Agranulocytosis Disopyramide ▪ It has more anticholinergic effect ▪ It has no ᾳ blocking effect ▪ It is well absorbed orally ▪ 30% is metabolized in liver to form mono-N-dealkylated metabolite ▪ Therapeutic uses: Supraventricular arrhythmia Ventricular arrhythmia ▪ Side effects: Cardiotoxicity: similar to quinidine GIT: similar to quinidine Class Ib Lidocaine Phenytoin Mexiletine Tocainide ▪ They block Na+ channels & they have fast rate of dissociation from Na+ channels ▪ They activate K+ channels ▪ According to their actions, they produce: Short phase 3 ↓ APD & ↓ ERP ↓ CV only in ventricular arrhythmia due to ischemia or digitalis toxicity Class I anti-arrhythmic drug effects Lidocaine ▪ It is anti-arrhythmic local anesthetic drug ▪ It is given IV to avoid extensive first pass metabolism in liver ▪ Therapeutic uses: Ventricular arrhythmia due to MI, digitalis toxicity & open heart surgery ▪ Side effects: Cardiac: less Cardiotoxicity Extracardiac: parasethesia, tremor & dizziness Phenytoin ▪ It is anti-arrhythmic anti-epileptic drug ▪ Therapeutic uses: Ventricular arrhythmia due to MI, digitalis toxicity & open heart surgery Mexiletine ▪ It is well absorbed orally ▪ Therapeutic uses: Ventricular arrhythmia due to MI, digitalis toxicity & open heart surgery Tocainide ▪ It is well absorbed orally ▪ Therapeutic uses: Ventricular arrhythmia due to MI, digitalis toxicity & open heart surgery Class Ic Propafenone Moricizine Flecainide ▪ They block Na+ channels & they have slow rate of dissociation from Na+ channels ▪ They have no effect on K+ channels ▪ According to their actions, they produce: Marked ↓ CV No effect on phase 3 No effect on APD & ERP Class I anti-arrhythmic drug effects Propafenone ▪ It is broad spectrum anti-arrhythmic drug ▪ It has weak β blocking activity ▪ Therapeutic uses: Supraventricular arrhythmia Ventricular arrhythmia Moricizine ▪ It has long t½ ▪ It is well absorbed orally ▪ Therapeutic uses: Ventricular arrhythmia Class II Propranolol Esmolol Metoprolol Pindolol ▪ They block β receptors in heart → ↓ cardiac sympathetic activity → slow HR → restore normal rhythm ▪ According to their actions, they produce: ↓ SAN & AVN activity ▪ Therapeutic uses: Supraventricular arrhythmia ▪ Prophylactic following MI to prevent ventricular arrhythmia Class III Amiodarone Sotalol Bretylium ▪ They block K+ channels → slow HR → restore normal rhythm ▪ According to their actions, they produce: Prolong phase 3 ↑ APD & ↑ ERP Amiodarone ▪ It is anti-arrhythmic anti-anginal drug ▪ It has broad spectrum activity: As class I → Na+ channel blockers As class II → β adrenoceptor blockers As class III → K+ channel blockers As class IV → Ca2+ channel blockers ▪ It contains iodine ▪ It blocks the conversion of T4 to T3 in the peripheral tissues ▪ It has vasodilator effect on coronary & peripheral vessels ▪ It has slow onset of action ▪ It has long t½ [several weeks] ▪ Therapeutic uses: Supraventricular arrhythmia Ventricular arrhythmia Wolf-Parkinson-White syndrome (WPW) ▪ Side effects: Hyper or hypothyroidism Pulmonary fibrosis Corneal microdeposits ▪ Drug- drug interactions: It ↑ digoxin levels Sotalol ▪ It has class II & III activity Bretylium ▪ It is anti-arrhythmic antihypertensive drug Class IV Verapamil Diltiazem Bepridil ▪ They block Ca2+ channels → slow HR → restore normal rhythm ▪ According to their actions, they produce: ↓ SAN & AVN activity ▪ Therapeutic uses: Supraventricular tachycardia ▪ Side effects: Hypotension due to vasodilatation effect on smooth muscles Heart block due to AV blocking effect Peripheral edema Constipation ▪ Drug- drug interactions: Verapamil displaces digoxin from tissue binding sites → toxicity Other anti-arrhythmic drugs Digoxin Adenosine Magnesium sulfate Digoxin ▪ It acts by inhibiting Na/K ATPase and produce: ↑ ERP & ↓ CV ▪ At toxic concentration it cause ectopic ventricular beats that may result in ventricular arrhythmias Adenosine ▪ It acts by stimulating adenosine receptors in AVN → blocks Ca channels & stimulates K channels producing: ↓ AVN activity ↓ CV ▪ It dilates coronary & peripheral blood vessels ▪ It is given IV & it has short t½ ▪ Therapeutic uses: Supraventricular tachycardia [DOC] ▪ Side effects: Flushing Chest pain Hypotension Dyspnea Magnesium sulfate ▪ It acts by stimulating Na/K ATPase and blocking Ca channels ▪ It is used in patient with digitalis induced arrhythmia if hypomagnesaemia is present Thank You