Antiarrhythmic Drugs Lecture Slides PDF

PN704 Antiarrhythmic drugs Prof. Ashraf Khalil, Ph.D. Feb. 12, 2025 1  Learning Objectives By the end of this series of lectures, students should be able to:  Describe the arrhythmia  Identify different types of drugs used for the treatment o...

PN704 Antiarrhythmic drugs Prof. Ashraf Khalil, Ph.D. Feb. 12, 2025 1  Learning Objectives By the end of this series of lectures, students should be able to:  Describe the arrhythmia  Identify different types of drugs used for the treatment of arrhythmia based on Vaughan Williams Classification  Explain the chemical properties, medicinal application, side effects and chemical structures of one example of each group AK-SS25AY 2 2  Sinus rhythm  Sinoatrial (SA) node is cardiac pacemaker  Normal sinus rhythm 60-100 beats/ minute  Conducts more slowly through AV node  Conducts rapidly through His bundles and Purkinje fibers AK-SS25AY 3 3  Physiology of cardiac rate and rhythm  Cardiac myocytes are electrically excitable  Resting intracellular voltage of myocardial cells is negative -90 mV (SA node is -40mV)  Resting state K+ inside and Na+ outside cell (Na+/K+ pump)  Action potential occurs when Na+ enters the cell and sets up a depolarizing current  Stimulation of a single muscle fiber causes electrical activity to spread across the myocardium. AK-SS25AY 4 4  Vaughan Williams Classification of antiarrhythmic  Class I: Block sodium channels  Ia (quinidine and procainamide) AP  Ib (lidocaine and phenytoin) AP  Ic (flecainide) AP  Class II:  adrenoceptor antagonists (e.g. atenolol)  Class III: prolong action potential and prolong refractory period (amiodarone)  Class IV: Calcium channel blockers (Verapamil) AK-SS25AY 5 5  Sinus Rhythm  SA rate controlled by autonomic nervous system  Parasympathetic system predominates (M2 muscarinic receptors)  Sympathetic system (1 receptors)  Increased heart rate (positive chronotropic effect)  Increased automaticity  Facilitation of conduction of AV node AK-SS25AY 6 6  Quinidine  Isolated from cinchona bark, isomer of quinine  Classified under Class I A.  Sodium channel blocker, increases action potential  Several side effect: e.g. cinchonism decreased hearing, headache, nausea, vomiting, dysphoria, and visual disturbances  Procainamide is equivalent to quinidine as an antiarrhythmic agent  Its use now is very limited Procainamide AK-SS25AY 7 7 Class Ib:  Lidocaine: Sodium channel blocker  Binds primarily to inactivated sodium channels mainly in damaged tissues  Decreases the action potential duration and increases the refractory period  It increases the ventricular fibrillatory threshold and can interrupt life‐threatening tachycardias, especially in ischemic tissue  Also used as a local anesthetic agent and in dental surgery.  Given parenterally as 96% suffer from first pass metabolism following oral administration AK-SS25AY 8 8  Class IC  Sodium channel blockers, not affecting the duration of action potential  Inhibits different channels e.g. Ca++, K+,  Decreases AV conduction  Example: Flecainide  Treatment of supraventricular tachycardia  Contraindicated in ischemic heart diseases as can cause a sudden death AK-SS25AY 9 9 Class II  blockers  Decrease the sympathetic over activity  Decrease AV conduction  Some b blockers have membrane stabilizing action  Mainly used in treatment of arrhythmia associate with thyroid dysfunction as they prevent conversion of T4 to T3 (cardiotoxic)  Arrhythmia due to sympathetic over activity  Example atenolol and propranolol Propranolol Atenolol AK-SS25AY 10 1  Class III  K+ channel blockers (act on phase 3 of action potential)  In addition, blocks Na+ and Ca++ channels and decrease AV conduction Amiodarone  Used for the treatment of all kinds of arrhythmia except in arrhythmia associated with hyperthyroidism as it contains iodine  Side effect: liver toxicity, chronic cough due to the iodine contents, hypotension AK-SS25AY 1 1 1 Class IV Ca++ channels blockers  Two main classes:  Dihydropyridine (Nifedipine), vaso- selective, can cause reflective tachycardia, has no use in treatment of arrhythmia.  Verapamil : cardio-selective, decrease AV conduction  On cardiomyocyte, increase phase 2 (plateau), increase action potential as it targets specifically voltage-gated L-type Ca2+ channels  Used for high blood pressure, angina and tachycardia  For supraventricular arrhythmia AK-SS25AY 12 1