Antiarrhythmics Tomáš Goněc 21.11.2011 Arrhythmia □ alteration in the normal sequence of heart electrical impulse activation □ abnormality in the rate, site of origin or conduction pathway of impulse Arrhythmias Normal sinus rhythm Atrial fibrillation Physiological contraction Inward Na* channels 50 T -50 - - Threshold -100 J- 1 P0 Inward Ca1* channels Outward K channels ß-Blockers Amioda rone Sotalol P3 Arrhythmia therapy □ Invazive: intracardial cardiostimulators, defibrilators □ Medication: antiarrhythmics 11 Antiarrhythmics: classification Class Agent Primary Pharmacologic Effect IA Quinidine Decrease maximal rate of depolarization; increases duration of action potential Procainamide Disopyramide IB Lidocaine Decrease maximal rate of depolarization; decrease duration of action potential Phenytoin Tocainide Mexiletine IC Flecainide Decrease maximal rate of depolarization; no change in duration of action potential Encainide Propafenone Moricizine II Propranolol Inhibition of sympathetic activity llf Sotalol Prolongation of duration of action potential Ibutilide Bretylium Amiodarone IV Verapamil Inhibition of inward slow calcium current Diltiazem Bepridil Class I A. CONH —CH2CH2 N /C2H5 \ C2H5 NH, CH30 COCK QUINIDINE PROCAINAMIDE ACEKAINIDE wrnwľeiap LUn!|BLUÍBJd V I 11 Class I A. disopyramide Class I B. H3a NHCO —CH2 —N CH, /-C2H5 C2H5 H lidocain CH, trimecain H3C CK NHCO —CH —NK CK tocainid H3a CK O—CH2—CH—NK .CH, mexiletine CONHCK F3CCH20 N H OCH2CF3 flecainid Class I C. propaphenon dipraphenon CH3 11 Class II. □ ß-adrenergic receptor antagonists, used as antihypertensives □ as antiarrhythmics used mainly: atenolol, acebutolol, bisoprolol, metipranolol, metoprolol, pindolol, Oxprenolol, karteolol, Penbutolol, talindolol, esmolol (ultra-short action), nadoxolol Class III. □ K+ channel inhibitors OH I ^CH3 CHChLNHCH \ CH, ,O.XH2CH2CH2CH3 NHS02CH3 Sotalol CO amiodaron OCHXH^N /C2H5 \ C2H5 CH3S02NH- CH2CH2 N —CH, CH3S02NH—