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1、Chapter 18 Agents Used in Cardiac Arrhythmias 【Learning points】1.The mechanisms of arrhythmias Arrhythmias may occur in different conditions,such as stress,heart diseases and poisons.Most arrhythmias occur due to the alteration of the conduction and automaticity.Increase of the automaticity or condu
2、ction may lead to tachyarrhythmia,inversely,decrease of automaticity or conduction may induce bradyarrhythmias.The mechanisms underlying the arrhythmias including:(1)Reentry,an impulse being passed down via different pathway at same time,accelerates the automaticity and stiumlates the same heart mus
3、cle twice at different time,because conduction of one pathway decelerates.(2)Alteration of automacity:The sympathetic activity,hypokalemia and stretched cardiac myocytes shorten the duration of or the slope of action potential,and then the automaticity is increased.Automaticity alteration is also in
4、duced by the delayed afterdepolarization(DAD)or early afterdepolarization(EAD).During the repolarization of action potential,myocytes produce an early depolarization before resting potential;while delayed afterdepolarization occurs during depolarization.Both trigger arrhythmias.(4)Genetic defects ar
5、e also mechanisms of arrhythmias,such as sodium,calcium and potassium channel variation.2.The basic mechanism of antiarrhythmic drugs Given roles of positive ions in action potential,many drugs bind to ion channels to modulate the automaticity and conduction,slowing down the 4-phase automatic depola
6、rization rate,increasing the threshold potential and the maximum diastolic potential,prolonging the APD and so on.The drugs also remove trigger activity and eliminate the reentry via alteration of conduction and prolongation of ERP.3.Classification of antiarrhythmias and Common Medicines Classificat
7、ion I sodium channel blockers Classification Ia has moderate blockade of sodium channels,slowing down conduction and prolonging repolarization.Procainamide,disopyramide and quinidine belong to this classification.Quinidine inhibits sodium,calcium and potassium channels,and reduces automaticity.Quini
8、dine prolongs refractory period and slow down conduction.Moreover,quinidine shows anti M-,anti-receptor action.It is commonly used in atrial fibrillation,atrial flutter,supraventricular and ventricular arrhythmias.However,quinidine shows many adverse effects,such as cinchonism,bradyarrhythmias.Class
9、ification Ib shows mild blockade of sodium channels,decrease of conduction,and accelerate srepolarization.Lidocaine,mexilethine and tocainide are the main drugs.Lidocaine inhibits Na+influx.Lidocaine shortens duration of action of potential(AP),but increase the percent of effective refractory period
10、(ERP)aganist AP duration.Lidocaine does not slow down conduction markedly.Lidocaine is used in ventricular arrhythmias.Lidocaine at large dose causes CNS inhibition and bradyarrhythmias.Classification Ic shows severe blockade of sodium channels,and significantly slows down conduction with little eff
11、ect on repolarization.Flecainide reduces upstroke of phase 0 in Purkinje fibers and ventricular muscles.Flecainide significantly slows down conduction velocity and prolongs ERP and APD.Flecainide is used in supraventricular and ventricular premature beats,tachycardia and atrial fibrillation.Flecaini
12、de can cause life-threatening ventricular tacharrhythmia.Calssification II adrenaline receptor antagonists Propranolol,metroprolol and esmolol are classic receptor blockers,reduce automaticity(including sinus rhythm)and slow down atrioventricular node conduction.receptor blockers prolong refractory
13、period and decrease DAD induced by catecholamine.They are mainly used in supraventricular arrhythmia.They relieve sinus tachycardia and on ventricular arrhythmias.They induce sinus bradycardia,atrioventricular block,heart failure,asthma,hypotension.Classificaiton III extended action potential time-h
14、istory drugs Amiodarone inhibits Na+,Ca2+,K+ion channels in the heart and reduces the automaticity and conduction of sinoatrial node and Purkinje fibers.Amiodarone obviously prolongs the APD and ERP.Amiodarone,as broad spectrum antiarrhythmic drugs,is used in most tachyarrhythmias.Amiodarone induces
15、 sinus bradycardia,hyperthyroidism or hypothyroidism,pulmonary interstitial fibrosis,etc.Classification IV calcium channel blockers Villapami reduces sinus node automaticity and conduction velocity.Villapami prolongs ERP in sinus node and atrioventricular node and blocks trigger activity.Villapami is used in supraventricular and atrioventricular tachyarrhythmias.Villapami can lower blood pressure and lead to temporary sinus arrest.Other antiarrhythmias drugs Digoxin and adenosine are used as antiarrhythmias.Digoxin is used to control atrial fibrillation and flutter.