Antiarrhythmic drugs. §2. Classification of antiarrhythmic drugs B. Electrophysiological effects and classification of antiarrhythmic drugs Prolongation.

Antiarrhythmic drugs Antiarrhythmic drugs

2.2. Classification of antiarrhythmic drugsClassification of antiarrhythmic drugs

B.B. Electrophysiological effects and clas Electrophysiological effects and classification of antiarrhythmic drugssification of antiarrhythmic drugs

Prolongation of action potential duration (APD)Prolongation of action potential duration (APD)

(1) Class I (1) Class I (Na(Na++ channel blockers) channel blockers)

Class IA (Class IA (moderate Namoderate Na+ + channchann

el blockersel blockers)) ：： moderately block Namoderately block Na++ channels, channels, conduction conduction , , APD and ERP APD and ERP

quinidine quinidine 奎尼丁奎尼丁 procainamide procainamide 普鲁卡因胺普鲁卡因胺

Class IB (Class IB (mild Namild Na++ channe channe

l blockersl blockers)) ：： mildly block Namildly block Na++ channels, channels, not markedly inhibit conduction,not markedly inhibit conduction, KK+ + outward flow outward flow ,, shorten repolarizationshorten repolarization

lidocaine lidocaine 利多卡因利多卡因 phenytoin phenytoin 苯妥英苯妥英

Class IC (Class IC (decideddecided NaNa++ channel bl channel bl

ockersockers)) ：： markedly block Namarkedly block Na++ channels, channels, depolarizaton velocity in phse 0 depolarizaton velocity in phse 0 conduction conduction no marked effect on repolarizationno marked effect on repolarization

propafenone propafenone 普罗帕酮普罗帕酮 flecainide flecainide 氟卡尼氟卡尼

(2) Class II (2) Class II adrenoceptor blockersadrenoceptor blockers propranololpropranolol 普萘洛尔普萘洛尔


(3) Class III(3) Class III Prologation of APD Prologation of APD ((KK++ channel blocker; channel blocker; prolongation of repolarizationprolongation of repolarization ) )

amiodaroneamiodarone 胺碘酮胺碘酮 , , sotalolsotalol 索他洛尔索他洛尔

(4) Class IV(4) Class IVCaCa2+2+ channel blocker channel blockerss

verapamilverapamil 维拉帕米维拉帕米

Class IClass I （（ NaNa++ channel blockers channel blockers ）） IA IA SV, VSV, V** IB IB VV IC IC SV, VSV, V**Class IIClass II （（ receptor blockersreceptor blockers ）） SVSV**,,

V V Class IIIClass III （（ prolongation of APDprolongation of APD ）） SV, VSV, V Class IVClass IV （（ CaCa2+2+ channel blockers channel blockers ）） SVSV**, V, V


* primary action sites* primary action sites

C.C. Antiarrhythmic drugs Antiarrhythmic drugsClass I drugs:Class I drugs: NaNa++ channel blockers channel blockersClass IA drugsClass IA drugs

Quinidine Quinidine 奎尼丁奎尼丁

1. 1. Pharmacological effectsPharmacological effects NaNa++ channel block channel block muscarinic / muscarinic / receptor block receptor block (1) Automaticity(1) Automaticity ：： depolarization slope in phase 4 depolarization slope in phase 4 abnormal automaticity abnormal automaticity (2) Conduction (2) Conduction : : direct action, one-way direct action, one-way two-way block two-way block

atrioventricular conduction atrioventricular conduction because of M receptor block because of M receptor block (3) ERP and APD(3) ERP and APD ：： ERP ERP , APD , APD , ERP/APD , ERP/APD (4) Other effects: (4) Other effects: hypotension:hypotension: receptor blockreceptor block

C.C. Antiarrhythmic drugs Antiarrhythmic drugs

2. 2. Clinical usesClinical uses

(1) Atrial fibrillation and flutter, pre- and po(1) Atrial fibrillation and flutter, pre- and post-cardioversionst-cardioversion

conversion to sinus rhythm (pretreated with digitalis)conversion to sinus rhythm (pretreated with digitalis) maintaining sinus rhythmmaintaining sinus rhythm

(2) Other arrhythmias(2) Other arrhythmias ventricular and supraventricular arrhythmiasventricular and supraventricular arrhythmias


3. 3. Adverse effectsAdverse effects

(1) Extracardiac effects:(1) Extracardiac effects: GI reactions GI reactions ((diarrhoeadiarrhoea, , etcetc)) hypotension,hypotension, Chichonism,Chichonism, allergyallergy

(2) Cardiac toxicity:(2) Cardiac toxicity: prolongedprolonged QRS and QT intervals,QRS and QT intervals, paradoxical ventricular tachycardiaparadoxical ventricular tachycardia,, quinidine syncopequinidine syncope

(3) Arterial embolism:(3) Arterial embolism: after cardioversionafter cardioversion


4. 4. Drug interactionsDrug interactions

(1) Hepatic enzyme inducers ((1) Hepatic enzyme inducers (barbiturates, phenytoibarbiturates, phenytoi

n, n, etcetc..):): increase the metabolism of quinidineincrease the metabolism of quinidine

(2) Hepatic enzyme inhibitors ((2) Hepatic enzyme inhibitors (cimitidine, verapamil,cimitidine, verapamil,

etcetc..):): decrease the metabolism of quinidinedecrease the metabolism of quinidine

(3) Other drugs(3) Other drugs nitroglycerine:nitroglycerine: postural hypotensionpostural hypotension

digoxin:digoxin: reducing the dose of digoxinreducing the dose of digoxin


Procainamide Procainamide 普鲁卡因胺普鲁卡因胺

Effects and uses are similar to quinidine, but weaEffects and uses are similar to quinidine, but weak to atrial fibrillation and flutterk to atrial fibrillation and flutter

induces GI reactions, hypotesion, allergy, occasioinduces GI reactions, hypotesion, allergy, occasionally nally systemic erythematosus lupussystemic erythematosus lupus (long-term us (long-term use)e)


Class IB drugsClass IB drugs

NHCCH2N

OC2H5

C2H5

CH3

CH3

Lidocaine Lidocaine 利多卡因利多卡因


1. 1. ADMEADME

Low bioavailability after oral administrationLow bioavailability after oral administrationRapid elimination afterRapid elimination after i.v. i.v. injectioninjectionGiven by Given by i.v.i.v. infusion ( infusion ( i.v. gtt i.v. gtt ))


2. 2. Pharmacological effectsPharmacological effects

(1) Automaticity(1) Automaticity ：： reducing spontaneous depolarization reducing spontaneous depolarization in phase 4 ofin phase 4 of PurkinjePurkinje fibers fibers

(2) Conduction:(2) Conduction: therapeutic dose:therapeutic dose: no remarkable effectsno remarkable effects larger doses, Klarger doses, K++ , pH , pH : : decreasedecrease MDP MDP , K, K++ :: increaseincrease

(3) APD and ERP(3) APD and ERP ：： NaNa+ + inward flow inward flow in phase 2 in phase 2 KK+ + outward flow outward flow in phase 3 in phase 3 ERP ERP , APD , APD , ERP/APD , ERP/APD



Ventricular arrhythmias:Ventricular arrhythmias: acute myocardial infarction acute myocardial infarction intoxication of digitalis and other drugsintoxication of digitalis and other drugs

Local anesthesiaLocal anesthesia



(1) CNS depression(1) CNS depression

(2) Hypotension(2) Hypotension

(3) Arrhythmias:(3) Arrhythmias: bradycardia, A-V blockbradycardia, A-V block


CO

N

N

HC6H5

C6H5

NaO

Phenytoin Sodium Phenytoin Sodium 苯妥英钠苯妥英钠


Effects and uses are similar to lidocaine; Effects and uses are similar to lidocaine; an antiepileptic drugan antiepileptic drug

More effective on digitalis toxicity because of competition to NMore effective on digitalis toxicity because of competition to Naa++-K-K++-ATPase-ATPase

Class IC drugsClass IC drugs


CCH2CH2

OCH2CHCH2NHCH2CH2CH3

O

OH

Propafenone Propafenone 普罗帕酮普罗帕酮

1. 1. Pharmacological effectsPharmacological effects Reducing automaticity and conduction of fast resReducing automaticity and conduction of fast res

ponse cells in atrium and ponse cells in atrium and Purkinje Purkinje fibersfibers

2. 2. Clinical usesClinical uses Supraventricular and ventricular arrhythmiasSupraventricular and ventricular arrhythmias

3. 3. Adverse effectsAdverse effectsGI reactions, postural hypotension, arrhythmiasGI reactions, postural hypotension, arrhythmias


Flecainide Flecainide 氟卡尼氟卡尼

NH

CF3CH2O

O

C

HN CH2

OCH2CF3


1. 1. Pharmacological effectsPharmacological effects Similar to propafenoneSimilar to propafenone

2. 2. Clinical usesClinical uses Supraventricular and ventricular arrhythmias, aSupraventricular and ventricular arrhythmias, a

s a second choices a second choice

3. 3. Adverse effectsAdverse effectsCNS, arrhythmias, CNS, arrhythmias, etc.etc.


Class II drugs:Class II drugs: β adrenoβ adrenoceptor blockersceptor blockers

O CH2CHCH2NHCH

OHCH3

CH3

Propranolol Propranolol 普萘洛尔普萘洛尔


1. 1. Pharmacological effectsPharmacological effects Reducing sinus, atrial, ventricular automaticityReducing sinus, atrial, ventricular automaticity Reducing A-V and Reducing A-V and PurkinjePurkinje fiber conduction fiber conduction Prolonging A-V node ERPProlonging A-V node ERP

2. 2. Clinical usesClinical uses Supraventricular arrhythmiasSupraventricular arrhythmias

Ventricular arrhythmiasVentricular arrhythmias caused by exercise, emotion, ischemicaused by exercise, emotion, ischemic heart diseases, anesthetics, digitalis, c heart diseases, anesthetics, digitalis, etc.etc.

3. 3. Adverse effectsAdverse effects Conduction block, bradycardia, contractility Conduction block, bradycardia, contractility , and many oth, and many oth

er reactionser reactions


Class III drugs:Class III drugs: Prolongation of APDProlongation of APD (K(K++ channel blockers; channel blockers; prolongation of repolarization)prolongation of repolarization)

Amiodarone Amiodarone 胺碘酮胺碘酮

O O(CH2)2N(C2H5)2

(CH2)3CH3

CO

I

I



(1) Cardiac electrophysiological effects(1) Cardiac electrophysiological effects KK++,, NaNa++, Ca, Ca2+2+ channel blockchannel block Prolonging repolarization: APD Prolonging repolarization: APD , ERP , ERP Reducing sinus and Reducing sinus and PurkinjePurkinje fiber automaticity, and fiber automaticity, and

A-V and A-V and PurkinjePurkinje fiber conduction fiber conduction

(2) Vasodilatation(2) Vasodilatation Reducing peripheral resistanceReducing peripheral resistance Reducing cardiac oxygen consumptionReducing cardiac oxygen consumption Increasing coronary blood flowIncreasing coronary blood flow



Supraventricular and ventricular arrhythmiasSupraventricular and ventricular arrhythmias

Longer action durationLonger action duration (t(t1/21/2:: 25 25 ± ± 12 days), effec12 days), effec

ts maintained for 4 – 6 weeks after withdrawalts maintained for 4 – 6 weeks after withdrawal



(1) Arrhythmias(1) Arrhythmias Bradycardia, A-V block, prolonged Q-T intervalsBradycardia, A-V block, prolonged Q-T intervals

(2) Iodine reactions(2) Iodine reactions Iodine allergy, hypo- and hyperthyroidism, iodine accumulIodine allergy, hypo- and hyperthyroidism, iodine accumul

ation in cornea and skination in cornea and skin

(3) Others(3) Others Hypotension, tremor, interstitial pulmonary fibrosis, Hypotension, tremor, interstitial pulmonary fibrosis, etc.etc.


Sotalol Sotalol 索他洛尔索他洛尔


CHCH2NHCH(CH3)2CH3SO2NH

OH

C.C. Antiarrhythmic drugs Antiarrhythmic drugsSelectively blocks delayed rectifier KSelectively blocks delayed rectifier K++ currents currents （快速激（快速激

活的延迟整流钾通道活的延迟整流钾通道 IIkrkr ））

No-selective No-selective receptor antagonist receptor antagonist

Prolonging repolarization: APD Prolonging repolarization: APD , ERP , ERP

No remarkable effects on conductionNo remarkable effects on conduction

Used for supraventricular and ventricular arrhythmiUsed for supraventricular and ventricular arrhythmias, arrhythmias in acute myocardial infarctionas, arrhythmias in acute myocardial infarction

Prolonged Q-T, dysfunction of sinus, cardiac failureProlonged Q-T, dysfunction of sinus, cardiac failure

Class IV drugs:Class IV drugs: CaCa2+2+ channel blockers channel blockers

CH(CH3)2

CH3O

CH3O

CH3

CH2CH2NCH2CH2CH2CCN

OCH3

OCH3

Verapamil Verapamil 维拉帕米维拉帕米



(1) Antiarrhythmic effects:(1) Antiarrhythmic effects: Reducing spontaneous depolarization in phase 4 and Reducing spontaneous depolarization in phase 4 and

depolarization rate in phase 0 of slow response cellsdepolarization rate in phase 0 of slow response cells Reducing automaticity and conduction of sinus and atReducing automaticity and conduction of sinus and at

rial tissuesrial tissues Effective on abnormal pacemaker cells from fast respEffective on abnormal pacemaker cells from fast resp

onse to slow response in cardiac injury (such as ischemia) onse to slow response in cardiac injury (such as ischemia)

(2) Other effects:(2) Other effects: depressing cardiac contraction, vasodepressing cardiac contraction, vasodilatationdilatation


2. 2. Clinical usesClinical uses Supraventricular:Supraventricular: tachycardia, atrial arrhythmiastachycardia, atrial arrhythmias

Ventricular:Ventricular: myocardial ischemia, digitalis toxicitymyocardial ischemia, digitalis toxicity

3. 3. Adverse effectsAdverse effectsDepressing cardiac electrophysiological function and Depressing cardiac electrophysiological function and

contractility, hypotension,contractility, hypotension, etc.etc.Combined with class II drugs and quinidine:Combined with class II drugs and quinidine: potentiating cardiac depressionpotentiating cardiac depression


Other antiarrhythmic drugsOther antiarrhythmic drugs

Adenosine Adenosine 腺苷腺苷

Activating adenosine receptors and ACh-sensitive KActivating adenosine receptors and ACh-sensitive K++ channels, prolonging ERP of A-V node, decreasing cchannels, prolonging ERP of A-V node, decreasing conduction and automaticityonduction and automaticity

Rapid elimination, tRapid elimination, t1/2 1/2 1010 ～～ 20 seconds, 20 seconds, i.v.i.v. injection injection

Used for Used for acute superventricular tachycardiaacute superventricular tachycardiaCardiac and respiration depression (Cardiac and respiration depression (i.v.i.v. injection) injection)


Other antiarrhythmic drugsOther antiarrhythmic drugs

Digoxin Digoxin 地高辛地高辛 Reducing AV conduction: Reducing AV conduction: ventricular rate ventricular rate Used forUsed for atrial fibrillation & atrial flutter:preventing paroxysatrial fibrillation & atrial flutter:preventing paroxys

mal surpraventricular tachycardia mal surpraventricular tachycardia

Atropine Atropine 阿托品阿托品 Used for sinus or nodal bradycardia, A-V blockUsed for sinus or nodal bradycardia, A-V block

Isoprenaline Isoprenaline 异丙肾上腺素异丙肾上腺素 Used for sinus or nodal bradycardia, A-V blockUsed for sinus or nodal bradycardia, A-V block


Sinus tachycardia: Sinus tachycardia: blockers; verapamil blockers; verapamil Atrial premature contraction: Atrial premature contraction: blockers; verapamil; blockers; verapamil; class I drugsclass I drugs Atrial flutter or fibrillation:Atrial flutter or fibrillation: Cardioversion:Cardioversion: quinidine (+ digitalis)quinidine (+ digitalis) Ventricular rate control:Ventricular rate control: blockers, verapamil, digitalis blockers, verapamil, digitalis Paroxysmal superventricular tachycardia: Paroxysmal superventricular tachycardia: verapamil;verapamil; digitalis, digitalis, blockers, adenosine, blockers, adenosine, etcetc. . Ventricular premature contraction: Ventricular premature contraction: procainamide, procainamide, lidocaine, phenytoin, lidocaine, phenytoin, etcetc.. Ventricular fibrillation: Ventricular fibrillation: lidocaine, procainamide, lidocaine, procainamide, amiodarone, amiodarone, etc.etc.

Drug choiceDrug choice

All antiarrhythmic drugs have the proaAll antiarrhythmic drugs have the proarrhythmic effectsrrhythmic effects

表现为：表现为：原有的心律失常加重原有的心律失常加重出现新的心律失出现新的心律失

常常严重者有：严重者有：尖端扭转型室性心动过速尖端扭转型室性心动过速室颤室颤心脏停搏心脏停搏对策：对策：谨慎用药谨慎用药控制病因控制病因合理选择和应用合理选择和应用用药的个体化用药的个体化

D.D. Proarrhythmoc effects of antiarrhyt Proarrhythmoc effects of antiarrhythmic drugshmic drugs

Other drugsOther drugs digitalisdigitalis ions (ions (iviv)) ：： CaCa2+2+, K, K++

antimicrobialsantimicrobials ：： amantadine,amantadine, SMZ, TMP,SMZ, TMP, chloroquine, erythromycinchloroquine, erythromycin neurolepticsneuroleptics ：： haloperidolhaloperidol antidepressantsantidepressants ：： imipramine, amitrylineimipramine, amitryline antihistaminesantihistamines ：： terfenadine, cimitidineterfenadine, cimitidine

D.D. Proarrhythmoc effects of antiarrhyt Proarrhythmoc effects of antiarrhythmic drugshmic drugs

Antiarrhythmic drugs. §2. Classification of antiarrhythmic drugs B. Electrophysiological effects and classification of antiarrhythmic drugs Prolongation.

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antiarrhythmic drugs

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