antiarrhythmic drugs
DESCRIPTION
Antiarrhythmic drugs. B. Electrophysiological effects and classification of antiarrhythmic drugs. 2. Classification of antiarrhythmic drugs. Prolongation of action potential duration (APD). (1) Class I (Na + channel blockers) Class IA ( moderate Na + channel blockers ) : - PowerPoint PPT PresentationTRANSCRIPT
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
B.B. Electrophysiological effects and clas Electrophysiological effects and classification of antiarrhythmic drugssification of antiarrhythmic drugs
(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
B.B. Electrophysiological effects and clas Electrophysiological effects and classification of antiarrhythmic drugssification of antiarrhythmic drugs
* 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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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)
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
Class IB drugsClass IB drugs
NHCCH2N
OC2H5
C2H5
CH3
CH3
Lidocaine Lidocaine 利多卡因利多卡因
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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 ))
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
3. 3. Clinical usesClinical uses
Ventricular arrhythmias:Ventricular arrhythmias: acute myocardial infarction acute myocardial infarction intoxication of digitalis and other drugsintoxication of digitalis and other drugs
Local anesthesiaLocal anesthesia
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
4. 4. Adverse effectsAdverse effects
(1) CNS depression(1) CNS depression
(2) Hypotension(2) Hypotension
(3) Arrhythmias:(3) Arrhythmias: bradycardia, A-V blockbradycardia, A-V block
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
CO
N
N
HC6H5
C6H5
NaO
Phenytoin Sodium Phenytoin Sodium 苯妥英钠苯妥英钠
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic 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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
Flecainide Flecainide 氟卡尼氟卡尼
NH
CF3CH2O
O
C
HN CH2
OCH2CF3
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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.
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
1. 1. Pharmacological effectsPharmacological effects
(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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
2. 2. Clinical usesClinical uses
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
3. 3. Adverse effectsAdverse effects
(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.
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
Sotalol Sotalol 索他洛尔索他洛尔
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
1. 1. Pharmacological effectsPharmacological effects
(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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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)
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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
C.C. Antiarrhythmic drugs Antiarrhythmic drugs
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