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",#(7),01444'9=82<.342ÿÛC  2!!22222222222222222222222222222222222222222222222222ÿÀ:€"ÿÄ ÿĵ}!1AQa"q2�‘¡#B±ÁRÑð$3br‚ %&'()*456789:CDEFGHIJSTUVWXYZcdefghijstuvwxyzƒ„…†‡ˆ‰Š’“”•–—˜™š¢£¤¥¦§¨©ª²³´µ¶·¸¹ºÂÃÄÅÆÇÈÉÊÒÓÔÕÖרÙÚáâãäåæçèéêñòóôõö÷øùúÿÄè“)é(€àà€ òú/È 0ÒÕ0·DArialngs¨¹¨¹0-»(¸¸ç0(¸z[ 0 ¸·D‹[SOalngs¨¹¨¹0-»(¸¸ç0(¸z[ 0 ¸† ·DTahomags¨¹¨¹0-»(¸¸ç0(¸z[ 0 ¸0·DWingdings¨¹¨¹0-»(¸¸ç0(¸z[ 0 ¸¤ €A¥ .©  @£nÿý?" dÿd@ÿÿïÿÿ  @@``€€  ðð ˆ#n    !#$?ð„Rð$qNÖa9ÒOŸþp­íÿ’Rð$ÀË ˃½:qØLí‚·ÿ;›’Rð$yT%X{YxYÅâpJÞmÿyͳƒ ð0�ƒ†A¿ÀÅAÿ@ñ÷ð8ó €ó €Ð3º“°öÊš;­”ÇÊš;úgþý4[d[d@¸z[ 0”ÿÿÿ’þÿÿpûppû@ <ý4ddddl¸ß 0¨¹-»ÿ ˆ8Š0º___PPT10‹ pµpµðÂ#óŸ¨Antiarrhythmic drugsªŸª óŸ¨ OVERVIEW Ÿ¨¨the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. ª2 kóŸ¨ INTRODUCTION TO THE ARRHYTHMIAS Ÿ¨˜cardiac arrhythmias may cause the heart (1) to beat too slowly (sinus bradycardia); (2) to beat too rapidly (sinus or ventricular tachycardia, atrial or ventricular premature depolarization, atrial flutter); (3) to respond to impulses originating from sites other than the SA node; (4) to respond to impulses traveling along accessory (extra) pathways that lead to deviant depolarizations (A-V reentry). ¡™P™ªPG ?*²óŸ¨Causes of arrhythmias Ÿ¨¾Abnormal automaticity: The SA node shows the fastest rate of Phase 4 depolarization if cardiac sites other than the SA node show enhanced automaticity, they may generate competing stimuli, ª, v (óŸ¨Effect of drugs on automaticityª Ÿ¨ÂMost of the antiarrhythmic agents suppress automaticity (1) by decreasing the slope of Phase 4 (diastolic) depolarization (2) by raising the threshold of discharge to a less negative voltage. ª,  ŒóŸ¨#Abnormalities in impulse conductionŸ¨/Impulses from higher pacemaker centers are normally conducted down pathways that bifurcate to activate the entire ventricular surface .A phenomenon called reentry can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway. ¡0Z0ó Ÿ¨,Effects of drugs on conduction abnormalitiesŸ¨«Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. ªžó Ÿ¨Antiarrhythmic drugs ªŸ¨Gthe antiarrhythmic drugs can modify impulse generation and conduction. ª.    5  óó  Ÿ¨CLASS I ANTIARRHYTHMIC DRUGS ¡$Ÿ¨ºClass I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. ª,AVó Ÿ¨Use-dependence Ÿ¨:Class I drugs bind more rapidly to open or inactivated sodium channels than to channels that are fully repolarized following recovery from the previous depolarization cycle. Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence¡;Z;ªg Éó Ÿ¨ Quinidine ª Ÿ¨”Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. ª Œóó ó Ÿ¨Mechanism of action¡Ÿ¨ÉQuinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0 . It also decreases the slope of Phase 4 spontaneous depolarization. ª Áó Ÿ¨ActionsŸ¨™Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity. Quinidine also prevents reentry arrhythmias ªH  D  %óŸ¨Therapeutic usesŸ¨in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. ªt=  7 KóŸ¨Adverse effectsŸ¨ðA potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole. At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. ªb $ A  óŸ¨ Procainamide ª Ÿ¨p1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of óŸ¨PharmacokineticsŸ¨cProcainamide is absorbed following oral administration. Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential. NAPA is eliminated via the kidney¡ddª6 - g¦óŸ¨Adverse effectsŸ¨Wprocainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients. Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias. Central nervious system (CNS) side effects include depression, hallucination and psychosis. ¡XZXªZ G P  3NóŸ¨ Lidocaine ª Ÿ¨Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels. Class IB drugs are particularly useful in treating ventricular arrhythmias. Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. ¡Zª$ § HóŸ¨ActionsŸ¨ÀLidocaine, shortens phase 3 repolarization and decreases the duration of the action potential lidocaine suppresses arrhythmias caused by abnormal automaticity. abolishes ventricular reentry. ªH 5 + "óŸ¨PharmacokineticsŸ¨\Lidocaine is given intravenously because of extensive first-pass transformation by the liverª TóŸ¨Adverse effectsŸ¨èLidocaine has a fairly wide toxic-to-therapeutic ratio; it shows little impairment of left ventricular function, The CNS effects include drowsiness, slurred speech, confusion, and convulsions; cardiac arrhythmias may also occur. ¡éZéª àóŸ¨CLASS II ANTIARRHYTHMIC DRUGS ¡$Ÿ¨3The Class II agents include the beta-adrenergic antagonists. These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility. 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ð0�ƒ†A¿ÀÅAÿ@ñ÷ð8ó €ó €Ð3º“°öÊš;­”ÇÊš;úgþý4[d[d ¸z[ 0”ÿÿÿ’þÿÿpûppû@ <ý4ddddL¸ß 0ˆ¹-»ÿ ˆ8Š0º___PPT10‹ pµpµðp%óŸ¨Antiarrhythmic drugsªŸª óŸ¨ OVERVIEW Ÿ¨¨the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. ª2 kóŸ¨ INTRODUCTION TO THE ARRHYTHMIAS Ÿ¨˜cardiac arrhythmias may cause the heart (1) to beat too slowly (sinus bradycardia); (2) to beat too rapidly (sinus or ventricular tachycardia, atrial or ventricular premature depolarization, atrial flutter); (3) to respond to impulses originating from sites other than the SA node; (4) to respond to impulses traveling along accessory (extra) pathways that lead to deviant depolarizations (A-V reentry). ¡™P™ªPG ?*²óŸ¨Causes of arrhythmias Ÿ¨¾Abnormal automaticity: The SA node shows the fastest rate of Phase 4 depolarization if cardiac sites other than the SA node show enhanced automaticity, they may generate competing stimuli, ª, v (óŸ¨Effect of drugs on automaticityª Ÿ¨ÂMost of the antiarrhythmic agents suppress automaticity (1) by decreasing the slope of Phase 4 (diastolic) depolarization (2) by raising the threshold of discharge to a less negative voltage. ª,  ŒóŸ¨#Abnormalities in impulse conductionŸ¨/Impulses from higher pacemaker centers are normally conducted down pathways that bifurcate to activate the entire ventricular surface .A phenomenon called reentry can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway. ¡0Z0ó Ÿ¨,Effects of drugs on conduction abnormalitiesŸ¨«Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. ªžó Ÿ¨Antiarrhythmic drugs ªŸ¨Gthe antiarrhythmic drugs can modify impulse generation and conduction. ª.    5  óó  Ÿ¨CLASS I ANTIARRHYTHMIC DRUGS ¡$Ÿ¨ºClass I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. ª,AVó Ÿ¨Use-dependence Ÿ¨:Class I drugs bind more rapidly to open or inactivated sodium channels than to channels that are fully repolarized following recovery from the previous depolarization cycle. Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence¡;Z;ªg Éó Ÿ¨ Quinidine ª Ÿ¨”Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. ª Œóó ó Ÿ¨Mechanism of action¡Ÿ¨ÉQuinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0 . It also decreases the slope of Phase 4 spontaneous depolarization. ª Áó Ÿ¨ActionsŸ¨™Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity. Quinidine also prevents reentry arrhythmias ªH  D  %óŸ¨Therapeutic usesŸ¨in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. ªt=  7 KóŸ¨Adverse effectsŸ¨ðA potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole. At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. ªb $ A  óŸ¨ Procainamide ª Ÿ¨p1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of óŸ¨PharmacokineticsŸ¨cProcainamide is absorbed following oral administration. Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential. NAPA is eliminated via the kidney¡ddª6 - g¦óŸ¨Adverse effectsŸ¨Wprocainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients. Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias. Central nervious system (CNS) side effects include depression, hallucination and psychosis. ¡XZXªZ G P  3NóŸ¨ Lidocaine ª Ÿ¨Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels. Class IB drugs are particularly useful in treating ventricular arrhythmias. Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. ¡Zª$ § HóŸ¨ActionsŸ¨ÀLidocaine, shortens phase 3 repolarization and decreases the duration of the action potential lidocaine suppresses arrhythmias caused by abnormal automaticity. abolishes ventricular reentry. ªH 5 + "óŸ¨PharmacokineticsŸ¨\Lidocaine is given intravenously because of extensive first-pass transformation by the liverª TóŸ¨Adverse effectsŸ¨èLidocaine has a fairly wide toxic-to-therapeutic ratio; it shows little impairment of left ventricular function, The CNS effects include drowsiness, slurred speech, confusion, and convulsions; cardiac arrhythmias may also occur. ¡éZéª àóŸ¨CLASS II ANTIARRHYTHMIC DRUGS ¡$Ÿ¨3The Class II agents include the beta-adrenergic antagonists. These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility. Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. ¡44ªH{     q    +  óŸ¨ Propranololª Ÿ¨óreduces the incidence of sudden arrhythmic death after myocardial infarction The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias. ª¤ Eó!Ÿ¨CLASS III ANTIARRHYTHMIC DRUGS ªŸ¨5Class III agents block potassium channels and thus diminish the outward potassium current during repolarization of cardiac cells. prolong the duration of the action potential without altering Phase 0 of depolarization or the resting membrane potential. Instead, they prolong the effective refractory period. ¡66ª0a�7  êî$ï € ”ðŒ@ðˆð$ð( ð ðˆðr ðˆ S ð€`Šë¿ÿ 0ð‡Õ ðà  ë ð žðr ðˆ S ð€,4ë¿ÿ 0ð÷é ðà ë ð žðH ðˆ ƒ ð0�ƒ“ŽŸ‹”Þ½h¿ÿ ?ð ÿÿÿ33™ä¨ÿÏÿ33̈8Š0º___PPT10‹ë.+…ÇpöwRr½!«õ? ™2­!Ðèá+é(€àà€ òú/È 0ÒÕ0·DArialngsˆ¹ˆ¹0-»¸ð·ç0 þÿÿÿþÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿþÿÕÍÕœ.“—+,ù®0àˆ�¨´¼ÄÌ Ô Üä ìôü  €¨ ÔÚÆÁÄ»ÉÏÏÔʾejdÁµN[$A )ArialËÎÌåTahoma WingdingsBlendsAntiarrhythmic drugs OVERVIEW !INTRODUCTION TO THE ARRHYTHMIAS Causes of arrhythmias Effect of drugs on automaticity$Abnormalities in impulse conduction-Effects of drugs on conduction abnormalitiesAntiarrhythmic drugs 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Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence¡;Z;ªg Éó Ÿ¨ Quinidine ª Ÿ¨”Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. ª Œóó ó Ÿ¨Mechanism of action¡Ÿ¨ÉQuinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0 . It also decreases the slope of Phase 4 spontaneous depolarization. ª Áó Ÿ¨ActionsŸ¨™Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity. Quinidine also prevents reentry arrhythmias ªH  D  %óŸ¨Therapeutic usesŸ¨in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. ªt=  7 KóŸ¨Adverse effectsŸ¨ðA potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole. At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. ªb $ A  óŸ¨ Procainamide ª Ÿ¨p1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of óŸ¨PharmacokineticsŸ¨cProcainamide is absorbed following oral administration. Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential. NAPA is eliminated via the kidney¡ddª6 - g¦óŸ¨Adverse effectsŸ¨Wprocainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients. Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias. Central nervious system (CNS) side effects include depression, hallucination and psychosis. ¡XZXªZ G P  3NóŸ¨ Lidocaine ª Ÿ¨Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels. Class IB drugs are particularly useful in treating ventricular arrhythmias. Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. ¡Zª$ § HóŸ¨ActionsŸ¨ÀLidocaine, shortens phase 3 repolarization and decreases the duration of the action potential lidocaine suppresses arrhythmias caused by abnormal automaticity. abolishes ventricular reentry. ªH 5 + "óŸ¨PharmacokineticsŸ¨\Lidocaine is given intravenously because of extensive first-pass transformation by the liverª TóŸ¨Adverse effectsŸ¨èLidocaine has a fairly wide toxic-to-therapeutic ratio; it shows little impairment of left ventricular function, The CNS effects include drowsiness, slurred speech, confusion, and convulsions; cardiac arrhythmias may also occur. ¡éZéª àóŸ¨CLASS II ANTIARRHYTHMIC DRUGS ¡$Ÿ¨3The Class II agents include the beta-adrenergic antagonists. These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility. Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. ¡44ªH{     q    +  óŸ¨ Propranololª Ÿ¨óreduces the incidence of sudden arrhythmic death after myocardial infarction The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias. ª¤ Eó!Ÿ¨CLASS III ANTIARRHYTHMIC DRUGS ªŸ¨5Class III agents block potassium channels and thus diminish the outward potassium current during repolarization of cardiac cells. prolong the duration of the action potential without altering Phase 0 of depolarization or the resting membrane potential. Instead, they prolong the effective refractory period. ¡66ª0a�7  ó"ó#êî„ï€ ôðìPðŒð|ð( ð ðŒðD² ðŒ C ð€€AÁ1ðÂÀÀðP ðŒ s ð*�“ŽŸ‹”Þ½h¿ÿ ?"ñ¿`ð ÿÿÿ33™ä¨ÿÏÿ33̈8Š0º___PPT10‹ë.,…ÇP^‡|î„ï€ ôðìpð�ð|ð( ð ð�ðD² ð� C ð€€AÁ2ð¿iðP ð� s ð*�“ŽŸ‹”Þ½h¿ÿ ?"ñ¿`ð ÿÿÿ33™ä¨ÿÏÿ33̈8Š0º___PPT10‹ë.,…Ç{Ä…rn­" WÙãÚõ? J­oÜ#Ðè‹-é(€àà€ òú/È 0ÒÕ0·DArialngsˆ¹ˆ¹0-»¸ð·ç0¸z[ 0¸·D‹[SOalngsˆ¹ˆ¹0-»¸ð·ç0¸z[ 0¸† ·DTahomagsˆ¹ˆ¹0-»¸ð·ç0¸z[ 0¸0·DWingdingsˆ¹ˆ¹0-»¸ð·ç0¸z[ 0¸¤ €A¥ .©  @£nÿý?" dÿd@ÿÿïÿÿ  @@``€€ |ðtð8”&u!    !#$%')_ðÜRð$qNÖa9ÒOŸþp­íÿ’Rð$ÀË ˃½:qØLí‚·ÿ;›’Rð$yT%X{YxYÅâpJÞmÿyͳRð$u`Ðè®5.ÏÉê¿£Š£mÿ"‹FÆRð$o³uí E‡¦zJÕ�ÿåhQƒ ð0�ƒ†A¿ÀÅAÿ@ñ÷ð8ó €ó €Ð3º“°öÊš;­”ÇÊš;úgþý4[d[d ¸z[ 0”ÿÿÿ’þÿÿpûppû@ <ý4ddddL¸ß 0ˆ¹-»ÿ ˆ8Š0º___PPT10‹ pµpµðJ'óŸ¨Antiarrhythmic drugsªŸª óŸ¨ OVERVIEW Ÿ¨¨the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. ª2 kóŸ¨ INTRODUCTION TO THE ARRHYTHMIAS Ÿ¨˜cardiac arrhythmias may cause the heart (1) to beat too slowly (sinus bradycardia); (2) to beat too rapidly (sinus or ventricular tachycardia, atrial or ventricular premature depolarization, atrial flutter); (3) to respond to impulses originating from sites other than the SA node; (4) to respond to impulses traveling along accessory (extra) pathways that lead to deviant depolarizations (A-V reentry). ¡™P™ªPG ?*²óŸ¨Causes of arrhythmias Ÿ¨¾Abnormal automaticity: The SA node shows the fastest rate of Phase 4 depolarization if cardiac sites other than the SA node show enhanced automaticity, they may generate competing stimuli, ª, v (óŸ¨Effect of drugs on automaticityª Ÿ¨ÂMost of the antiarrhythmic agents suppress automaticity (1) by decreasing the slope of Phase 4 (diastolic) depolarization (2) by raising the threshold of discharge to a less negative voltage. ª,  ŒóŸ¨#Abnormalities in impulse conductionŸ¨/Impulses from higher pacemaker centers are normally conducted down pathways that bifurcate to activate the entire ventricular surface .A phenomenon called reentry can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway. ¡0Z0ó Ÿ¨,Effects of drugs on conduction abnormalitiesŸ¨«Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. ªžó Ÿ¨Antiarrhythmic drugs ªŸ¨Gthe antiarrhythmic drugs can modify impulse generation and conduction. ª.    5  óó  Ÿ¨CLASS I ANTIARRHYTHMIC DRUGS ¡$Ÿ¨ºClass I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. ª,AVó Ÿ¨Use-dependence Ÿ¨:Class I drugs bind more rapidly to open or inactivated sodium channels than to channels that are fully repolarized following recovery from the previous depolarization cycle. Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence¡;Z;ªg Éó Ÿ¨ Quinidine ª Ÿ¨”Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. ª Œóó ó Ÿ¨Mechanism of action¡Ÿ¨ÉQuinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0 . It also decreases the slope of Phase 4 spontaneous depolarization. ª Áó Ÿ¨ActionsŸ¨™Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity. Quinidine also prevents reentry arrhythmias ªH  D  %óŸ¨Therapeutic usesŸ¨in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. ªt=  7 KóŸ¨Adverse effectsŸ¨ðA potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole. At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. ªb $ A  óŸ¨ Procainamide ª Ÿ¨p1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of óŸ¨PharmacokineticsŸ¨cProcainamide is absorbed following oral administration. Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential. NAPA is eliminated via the kidney¡ddª6 - g¦óŸ¨Adverse effectsŸ¨Wprocainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients. Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias. Central nervious system (CNS) side effects include depression, hallucination and psychosis. ¡XZXªZ G P  3NóŸ¨ Lidocaine ª Ÿ¨Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels. Class IB drugs are particularly useful in treating ventricular arrhythmias. Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. ¡Zª$ § HóŸ¨ActionsŸ¨ÀLidocaine, shortens phase 3 repolarization and decreases the duration of the action potential lidocaine suppresses arrhythmias caused by abnormal automaticity. abolishes ventricular reentry. ªH 5 + "óŸ¨PharmacokineticsŸ¨\Lidocaine is given intravenously because of extensive first-pass transformation by the liverª TóŸ¨Adverse effectsŸ¨èLidocaine has a fairly wide toxic-to-therapeutic ratio; it shows little impairment of left ventricular function, The CNS effects include drowsiness, slurred speech, confusion, and convulsions; cardiac arrhythmias may also occur. ¡éZéª àóŸ¨CLASS II ANTIARRHYTHMIC DRUGS ¡$Ÿ¨3The Class II agents include the beta-adrenergic antagonists. These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility. Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. ¡44ªH{     q    +  óŸ¨ Propranololª Ÿ¨óreduces the incidence of sudden arrhythmic death after myocardial infarction The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias. ª¤ Eó!Ÿ¨CLASS III ANTIARRHYTHMIC DRUGS ªŸ¨5Class III agents block potassium channels and thus diminish the outward potassium current during repolarization of cardiac cells. prolong the duration of the action potential without altering Phase 0 of depolarization or the resting membrane potential. Instead, they prolong the effective refractory period. ¡66ª0a�7  ó"ó#ó$ Ÿ¨CLASS IV ANTIARRHYTHMIC DRUGS ªŸ¨ðare calcium channel blockers. They decrease the inward current carried by calcium, resulting in a decrease in the rate of Phase 4 spontaneous depolarization and slowed conduction in tissues dependent on calcium currents, such as the AV nodeª.¶/êî$ï € ”ðŒ�ð”ð$ð( ð ð”ðr ð” S ð€°4Ä¿ÿ 0ð‡Õ ðà  Ä ð žðr ð” S ð€Ä¿ÿ 0ð÷é ðà Ä ð žðH ð” ƒ ð0�ƒ“ŽŸ‹”Þ½h¿ÿ ?ð ÿÿÿ33™ä¨ÿÏÿ33̈8Š0º___PPT10‹ë.,…Ç04Þ«r¯Ü$B õ ? ‹Ün $ÐèÛ6é(€àà€ òú/È 0ÒÕ0·DArialngsˆ¹ˆ¹0-»¸ð·ç0¸z[ 0¸·D‹[SOalngsˆ¹ˆ¹0-»¸ð·ç0¸z[ 0¸† ·DTahomagsˆ¹ˆ¹0-»¸ð·ç0¸z[ 0¸0·DWingdingsˆ¹ˆ¹0-»¸ð·ç0¸z[ 0¸¤ €A¥ .©  @£nÿý?" dÿd@ÿÿïÿÿ  @@``€€ ¤ðœð`¨+„&    !#$%')*+,-._ðÜRð$qNÖa9ÒOŸþp­íÿ’Rð$ÀË ˃½:qØLí‚·ÿ;›’Rð$yT%X{YxYÅâpJÞmÿyͳRð$u`Ðè®5.ÏÉê¿£Š£mÿ"‹FÆRð$o³uí E‡¦zJÕ�ÿåhQƒ ð0�ƒ†A¿ÀÅAÿ@ñ÷ð8ó €ó €Ð3º“°öÊš;­”ÇÊš;úgþý4[d[d ¸z[ 0”ÿÿÿ’þÿÿpûppû@ <ý4ddddL¸ß 0ˆ¹-»ÿ ˆ8Š0º___PPT10‹ pµpµðr0óŸ¨Antiarrhythmic drugsªŸª óŸ¨ OVERVIEW Ÿ¨¨the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. ª2 kóŸ¨ INTRODUCTION TO THE ARRHYTHMIAS Ÿ¨˜cardiac arrhythmias may cause the heart (1) to beat too slowly (sinus bradycardia); (2) to beat too rapidly (sinus or ventricular tachycardia, atrial or ventricular premature depolarization, atrial flutter); (3) to respond to impulses originating from sites other than the SA node; (4) to respond to impulses traveling along accessory (extra) pathways that lead to deviant depolarizations (A-V reentry). ¡™P™ªPG ?*²óŸ¨Causes of arrhythmias Ÿ¨¾Abnormal automaticity: The SA node shows the fastest rate of Phase 4 depolarization if cardiac sites other than the SA node show enhanced automaticity, they may generate competing stimuli, ª, v (óŸ¨Effect of drugs on automaticityª Ÿ¨ÂMost of the antiarrhythmic agents suppress automaticity (1) by decreasing the slope of Phase 4 (diastolic) depolarization (2) by raising the threshold of discharge to a less negative voltage. ª,  ŒóŸ¨#Abnormalities in impulse conductionŸ¨/Impulses from higher pacemaker centers are normally conducted down pathways that bifurcate to activate the entire ventricular surface .A phenomenon called reentry can occur if a unidirectional block caused by myocardial injury or a prolonged refractory period results in an abnormal conduction pathway. ¡0Z0ó Ÿ¨,Effects of drugs on conduction abnormalitiesŸ¨«Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. ªžó Ÿ¨Antiarrhythmic drugs ªŸ¨Gthe antiarrhythmic drugs can modify impulse generation and conduction. ª.    5  óó  Ÿ¨CLASS I ANTIARRHYTHMIC DRUGS ¡$Ÿ¨ºClass I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. ª,AVó Ÿ¨Use-dependence Ÿ¨:Class I drugs bind more rapidly to open or inactivated sodium channels than to channels that are fully repolarized following recovery from the previous depolarization cycle. Therefore, these drugs show a greater degree of blockade in tissues that are frequently depolarizing. This property is called use-dependence¡;Z;ªg Éó Ÿ¨ Quinidine ª Ÿ¨”Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation. ª Œóó ó Ÿ¨Mechanism of action¡Ÿ¨ÉQuinidine binds to open and inactivated sodium channels and prevents sodium influx, thus slowing the rapid upstroke during Phase 0 . It also decreases the slope of Phase 4 spontaneous depolarization. ª Áó Ÿ¨ActionsŸ¨™Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity. Quinidine also prevents reentry arrhythmias ªH  D  %óŸ¨Therapeutic usesŸ¨in the treatment of a wide variety of arrhythmias, including atrial, AV junctional, and ventricular tachyarrhythmias. Quinidine is used to maintain sinus rhythm after direct current cardioversion of atrial flutter or fibrillation and to prevent frequent ventricular tachycardia. ªt=  7 KóŸ¨Adverse effectsŸ¨ðA potential adverse effect of quinidine is exacerbation of the arrhythmia. Quinidine may cause SA and AV block or asystole. At toxic levels, the drug may induce ventricular tachycardia. Cardiotoxic effects are exacerbated by hyperkalemia. ªb $ A  óŸ¨ Procainamide ª Ÿ¨p1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of óŸ¨PharmacokineticsŸ¨cProcainamide is absorbed following oral administration. Procainamide has a relatively short half-life of 2-3 hours. A portion of the drug is acetylated in the liver to N- acetylprocainamide (NAPA), which has little effect on the maximum polarization of Purkinje fibers but prolongs the duration of the action potential. NAPA is eliminated via the kidney¡ddª6 - g¦óŸ¨Adverse effectsŸ¨Wprocainamide causes a high incidence of side effects, including a reversible lupus erythematosus-like syndrome that develops in 25 to 30% of patients. Toxic concentrations of procainamide may cause asystole or induction of ventricular arrhythmias. Central nervious system (CNS) side effects include depression, hallucination and psychosis. ¡XZXªZ G P  3NóŸ¨ Lidocaine ª Ÿ¨Lidocaine is a Class IB drug. The IB agents rapidly associate and dissociate from sodium channels. Class IB drugs are particularly useful in treating ventricular arrhythmias. Lidocaine is the drug of choice for emergency treatment of cardiac arrhythmias. ¡Zª$ § HóŸ¨ActionsŸ¨ÀLidocaine, shortens phase 3 repolarization and decreases the duration of the action potential lidocaine suppresses arrhythmias caused by abnormal automaticity. abolishes ventricular reentry. ªH 5 + "óŸ¨PharmacokineticsŸ¨\Lidocaine is given intravenously because of extensive first-pass transformation by the liverª TóŸ¨Adverse effectsŸ¨èLidocaine has a fairly wide toxic-to-therapeutic ratio; it shows little impairment of left ventricular function, The CNS effects include drowsiness, slurred speech, confusion, and convulsions; cardiac arrhythmias may also occur. ¡éZéª àóŸ¨CLASS II ANTIARRHYTHMIC DRUGS ¡$Ÿ¨3The Class II agents include the beta-adrenergic antagonists. These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility. Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. ¡44ªH{     q    +  óŸ¨ Propranololª Ÿ¨óreduces the incidence of sudden arrhythmic death after myocardial infarction The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias. ª¤ Eó!Ÿ¨CLASS III ANTIARRHYTHMIC DRUGS ªŸ¨5Class III agents block potassium channels and thus diminish the outward potassium current during repolarization of cardiac cells. prolong the duration of the action potential without altering Phase 0 of depolarization or the resting membrane potential. Instead, they prolong the effective refractory period. ¡66ª0a�7  ó"ó#ó$ Ÿ¨CLASS IV ANTIARRHYTHMIC DRUGS ªŸ¨ðare calcium channel blockers. They decrease the inward current carried by calcium, resulting in a decrease in the rate of Phase 4 spontaneous depolarization and slowed conduction in tissues dependent on calcium currents, such as the AV nodeªðó%!Ÿ¨Verapamil and diltiazem ª.  Ÿ¨Verapamil shows greater action on the heart than on vascular smooth muscle, whereas nifedipine, a calcium channel-blocker used to treat hypertension exerts a stronger effect on vascular smooth muscle than on the heart. Diltiazem is intermediate in its actions. ª@ K } !ó&"Ÿ¨ActionsªŸ¨£verapamil and diltiazem, are more effective against the voltage-sensitive channels, causing a decrease in the slow inward current that triggers cardiac contraction Verapamfl and diltiazem bind only to open, depolarized channels, thus preventing repolarization until the drug dissociates from the channel. These drugs are therefore use-dependent that is, they block most effectively when the heart is beating rapidly, ¡¤P¤ªd  Ž  :Ÿó'#Ÿ¨Therapeutic usesªŸ¨%Verapamil and diltiazem are more effective against atrial than ventricular dysrhythmias. They are useful in treat- ing reentrant supraventricular tachycardia and reducing ventricular rate in atrial flutter and fibrillation. In addition, these drugs are used to treat hypertension and angina ªˆ    .`ó($Ÿ¨PharmacokineticsªŸ¨@Verapamil and diltiazem are absorbed after oral administration. ª.  )ó)%Ÿ¨Adverse effectsªŸ¨óVerapamil and diltiazem have negative inotropic properties and therefore may be contraindicated in patients with preexisting depressed cardiac function. Both drugs can also cause a decrease in blood pressure caused by peripheral vasodilation. ªd   «  êî$ï € ”ðŒ ð˜ð$ð( ð ð˜ðr ð˜ S ð€pAÄ¿ÿ 0ð‡Õ ðà  Ä ð žðr ð˜ S ð€¸DÄ¿ÿ 0ð÷é ðà Ä ð žðH 𘠃 ð0�ƒ“ŽŸ‹”Þ½h¿ÿ ?ð ÿÿÿ33™ä¨ÿÏÿ33̈8Š0º___PPT10‹ë.-…Çðc5î$ï € ”ðŒ°ðœð$ð( ð ðœðr ðœ S ð€°9Ä¿ÿ 0ð‡Õ ðà  Ä ð žðr ðœ S ð€ÄRÄ¿ÿ 0ð÷é ðà Ä ð žðH 𜠃 ð0�ƒ“ŽŸ‹”Þ½h¿ÿ ?ð ÿÿÿ33™ä¨ÿÏÿ33̈8Š0º___PPT10‹ë.-…ÇÐtûHî$ï € ”ðŒÀð ð$ð( ð ð ðr ð  S ð€pTP¿ÿ 0ð‡Õ ðà  P ð žðr ð  S ð€¸WP¿ÿ 0ð÷é ðà P ð žðH ð  ƒ ð0�ƒ“ŽŸ‹”Þ½h¿ÿ ?ð ÿÿÿ33™ä¨ÿÏÿ33̈8Š0º___PPT10‹ë.-…Çpz{ªî$ï € ”ðŒÐð¤ð$ð( ð ð¤ðr ð¤ S ð€Ü&P¿ÿ 0ð‡Õ ðà  P ð žðr ð¤ S ð€ô™P¿ÿ 0ð÷é ðà P ð žðH 𤠃 ð0�ƒ“ŽŸ‹”Þ½h¿ÿ ?ð ÿÿÿ33™ä¨ÿÏÿ33̈8Š0º___PPT10‹ë.-…Ç7NÚî$ï € ”ðŒàð¨ð$ð( ð ð¨ðr ð¨ S ð€Ü§P¿ÿ 0ð‡Õ ðà  P ð žðr ð¨ S ð€ØP¿ÿ 0ð÷é ðà P ð žðH 𨠃 ð0�ƒ“ŽŸ‹”Þ½h¿ÿ ?ð ÿÿÿ33™ä¨ÿÏÿ33̈8Š0º___PPT10‹ë.-…Ljôr ª %P�C¹EåGJ=Lõ%? † iN)ÐRoot Entryÿÿÿÿÿÿÿÿ��d›Oφꪹ)èQÞpDµÇô€Picturesÿÿÿÿÿÿÿÿ…6Current Userÿÿÿÿÿÿÿÿÿÿÿÿ8SummaryInformation(ÿÿÿÿ¤€C�‚ƒ„…†‡ˆ‰Š‹Œ�Ž��‘’“”•–—˜™š›œ�žŸ þÿÿÿ¢£¤¥¦§¨©ª«¬­®¯°±²³´µ¶·¸¹º»¼½¾¿ÀÁÂÃÄÅÆÇÈÉÊËÌÍÎÏÐÑÒÓÔÕÖרÙÚÛÜÝÞßàáâãäåæçèéêëìíîïðñþÿÿÿÛýÿÿÿýÿÿÿýÿÿÿþÿÿÿþÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿ      !"#$%&'()*+,.ÿÿÿÿ/0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~€�‚ƒ„…†‡ˆ‰Š‹Œ�Ž��‘’“”•–—˜™š›œ�žŸ ¡¢£Ü¥¦§¨©ª«¬­®¯°±²³´µ¶·¸¹º»¼½¾¿ÀÁÂÃÄÅþÿÿÿÿÿÿÿÈÉÊËÌÍÎÏÐÑÒÓÔÕ÷ýÿÿÿýÿÿÿýÿÿÿÿÿÿÿÿÿÿÿþÿÿÿÝÞßàáâãäåæçèéêëìíîïðñò¡ÿÿÿÿõ÷ÿÿÿÿøùúûüýþÿ þÿÿÿþÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿIC DRUGS »ÃµÆÆ¬ 29 »ÃµÆÆ¬ 30CLASS IV ANTIARRHYTHMIC DRUGS Verapamil and diltiazem ActionsTherapeutiö _À‘ã‘Nô΢ÈíÓû§®_o�(u7bc usesPharmacokineticsAdverse effects  ÒÑÓõÄ×ÖÌåÑÝʾÎĸåÉè¼ÆÄ£°å »ÃµÆÆ¬±êÌâ$