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DTahomagsüü0-(0(z[ 0 0DWingdingsüü0-(0(z[ 0  ?A .  @n??" d?d@????  @@``??   ?#n    !#$??R?qN?9?????R?浪 ?:q???;??R?yT%X{YxY赔pJ??y统? ????A??@8 ? ?3?蚌?;??;g4[d[d@z[ 0???????ppp@ <4ddddl 0ü-? ?8?0___PPT10? pp??Antiarrhythmic drugs? ? OVERVIEW ?the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. 2 k? INTRODUCTION TO THE ARRHYTHMIAS ??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?PG ?*?Causes of arrhythmias ?Abnormal 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, , v (?Effect of drugs on automaticity ?Most 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. ,  ??#Abnormalities in impulse conduction?/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. 0Z0 ?,Effects of drugs on conduction abnormalities?Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. ? ?Antiarrhythmic drugs ?Gthe antiarrhythmic drugs can modify impulse generation and conduction. .    5    ?CLASS I ANTIARRHYTHMIC DRUGS $?Class I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. ,AV ?Use-dependence ?: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;g  ? Quinidine  ??Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation.  ?  ?Mechanism of action?Quinidine 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.   ?Actions??Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity. Quinidine also prevents reentry arrhythmias H  D  %?Therapeutic uses?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. t=  7 K?Adverse effects?A 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. b $ A  ? Procainamide  ?p1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of ?Pharmacokinetics?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 kidneydd6 - g?Adverse effects?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. XZXZ G P  3N? Lidocaine  ?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. Z$  H?Actions?Lidocaine, shortens phase 3 repolarization and decreases the duration of the action potential lidocaine suppresses arrhythmias caused by abnormal automaticity. abolishes ventricular reentry. H 5 + "?Pharmacokinetics?\Lidocaine is given intravenously because of extensive first-pass transformation by the liver T?Adverse effects?Lidocaine 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. Z ?CLASS II ANTIARRHYTHMIC DRUGS $?3The Class II agents include the beta-adrenergic antagonists. These drugs diminish Phase 4 depolarization, thus depressing automaticity, prolonging AV conduction, and decreasing heart rate and contractility. Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. 44H{     q    +  ? Propranolol ?reduces the incidence of sudden arrhythmic death after myocardial infarction The mortality rate in the first year after a heart attack is significantly reduced by propranolol, partly because of its ability to prevent ventricular arrhythmias.  E!? ? 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DTahomags??0-鸱0z[ 00DWingdings??0-鸱0z[ 0 ?A .  @n??" d?d@????  @@``??   ?#n    !#$??R?qN?9?????R?浪 ?:q???;??R?yT%X{YxY赔pJ??y统? ????A??@8 ? ?3?蚌?;??;g4[d[d z[ 0???????ppp@ <4ddddL 0?-? ?8?0___PPT10? ppp%?Antiarrhythmic drugs? ? OVERVIEW ?the heart contains specialized cells that exhibit automaticity, that is, they can intrinsically generate rhythmic action potentials in the absence of external stimuli. 2 k? INTRODUCTION TO THE ARRHYTHMIAS ??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?PG ?*?Causes of arrhythmias ?Abnormal 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, , v (?Effect of drugs on automaticity ?Most 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. ,  ??#Abnormalities in impulse conduction?/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. 0Z0 ?,Effects of drugs on conduction abnormalities?Antiarrhythmic agents prevent reentry by slowing conduction and/or increasing the refractory period required to convert a unidirectional block into a bidirectional block. ? ?Antiarrhythmic drugs ?Gthe antiarrhythmic drugs can modify impulse generation and conduction. .    5    ?CLASS I ANTIARRHYTHMIC DRUGS $?Class I antiarrhythmic drugs act by blocking voltage-sensitive sodium channels Class I antiarrhythmic drugs therefore generally cause a decrease in excitability and conduction velocity. ,AV ?Use-dependence ?: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;g  ? Quinidine  ??Quinidine is the prototype Class IA drug. At high doses, it can actually precipitate arrhythmias, which can lead to fatal ventricular fibrillation.  ?  ?Mechanism of action?Quinidine 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.   ?Actions??Quinidine inhibits ectopic arrhythmias and ventricular arrhythmias caused by increased normal automaticity. Quinidine also prevents reentry arrhythmias H  D  %?Therapeutic uses?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. t=  7 K?Adverse effects?A 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. b $ A  ? Procainamide  ?p1. Actions: This Class IA drug, a derivative of the local anesthetic procaine shows actions similar to those of ?Pharmacokinetics?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 kidneydd6 - g?Adverse effects?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. XZXZ G P  3N? Lidocaine  ?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. Z$  H?Actions?Lidocaine, shortens phase 3 repolarization and decreases the duration of the action potential lidocaine suppresses arrhythmias caused by abnormal automaticity. abolishes ventricular reentry. H 5 + "?Pharmacokinetics?\Lidocaine is given intravenously because of extensive first-pass transformation by the liver T?Adverse effects?Lidocaine 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. Z ?CLASS II ANTIARRHYTHMIC DRUGS $?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. 44H{     q    +  ? Propranolol ?reduces 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.  E!?CLASS III ANTIARRHYTHMIC DRUGS ?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. 660a?7  $ ? ??@???  ?? ? S ?`?? 0?    ?? ? 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