: resting potential, low -50~ -70mv (sinus, atrioventri- slow depolarization, Ca 2+ influx cular (AV) nodel action potential propagates slowly cells, impaired fast Response cells)
1 2 0mV 0 3 100ms 4 -85mV Na+ Ca2+ Na+ Na+ Outside Membrance intside K+ Ca2+ K+,Cl-Channel currents Pump Exchanger Phase 0 : depolarization Phase 1,2,3 : repolarization Phase 4 : diastolic voltage time course 0 ~ 3 : action potential duration APD Fast response
Excitability: relationship between threshold potentialand restingpotential level • Automaticity: • ventricular muscles autonomic cell resting potential : -60mv abnormal autonomy 单向传导阻滞 折返形.
A. Antiarrhythmic drugs can depress Na + inward of non-autonomic • Slow the rate of rise of the membrane action potential (Phase 0; dV/dt ) • Slow conduction velocity (PR; QRS) • Prolong refractoriness (QT) • Examples - • Quinidine* • Procainamide • Disopyramide
Classification of Antiarrhythmic Drugs • Class Ib -Characteristics Weak level sodium channel block，and potassium channel open • Limited effect on dV/dt of Phase 0 • Slight slowing of conduction velocity • No change or a decrease in refractory period • Examples • Lidocaine* • Tocainide • Mexiletine • Moricizine ?
Classification of Antiarrhythmic Drugs Class Ic- Characteristics Strong level sodium channel block，and weak level calcium channel block • Marked slowing of conduction velocity (prolongs PR and QRS) • No change in refractoriness or repolarization • Examples • Flecainide* • Propafenone (also Class II) • Moricizine (also Class Ib) • Encainide (discontinued)
Classification of Antiarrhythmic Drugs • Class II-Characteristics • Produce beta-adrenergic receptor blockade (prolongs PR; slows heart rate) • Decrease in refractory period duration (decrease in QT) • Examples • Propranolol* • Acebutolol • Esmolol • Sotalol (also Class III)
Classification of Antiarrhythmic Drugs • Class III-Characteristics potassium channel block • Prolong the action potential duration • Increase the refractory period (increase in the QT) • Examples • Amiodarone (also some Class Ia,II,III,&IV) • Bretylium • Sotalol (also Class II) • Ibutilide*
Classification of Antiarrhythmic Drugs • Class IV-Characteristics • Blockade of calcium entry via slow inward channel (prolong the PR interval) • Examples • Verapamil • Diltiazem
Other Miscellaneous Agents • Adenosine • Depresses sinus node automaticity • Depresses atrioventricular node conduction • Uses • Acute termination of AV nodal tachycardia • Acute termination of AV nodal reentrant tachycardia
Other Miscellaneous Agents • Digitalis (Digoxin) • Prolongs atrioventricular nodal conduction time and increases functional refractory period - directly and indirectly (increase in vagal cholinergic tone) • Slows sinus rate when ventricular function is impaired by virtue of its direct positive inotropic effect (withdrawal of sympathetic tone) • Uses: • Atrial fibrillation or flutter - primarily to control the ventricular rate •颤 and flutter心室扑动).
Toxicity • 1 Toxic dosage • depresses conduction of sinoatrial, atrial-vent
4 cinchonism 金鸡钠中毒 • headache, dizziness, tinnitus(耳鸣）,confused vision(视力模糊),double vision(复 • Lidocaine* （利多卡因） • abolishing delayed Purkinje fibers ( negtive potential) Amplitude of action potential Conduction velocity Abolishing reentry.
3.Responsiveness and conduction. Increasing phase-0 depolarization rate of atrial muscle, atrioventricular node, Purkinje fibers of digitalis toxicity. Improving conduction.
Therapeutic uses: • 1.Ventricular arrhythmias. • 2.Paroxysmal atrial flutter or fibrillation. • 3.Supraventricular arrhythmias (tachycardia) • 4.Ventricular arrhythmias caused by acute myocardial infarction, open-heart surgery and digitalis toxication