adenosine (Adenocard) amiodarone (Cordarone) atropine bretylium (Bretylol) digoxin (Lanoxin) diltiazem (Cardizem)
isoproterenol (Isuprel) lidocaine (Xylocaine) procainamide (Pronestyl) propranolol (Inderal) quinidine (Quinidex) verapamil (Calan, Isoptin)
Excitability
ability to respond to stimuli and conduct action potentials
Refractory period
time following excitation during which a second action potential can not be elicited and conducted
Membrane responsiveness
relationship between membrane activation voltage and the maximal rate of rise of the action potential
Slow response tissues (mainly Ca channels) SA node AV node Fast response tissues (mainly Na channels) atrium ventricle bundle of His Purkinje fibers
Influence of diastolic membrane potential on action potential upstroke rate in a given cell: Membrane Responsiveness
Agents which partially block AV nodal conduction may be useful in the treatment of supraventricular tachyarrhythmias
Digitalis - by increasing vagal tone increases AV nodal refractory period Beta blockers - by preventing sympathetically mediated increases in AV nodal conduction slow or block conduction, also depress catecholamine augmented automaticity Ca channel blockers - by inhibiting Ca channels depress AV nodal conduction velocity and increase refractory period, also suppress automaticity
II. Sympatholytic drugs III. Drugs that prolong repolarization IV. Calcium channel blockers
For a less arbitrary classification based on arrhythmogenic mechanisms and potentially vulnerable parameters, see the report of the Task Force of the Working Group on Antiarrhythmias of the European Society of Cardiology, Circulation 84: 1831-1851, 1991
Relatively speaking, this gives more time for recovery of membrane potential and makes slow conduction less likely. Slow conduction is a formula for disaster.
Atropine-like properties
(may promote AV conduction - paradoxical tachycardia)
High doses promote bizarre cardiac arrhythmias, torsades des pointes Cinchonism
GI upset, tinnitus, loss of hearing, blurred vision, headache, diplopia, delerium, psychosis, rarely thrombocytopenia
Quinidine
Membrane Responsiveness: Relation between membrane activation voltage and max dV/dt
Lidocaine
Flecainide or encainide
Amiodarone in out-of-hospital Resuscitation of REfractory sustained ventricular Tachyarrhythmias (ARREST) (504 pts, out of hospital arrest, >= 3 precordial shocks, 1 mg EPI, IV then:
Oral erythromycin and the risk of sudden death from cardiac causes*
Erythromycin is metabolized by CYP3A4 Commonly prescribed drugs increase the AUC of erythromycin by at least 2-fold:
Nitroimidazole antifungals Diltiazem, Verapamil
Incidence ratio of sudden cardiac death was 5.35 (1.72-16.64, 95% CI) in patients using erythromycin and a CYP3A inhibitor
*Ray et al., NEJM 351:1089-1096, 2004
2C9
Amitriptyline, tamoxifen
2D6
Amitriptyline, desipramine, imipramine, haloperidol, thioridazine, tamoxifen
3A4
Cisapride, disopyramide, quinidine, pimozide, tamoxifen, erythromycin, clarithromycin