Phase 0
-Na channels open
-Ventricular depolarization
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-Class I antiarrhythmic drugs
|
Phase 1
|
-Na channels are inactivated
-Transient outward K+ currents and inward Cl- currents contribute to the “notch”and overshoot
|
-No significant drug interactions
|
Phase 2
|
-Plateau phase in which slow Ca2+ influx is balanced by a late appearing K+ current.
|
-No significant drug interactions
|
Phase 3
|
-Repolarization phase in which delayed K+ current rapidly increases as the Ca2+ current dies out
|
-Class III antiarrhythmics
|
Phase 4
|
-Return of membrane to resting potential maintained by activity of a Na/K/ATP ase
|
|
DRUG
|
MECHANISM
|
USE
|
ADVERSE/COMMENTS
|
Quinidine
Class I
|
-“M” blockade
-Increased HR and AV conduction
-Blockade of fast Na+ channels
|
-Atrial fibrillation
-Wide clinical use
|
-N/V, cinchonism (GI / tinnitus / ocular dysfunction / CNS excitation)
-QT prolongation
-Drug interactions: hypokalemia enhances effects. May oppose effects of ACHe inhibitors in myasthenia
-May cause vasodilation via alpha blockade with possible reflex tachycardia
|
Procainamide
Class I
|
-Less M blockade
-No alpha blockade
-Sodium channel blockade
|
-Orally effective
-Atrial and ventricular dysrhythmas
|
-Metabolized by N acetyltransferase
-Adverse eefects include SLE type syndrome (caution in slow acetylators)
-CNS effects
-Agranulocytosis
-Torsades
|
Lidocaine
Class Ib
|
-Blocks Na channels
-Prefers action in ischemic tissues (blocks inactivated channels)
|
-Post MI arrhythmias
-Ventricular dysrhythmias
|
-Clearance dependent on liver blood flow
-Extensive first passm metabolism
-Seizures evidence of CNS toxicity
|
Phenytoin
Class Ib
|
-Na block
|
-Used occasionally in digitalis OD to reverse AV block
|
-
|
Flecainide / Encainide
Class Ic
|
-Limited use, Na channel block
|
-Limited
|
-Pro arrhythmic
-May lead to sudden death post MI
|
Beta Blockers
Class II
|
-Decrease Sa and nodal activity, decrease slop of phase 4 action potential in pacemakers (slow response currents in the SA and AV nodes)
-Prevent B1 adrenoreceptor activation
|
-Post MI
-Suppression of SVTs
-Esmolol in SVTs
|
-Hypotension
-Bradycardia
|
Amiodarone
Class III
|
-K+channel blockade
-Mimics activity of all antiarrhythmic drug classes
-Blocks Na/Ca/K channels
-Long half life
|
-Atrial and ventricular dysrhythmias
|
-Pulmonary fibrosis
-Blue pigmentation (smurf skin)
-Increases LDL-C
-Hepatic disease
-Decreases clearance of dig, phenytoin, quinidine, theophylline, and warfarin
|
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