Phase 0
-Na channels open
-Ventricular depolarization
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-Class I antiarrhythmic drugs
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Phase 1
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-Na channels are inactivated
-Transient outward K+ currents and inward Cl- currents contribute to the “notch”and overshoot
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-No significant drug interactions
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Phase 2
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-Plateau phase in which slow Ca2+ influx is balanced by a late appearing K+ current.
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-No significant drug interactions
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Phase 3
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-Repolarization phase in which delayed K+ current rapidly increases as the Ca2+ current dies out
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-Class III antiarrhythmics
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Phase 4
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-Return of membrane to resting potential maintained by activity of a Na/K/ATP ase
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DRUG
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MECHANISM
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USE
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ADVERSE/COMMENTS
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Quinidine
Class I
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-“M” blockade
-Increased HR and AV conduction
-Blockade of fast Na+ channels
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-Atrial fibrillation
-Wide clinical use
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-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
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-Less M blockade
-No alpha blockade
-Sodium channel blockade
|
-Orally effective
-Atrial and ventricular dysrhythmas
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-Metabolized by N acetyltransferase
-Adverse eefects include SLE type syndrome (caution in slow acetylators)
-CNS effects
-Agranulocytosis
-Torsades
|
Lidocaine
Class Ib
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-Blocks Na channels
-Prefers action in ischemic tissues (blocks inactivated channels)
|
-Post MI arrhythmias
-Ventricular dysrhythmias
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-Clearance dependent on liver blood flow
-Extensive first passm metabolism
-Seizures evidence of CNS toxicity
|
Phenytoin
Class Ib
|
-Na block
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-Used occasionally in digitalis OD to reverse AV block
|
-
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Flecainide / Encainide
Class Ic
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-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
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-Hypotension
-Bradycardia
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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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