Anti arrhythmics Flashcards
Vaughn Williams scheme classification
classify drugs according to their primary electrophysiologic action/ability to block channels
Class I-V
Vaughn Williams scheme limitations
Many anti arrhythmic agents have multiple action mechanisms
No consideration of drug metabolites effects
Antiarrhythmic effect based on channel blockers → no channel activation
Based on action on normal tissues vs diseased
Sicilian gambit
How drug affect ionic current, R, pumps
o Vulnerable parameter to target to abolish the arrhythmia
Class I: MOA
Na+ channel blockers
* ↓ Na+ flux → depress phase 0 of action potential
* Membrane stabilizers
Class I subgroups classification based on
based on ability to slow conduction and alter AP: variable blocking effect (+)
Class Ia: drugs
Quinidine, Procainamide
Class Ia: blocking ability
++
Class Ia: effects on AP
- ↓phase 0 and conduction velocity
- Prolong AP duration
o ↑ effective refractory period - Delay repolarization → mild class III action
o Block some K+ channels
Class Ib: drugs
Lidocaine, Mexiletine, Tocainide, Phenytoin (Lettuce, Tomato, Mayo, Please!)
Class Ib: effects on AP
- Little to no effect on phase 0 or conduction velocity in normal tissue
o Will ↓ in diseased tissue - ↓AP duration
o ↑ effective refractory period - ↑ ventricular fibrillation threshold
Class Ib: blocking ability
+
Class Ic: blocking ability
+++
Class Ic: drugs
Morcizine, Flecainide, propafenone
Class Ic: effects on AP
- Marked depression in phase 0 and conduction velocity
- Minimal effects on repolarization and refractoriness
Class II: MOA
Beta blockers
Anti sympathetic/sympatholytic effects → prevent effects of catecholamines on the heart
- Antiarrhythmic effect: β1-adrenoreceptor blockade
o Can also affect α1-R depending on drug
o α1-R stimulation may be important in arrhythmias related to ischemia or drugs
Class II: drugs
Atenolol, esmolol, propranolol, metoprolol, timolol, bisoprolol
Class II: effect on AP
o Depress sinus node automaticity
- inotrope & chronotope
- dromotrope
o ↓ slope of phase 4 depolarization
↓ current If = important pacemaker current
* Promotes proarrhythmic depolarization in damaged heart tissue
o Inhibits inward Ca2+ current ICa-L
Indirectly inhibited by fall in AMPc levels
Ca2+ dependant triggered arrhythmias
o Slow down AV node conduction; not really a direct anti arrhythmic effect
Prolong repolarization → ↑ PR
Class III MOA
K+ channel blockers
Class III drugs
Amiodarone, Sotalol, Ibutilide, Dofetilide, Dronedarone
Class III effects on AP
- ↑ AP duration → prolong phase 3 of repolarization
o Delayed repolarization
o W/o affecting rate of phase 0 or conduction velocity
o Some can have Na+ channel blocking effects
Class IV drugs
Diltiazem, Verapamil (cardiac), Amlodipine (Vascular)
Class IV MOA
o Block L-type Ca2+channels
o Important ion to maintain normal automaticity and conduction in SA/AV nodes
- chronotrope and dromotrope
What types of arrhythmias controlled by class IV
SVT
Class IV effect on AP
o Cardiomyocytes: shorten phase 2
o Nodal cells
↓ slopes of phase 0, 3 and 4
Prolonged repolarization via AV node (phase 3
What determines selectivity of class IV to cardiac tissue
o Depend on specific binding site on channel
Dihydropyridines: selective for vascular smooth muscle cell
* Amlodipine
* Indication for systemic hypertension
Non-dihydropyridines: cardio selective
* Diltiazem and Verapamil
Class V drugs
Others
Digoxin
Class IV-like – K+ channel opener = Adenosine
Magnesium sulfate
Adenosine MOA
- Causes cell hyperpolarization
o Stimulates A1-Receptor on atrium, SA/AV node → opening adenosine sensitive K+ channel → hyperpolarize and inhibit AV node → hyperpolarization inhibit Ca2+ channels
Adenosine effect on AP
- ↓ automaticity, conduction velocity
- ↑ refractory period
Digoxin MOA
- Blocks Na+/K+ exchanger
o ↑ intra¢ Na+ → activate Na+/Ca2+ exchanger to pump out Na+ in exchange for Ca2+ → ↑ intra¢ Ca2+ - ↑ myocardial contractility
- Stimulates p∑ system = ↑ activity of vagal nerve
o ↓ SN discharge rate
o ↓ conduction through AV node
o → Negative chronotrope
Mg sulfate MOA
- Transport of Na, K, Ca
- Precise mechanism for arrhythmia unknown
o Weakly blocks Ca2+ channel
o Inhibits K+ and Na+ channels
Sicilian gambit classification
based on modification of vulnerable parameter
↓ phase 4 of depolarization
↓ AP duration/suppress EADs
Ca2+ overload/suppress DADs
↓conduction/excitability
↑refractory period
Sicilian gambit: ↓ phase 4 of depolarization
-MOA
-Arrhythmias
-Drugs
- Mechanism: enhanced automaticity
- Arrhythmias
o Inappropriate sinus tachycardia
o Idiopathic ventricular tachycardia
o AIVR - Drugs
o β-blockers
o Na+ channel blockers
o Ca2+ channel blockers