Antiarrythmics Flashcards
Classes of antiarrythmics
a. Class I: Fast Sodium Channel Blockers
b. Class II: Beta-Adrenergic Antagonists
c. Class III: Inhibitors of Repolarization
d. Class IV: Calcium Channel Blockers
e. Other: (adenosine, digitalis, etc.)
Phases of cardiac cycle
Phase 0 rapid depolarization (fast sodium channels open; fast inward flow of Na+ ) Phase 1 begin repolarization (sodium channels close) Phase 2 plateau (slow calcium channels open; slow inward flow of Ca2+) Phase 3 repolarization (calcium channels close; potassium channels open; slow outward K+ current) Phase 4 pacemaker potential; return to resting membrane potentials Refractory period (phases 1-3) (periods of repolarization)
Sympathetic stimulation effects
(ß1 receptors activated) Increases catecholamines Increased heart rate (positive chronotropic effect) Increased automaticity Facilitation of conduction of AV node
Parasympathetic system effects
(M2 muscarinic receptors)
Decreases heart rate
Inhibits AV conduction
Classification of arrythmias
Site of origin of abnormality (atrial/ junctional / ventricular)
Complexes on ECG (narrow/broad)
Heart rhythm (regular/irregular)
Heart rate is increased or decreased
Mechanisms of Arrhythmia Production
Altered automaticity - latent pacemaker cells take over the SA node’s role; escape beats
Delayed after-depolarization - normal action potential of cardiac cell triggers a train of abnormal depolarizations
Re-entry - refractory tissue reactivated repeatedly and rapidly due to unidirectional block, which causes abnormal continuous circuit
Conduction block – impulse fail to propagate in non-conducting tissue
Reasons for arrythmias
Arterial hypoxemia Electrolyte imbalance Acid-base abnormalities Myocardial ischemia Altered sympathetic nervous system activity Bradycardia Administration of certain drugs Enlargement of a failing ventricle
Class I agents
Block sodium channels which depresses Phase O in depolarization of the cardiac action potential with resultant decreases in action potential propagation (decrease in depolarization rate) and slowing of conduction velocity
Class IA
Quinidine - Class IA Prototype
Procainamide
Disopyramide
Moricizine
Intermediate Na+ channel blocker (intermediate dissociation) Decreased depolarization rate (phase 0) Decreased conduction velocity Prolonged repolarization Increased AP duration
Disopyramide
Suppresses atrial and ventricular tachyarrhythmias
Oral agent
Has significant myocardial depressant effects and can precipitate congestive heart failure and hypotension
Class IB Agents
Lidocaine - Class IB Prototype
Mexiletine
Tocainide
Phenytoin
Fast Na+ channel blocker (fast dissociation)
Alters the action potential by inhibiting sodium ion influx via rapidly binding to and blocking sodium channels (fast)
Produces little effect on maximum velocity depolarization rate, but shortens AP duration and shortens refractory period
Decreases automaticity
Lidocaine
Class IB Antiarrhythmic Drug- Prototype
Sodium channel blocker (fast)
Used in acute treatment and prevention of ventricular dysrhythmias in immediate aftermath of MI
Ventricular tachycardia, fibrillation, PVCs, especially associated with ischemia; Pulseless VT and VF
Pharmacokinetics: Lidocaine
Elimination half-time (h) 1.4-8.0
Therapeutic plasma concentration 1-5 ug/mL
Dose: 1-1.5 mg/kg IV, infusion 1-4 mg/min (max dose 3 mg/kg)
50% protein binding
Hepatic metabolism
Active metabolite, which prolongs elimination half-time.
Metabolism may be impaired by drugs such as cimetidine and propanolol, or physiologic altering conditions such CHF, acute MI, liver dysfunctioin, GA; or can be induced by drugs like barbiturates, phenytoin, or rifampin
10% renal elimination
Adverse effects: Lidocaine
hypotension, bradycardia, seizures, CNS depression, drowsiness, dizziness, lightheadedness, tinnitus, confusion, apnea, myocardial depression, sinus arrest, heart block, ventilatory depression, cardiac arrest and can augment preexisting neuromuscular blockade
Mexiletine
Chronic suppression of ventricular cardiac tachyarrhymias
Oral agent
Class IC Agents
Flecainide - Class IC Prototype
Propafenone
Slow Na+ channel blocker (slow dissociation), so does not vary much during the cardiac cycle
Potent decrease of depolarization rate phase 0 and decreased conduction rate, with increased AP
Markedly inhibit conduction through the His-Purkinje system