Class III: Potassium Channel Blockers

• Blockade of potassium channels delay repolarization and prolong the action potential. As a result, the effective refractory period is increased.

• Drugs in this group: Bretylium, Amiodarone
  

• Bretylium

  • Overview:

    • Initially released as an antihypertensive agent.

      • Orthostatic hypotension may occur following chronic use

    • Inhibits neuronal catecholamine release, following an initial direct early release of norepinephrine from adrenergic nerve terminals (transient hypertension)

    • Direct antiarrhythmic properties

  • Pharmacokinetics:

    • IV or IM Route of Administration

    • Following rapid IV administration: nausea & hypotension

    • After the first doses: bretylium-mediated norepinephrine release causes:

      • transient hypertension

      • increased ventricular irritability (particularly in patients also receiving digitalis)

    • Renal elimination: 8-12 hour halftime

    • Dosage reduction required in patients with renal dysfunction

    • Hepatic metabolism: not demonstrated

  • Cardiac Actions:

    • Antiarrhythmic effect due to prolongation of the cardiac action potential and inhibition of norepinephrine reuptake by sympthetic nerves

    • Increased ventricular (not atrial) action potential duration and effective refractory period

    • Somewhat selective for ischemic cells which have shortened action potential durations

      • Bretylium may reverse shortening of action potential duration due to ischemia

    • Possesses anti-fibrillatory activity; independent of sympatholytic action

    • Initial catecholamine release (prior to inhibition of release), results in some positive inotropic effect; however, this action may induce ventricular arrhythmias (catecholamines generally are pro-arrhythmogenic).

    • Inhibition of catecholamine release may result in bradycardia.

  • Clinical Use:

    • Management of serious ventricular arrhythmias refractory to lidocaine or procainamide

    • Possible initial drug for treatment of ventricular fibrillation--Rationale:

      • Increases ventricular fibrillation threshold;

      • Prolongs action potential duration;

      • Prolongs effective refractory period

      
      

Category: Pharmacology Notes