VPT 311: General and Systemic Veterinary Pharmacology (2+1)

ACTIONS ON POTASSIUM CURRENTS

• Potassium currents, predominantly the current known as the delayed rectifier, are responsible for repolarizing the membrane during the action potential.
• Block of potassium currents during the plateau phase of the action potential is thought to be the mechanism of action of many drugs that prolong the refractory period.
• Drugs that are thought to act, at least in part, by inhibiting potassium currents include quinidine, sotalol, N-acetylprocainamide, and amiodarone.
• These drugs tend to have a higher propensity to cause torsades de pointes (a proarrhythmia also referred to as drug-induced long QT syndrome).
• Most of the available drugs that prolong repolarization exhibit negative rate-dependence, whereas positive rate-dependence (i.e.- greater efficacy in tachycardias) is the ideal characteristic for drugs used to convert spontaneous tachycardia.
• Some drugs used to treat hypertension and angina (nicorandil, pinacidil, and several other drugs) activate or open potassium channels and thereby act to shorten refractoriness of myocardial tissue which leads to arrhythmogenic states in animal models.