Phenytoin

• Overview

  • Effective in suppression of ventricular arrhythmias associated with digitalis toxicity

  • Less effective than quinidine, procainamide, or lidocaine, in treatment of ventricular arrhythmias due to other etiologies

• Pharmacokinetics:

  • Routes of administration: oral, or IV

  • Normal saline preferred -- phenytoin may precipitate in 5% dextrose in water

  • Slow IV injection into large peripheral or central vein preferable-- decreased chance of:

    1. discomfort

    2. thrombosis at injection site

  • Hepatic Metabolism --hydroxylation and conjugation (glucuronidation):

    • Elimination half-life: approximately 24 hours

    • Impaired hepatic function may cause excessive phenytoin blood levels

• Mechanism of Action/Cardiac Effects:

  • Electrophysiological effects on automaticity and conduction velocity--somewhat like lidocaine

  • Shortens QT interval more than any other antiarrhythmic agent

  • No significant effect on ST-T waves or QRS complex

  • No significant myocardial depression

  • Improvement in AV Node Conduction;

  • Depression of SA Nodal Activity

• Drug-Drug Interaction:

  • Significant SA nodal depression may occur when combining those volatile anesthetics that depress SA nodal activity and phenytoin

  • Drugs that lower phenytoin levels:

    • barbiturates (mechanism:metabolizing enzyme induction)

  • Drugs that increase phenytoin level (inhibit metabolism):

    • warfarin, phenylbutazone, isoniazid

• Side effect/Toxicities:

  • Primary Toxicity: CNS disturbance (particularly cerebellar-- dose correlated > 18 ug/ml-- exceeding this concentration is unlikely to improve cardiac rhythm)

  • CNS symptoms:

    • ataxia, vertigo, slurred speech, sedation, nystagmus, confusion

  • Partial inhibition of insulin secretion: enhances blood glucose levels in hyperglycemic patients

Stoelting, R.K., "Cardiac Antidysrhythmic Drugs", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, 331-343

Category: Pharmacology Notes