Phenytoin (Dilantin) was originally introduced for the control of convulsive disorders but has now also been shown to be effective in the treatment of cardiac arrhythmias. Phenytoin appears to be particularly effective in treating ventricular arrhythmias in children.
Most clinically used concentrations of phenytoin do not significantly alter sinus rate in humans. However, the hypotension that may follow IV administration of phenytoin can result in an increase in sympathetic tone and therefore an increased sinus heart rate.
Phenytoin, like lidocaine, usually does not alter the action potential duration or ERP of atrial tissue except at very high concentrations. Atrial conduction velocity is either unchanged or slightly depressed.
Phenytoin lacks the anticholinergic properties of quinidine, disopyramide, and procainamide. However, the direct actions of phenytoin on the A-V node facili-tate transmission.
The electrophysiological effects of phenytoin on the His-Purkinje system resemble those of lidocaine; that is, action potential duration and ERPs are shortened. Phenytoin decreases the rate of phase 4 depolarization in Purkinje tissue and reduces the rate of discharge of ventricular pacemakers.
Because phenytoin improves A-V conduction and shortens the action potential duration of ventricular myocardium, it may decrease the PR and QT intervals of the surface electrocardiogram.
The effects of phenytoin on the cardiovascular system vary with the dose, the mode and rate of administration, and any cardiovascular pathology. Rapid administration can produce transient hypotension that is the combined result of peripheral vasodilation and depression of myo-cardial contractility. These effects are due to direct ac-tions of phenytoin on the vascular bed and ventricular myocardium. If large doses are given slowly, dose-related decreases in left ventricular force, rate of force develop-ment, and cardiac output can be observed, along with an increase in left ventricular end-diastolic pressure.
The pharmacokinetic characteristics of phenytoin:
Oral bioavailability : Slow and variable
Onset of action : 1–2 hours
Peak response : 1.5–6 hours
Duration of action : Variable
Plasma half-life : 22 hours
Primary route of metabolism : Hepatic
Primary route of excretion : 5% renal (unchanged); remain der as metabolites
Therapeutic serum concentration : 10–18 μg/mL
Phenytoin, like lidocaine, is more effective in the treat-ment of ventricular than supraventricular arrhythmias. It is particularly effective in treating ventricular ar-rhythmias associated with digitalis toxicity, acute myo-cardial infarction, open-heart surgery, anesthesia, car-diac catheterization, cardioversion, and angiographic studies.
Phenytoin finds its most effective use in the treat-ment of supraventricular and ventricular arrhythmias associated with digitalis intoxication. The ability of phenytoin to improve digitalis-induced depression of A-V conduction is a special feature that contrasts with the actions of other antiarrhythmic agents.
The rapid IV administration of phenytoin can present a hazard. Respiratory arrest, arrhythmias, and hypoten-sion have been reported.
Phenytoin either should not be used or should be used cautiously in patients with hypotension, severe brady-cardia, high-grade A-V block, severe heart failure, or hypersensitivity to the drug.
Because of the increase in A-V transmission ob-served with phenytoin administration, it should not be given to patients with atrial flutter or atrial fibrillation. Phenytoin will probably not restore normal sinus rhythm and may dangerously accelerate the ventricular rate.
Plasma phenytoin concentrations are increased in the presence of chloramphenicol, disulfiram, and isoniazid, since the latter drugs inhibit the hepatic metabolism of phenytoin. A reduction in phenytoin dose can alleviate the consequences of these drug–drug interactions.