Phenytoin: Effects, Uses & Risks

Phenytoin is a drug in the anticonvulsant drug class. Depending on its use, phenytoin is also classified as an antiarrhythmic agent.

What is phenytoin?

Anticonvulsants are used to inhibit impulses in the CNS to prevent incipient seizures. Phenytoin is a drug used primarily to treat epilepsy. However, the substance is also used for the treatment of cardiac arrhythmias. Phenytoin was first synthesized in 1908 by the chemist and university lecturer Heinrich Biltz. For this purpose, Biltz heated benzil and urea. After a rearrangement of the benzilic acid, phenytoin was formed. In Europe, phenytoin is sold under the trade names Phenhydan, Zentropil or Epanutin. Generic versions are also available. Phenytoin is a hydantoin derivative. Hydantoins are saturated heterocyclic compounds and are themselves a derivative of imidazoles. The bioavailability of phenytoin is good. The drug is metabolized in the liver. This metabolization is dose-dependent and the half-life of the drug is thus variable. Phenytoin is excreted predominantly by the kidney.

Pharmacologic effects

Phenytoin blocks sodium channels on body cells. Blockage of the channels and delayed recovery after excitation of the cells prevent rapid influx of sodium ions. The influx of sodium into cells triggers action potentials. When sodium influx is prevented, the action potentials do not rise as quickly, for one thing. For another, the action potentials last for a shorter time. In addition to the reduced influx of sodium ions, there is simultaneously an increased outflow of potassium ions. Thus, the stimulus threshold increases. For an action potential to be triggered, a much stronger stimulus must hit the target cell. The membrane potential is thus stabilized by phenytoin. However, unlike many other antiarrhythmic drugs, phenytoin does not affect AV conduction at the heart.

Medical application and use

Phenytoin is used primarily in the treatment of epilepsy. It is suitable as a continuous treatment for simple and complex focal seizures. Focal seizures originate in a specific area of the brain and always affect only one side of the brain. They can be manifested by muscle twitching, tingling sensations, feelings of warmth, numbness, flashes of light in front of the eyes, or dizziness. Patients with complex focal seizures often lose consciousness. Phenytoin is also administered for primary generalized tonic-clonic epileptic seizures. These epileptic seizures are also called grand mal seizures. For status epilepticus, phenytoin is also approved for intravenous administration. Status epilepticus refers to epileptic seizures that last for a very long time. The seizures may also occur in a series, with the interval between each seizure being so short that the affected person does not regain consciousness. Depending on its severity, status epilepticus can result in severe damage and, in the worst case, can be fatal. In generalized seizures of the absence type, so-called petit mal seizures, phenytoin is ineffective. In exceptional cases, phenytoin is also used to treat neurogenic pain conditions. Because of the side effects that can occur during therapy with phenytoin, the drug is only used here if other therapeutic measures are not effective. Phenytoin is also used to treat ventricular tachycardia (rapid heartbeat). Ventricular tachycardia is a cardiac arrhythmia that originates in the ventricles. Ventricular tachycardia is an emergency that usually occurs after digitalis intoxication. Digitalis glycosides are used to treat heart disease. In an overdose, they can result in life-threatening cardiac arrhythmias.

Risks and side effects

A typical side effect of phenytoin is bradycardia. Bradycardia is a heart rate of less than 60 beats per minute. This slowing of the heartbeat can be very dangerous, which is why phenytoin is given only under close supervision. Other side effects include impaired motor coordination with tremors or gait disturbances, nystagmus, dizziness, and gum growths. Anemia is also observed more frequently. Furthermore, osteomalacia may occur. In osteomalacia, the bones soften.The condition is associated with dull pain and an increased risk of fracture. Patients taking phenytoin may also develop an acne-like skin rash. Similarly, hair growth in excess of normal may occur in otherwise hairless areas. Hair growth may be localized or may affect the entire body, excluding the palms of the hands and soles of the feet. Adverse effects may also manifest on a mental level. Thus, perceptual disturbances and disturbances in memory may occur. These disturbances in intellectual performance are often accompanied by fatigue and headaches. Phenytoin often interacts with other drugs. Thus, the level of action is increased by antihistamines, antibiotics, benzodiazepines, antidepressants, certain anesthetics, antirheumatic drugs, and proton pump inhibitors. The effect of phenytoin is decreased by alcohol, carbamazepine, primidone, and phenobarbital. Oral anticoagulants, oral contraceptives, tricyclic antidepressants, verapamil, and corticosteroids are less effective in combination with phenytoin. Contraindications to phenytoin use include liver disease, pregnancy, bone marrow disease, heart failure, higher-grade AV block of the heart, and sick sinus syndrome.