Phenytoin

5,5- Diphenylimidazolidin -2 ,4- dione

N03AB02

• Anticonvulsant
• Antiarrhythmic

286 ° C

8.33

Water: 32 mg · l-1 (22 ° C)

Risk

Template: Infobox chemical / molecular formula search available

Phenytoin is a hydantoin derivative, as a drug for the maintenance treatment of epilepsy ( anticonvulsant ) is used and, moreover, in the treatment of cardiac arrhythmias ( antiarrhythmic drug, off- label use ) is effective. Phenytoin is subject to medical prescription.

Pharmacology

Operation

The presumed mechanism of action is based on inhibition of sodium channels and the consequent stabilization of the membrane potential.

Areas of application

Phenytoin is ( grand mal ) and approved for prophylaxis of seizures (eg neurosurgery ) for the duration of treatment of partial seizures (simple partial seizures, complex partial seizures ), focal initiated and primary generalized tonic-clonic seizures. In addition, it is used as an intravenous therapy for status epilepticus. Another admission is for the treatment of neurogenic pain when other treatment measures have not been successful or are not feasible.

Side effects

Typical side effects that may occur during therapy with phenytoin, are perceptual disturbances, bradycardia ( therefore transfer only under intensive monitoring), tremor, particularly associated with nystagmus, impaired motor coordination, dizziness, headache, fatigue, ataxia, nystagmus, confusion, gingival overgrowth ( gingival hyperplasia ), memory disorders, megaloblastic anemia, osteomalacia and disorders of intellectual performance. Since phenytoin has only a narrow therapeutic index, plasma levels should be monitored regularly.

Likewise, a hypertrichosis occur. Phenytoin is considered to be teratogenic.

Interactions

Phenytoin is metabolized via the cytochrome P450 enzyme system CYP3A4. Inhibitors of this enzyme system such as cimetidine, erythromycin, ciprofloxacin, sertraline and fluoxetine, may increase the plasma concentrations of phenytoin and thus intensify its effects and side effects. Valproic acid via a competition for the same plasma protein binding site also leads to a gain of Phenytoinwirkungen and side effects.

Inducers of CYP3A4, such as carbamazepine and St. John's wort, accelerate the reduction of phenytoin and thus may limit its effectiveness. In addition, phenytoin CYP 3A4, which is called auto-induction induced. As a result, the activity of CYP 3A4 is increased in the course of therapy, which may necessitate dose increases required. This is one of the reasons for the complicated pharmacokinetics of phenytoin.

History

Phenytoin was first synthesized in 1908 by Heinrich Biltz. This benzil and urea were heated, which was formed after benzylic rearrangement phenytoin.

Trade names

Phenytoin is marketed in Europe, inter alia, under the trade names Epanutin, Phenhydan and Zentropil, in Austria as Epilan, in the U.S. as Dilantin and is also available as a generic.