💊 Phenytoin

Phenytoin is an antiepileptic drug, classified as a hydantoin derivative. It is a first-line treatment for certain types of seizures.

Phenytoin primarily acts by blocking voltage-gated sodium channels in the neuronal membrane. This stabilises the inactive state of the channel, preventing repetitive firing of action potentials and thus reducing neuronal excitability. It also has some effects on calcium channels and neurotransmitter release.

Phenytoin is used for the treatment of tonic-clonic seizures and focal (partial) seizures. It can also be used in the management of status epilepticus, particularly when benzodiazepines are ineffective or contraindicated. It is not effective for absence seizures and can sometimes worsen them.

Absolute contraindications include hypersensitivity to phenytoin or other hydantoins, and certain cardiac conditions such as second- or third-degree AV block, sinus bradycardia, and Adams-Stokes syndrome. Relative contraindications include hepatic impairment due to its extensive metabolism, and porphyria. Caution is also advised in patients with pre-existing blood dyscrasias.

Common adverse effects include nystagmus, ataxia, dizziness, and drowsiness, particularly with higher doses. Long-term use can lead to gingival hyperplasia, hirsutism, coarsening of facial features, and folate deficiency. Serious adverse effects include severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome), blood dyscrasias (e.g., aplastic anaemia), and hepatotoxicity.

Therapeutic drug monitoring of plasma phenytoin concentrations is crucial due to its narrow therapeutic index and saturable metabolism. Liver function tests, full blood count, and renal function should be monitored periodically. Regular dental check-ups are also recommended due to the risk of gingival hyperplasia.

When prescribing, always check for allergies to phenytoin or hydantoins. Be mindful of numerous drug interactions, particularly with other antiepileptics, warfarin, and oral contraceptives, which can alter phenytoin levels or be affected by it. Counselling should include advice on consistent dosing, the importance of regular blood tests, and potential side effects like gingival overgrowth and the need for good oral hygiene.

Phenytoin exhibits zero-order kinetics at higher concentrations, meaning a small dose increase can lead to disproportionately large increases in plasma levels, necessitating careful titration. It is a potent enzyme inducer, impacting the metabolism of many other drugs. Fosphenytoin is a prodrug of phenytoin, used parenterally, with a better safety profile for intravenous administration.

SBAs often focus on the adverse effects of long-term phenytoin use, such as gingival hyperplasia or hirsutism. Questions might also test knowledge of its narrow therapeutic index and the need for therapeutic drug monitoring. Another common theme is its contraindications in certain cardiac conditions or its ineffectiveness in absence seizures.