Phenytoin
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Phenytoin is an anti-seizure medication that may be used in the following circumstances:
Phenytoin may exacerbate myoclonic seizures absence seizures.
Phenytoin has a narrow therapeutic index with the relationship between dose and plasma-drug concentration being non-linear i.e. small dose increases in some patients may produce large increases in plasma-drug concentration with acute toxic side-effects. Similarly, a few missed doses or a small change in drug absorption may result in a marked drop in plasma-drug concentration and increase proneness to seizure.
Phenytoin blocks sustained high frequency repetitive firing of action potentials in both neuronal and cardiac tissue which explains the risk of arrhythmias when phenytoin is used intravenously.
Phenytoin is a potent cytochrome p450 enzyme inducer and may increase the clearance of may drugs e.g. diltiazem.
Phenytoin is associated with a large number of adverse effects. These may be divided into acute, chronic, idiosyncratic and teratogenic
Acute
Chronic
Idiosyncratic
Teratogenic
- Epilepsy (tonic-clonic seizures or focal seizures)
- Status epilepticus
- Seizures associated with head trauma or neurosurgery
Phenytoin may exacerbate myoclonic seizures absence seizures.
Phenytoin has a narrow therapeutic index with the relationship between dose and plasma-drug concentration being non-linear i.e. small dose increases in some patients may produce large increases in plasma-drug concentration with acute toxic side-effects. Similarly, a few missed doses or a small change in drug absorption may result in a marked drop in plasma-drug concentration and increase proneness to seizure.
Mechanism of action
Phenytoin binds to and blocks sodium channels. This stabilises the inactive state of the sodium channel and prolongs the neuronal refractory period.Phenytoin blocks sustained high frequency repetitive firing of action potentials in both neuronal and cardiac tissue which explains the risk of arrhythmias when phenytoin is used intravenously.
Phenytoin is a potent cytochrome p450 enzyme inducer and may increase the clearance of may drugs e.g. diltiazem.
Side effects
Phenytoin is associated with a large number of adverse effects. These may be divided into acute, chronic, idiosyncratic and teratogenic
Acute
- initially: dizziness, diplopia, nystagmus, slurred speech, ataxia
- later: confusion, seizures
Chronic
- common: gingival hyperplasia (secondary to increased expression of platelet derived growth factor, PDGF), hirsutism, coarsening of facial features, drowsiness
- megaloblastic anaemia (secondary to altered folate metabolism)
- peripheral neuropathy
- enhanced vitamin D metabolism causing osteomalacia
- lymphadenopathy
- dyskinesia
Idiosyncratic
- fever
- rashes, including severe reactions such as toxic epidermal necrolysis
- hepatitis
- Dupuytren's contracture*
- aplastic anaemia
- drug-induced lupus
Teratogenic
- associated with cleft palate and congenital heart disease
Phenytoin toxicity
Symptoms of phenytoin toxicity include nystagmus, diplopia, slurred speech, ataxia, confusion, and hyperglycaemia.
Symptoms of phenytoin toxicity include nystagmus, diplopia, slurred speech, ataxia, confusion, and hyperglycaemia.
Contra-indications
- Acute porphyrias
- 2nd or 3rd third-degree heart block
- Sino-atrial block
- Sinus bradycardia
- Stokes-Adams syndrome
Monitoring
Phenytoin levels do not need to be monitored routinely but trough levels, immediately before dose should be checked if:
Note the above is not listed in the BNF but routine practice in many NHS trusts
Phenytoin levels do not need to be monitored routinely but trough levels, immediately before dose should be checked if:
- adjustment of phenytoin dose
- suspected toxicity
- detection of non-adherence to the prescribed medication
Note the above is not listed in the BNF but routine practice in many NHS trusts