Phenytoin-Induced Toxicity Due To Drug Interactions
Dr. Chanda Kulkarni.
Department of Clinical Pharmacology
St. Johnâ€™s Medical College and Hospital, Bangalore-560034, India
E-mail : firstname.lastname@example.org
Phenytoin is effective against both partial and tonic-clonic seizures. It is said to act by limiting repetitive firing of action potentials evoked by sustained depolarization, mediated by slowing the rate of recovery of voltage activated sodium channels from inactivation. The optimal initial dose, suggested for phenytoin is 3 to 4 mg/kg, body weight /day, while the usual maintenance dose is 200 to 500 mg/day for an adult. Phenytion is completely absorbed from upper intestine and is metabolized by liver. It undergoes entero-hepatic recycling and is excreted in urine, either as free or conjugated form. It is widely distributed throughout the body and is extensively plasma protein bound (90%). The toxic effects of phenytoin depend upon the route of administration, duration of exposure and dosage. Its toxic manifestations present as a syndrome comprising of cerebellar, vestibular and ocular effects such as nystagmus, diplopia, slurred speech and ataxia. Mental confusion and exacerbation of seizure frequency have also been noted. Overdose leads to hypotension, coma and respiratory depression. The dosage adjustments of phenytoin are necessary, to achieve adequate control of seizures, along with monitoring of its plasma concentration. This is because it follows saturation kinetics such as the rate of elimination varies as a function of its concentration. The plasma half-life ranges from 6 to 24 hrs at plasma concentration below 10 mg/ml, but increases with higher concentration. As a result, even with small increments in itâ€™s dosage to attain the levels towards therapeutic range, plasma drug concentration may increase disproportionately leading to toxicity. While, several reports are available indicating adverse drug reactions to phenytoin, the following case illustrates how phenytoin toxicity is affected by its interaction with other drugs especially in situations of polypharmacy.