A 23-year-old female is brought to the ER after having a tonic-clonic seizure. She has a history of seizures and takes phenytoin. She does not use tobacco, alcohol or illicit drugs. On physical examination, no focal abnormalities are noted. Blood tests reveal her plasma phenytoin level to be low. She states that she has been compliant with her medication. Which of the following drugs may be responsible for this patient's condition if co-administered with phenytoin?

Question

A 23-year-old female is brought to the ER after having a tonic-clonic seizure.  She has a history of seizures and takes phenytoin.  She does not use tobacco, alcohol or illicit drugs.  On physical examination, no focal abnormalities are noted.  Blood tests reveal her plasma phenytoin level to be low.  She states that she has been compliant with her medication.  Which of the following drugs may be responsible for this patient's condition if co-administered with phenytoin?

Quizplus · Accepted Answer

As with many other medications, phenytoin is metabolized by hepatic P450 oxidase. Plasma drug level, efficacy, and the severity of side effects are directly influenced by the rate of metabolism of phenytoin. The following features of phenytoin metabolism are important: (Choices A) Amoxicillin do not affect the hepatic metabolism of phenytoin. (Choices C and G) Both metronidazole and oral contraceptives are metabolized by hepatic P450 oxidase, but these two drugs neither induce nor inhibit the activity of P450 oxidase. (Choices D, E and F) Fluconazole, cimetidine, and omeprazole inhibit P450 enzymes and increase the concentration of phenytoin in the serum. Educational objective: Phenytoin metabolism depends on the function of hepatic P450 oxidases and is dose-dependent. Drugs that induce hepatic microsomal enzymes (phenobarbital, carbamazepine, and rifampin) enhance phenytoin metabolism and decrease its serum concentration. You should know all of the commonly-prescribed medications that are metabolized by the P450 system, and you should know which drugs induce or inhibit the function of these enzymes. __________ References: Cytochrome P450: new nomenclature and clinical implications (http://www.ncbi.nlm.nih.gov/pubmed/9447218) Pharmacokinetic drug interactions with phenytoin (Part I). (http://www.ncbi.nlm.nih.gov/pubmed/2178849)

A 23-Year-Old Female Is Brought to the ER After Having