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Chapter: Clinical Pharmacology: Neurologic and neuromuscular drugs


The two most commonly prescribed anticonvulsants—phenytoin and phenytoin sodium—belong to the hydantoin class. Other hy-dantoins include fosphenytoin and ethotoin.



The two most commonly prescribed anticonvulsants—phenytoin and phenytoin sodium—belong to the hydantoin class. Other hy-dantoins include fosphenytoin and ethotoin.




The pharmacokinetics of hydantoins vary from drug to drug.


Phenytoin fits in slowly


Phenytoin is absorbed slowly after both oral and I.M. administra-tion. It’s distributed rapidly to all tissues and is highly (90%) protein-bound. Phenytoin is metabolized in the liver. Inactive metabolites are excreted in bile and then reabsorbed from the GI tract. Eventually, however, they’re excreted in urine.

Fosphenytoin for the short term


Fosphenytoin is indicated for short-term I.M. or I.V. administra-tion. It’s widely distributed throughout the body and is highly (90%) protein-bound. Fosphenytoin is metabolized by the liver and excreted in urine.


Talkin’ ethotoin


Ethotoin is readily absorbed from the GI tract and is metabolized by the liver. Extensively protein-bound, ethotoin is excreted in urine, primarily as metabolites.




In most cases, the hydantoin anticonvulsants stabilize nerve cells to keep them from getting overexcited. Phenytoin appears to work in the motor cortex of the brain, where it stops the spread of seizure activity. The pharmacodynamics of fosphenytoin and etho-toin are thought to mimic those of phenytoin. Phenytoin may alsobe used as an antiarrhythmic drug to control irregular heart rhythms, with properties similar to those of quinidine or pro-cainamide, although this use is decreasing.




Because of its effectiveness and relatively low toxicity, phenytoin is the most commonly prescribed anticonvulsant. It’s one of the drugs of choice to treat:


complex partial seizures (also called psychomotor or temporallobe seizures)

tonic-clonic seizures.

Hydantoins (phenytoin and fosphenytoin) are the long-acting anticonvulsant of choice to treat status epilepticus after initial I.V. benzodiazepines.


Resistance is futile


Health care providers sometimes prescribe phenytoin and etho-toin in combination with other anticonvulsants for partial and tonic-clonic seizures in patients who are resistant to or intolerant of other anticonvulsants.


Drug interactions


Hydantoins interact with a number of other drugs. Here are some drug interactions of major to moderate clinical significance:


·                 Phenytoin’s effect is decreased when it’s taken with phenobarbi-tal, diazoxide, theophylline, carbamazepine, rifampin, antacids, or sucralfate.


·                 Phenytoin’s effect and potential for toxicity increase when it’s taken with cimetidine, disulfiram, fluconazole, isoniazid, omepra-zole, sulfonamides, oral anticoagulants, chloramphenicol, valproic acid, or amiodarone.

·                 Enteral tube feedings may interfere with the absorption of oral phenytoin. Stop feedings for 2 hours before and after phenytoin administration.

·                 The effect of these drugs is decreased when they’re taken with a hydantoin anticonvulsant: oral anticoagulants, antiretrovirals, lev-odopa, amiodarone, corticosteroids, doxycycline, methadone, metyrapone, quinidine, theophylline, thyroid hormone, hormonal contraceptives, valproic acid, cyclosporine, and carbamazepine. (See Adverse reactions to hydantoins.)


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