Hydantoins
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 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 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.
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.
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.
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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