Interactions
Valproate inhibits CYP2C9, glucuronyl transferase, and epoxide hydrolase and is highly protein bound and hence may interact with drugs that are substrates for any of these enzymes or are highly protein bound themselves. It may also potentiate the CNS depressant effects of alcohol. It should not be given in conjunction with other antiepileptics due to the potential for reduced clearance of other antiepileptics (including carbamazepine, lamotrigine, phenytoin and phenobarbitone) and itself. It may also interact with:
Aspirin: may increase valproate concentrations. May also interfere with valproates metabolism. Benzodiazepines: may cause CNS depression and there are possible pharmacokinetic interactions. Carbapenem antibiotics: reduce valproate levels, potentially leading to seizures. Cimetidine: inhibits valproates metabolism in the liver, leading to increased valproate concentrations. Erythromycin: inhibits valproates metabolism in the liver, leading to increased valproate concentrations. Ethosuximide: valproate may increase ethosuximide concentrations and lead to toxicity. Felbamate: may increase plasma concentrations of valproate. Mefloquine: may increase valproate metabolism combined with the direct epileptogenic effects of mefloquine. Oral contraceptives: may reduce plasma concentrations of valproate. Primidone: may accelerate metabolism of valproate, leading to a decline of serum levels and potential breakthrough seizure. Rifampicin: increases the clearance of valproate, leading to decreased valproate concentrations
Warfarin: valproate may increase free warfarin concentration and prolong bleeding time. Zidovudine: valproate may increase zidovudine serum concentration and lead to toxicity. Pharmacology
Pharmacodynamics
Although the mechanism of action of valproate is not fully understood, traditionally, its anticonvulsant effect has been attributed to the blockade of voltage-gated sodium channels and increased brain levels of gamma-aminobutyric acid (GABA).
Tight hymenal ring is a disorder of the hymen, characterized by a rigid hymen and tight introitus, whether acquired or congenital. It excludes an imperforate hymen. The condition can be relieved by outpatient surgery or manual dilation. References


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