Valproic acid pharmacological effects

The following drugp have a decreased pharmacologic effect when administered with an antacid corticosteroids, digoxin, chlorpromazine, oral iron products, isoniazid, phenothiazines, ranitidine, phenytoin, valproic acid, and the tetracyclines. 

There is strong evidence that bipolar disorder is associated with SUD in adolescents (Wilens et ah, 1999) and that pharmacological interventions are an effective treatment for youth with SUD and bipolar disorder. Two studies, including one randomized controlled study, have reported that mood stabilizers, specifically lithium and valproic acid (Depakote), significantly reduced substance use in bipolar youth (Donovan and Nunes, 1996 Geller et ah, 1998). In addition, these agents are considered effective agents for the treatment... 

Plasma protein binding interactions are usually clinically unimportant, but they should be recognized, because they alter the relation between serum drug concentration and the clinical response if displacement occurs, therapeutic and toxic effects are reached at a total drug concentration lower than usual. For example, valproic acid and salicylate displace phenytoin from plasma proteins this usually results in a fall in total phenytoin concentration without any change in the concentration of unbound (pharmacologically active) phenytoin. 

Valproic add modulates the action of various other common antiepileptic drugs. It inhibits the nonrenal clearance of phenobarbital, resulting in elevated phenobarbital levels. It competes -with phenytoin for protein-binding sites. The free phenytoin concentration remains approximately the same, but the total phenytoin in the plasma decreases. Because the free phenytoin concentration remains unchanged, the pharmacological effect is retained. Other common antiepileptic drugs that induce hepatic oxidative enzymes result in increased valproic acid clearance this increased clearance rate requires a higher dose to maintain effective therapeutic levels. 

PHARMACOLOGICAL EFFECTS The antiseizure properties of valproic acid (DEPAKENE, others) were discovered serendipitously when it was employed as a vehicle for other compounds that were being screened for antiseizure activity. Its efficacy in animal models parallels its efficacy against absence as well as partial and generalized tonic-clonic seizures in humans. 

Mattson RH, Cramer JA, WiUiamson PD, Novelly RA. Valproic acid in epilepsy clinical and pharmacological effects. Arm Neurol (1978) 3, 20-5. 

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