Pharmacology valproic acid

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. 

W. Loscher, H. Nau, Pharmacological Evaluation of Various Metabolites and Analogues of Valproic Acid , Neuropharmacology 1985, 24, 427-435. 

Kotchetkov, R., Busse, R., Nau, H. and Cinafl, J. Jr. (2004) Valproic acid inhibits angiogenesis in vitro and in vivo. Molecular Pharmacology, 65, 520-527. 

Pharmacology This group includes valproic acid, sodium valproate (the sodium salt), and divalproex sodium (a compound containing equal proportions of valproic acid and sodium valproate). Regardless of form, dosage is expressed as valproic acid equivalents. 

Davis, R., Peters, D.H., and McTavish, D. (1994) Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Drugs 47 332-372. 

FIGURE 43.1 Pharmacologic treatment algorithm for full syndrome pediatric PTSD. Based on a snythesis of consensus data and clinical reports in the adult and child literature. The author hers no responsibility for the use of this guideline by third parties. SSRI, selective serotonin reuptake inhibitor NEE, nefaza-done SIB, self injurious behavior VLF, venlafaxine VPA, valproic acid. 

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... 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

Nau, H. and Loscher, W. (1984) Valproic acid and metabolites pharmacological and toxicologic studies. Epilepsia 25(Suppl 1) S14-S22. 

FIGURE 7-23. Shown here is an icon of valproic acid s pharmacologic actions. By interfering with calcium channels and sodium channels, valproate is thought both to enhance the inhibitory actions of gamma aminobutyric acid (GABA) and to reduce the excitatory actions of glutamate. 

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. 

Kassahun, K., Baillie, T. A. Cytochrome P-450-mediated dehydrogenation of 2-n-propyl-2(E)-pentenoic acid, a pharmacologically active metabolite of valproic acid in rat liver microsomal preparations. Drug Metab. Dispos. 1993, 21, 242-248. 

Pharmacology and Mechanism of Action. The exact mechanism of action of valproic acid is not known (see Table 68-10). ° ... 

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. 

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