Valproate characteristics

Sodium valproate is a white crystalline powder with a very slight characteristic odor of valproic acid. 

Immediately after remission of an episode of mania treated with perphenazine + a mood stabilizer (lithium, car-bamazepine, or valproate), patients were randomly assigned to 6 months of double-blind treatment in which, in addition to the mood stabilizer, they received either continued perphenazine (n = 19) or placebo (n = 18) (113). There were no between-group differences in various important demographic and clinical characteristics. Those given placebo were more likely than those who... 

Drugs known to be teratogenic include cytotoxics, warfarin, alcohol, lithium, methotrexate, phenytoin, valproate, ACE inhibitors and isotretinoin. Selective interference can produce characteristic anatomical abnormalities, and the phocomelia (flipper-Uke) limb defect was one factor that caused thalidomide to be so readily recognised. (For an account of thalidomide see p. 81.)... 

Importantly, its precise mechanism of its anticonvulsant action is still not fully understood. However, it has been duly advocated that its administration specifically inhibits GABA-transaminase, and thereby enhancing the concentration of cerebral GABA. It has also been observed that a few other straight-chain saturated fatty acids i.e., lower fatty acids, such as propanoic acid, butyric acid, and pentanoic acid which are devoid of anticonvulsant characteristic features are relatively more potent and efficacious inhibitors of GABA-transaminase than is valproic acid. Furthermore, it has been adequately substantiated that there exists a rather stronger correlation between the anticonvulsant potency of valproate and other branched-chain fatty acids besides, their capability to minimise the prevailing concentration of cerebral aspartic acid (an amino acid). 

Epilim (Sodium valproate). Sanofi-Aventis. UK Summary of product characteristics, October... 

A 2-month-old boy bom to a mother taking valproate had typical dysmorphic features characteristic of fetal valproate syndrome [342 ]. He had a distinctive facial appearance, a cluster of minor and major anomalies, central nervous system dysfunction, a persistent left superior vena cava draining into a dilated coronary sinus, and mild pulmonary hypertension. 

Liver The pathogenesis and clinical characteristics of drug-induced liver injury associated with antiepileptic drugs has been reviewed [41 ]. Reactive metabolites can, in some cases, lead to direct cytotoxicity and liver cell necrosis, whereas in other cases they can cause neoantigen formation, inducing immunoallergic mechanisms. In fact, hypersensitivity features are found in more than 70% of patients with pheny-toin-induced liver injury, whereas this is only observed in 30% of carbamazepine-associated hepatotoxicity and very rarely with valproate-induced liver injury. No specific therapy is of proven value in these cases. However, carnitine, which is an important co-factor in mitochondrial beta-oxidation of fatty acids, is recommended in valproate-associated liver injury, and N-acetylcysteine is an appropriate treatment in patients with liver injury due to pheny-toin and carbamazepine. Liver transplantation may be required for patients with the most severe liver reactions. 

Further cases of fetal valproate syndrome with unusual characteristics have been described [393, 394 ]. 

In addition to its use in mood disorders, lithium has been suggested or examined in a wide range of neuropsychiatric conditions. Lithium is one of the pharmaceuticals that is frequently recommended for the management of aggressive behavior independent of diagnosis. In a review of 16 published studies, 7 or 8 (depending on definition of response) were foxmd to be positive [43" " ], and indeed, it appears to reduce impulsive behavior in rats—a characteristic not shared by tire otiier common mood stabilizers, carbamazepine, or valproate [44an nia> study]... 

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