Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Valproic acid is a new antiepileptic drug. It has a marked effect on generalized spike-wave discharges. The exact mechanism of action is uncertain; however, some evidence suggests an effect on the metabolism of gamma-aminobutyric acid. It is rapidly absorbed from the gastrointestinal (GI) tract. Concurrent administration with phenobarbital may result in elevated phenobarbital plasma concentrations. Administration with phenytoin sodium may transiently result in lower total phenytoin plasma levels. Side effects are generally mild and include fatigue, GI disturbances, weight gain, a fine postural and resting tremor, mild thrombocytopenia, and an increase in hepatic enzymes. Platelet counts and liver function monitoring should be done during valproic acid therapy. Drowsiness may be seen in patients receiving other antiepileptic drugs concurrently.
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PMID:Valproic acid. Review of a new antiepileptic drug. 11 Feb 94

2-Propyl-1-aminopentane (2-PAPN), a branched aliphatic amine, was found to be readily deaminated by monoamine oxidase B in the liver of the rat and semicarbazide-sensitive amine oxidase in the aorta of the rat. The deaminated product, 2-propyl-1-pentaldehyde, could be subsequently converted to valproic acid in the presence of aldehyde dehydrogenase and beta-NAD cofactor in vitro as well as in vivo. Valproic acid was identified after derivatization with 4-bromomethyl-6,7-dimethoxycoumarin, followed by HPLC-fluorometric assessment. Absorption and biotransformation of a single intraperitoneal dose of 2-PAPN resulted in the rapid appearance of the drug and its metabolite in the blood and in the brain. The formation of valproic acid from 2-PAPN in vivo, however, was insufficient to facilitate anticonvulsant action. In fact, 2-PAPN itself, at relatively small doses, exhibited distinct tremor effects. Such tremor effects could be prevented by valproic acid. However, 2-PAPN was also found to potentiate the convulsant effect induced by mercaptopropionic acid (MPA) and, in addition, the 2-PAPN-induced tremor could be potentiated by MPA in mice.
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PMID:2-propyl-1-aminopentane, its deamination by monoamine oxidase and semicarbazide-sensitive amine oxidase, conversion to valproic acid and behavioral effects. 186 97

Thirty patients with persistent chronic daily headache, unresponsive to various combinations of pharmacological and nonpharmacological treatment were selected for an open label study using divalproex sodium. All patients had normal liver function tests. After a baseline observation period of 1 month, patients were given divalproex sodium 1000 to 2000 mg per day, for a period of 3 months. Blood valproic acid levels were kept between 75 and 100 mcg/ml. Liver function studies and blood ammonia levels were obtained periodically. Based on weekly headache index, headache-free days, dysfunctional days and patients' general well-being rating and physicians' global assessment, two thirds of the patients improved significantly. The common side effects included weight gain, tremor, hair loss and nausea. Liver functions were unaffected by treatment. The possible mechanism of action of valproate in headache is discussed. Valproate appears to be a worthwhile addition to the prophylactic treatment of chronic recurrent headache.
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PMID:Valproate in the treatment of persistent chronic daily headache. An open label study. 203 76

Valproate has rapidly advanced as an antiepileptic drug in the last 15 years. This simple branched-chain fatty acid is strikingly different from previous antiepileptic drugs. Numerous clinical studies have found valproate to be highly effective in controlling generalized seizures, particularly as monotherapy. Ideally, valproate is given in three to four doses per day, because the elimination half-life varies from 6 to 15 hours, depending on concomitantly administered drugs and metabolic variations. Increasing the dosage raises the peak serum level and also increases the duration of time during which a minimum effective serum concentration is obtained. Drug interactions occur when valproate is administered with other drugs, especially other antiepileptic drugs. Side effects attributed to valproate include tremor, weight gain, hair loss, hair growth, hepatotoxicity, and neural tube defects in offspring of mothers. Monitoring serum valproate concentrations and seizure frequency are essential aspects of patient follow-up.
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PMID:The scope and use of valproate in epilepsy. 249 54

In a prospective open study of 20 male epileptic residents of a mental handicap institution, polytherapy was gradually reduced to valproate monotherapy in 18 subjects. In terms of seizure frequency this was significantly disadvantageous but when carbamazepine was added or substituted, seizure control improved significantly. Drugs with documented adverse effects on cognitive function such as phenobarbitone and phenytoin were phased out. In the 18 subjects who achieved valproate monotherapy, no association between serum levels and seizure control could be demonstrated. Adverse effects of valproate were pancreatitis and thrombocytopenia; in one subject thrombocytopenia appeared to be associated with levels in the toxic range but in six other subjects 'toxic' levels of valproate did not give rise to any clinically detectable toxic signs. There was no instance of tremor or weight gain. It was concluded that, in the population studied (institutionalized patients with chronically uncontrolled seizures) valproate monotherapy was inappropriate but carbamazepine with or without valproate was a better option. Phasing out phenytoin and phenobarbitone was successful. Valproate serum levels did not contribute significantly to the conduct of the study; no general relationship between valproate serum levels and either seizure control or toxicity could be demonstrated.
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PMID:Is valproate monotherapy a practical possibility in chronically uncontrolled epilepsy? 312 41

The influence of antiepileptic drugs on the wet dog shakes (WDS) induced by intracerebroventricular injections of carbachol (30 micrograms icv) was investigated in rats. Diphenylhydantoin (DPH, 8 and 4 mg/kg), diazepam (0.4, 0.2 and 0.1 mg/kg), phenobarbital (12.5, 6.25 and 3.12 mg/kg), sodium valproate (Depakine, 200, 100 and 50 mg/kg) and trimethadione (200, 100 and 50 mg/kg) given ip inhibited the WDS in a dose-dependent manner. These drugs at the same doses did not change the intensity of shaking behavior induced by lithium chloride or 5-hydroxytryptamine. As the antiepileptic drugs tested in these experiments did not have anticholinergic activity and at used doses were not able to prevent electrical convulsions or pentetrazol-induced seizures, it appears that carbachol-induced WDS could be connected with convulsive activity and could be the initial stage of seizures.
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PMID:Inhibition by antiepileptics of carbachol but not lithium- or 5-methoxytryptamine-induced wet dog shakes in rats. 314 10

Sodium valproate was administered to 38 patients, admitted to our unit in the last 18 months, and chosen because they had: (1) poor control of their seizures; (2) therapeutic concentrations in their plasma of at least two major antiepileptic drugs. In 8 of them, a therapeutic dosage of VPA caused modifications of the state of consciousness ranging from coma to drowsiness and stupor. These patients also showed gastrointestinal disturbances, asterixis, ataxia, tremor and a worsening of EEG abnormalities. The side effects of the drug were constantly associated with increased concentration of blood ammonia. Better penetration of ammonia into the CNS of patients undergoing frequent seizures and possibly having imperfectly functioning biological barriers, could explain our observations. In view of the unusually high percentage of patients suffering from serious VPA side effects, it is probably advisable to carefully monitor ammonemia in the first few days of VPA therapy in every patient treated with multiple anticonvulsants.
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PMID:Hyperammonemia and valproate-induced alterations of the state of consciousness. A report of 8 cases. 642 61

Valproic acid is a branched-chained fatty acid, structurally unrelated to any other antiepileptic drug. Since publication of the original review in the Journal in 1977, several clinical trials have documented its efficacy and safety in adults and children for the treatment of generalised seizures (absence, tonic-clonic, myoclonic), partial seizures (simple, complex, secondarily generalised) and compound/combination seizures (including those refractory to treatment with other antiepileptic drugs). Valproic acid monotherapy has demonstrated efficacy equivalent to that of carbamazepine, phenytoin, and phenobarbital in the treatment of both generalised and partial seizures and ethosuximide in the treatment of absence seizures. Adverse effects associated with the drug are primarily gastrointestinal (nausea, vomiting, dyspepsia) in nature, although the use of enteric-coated formulations has reduced the incidence of abdominal discomfort. Weight gain, tremor and transient hair loss are commonly reported. Importantly, valproic acid has minimal neurological adverse effects (sedation, ataxia, impairment of cognitive function) compared with other antiepileptic drugs, a finding that may be of particular relevance in many patients with epilepsy. The incidence of rare, fatal liver failure has been greatly reduced by identifying and avoiding administration of valproic acid to high risk patient populations. An estimated risk of 1 to 2% for neural tube defects, predominantly spina bifida aperta, with maternal use of valproic acid therapy has been reported. Valproic acid inhibits hepatic drug metabolism and displaces other highly bound drugs from their plasma protein binding sites. Therefore, coadministered drugs which are highly protein bound or hepatically metabolised may require dosage adjustment. Enzyme-inducing antiepileptic drugs may increase valproic acid metabolism and necessitate increasing its dosage. Thus, comparative trials and extensive clinical experience have demonstrated the efficacy and tolerability of valproic acid and support its role as a valuable and well established first-line treatment for patients with a broad range of seizure types.
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PMID:Valproic acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. 751 5

We examined the effects of conventional antiepileptic drugs (AEDs) on absence-like seizures in homozygous tremor rats (tm/tm) to determine if they corresponded pharmacologically to human absence seizures and absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tm/tm) with both tonic convulsive and absence-like seizures. Cortical and hippocampal EEG activity was recorded with chronically implanted electrodes. The effects of AEDS on seizures of the tremor rat showed profiles similar to those observed in human absence seizures and also in absence-like seizures of SER. The absence-like seizures, associated with paroxysmal bursts of 5-7-Hz spike-wave complexes, were inhibited by trimethadione (TMO 200 mg/kg intraperitoneally, i.p.), ethosuximide (ESM 100 and 200 mg/kg, i.p.), valproate (VPA 100 mg/kg, i.p.), and phenobarbital (PB 10 and 20 mg/kg, i.p.). Phenytoin (PHT 20 mg/kg, i.p.) was ineffective. These results are consistent with the conclusion that the tremor rat is a useful model for evaluating new AEDS for human absence seizures.
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PMID:Effect of antiepileptic drugs on absence-like seizures in the tremor rat. 764 34

A 40-year-old female receiving divalproex sodium (VPA) monotherapy for epilepsy developed a tremor secondary to the drug. Propranolol treatment was initiated. While receiving propranolol 40 mg, VPA clearance was reduced from 1.66 L/hr to 1.19 L/hr and dropped to 1.08 L/hr on propranolol 80 mg. The mechanism of this interaction is unknown. To evaluate the potential for a drug interaction between these two agents, 12 patients on VPA monotherapy, ages 19-55, were studied. The subjects were maintained on a constant dose of VPA. Each was then randomly assigned to receive placebo, or long-acting propranolol 60 mg/day or 120 mg/day. Mean VPA serum concentrations did not change among the three groups. Plasma half-life of VPA ranged from 7.3-18 hours and did not change with coadministration of propranolol. We concluded that VFA metabolism is not affected by coadministration of propranolol in this group of patients.
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PMID:A pharmacokinetic study to determine the drug interaction between valproate and propranolol. 894 79


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