Antiepileptics valproate

ACARBOSE ANTIEPILEPTICS-VALPROATE Case of 1 valproate levels Uncertain Monitor valproate levels... 

ERTAPENEM, MEROPENEM ANTIEPILEPTICS - VALPROATE i valproate levels Induced metabolism Monitor levels... 

BC, a 22-year-old woman, was diagnosed 2 years ago with juvenile myoclonic epilepsy. She has been treated with valproate 1500 mg/day. Since starting valproate she has gained 45 pounds (20.5 kg), continues to have occasional myoclonic jerks, had a generalized tonic-clonic seizure 3 months ago, and is sexually active. Additionally, she complains of easily falling asleep during the day. Due to adverse effects, poor seizure control, and the risk of birth defects with valproate, the decision is made to switch to a different antiepileptic drug. 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Turning to the pharmacotherapy for mania, for decades lithium was the only effective drug treatment. More recently, a number of antiepileptic drugs including carba maze pine, lamotrigine and valproate have been shown to also act as mood stabilisers and are becoming established for the treatment and prophylaxis of both unipolar mania and bipolar manic depressive disorders. 

Valproic acid (dipropylacetic acid) is a single branched chain carboxylic acid that is structurally unlike any of the other drugs used in the treatment of bipolar disorder or epilepsy. The amide derivative, valproamide, is available in Europe as a more potent form of valproate. Valproate was first developed in Erance as an antiepileptic agent in 1963. As an antiepileptic agent, it was shown to be active against a variety of epilepsies without causing marked sedation. 

Epilepsy, monotherapy Indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED). 

Metaboiism/Excretion- Primarily metabolized in liver. Mean terminal half-life for valproate monotherapy ranges from 9 to 16 hours. Half-lives in the lower part of the range usually are found in patients taking other enzyme-inducing antiepileptic drugs. 

Valproic acid, valproate sodium, and (DVP) are carboxylic acid-derivative anticonvulsants. Divalproex sodium is a stable coordination compound consisting of valproic acid and valproate sodium in a 1 1 molar ratio (AHFS, 2000). It is a pro-drug of valproate, dissociating into valproate in the GI tract (AHFS, 2000), and a simple branched-chain carboxylic acid (w-dipropylacetic acid) with antiepileptic activity against a variety of types of seizures (Beydoun et al., 1997). Divalproex sodium has been approved for treating adults with simple and complex absence seizures (Mattson et al., 1992), and for mania. It has shown efficacy across a broad spectrum of BD subtypes (i.e., pure mania, mixed mania, and rapid cycling) (Pope et al., 1991 Bowden et al., 1994). 

Valproate has antiepileptic efficacy in different types of epilepsy. It is therefore sometimes called the hroad range antiepileptic drug. It has no significant hypnosedative effects nor does it have respiratory depressant activity. In addition it does not have undesirable effects on blood pressure, heart rate, kidney function and body temperature. 

The anticonvuisanf hypothesis has been developed to explain the efficacy of ECT, as well as certain antiepileptic drugs. Thus, agents such as carbamazepine (CBZ) and valproate have several effects on seizure activity, including the following ... 

Concentrations of lipoprotein(a) were measured in 51 patients taking long-term carbamazepine, phenobarbital, phenytoin, or valproate and 51 age- and sex-matched controls (133). Lipoprotein(a) concentrations were above 450 pg/ml in 11 patients compared with only 4 controls, and the mean serum lipoprotein(a) concentrations were 330 and 169 pg/ml respectively. The epileptic patients also had a thicker intima media of the common carotid artery. These results suggest that patients taking antiepileptic drugs may be at a higher risk of atherosclerosis. 

In the absence of drug, a series of high-frequency repetitive action potentials filled the entire duration of the current pulse. Phenytoin, carbamazepine, and sodium valproate all markedly reduced the number of action potentials elicited by the current pulses. (Modified and reproduced, with permission, from Macdonald RL, Meldrum BS Principles of antiepileptic drug action. In Levy RH, et al [editors]. Antiepileptic Drugs, 4th ed. Raven Press, 1995.)... 

Valproic acid (valproate), discussed in detail elsewhere as an antiepileptic (see Chapter 24 Antiseizure Drugs), has been demonstrated to have antimanic effects and is now being widely used for this indication in the USA. Overall, it shows efficacy equivalent to that of lithium during the... 

Carbamazepine is a hepatic microsomal enzyme inducer and therefore will lower the serum concentration of a wide variety of drugs given concurrently. These include the antiepileptic drugs phenytoin, primidone, valproate, ethosuximide and clonazepam. In addition, carbamazepine can compromise the therapeutic effects of oral contraceptives, oral anticoagulants, beta-blockers, haloperidol and theophylline. 

Valproate is now the most commonly used antiepileptic drug worldwide. It is the drug of choice in primary generalized epilepsy, particularly in the treatment of generalized absence, myoclonus and tonic-clonic seizures. Valproate is the drug of first choice in atypical absence and atonic seizures, for Lennox-Gastaut syndrome and myoclonic epilepsy. 

It is generally accepted that there is a good correlation between potentiation or antagonism of experimentally induced convulsions in animals and effects observed in man (Kupferberg 2001). Most substances with antiepileptic properties in man antagonize experimental convulsions, whereas many substances which either induce convulsions or lower the convulsive threshold in man (certain CNS stimulants, some neuroleptics) show similar effects in animals. There are nonetheless differences in the efficacy of certain substances in antagonizing experimental convulsions. For example, sodium valproate appears to be more widely effective in different experimental models than benzodiazepines (Loscher 2002). 

---