Anticonvulsant drugs efficacy

Obtain cultures Obtain cultures and determine susceptibility before treatment. Determine blood levels Determine blood levels weekly for patients having reduced renal function, for individuals receiving more than 500 mg/day, and for those with symptoms of toxicity. Adjust dosage to maintain blood level less than 30 mcg/mL. Anticonvulsant drugs or sedatives Anticonvulsant drugs or sedatives may be effective in controlling symptoms of CNS toxicity, such as convulsions, anxiety, and tremor. Closely observe patients receiving more than 500 mg/day for such symptoms. Pyridoxine may prevent CNS toxicity, but its efficacy has not been proven. 

This anticonvulsant drug blocks voltage-gated sodium channels and inhibits release of glutamate. A controlled study found efficacy in PTSD (Hertzberg et al. 1999). Important side-effects include fever and skin reactions. 

Furthermore, clinical trials are performed in various cultural and geographical settings. Transcultural differences may play a significant role in drug efficacy e.g. oriental populations require much lower doses of antipsychotic drugs compared with Caucasian patient populations. Phase IV trials also may be performed to explore possible novel uses for compounds approved and marketed in other indications (e.g. treatment of anxiety disorders with antidepressants, treatment of bipolar disorder with anticonvulsants, etc.). 

Unlike most classes of psychotropic drugs where there is no direct correlation between the blood concentration and the therapeutic effect, for most of the commonly used anticonvulsants there is a high degree of correlation between the blood and brain concentrations and the therapeutic effect. A knowledge of the pharmacokinetic properties of the anticonvulsant drugs is therefore essential if their therapeutic efficacy is to be maximized and side effects minimized. 

Is the clinical efficacy of anticonvulsant drugs manifested immediately upon initiation... 

The anticonvulsant activity of a drug may also be evaluated by measuring its ability to raise the convulsive threshold, i.e. the amount of applied current or infused PTZ required to just evoke a seizure. Comparison of the efficacy of drugs in the threshold and maximal seizure tests may distinguish between their abilities to raise seizure threshold or reduce seizure spread and development. 

A complete dose-response analysis was generated for PCP for doses from 0.625 to 20 mg/kg IP (data not shown). PCP exhibited dose-related anticonvulsant action when day one minus day three differ ence scores were compared for all doses tested. When retested with saline only on day five, no reduction in convulsant sever it or super-sensitive response was observed (day one minus day five), indicating no carryover drug effect 48 hours after dosing. At behavioral ly equivalent doses, all compounds assayed were clearly anticonvulsant (table 3). TCP was most potent at the doses tested. PCA was the most efficacious, and reduced convulsant severity by 2.58 points. As with PCP, none of the other phencycli-noids had any carryover effects 48 hours after dosing (day one minus day five). 

Phenobarbital, carbamazepine, and phenytoin potentially reduce efficacy of OCs, and many anticonvulsants are known teratogens. The use of condoms in conjunction with high-estrogen OCs or intrauterine devices (IUDs) may be considered for women taking these drugs. 

Phenobarbital is effective orally and is distributed widely throughout the body. It is metabolized by microsomal drug-metabolizing enzymes, but up to 50% of the parent drug is excreted unchanged by the kidneys. Primidone is metabolized to phenobarbital and phenyl-ethylmalonamide. The latter metabolite has anticonvulsant activity, but most of the anticonvulsant efficacy of primidone is due to the phenobarbital that is produced. 

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