Carbamazepine pharmacological effects

Bertilsson L, Tomson T. Clinical pharmacokinetics and pharmacological effects of carbamazepine and carbamazepine-10,11-epoxide. Clin Pharmacokinei 1986 11 177-198. 

C. S. Effect of baclofen enantiomorphs on the spinal trigeminal nucleus and steric similarites of carbamazepine. Pharmacology 1983, 27, 85-94. 

The therapeutic concentration range for optimal pharmacological effect of carbamazepine is 4 to 12p,g/mL. Toxicity associated with excessive carbamazepine ingestion occurs at plasma concentrations in excess of 15p.g/mL and is characterized by symptoms of blurred vision, paresthesia, nystagmus, ataxia, drowsiness, and diplopia. Side effects unrelated to plasma concentration include development of an urticarial rash, which usually disappears on discontinuation of the drug, and hematological depression (leukopenia, thrombocytopenia, and aplastic anemia). 

PHARMACOLOGICAL EFFECTS AND MECHANISM OF ACTION Zonisamide inhibits both the T-type Ca-+ currents and the sustained, repetitive firing of spinal cord neurons, presumably by prolonging the inactivated state of voltage-gated Na+ channels in a manner similar to that of phenytoin and carbamazepine. 

Oral absorption of carbamazepine is quite slow and often erratic. Its half-life is reported to vary from 12 to 60 hours in humans. The development of blood level assays has markedly improved the success of therapy with this drug, since serum concentration is only partially dose related. Carbamazepine is metabolized in the liver, and there is evidence that its continued administration leads to hepatic enzyme induction. Carbamazepine-10,11-epoxide is a pharmacologically active metabolite with significant anticonvulsant effects of its own. 

Oxcarbazepine is chemically and pharmacologically closely related to carbamazepine, but it has much less capacity to induce drug-metabolizing enzymes. This property decreases the problems associated with drug interactions when oxcarbazepine is used in combination with other drugs. The clinical uses and adverse effect profile of oxcarbazepine appear to be similar to those of carbamazepine. 

Stemebring B., A. Linden, K. Anderson, and A. Melander (1992). Carbamazepine kinetics and adverse effects during and after ethanol exposure in alcoholics and healthy volunteers. European Journal of Clinical Pharmacology 43 393-397. 

If these measures fail, clonidine, fluphenazine, clonazepam, or carbamazepine should be tried. The pharmacologic properties of these drugs are discussed elsewhere in this book. Clonidine reduces motor or vocal tics in about 50% of children so treated. It may act by reducing activity in noradrenergic neurons in the locus coeruleus. It is introduced at a dose of 2-3 mcg/kg/d, increasing after 2 weeks to 4 mcg/kg/d and then, if required, to 5 mcg/kg/d. It may cause an initial transient fall in blood pressure. The most common adverse effect is sedation other adverse effects include reduced or excessive salivation and diarrhea. Phenothiazines such as fluphenazine sometimes help the tics, as do dopamine... 

Pharmacologic treatment of RLS includes dopaminergic agents, benzodiazepines, opioids, or anticonvulsants. In mild cases of RLS, benzodiazepines may be first-line agents. Clonazepam, lorazepam, triazolam, and temazepam have been effective. Clonazepam 0.5 to 2 mg is most frequently studied. Opiates such as methadone 5 to 20 mg, codeine 30 to 120 mg, and oxycodone 2.5 mg are very effective, but the development of tolerance is a concern. Abuse potential with opiates is also a concern due to the chronic nature of the condition. Other agents that have been used include apomorphine, amantadine, tramadol, magnesium, oxycodone, propoxyphene, gabapentin, bromocriptine, clonidine, and carbamazepine. Tolerance may de-... 

Phenobarbital has been shown to decrease serum carbamazepine half-life and plasma concentration levels when given in combination. Significant changes in carbamazepine serum concentrations were seen within 5 days after the addition of phenobarbital to the therapeutic regimen. Conversely, carbamazepine appears to have no effect on serum phenobarbital levels. It has been reported to lower serum concentrations of primidone, but the decrease does not appear to be clinically significant. Other barbiturates (e.g., amobarbital, butabarbital, secobarbital) may interact in a manner similar to phenobarbital because of pharmacologic similarity. 

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