Antiepileptic drugs carbamazepine

Many authors reported poor elimination of antiepileptic drug carbamazepine [6,13,17,49, 54]. Pharmacokinetic data indicate that only 1-2% of carbamazepine is excreted unmetabolized. However, glucuronide conjugates of carbamazepine can presumably be cleaved in the sewage, and thus increase its environmental concentrations [51]. This is confirmed by its high ubiquity in the enviromnent at concentration levels of several hundred nanograms per liter in different surface waters. Due to its recalcitrant nature, it can be used as anthropogeiuc marker for the contamination of aquatic environment. 

Vogna D, Marotta R, Andreozzi R, Napolitano A, d Ischia M (2004) Kinetic and chemical assessment of the UV/H2O2 treatment of antiepileptic drug carbamazepine. Chemosphere... 

Ozonation of the antiepileptic drug carbamazepine resulted in the formation of three main DBFs l-(2-benzaldehyde)-4-hydro-(7//,i//)-quinazoline-2-one, l-(2-benzaldehyde)-(7/7,5/7)-quinazoline-2,4-dione, and l-(2-benzoic... 

Enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, and primidone) may decrease plasma levels of zonisamide... 

The rationale and use of modified-release formulations of antiepileptic drugs (carbamazepine, valproic acid, and tiagabine) have been reviewed (171). The authors concluded that modified-release formulations afford the advantages of better patient compliance, fewer adverse effects, and less fluctuation in plasma concentrations, making monitoring of drug concentrations easier. They concluded that these advantages should lead to better seizure control and improved quahty of life. 

Potschka, H., Fedrowitz, M., and Loscher. W. (2001) P-glycoprotein and multidrug resistance-associated protein are involved in the regulation of extracellular levels of the major antiepileptic drug carbamazepine in the brain. Neuroreport, 12 (16). 3557-3560. 

Drug Interactions Carbamazepine induces the hepatic metabolism of many drugs, including other antiepileptic drugs, antipsychotics, some antidepressants, oral contraceptives, and... 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

Tolerability" should not be confused with the term "tolerance", which describes the diminution in effects of a drug on prolonged exposure. Tolerance may be due to increased clearance because of autoinduction of the enzymes that metabolise the drug, such as occurs with some antiepileptic drugs, for example, carbamazepine. Tolerance may also result from altered pharmacodynamics, which is common with drugs acting on the CNS. 

M14. Meijer, J. W. A., Simultaneous quantitative determination of antiepileptic drugs including carbamazepine in body fiuids. Epilepsia 12, 341-352 (1971). 

From the clinical point of view, antiepileptic drugs are primarily divided into two categories those effective in treating major attacks (phenytoin, carbamazepine, mephobarbi-tal, and also primidone), and those effective in treating minor attacks (ethosuximide, acetazolamide, clonazepam, trimethadione, and valproic acid). 

From the chemical point of view, formally, antiepileptic drugs could be classified as derivatives of hydantoins (phenytoin, mephenytoin, ethotoin), barbiturates (phenobarbital, mephobarbital, and primidone), succinimides (ethosuximide, methosuximide, phensux-imide), benzodiazepines (diazepam, chlorodiazepoxide, clonazepam, lorazepam), oxazo-lidines (trimethadione, paramethadione), and also valproic acid, carbamazepine, and acetazolamide. 

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). 

The apparent clearance of lamotrigine is affected by the coadministration of AEDs. Lamotrigine is eliminated more rapidly in patients who have been taking hepatic enzyme inducing antiepileptic drugs (ElAEDs), including carbamazepine, phenytoin, phenobarbital, and primidone. 

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 ... 

Masland RL. Carbamazepine neurotoxicity. In Woodbury DM, Perry JK, PippingerCE, eds. Antiepileptic drugs. New York Raven Press, 1982 521-531. 

Praziquantel is a synthetic isoquinoline-pyrazine derivative. It is rapidly absorbed, with a bioavailability of about 80% after oral administration. Peak serum concentrations are reached 1-3 hours after a therapeutic dose. Cerebrospinal fluid concentrations of praziquantel reach 14-20% of the drug s plasma concentration. About 80% of the drug is bound to plasma proteins. Most of the drug is rapidly metabolized to inactive mono- and polyhydroxylated products after a first pass in the liver. The half-life is 0.8-1.5 hours. Excretion is mainly via the kidneys (60-80%) and bile (15-35%). Plasma concentrations of praziquantel increase when the drug is taken with a high-carbohydrate meal or with cimetidine bioavailability is markedly reduced with some antiepileptics (phenytoin, carbamazepine) or with corticosteroids. 

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

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. 

Some antiepileptic drugs have been associated with low serum and erythrocyte folate concentrations and high total plasma homocysteine concentrations in some patients. The concentrations of folate and homocysteine have been measured in 42 patients taking carbamazepine and 42 matched healthy controls (241). Patients taking carbamazepine had significantly lower serum and erythrocyte folate concentrations. There was hyperhomocystinemia (over 15 gmol/l) in 24% of the patients and 5% of the controls. 

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.)... 

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