Antiepileptic drug toxicity

Leone, A.M. et al. (2007) Evaluation of felbamate and other antiepileptic drug toxicity potential based on hepatic protein covalent binding and gene expression. Chemical Research in Toxicology, 20 (4), 600-608. 

Gait Do not test in hospitalized patient (ask the patient if he/she has been walking) observe patient walking normally, heel-to-toe, and turning. Stroke, vertigo, Parkinson s disease, antiepileptic drug toxicity... 

Treatment of epilepsy is often more complex in the elderly (Tallis et al. 2002). Plasma concentration of antiepileptic drugs that are adequate for younger patients may be toxic for older adults. Clinical response, and not only plasma concentration of the drug, is more important in the elderly for evaluation of antiepileptic treatment. 

This is a widely used antiepileptic drug, which occasionally causes liver dysfunction. There are two types of dysfunction, the first type is a mild transient elevation of the transaminases (ALT, AST), which resolves the second type is of a more severe hepa to toxicity, manifested as fatty liver with jaundice and necrosis, which may lead to fatal liver failure. 

Regarding the usefulness in measuring the serum concentrations of antiepileptic drugs, it is often of value to do so with those drugs that are liable to cause toxic side effects such as carbamazepine, ethosuximide, phenobarbitone and phenytoin. In general, there seems to be little advantage in determining the serum concentrations of the newer, and better tolerated, antiepileptics. 

Holmes GL. Carbamazepine toxicity. In Levy RH, Mattson RH, Meldrum BS, eds. Antiepileptic Drugs. 4th ed. New York Raven Press, 1995 567-579. 

Chloramphenicol Palmitate Chloramphenicol has concentration-dependent incompatibility with many drugs. Chloramphenicol has severe toxic effects, and overdose may be treated by hemoperfusion of charcoal. It interacts with coumarin anticoagulants, some oral hypoglycemics, antiepileptic drugs, and nutrients such as iron and vitamin B12. 

Schmidt D. Connective tissue disorders induced by antiepileptic drugs. In Oxley J, Janz D, Meinardi H, editors. Chronic Toxicity of Antiepileptic Drugs. New York Raven Press, 1983 115. 

Piperonyl butoxide, isoniazid, and SKF 525A and related chemicals are inhibitors of various xenobiot-ic-metabolizing enzymes. For instance, piperonyl butoxide increases the toxicity of pyrethrum (an insecticide) by inhibiting MFO activity in insects that detoxifies this agent. Isoniazid, when taken along with phenytoin, lengthens the plasma half-life of the antiepileptic drug and increases its toxicity. Iproniazid inhibits monoamine oxidase and increases the cardiovascular effects of tyramine, which is found in cheese and which is normally readily metabolized by the oxidase. 

Epilepsy Antiepileptic drugs, surgery Medication serum concentrations, sedation, cognitive abilities, liver function tests, blood dyscrasias, bleeding abnormalities, CNS toxicities, rashes, seizure counts, other drug-specific adverse effects... 

Clinical evidence indicates that epileptic patients are either slow or rapid metabohzers of phenytoin. hi the slow metabo-lizers, 4 mg/kg of phenytoin may produce toxicity, whereas, in the rapid metabohzers, this may be a subtherapeutic dose. In addition, the results of randomized, double-blind, controlled clinical trials of antiepileptic drugs conducted in adult patients with mostly partial onset or generalized tonic-clonic seizures, or both, have shown that there are considerable individual differences between patients responses to the same drug. Side effects are common with all of the antiepileptic drugs. 

Disubstituted derivatives of barbituric acid 25 (barbiturates) are used therapeutically. 5,5-Diethylbarbituric acid 36 was the first barbiturate to be used (E. Fischer 1903, veronal, barbital). Barbital and its Na salts are sedatives, as are phenobarbital 37 and hexobarbital 38, which are more potent [145]. Methylphenobarbital 39 is an antiepileptic drug and the thiobarbiturate thiopental 40 is a short-acting anaesthetic. Sedative barbiturates have now been replaced by other drugs because of their toxicity and dependence problems. 

It must be emphasized that the combination of extra-pyramidal and cerebellar dysfunction is quite characteristic for hepatic encephalopathy, and cannot be found in any other kind of metabolic encephalopathy, except Wilson s disease. Asterixis, however, which is considered a classic sign of HE, is also seen in other metabohe or toxic encephalopathies, such as urania, CO retention, hypomagnesemia or intoxication with antiepileptic drugs, for example. 

Patients with Stevens—Johnson syndrome or toxic epidermal necrolysis due to antiepileptic drugs have been compared with patients with antiepileptic drug-related hypersensitivity syndrome the results are shown in Table 1 [79 ]. The authors concluded that these cutaneous syndromes may share some clinical and laboratory features. 

Genetic factors associated with severe adverse skin reactions induced by antiepileptic drugs in different ethnic populations have been discussed [80 , 81" ]. Several studies have shown that Han Chinese patients carrying the HLA-B 1502 are at high risk of Stevens-Johnson syndrome or toxic epidermal necrolysis when exposed to carbamazepine. 

HLA-B 1301, Cw 0801, and DRB1 1602 also showed an association with phenytoin. The authors concluded that HLA-B 1502 is a susceptibility factor for Stevens-Johnson syndrome/toxic epidermal necrolysis in patients taking these aromatic antiepileptic drugs, as has previously been shown with carbamazepine. 

Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS, Hui RC, Chu CY, Chen YT. Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics 2010 11(3) 349-56. 

Drug overdose Of 16 796 toxic exposures to antiepileptic drugs (phenytoin, valproic acid, and carbamazepine) in the USA in 2006, 12 resulted in death, as reported by the US Toxic Surveillance System [67 ]. Some specific problems determined by overdose of some old and new antiepileptic drugs have been briefly reviewed. For example, topiramate can cause a significant metabolic acidosis, lamotrigine Stevens-Johnson syndrome, oxcarbazepine hyponatremia, and levetiracetam psychosis. Possible adoption of guidelines for critical care management of overdose are discussed. 

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