Archive for the ‘Antiepileptics’ Category


Diagnosis is dependent on clinical recognition and judgment. The lymphocyte toxicity assay is expensive and cumbersome to perform; it is only used in certain research centres. Some studies have evaluated the usefulness of patch testing in the diagnosis of anticonvulsant HSR. However, most of the studies have shown inconsistent results. For example, in five patients with systemicsymptoms, oral challenges were performed with positive results; two of these patients had negative patch tests. If patch testing is to be carried out in these patients, 1% or 10% carbamazepine or phenytoin in petrolatum compound is recommended. In addition, at least two months should elapse from the eruption to the testing date.

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MULTISYSTEMIC ADVERSE EFFECTS(2)

HSR has been associated with the aromatic anticonvulsants, namely phenytoin, phenobarbital and carbamazepine and lamotrigine . In many of the case reports, the hypersensitivity syndrome is often not recognized or diagnosed as an entity. In fact, the adverse event is likely to be reported as either the most prominent or most severe organ manifestation. For example, there are a large number of cases in the literature that have been termed ‘hep-atotoxicity’, yet closer investigation of these cases reveals that a rash and fever were also evident, heralding a diagnosis of HSR . It has been suggested that the formation of toxic metabolites by phenytoin, carbamazepine and phenobarbital may play a pivotal role in the development of the HSR (Figure 1) . Phenytoin, carbamazepine and phenobarbital are metabolized by cytochrome P450 to an arene oxide metabolite. This metabolite is usually detoxified by epoxide hydrolase; however, if detoxification is defective, the toxic metabolite may act as a hapten and initiate an immune response, or cell necrosis or apoptosis. (more…)

Anticonvulsant HSR

A triad of fever, skin eruption and internal organ involvement signal anticonvulsant HSR, a potentially life-threatening syndrome (Figure 1). HSR occurs most frequently with the first exposure to the drug, with initial symptoms starting one to six weeks after exposure to the drug. In previously sensitized individuals, anticonvulsant HSR may occur within one day on rechallenge. This reaction occurs in approximately one/ 10,000 exposures; anticonvulsants, sulphonamide antibiotics, dapsone and allopurinol have been most frequently associated with HSR.

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The pathogenesis of these severe cutaneous adverse drug reactions (ADRs) is unknown, although a metabolic basis has been hypothesized . Sulphonamides and aromatic anticonvulsants (ie, phenobarbital, phenytoin, carbamazepine), which are the two groups most frequently associated with SJS and TEN, are metabolized to toxic metabolites, which are subsequently detoxified in most individuals. However, in predisposed patients with a genetic defect, the metabolite may bind covalently to proteins. In some patients, the metabolite-protein adducts may trigger an immune response, which may lead to a cutaneous ADR.

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DERMATOLOGICAL ADVERSE EFFECTS(3)

Coarsening of facial features, which includes enlargement of the lips and nose and thickening of the face and scalp, can occur in up to 30% of phenytoin-treated patients. As well, 58% of patients on phenytoin may develop heel pad thickening, which increases with the duration of anticonvulsant therapy.

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Cutaneous reactions are the most common reason for la-motrigine discontinuation, with 2% to 3% of patients requiring drug withdrawal in clinical studies . Factors that increase the risk of rash with lamotrigine include higher plasma concentrations, coadministration with valproic acid and exceeding the recommended dose escalation schedule . Valproic acid interacts with lamotrigine metabolism, leading to a reduced total clearance and a marked increase of the elimination half-life of lamotrigine. Getting high quality medications online is becoming more and more affordable: visit this respectable canadian family pharmacy com and find out more about the options you have when buying drugs from the comfort of your home.

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DERMATOLOGICAL ADVERSE EFFECTS(1)

A number of factors need to be considered in the choice of an anticonvulsant, including efficacy, pharmacokinetics, cost, teratogenic effects and potential adverse effects of the drug, and age and sex of the patient. Adverse effects, which are observed in up to one-third of patients on anticonvulsant therapy, are generally divided into two groups – common dose-related toxicity and the rarer and unpredictable idiosyncratic toxicity. This review discusses both types of adverse events associated with the anticonvulsants according to the organ system affected. However, issues that will not be addressed include drug interactions, teratogenicity and seizure-inducing effects of anticonvulsant medications.

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