Idiosyncratic reaction

An idiosyncratic reaction is a harmful, sometimes fatal reaction, that occurs in a small minority of individuals. The reaction may occur with low doses of drags. Genetic factors may be responsible, e.g. glucose-6-phosphate dehydrogenase deficiency, although the cause is often poorly understood. 

R. H. Lavey, and J. K. Penny (eds.), Idiosyncratic Reactions to Valproate Clinical Risk Patterns and Mechanism of Toxicity, Raven Press, New York, 1991, pp. 19-24. 

Excessive doses of thyroid hormone may lead to heart failure, angina pectoris, and myocardial infarction. Allergic or idiosyncratic reactions can occur with the natural animal-derived products such as desiccated thyroid and thyroglobulin, but they are extremely rare with the synthetic products used today. Excess exogenous thyroid hormone may reduce bone density and increase the risk of fracture. 

Ester glucuronides are somewhat chemically reactive and can covalently bind to protein. It has been proposed that this type of metabolite is responsible for the idiosyncratic reactions associated with several drugs that are carboxylic acids as discussed in Chapter 8. 

Dieckhaus C, Miller T, Sofia RD, et al. A mechanistic approach to understanding the species differences in felbamate bioactivation relevance to drug-induced idiosyncratic reactions. Chem... 

This statement is somewhat at odds with the conventional view that idiosyncratic toxicology is dose-size independent. Idiosyncratic reactions are thought to result from an immune-mediated cell injury triggered by previous contact with the drug. The toxicity may appear after several asymptomatic administrations of the com-... 

Elevated blood pressure In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. Monitor blood pressure at regular intervals with estrogen use. 

Isosorbide dinitrate Allergic reactions to isosorbide dinitrate or any of its ingredients. Isosorbide mononitrate Hypersensitivity or idiosyncratic reactions to other nitrates or nitrites. 

Test dose Administer a single 200 mg tablet of quinidine sulfate or 200 mg IM quinidine gluconate to determine whether the patient has an idiosyncratic reaction. Adjust the dosage to maintain plasma concentration between 2 to 6 mcg/mL. 

Monitoring Observe for blood dyscrasias, liver or kidney damage, or idiosyncratic reactions. Perform frequent serum electrolyte, calcium, glucose, uric acid, CO2,... 

When triamterene is added to other diuretic therapy, or when patients are switched to triamterene from other diuretics, discontinue potassium supplementation. Hypersensitivity reactions Monitor patients regularly for blood dyscrasias, liver damage, or other idiosyncratic reactions. 

Potentially alarming idiosyncratic reactions may occur with therapeutic doses. Pregnancy Category C. Use in pregnancy only if potential benefits justify potential risk to the fetus. 

Acute intermittent porphyria allergic or idiosyncratic reactions to meprobamate or... 

Adverse reactions may include drowsiness ataxia dizziness slurred speech headache vertigo weakness impairment of visual accommodation euphoria overstimulation paradoxical excitement nausea vomiting diarrhea palpitations tachycardia various arrhythmias syncope hypotensive crises allergic/idiosyncratic reactions leukopenia acute nonthrombocytopenic purpura petechiae ecchymoses eosinophilia peripheral edema fever hyperpyrexia chills angioneurotic edema bronchospasm oliguria anuria anaphylaxis erythema multiforme exfoliative dermatitis stomatitis proctitis Stevens-Johnson syndrome bullous dermatitis paresthesias agranulocytosis aplastic anemia thrombocytopenic purpura. 

Whilst this may explain potentially explain many cases, this does not represent the full mechanism which is undoubtedly more complex as not all reactions appear to be immunological. For example, paracetamol is known to form reactive intermediates but yet is not involved in idiosyncratic reactions. Indeed, with some notable exceptions such as the penicillins, many drugs involved in idiosyncratic reactions do not mediate their toxicity through a immune response. 

Where drug are shown to form reactive intermediates by specific enzyme systems, it might be expected that the polymorphism or absence of these systems would track idiosyncratic reactions but to date no such link has been established. In fact, the most confounding element of idiosyncratic reactions is their unpredictable nature and whilst reactive intermediates may present a risk factor the true nature of the response is likely to be multifactorial. Changes in dmg metabolizing capacity, affecting the balance of bioactivation and bioinactivation processes which may be mediated through concomitant infection may also be a contributory factor. 

An alternative theory to the hapten hypothesis that goes some way to explain why not all drugs that form reactive intermediates are associated with idiosyncratic reactions... 

Retinitis pigmentosa and agranulocytosis are rare idiosyncratic reactions. During treatment with clozapine leucocyte counts should be carried out frequently, especially the first few month, as there is a considerable risk of agranulocytosis. 

Haloperidol is less likely to cause hypotension than chlorpromazine, which has a-adrenoceptor antagonist effects. Both can cause cardiac arrhythmias if used in high dosage or in patients with pre-existing heart disease, or as an idiosyncratic reaction. There have been numerous reports of sudden and unexplained deaths, probably due to cardiac arrhythmia, in patients given chlorpromazine and other neuroleptics. The risk of serious arrhythmia is higher in the obese, and possibly in those of African ancestry. 

A variety of idiosyncratic reactions may be seen shortly after therapy has begun. Skin rashes, usually morbilliform in character, are most common. Exfoliative dermatitis or toxic epidermal necrolysis (Lyellis syndrome) has been observed but is infrequent. Other rashes occasionally have been reported, as have a variety of blood dyscrasias and hepatic necrosis. 

Agranulocytosis is a potentially catastrophic idiosyncratic reaction that usually appears within the first 3 months of therapy. Although the incidence is extremely low (except for clozapine), mortality is high. Thus, any fever, sore throat, or cellulitis is an indication for discontinuing the antipsychotic and immediately conducting white blood cell and differential counts. 

Hepatic dysfunction and urinary abnormalities were seen In some subjects after CS exposure at Edgewood. Little is known of the effects of CS on the kidneys and liver. The small proportion of subjects who had abnormal urinalysis (7 of 50 14Z) and high transaminase (3 of 50 6Z) Indicates Idiosyncratic reactions, If the abnormalities were indeed due to CS exposure. The most likely course of idiosyncratic drug-induced, nonfulmlnant hepatitis is complete recovery after removal of the agent. Recurrence of hepatic reactions would be expected on re-exposure to CS If the original transaminase Increases were due to CS. 

The nephrotic syndrome, characterized clinically by proteinuria, is a rare and idiosyncratic reaction to lithium. As with other uncommon adverse effects, the issue of causation versus coincidence must be considered. Treatment includes cessation of the drug and, when necessary, corticosteroids such as prednisone ( 322). 

Serious hepatotoxicity is possibie but rare. Hepatic failure occurs in only one in 40,000 cases and appears to be an idiosyncratic reaction that is not dose-related. Children under the age of 2, especially those receiving anticonvulsant polypharmacy, with mental retardation, and/or with poor nutritional status have been shown to be at greatest risk (351, 352). To our knowledge, no cases of hepatic failure have been reported in adults with bipolar disorder who were receiving VPA monotherapy, but liver failure has been reported in older children and in a mentally retarded adult with epilepsy taking VPA alone ( 77, 352, 353). 

Considerable concern exists regarding the occurrence of idiosyncratic blood dyscrasias with carbamazepine, including fatal cases of aplastic anemia and agranulocytosis. Most of these have been in elderly patients with trigeminal neuralgia, and most have occurred within the first 4 months of treatment. The mild and persistent leukopenia seen in some patients is not necessarily an indication to stop treatment but requires careful monitoring. The most common idiosyncratic reaction is an erythematous skin rash other responses such as hepatic dysfunction are unusual. 

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