Hypersensitivity, idiosyncratic

Chronic toxic effects are dose related and typically involve cerebellar and vestibular functions (nystagmus and ataxia). Nausea, dizziness, diplopia, behavioral changes, gingival hyperplasia, hirsutism, hyperglycemia, osteomalacia, pancytopenia, and skin eruptions are reported complications of chronic therapy. Hypersensitivity (idiosyncratic) reactions, including hepatic necrosis and Stevens-Johnson syndrome, can occur and are potentially fatal. 

Regrettably, all chemotherapeutic agents have the potential to produce adverse reactions with varying degrees of frequency and severity, and these include hypersensitivity reactions and toxic effects. These may be dose-related and predictable in a patient with a history of hypersensitivity or a previous toxic reaction to a drug or its chemical analogues. However, many adverse events are idiosyncratic and therefore unpredictable. 

Etiology probably multifactorial (i.e., hypersensitivity reactions, pharmacological action of the drug and/or metabolites, infusion-related, altered thermoregulation, idiosyncratic)... 

Sulfasalazine is associated with various adverse effects, most of which are thought to be due to the sulfapyridine component. Common adverse effects that may be dose related include headache, dyspepsia, nausea, vomiting, and fatigue.19 Idiosyncratic effects include bone marrow suppression, reduction in sperm counts in males, hepatitis, and pulmonitis. Hypersensitivity reactions may occur in patients allergic to sulfonamide-containing medications. 

A rare but serious event that can result from irreversible CYP inhibition is the development of a hypersensitivity reaction. The bioactivation of a drug and the formation of a covalent adduct between the activated substrate and the enzyme can lead to hapten formation and eventually to an idiosyncratic autoimmune response (usually in the form of autoimmune hepatitis) [14]. The hapten formation is the first key step toward the autoimmune response. The CYP macromolecule is made immunogenic ( foreign ) by the covalent binding of the electrophilic metabolites, and the immune reaction follows with the production of autoantibodies against the target molecule (not necessarily alkylated). 

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

Complete heart block idiosyncratic hypersensitivity lupus erythematosus torsades... 

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. 

Hepatic effects Fatal and nonfatal liver disorders of an idiosyncratic or hypersensitivity type may occur. At the start of therapy, perform baseline liver function studies. If abnormalities exist, the potential for hepatotoxicity could be enhanced. 

Carbamazepine causes a variety of rashes and other allergic reactions including fever, hepatosplenomegaly, and lymphadenopathy, but the incidence of serious hypersensitivity reactions is rare. Systemic lupus erythematosus can occur, but discontinuation of the drug leads to eventual disappearance of the symptoms. Idiosyncratic hematological reactions to carbamazepine... 

In some drug reactions, several of these hypersensitivity responses may present simultaneously. Some adverse reactions to drugs may be mistakenly classified as allergic or immune when they are actually genetic deficiency states or are idiosyncratic and not mediated by immune mechanisms (eg, hemolysis due to primaquine in glucose-6-phosphate dehydrogenase deficiency, or aplastic anemia caused by chloramphenicol). 

Hypersensitivity reactions are usually idiosyncratic and difficult, if not impossible, to predict in safety evaluation studies in experimental animals or humans. 

Classification of chemically induced hepatotoxicity is primarily based upon pattern of incidence and histopathological morphology. Intrinsic hepatotoxic drugs demonstrate a broad incidence, dose-response relationship and will usually give similar results in humans and experimental animals. The incidence of liver damage from idiosyncratic hepatotoxicants is limited to susceptible individuals and results from hypersensitivity reactions or unusual metabolic conversions that can occur due to polymorphisms in drug metabolism genes (see Chapters 11 and 13). 

The mechanism for most NSAID-induced hepatotoxic reactions is idiosyncratic, either immunological (hypersensitivity) or metabolic in type [29]. 

Initially, unspecific complaints frequently include nausea, inappetence and fatigue. In some patients, idiosyncratic hepatocellular damage may be accompanied by hypersensitive reactions (e.g. fever, exanthema, eosino-philia, lymphocytosis, arthralgia). 

A 66-year-old man with giant cell arteritis and hypertension developed a hjrpersensitivity reaction 4.5 weeks after starting to take terbinafine, with a skin emption, fever, Ijmphadenopathy, and hepatic dysfnnction (63). Concomitant medications included prednisone, doxazosin, and aspirin. His symptoms and signs resolved within 6 weeks after withdrawal of terbinafine and continuation of aU the other medications. The hypersensitivity sjmdrome reaction in this case was idiosyncratic, with no apparent predisposing factors. 

Yet another classification system refers to the nature of the host s response to the causative agent. Some agents, referred to as intrinsic hepatotoxicants, will cause hepatotoxicity in most individuals of most species. In the case of idiosyncratic hepatotoxicants, where a chemical s toxic effects are a function of unusual susceptibility of the exposed individual, it may not be clear whether the lesion is a manifestation of the hepatotoxic properties of the substance in question or a manifestation of the individual s untoward response to the agent. This response may mean hypersensitivity (allergic) reactions or exaggerated responses to minor alterations in liver function. For example, anabolic or contraceptive steroids cause diminished biliary excretion (cholestasis) in most... 

Rare adverse cardiac effects have been reported secondary to ranitidine. These effects may be either due to direct ranitidine blockade of cardiac H2 receptors or due to potentiation of acetylcholine activity on the heart by ranitidine-induced inhibition of acetylcholinesterases. Ranitidine-induced hepatic injury is thought to be secondary to an idiosyncratic reaction or a hypersensitivity reaction. 

Acrodynia is an idiosyncratic hypersensitivity response from exposure to mercury and is characterized by certain cardiovascular, dermal, and neurological effects, among others. In the section on health effects by route of exposure, the relevant symptoms are discussed under the appropriate headings without reference to the syndrome. This occurs, in part, because there is some overlap between symptoms characteristic of acrodynia and those seen in persons who are not hypersensitive and, in part, because not every report of a study in which the symptoms were observed states whether the authors considered the affected person to have suffered from acrodynia. 

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