Drug idiosyncratic

Williams DP, Park BK. Idiosyncratic toxicity the role of toxicophores and bioactivation. Drug Discov Today 2003 8 1044-50. 

Uetrecht J. Screening for the potential of a drug candidate to cause idiosyncratic drug reactions. Drug Discov Today 2003 8 832-7. 

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)... 

Drug Mechanism of Action Dose Pharmacokinetic Usual Serum Parameters Concentration Range Dose-Related Adverse Effects Idiosyncratic Adverse Effects... 

Once the loading dose of the AED is administered, it is important to remember to initiate maintenance doses to ensure that therapeutic levels are sustained. Chronic and idiosyncratic side effects as well as potential drug interactions should be considered if the patient will continue AED therapy indefinitely. All drug therapy should be adjusted for any hepatic or renal disease states. Table 28-1 summarizes the drug doses used in SE, and Table 28-2 provides an example of an algorithm for the treatment of patients in SE. Published studies comparing these treatment strategies are summarized in Table 28-3. 

Genetic variants resulting in an unintended action of a drug outside of its therapeutic indication (Idiosyncratic)... 

The presence of chemically reactive structural features in potential drug candidates, especially when caused by metabolism, has been linked to idiosyncratic toxicity [56,57] although in most cases this is hard to prove unambiguously, and there is no evidence that idiosyncratic toxicity is correlated with specific physical properties per se. The best strategy for the medicinal chemist is avoidance of the liabilities associated with inherently chemically reactive or metabolically activated functional groups [58]. For reactive metabolites, protein covalent-binding screens [59] and genetic toxicity tests (Ames) of putative metabolites, for example, embedded anilines, can be employed in risky chemical series. 

Sulfasalazine is often associated with either dose-related or idiosyncratic adverse drug effects. Dose-related side effects usually include GI disturbances such as nausea, vomiting, diarrhea, or anorexia, but may also include headache and arthralgia. 

Ultrecht, J., Is it possible to more accurately predict which drug candidates will cause idiosyncratic drug reactions Curr. Drug Metab., 1, 133, 2000. 

Uetrecht, J.P., Drug metabolism by leukocytes, its role in drug-induced lupus and other idiosyncratic drug reactions, CRC Crit. Rev. Toxicol., 20, 213, 1990. 

Pirmohamed, M. et al., The danger hypothesis—potential role in idiosyncratic drug reactions, Toxicology, 181, 55-63, 202. 

Seguin, B., and Uetrecht, J., The danger hypothesis applied to idiosyncratic drug reactions, Curr. Opin. Allergy Clin. Immunol., 3, 235, 2003. 

Shenton, J.M. et al., Characterization of a potential animal model of an idiosyncratic drug reaction Nevirapine-induced skin rash in the rat. Chem. Res. Toxicol., 16, 1078, 2003... 

Shenton, J.M., Chen, J., and Uetrecht, J.P. (2004) Animal models of idiosyncratic drug reactions. Chem. Biol. Interact., 150, 53, 2004. 

Knowles, S.R., Uetrecht, J., and Shear, N.H., Idiosyncratic drug reactions The reactive metabolite syndromes, Lancet, 356, 1587, 2000. 

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