Drugs idiosyncratic reactions

Idiosyncratic dmg reactions (IDRs) are most commonly characterized by a reaction involving fever or rash, with or without internal organ involvement. The spectrum of responses ranges from a minor rash, to potentially fatal toxic epidermal necrosis and Stevens-Johnson syndrome. Immunoglobulin E (IgE)-mediated anaphylactic shock, occasional joint pain, hepatotoxicity or nephrotoxicity are also well documented [24]. The frequency of such reactions are unknown but estimated to be between 1 1000 and 1 10000 exposures and may be enhanced on re-challenging susceptible individuals with the same dmg. 

---

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

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. 

Uetrecht J. Idiosyncratic drug reactions Current understanding. Annu Rev Pharmacol Toxicol 2007 47 513-539. 

Uetrecht J. N-oxidation of drugs associated with idiosyncratic drug reactions. Drug Metab Rev 2002 34(3) 651-665. 

Boelsterli UA. Xenobiotic acyl glucuronides and acyl CoA thioesters as protein-reactive metabolites with the potential to cause idiosyncratic drug reactions. Curr Drug Metab 2002 3(4) 439-450. 

Ju, C. andUetrecht, J.P. (2002) Mechanism of idiosyncratic drug reactions reactive metabolites formation, protein binding and the regulation of the immune system. Current Drug Metabolism, 3, 367-377. 

Dieckhaus, C.M. etal. (2002) Mechanisms of idiosyncratic drug reactions the case of felbamate. Chemico-Biological Interactions, 142 (1-2), 99-117. 

Uetrecht, J. (2008) Idiosyncratic drug reactions past, present, and future. Chemical Research in Toxicologf, 21 (1), 84-92. 

Popovic, M., Nierkens, S., Pieters, R. and Uetrecht, J. (2004) Investigating the role of 2-phenylpropenal in felbamate-induced idiosyncratic drug reactions. Chemical Research in Toxicology, 17, 1568-1576. 

Pirmohamed M, Madden S, Park BK. Idiosyncratic drug reactions metabolic bioactivation as a pathogenic mechanism. Clin Pharmacokinet 1996 31 215-230. 

---