Xenobiotic Acyl Glucuronides and Acyl CoA Thioesters as Protein- Reactive Metabolites With the Potential to Cause Idiosyncratic Drug Reactions

2002 ◽  
Vol 3 (4) ◽  
pp. 439-450 ◽  
Author(s):  
Urs Boelsterli
Keyword(s):  
Reactive Metabolites ◽  
Idiosyncratic Drug Reactions ◽  
Drug Reactions ◽  
Acyl Glucuronides ◽  
Coa Thioesters

Myeloperoxidase as a generator of drug free radicals

1995 ◽  
Vol 61 ◽  
pp. 163-170 ◽  
Author(s):  
Jack P. Uetrecht
Keyword(s):  
Neutrophil Function ◽  
Reactive Metabolites ◽  
Therapeutic Effects ◽  
Aminosalicylic Acid ◽  
Idiosyncratic Drug Reactions ◽  
Drug Reactions ◽  
Drug Induced ◽  
Nitrenium Ion ◽  
High Incidence ◽  
Inflammatory Bowel

Reactive metabolites are believed to be responsible for many types of toxicity, including idiosyncratic drug reactions. Bone marrow is a frequent target of idiosyncratic reactions, and, since these reactions have characteristics that suggest involvement of the immune system, the formation of reactive metabolites by leucocytes could also play a role in the aetiology of idiosyncratic drug reactions. The major oxidation system in neutrophils and monocytes is a combination of NADPH oxidase and myeloperoxidase. This system oxidizes primary arylamines, such as sulphonamides, to reactive metabolites and these drugs are also associated with a high incidence of agranulocytosis, generalized idiosyncratic reactions and/ or drug-induced lupus. Clozapine is oxidized by this system to a relatively stable nitrenium ion; clozapine is also associated with a high incidence of agranulocytosis. Arylamines that have an oxygen or nitrogen in the para position, such as amodiaquine, vesnarinone and 5-aminosalicylic acid, are oxidized to quinone-like reactive intermediates. Aminopyrine is oxidized to a very reactive dication. Such reactive metabolites could also inhibit neutrophil function and mediate some of the therapeutic effects of these drugs: for example, the use of dapsone for dermatitis herpetiformis and the use of 5-aminosalicylic acid for inflammatory bowel disease.

Reactive metabolites and their role in drug reactions

2001 ◽  
Vol 1 (4) ◽  
pp. 317-325 ◽  
Author(s):  
Dean J. Naisbitt ◽  
Dominic P. Williams ◽  
Munir Pirmohamed ◽  
Neil R. Kitteringham ◽  
B. Kevin Park
Keyword(s):  
Reactive Metabolites ◽  
Drug Reactions

Reactive metabolites and their role in drug reactions

2001 ◽  
Vol 1 (4) ◽  
pp. 317-325 ◽  
Author(s):  
Dean J. Naisbitt ◽  
Dominic P. Williams ◽  
Munir Pirmohamed ◽  
Neil R. Kitteringham ◽  
B. Kevin Park
Keyword(s):  
Reactive Metabolites ◽  
Drug Reactions
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