Mechanism of Idiosyncratic Drug Reactions: Reactive Metabolites Formation, Protein Binding and the Regulation of the Immune System

2002 ◽  
Vol 3 (4) ◽  
pp. 367-377 ◽  
Author(s):  
C. Ju ◽  
J. Uetrecht
Keyword(s):  
Immune System ◽  
Protein Binding ◽  
Reactive Metabolites ◽  
Idiosyncratic Drug Reactions ◽  
Drug Reactions

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.

Corrections to “Involvement of the Immune System in Idiosyncratic Drug Reactions”

2011 ◽  
Vol 26 (4) ◽  
pp. 440
Author(s):  
Xiachu Zhang ◽  
Feng Liu ◽  
Xin Chen ◽  
Xu Zhu ◽  
Jack Uetrecht
Keyword(s):  
Immune System ◽  
Idiosyncratic Drug Reactions ◽  
Drug Reactions

Involvement of the Immune System in Idiosyncratic Drug Reactions

2011 ◽  
Vol 26 (1) ◽  
pp. 47-59 ◽  
Author(s):  
Xiachu Zhang ◽  
Feng Liu ◽  
Xin Chen ◽  
Xu Zhu ◽  
Jack Uetrecht
Keyword(s):  
Immune System ◽  
Idiosyncratic Drug Reactions ◽  
Drug Reactions

scholarly journals The Wonderful DMARD with Multiple Toxicities

2021 ◽  
Vol 5 (7) ◽  
pp. RV5-RV10
Author(s):  
Yashika Kaushal ◽  
Ratibha Kausal ◽  
Isha Sharma
Keyword(s):  
Immune System ◽  
Adverse Drug Reactions ◽  
Adverse Reactions ◽  
Close Monitoring ◽  
Drug Reactions ◽  
Therapy Discontinuation ◽  
Chemotherapy Agent ◽  
Reduce Activity ◽  
Potential Risk Factors ◽  
Rheumatic Drug

Methotrexate is a type of disease-modifying anti-rheumatic drug (DMARD). It is used to reduce activity of the immune system for people who have certain conditions. Methotrexate is a chemotherapy agent and immune system suppressant. Its use may be limited by concerns regarding its adverse reactions. The occurrence of adverse drug reactions in some cases leads to the therapy discontinuation. Although adverse drug reactions (ADR) of methotrexate generally do not pose a serious threat to the health of patients and a reduction in the dose of methotrexate leads to their elimination, in some cases severe toxicities of the drug occur unpredictably. These facts explain the need for close monitoring of the patient’s condition and the identification of potential risk factors for drug toxicity on the part of different organs and functional systems. The purpose of this review is to detail about safety and tolerability of methotrexate.

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