Idiosyncratic side effects of drugs

Genetic mechanisms may underlie individual susceptibility to side effects, e.g. G6PD deficiency (see Chapter 14). Genetic traits may also influence drug metabolism, e.g. some individuals metabolize purines so that antipurine drugs, e.g. 6-mercaptopurine, azathioprine, are more likely to cause bone marrow suppression. Others are very sensitive to cyclophosphamide or to warfarin.

Recognizing, monitoring and reporting haematologic toxicity are important parts are of the marketing and post-marketing surveillance and assessment of new drugs. Mechanisms of haematologic toxicity include the following:

• Direct toxicity of the drug or its metabolites to haemopoietic stem cells or more mature cells;
  
• Induction of immune-mediated damage to haematologic stem cells;
  
• Effects on folate metabolism;
  
• Indirect effects via damage to other organs, e.g. the liver; and
  
• Predisposition to malignant change.

Drug-induced haematological abnormalities