Role of viral infections in the induction of adverse drug reactions

A spectrum of adverse drug reactions that are caused by the combined action of drugs and viruses has been described: ampicillin rash in acute infectious mononucleosis; Reye's syndrome; hypersensitivity reactions to sulphonamides in patients with HIV infection; drug-induced agranulocytosis; paracetamol (acetaminophen) hepatotoxicity; aspirin (acetylsalicyclic acid)-induced asthma; Epstein-Barr virus-associated lymphoma and methotrexate; and AIDS-related Kaposi's sarcoma and nitrite use. Changes in pharmacokinetics have been reported for: caffeine, sulfamethoxazole and fluconazole in patients with HIV infection; theophylline, following influenza and influenza vaccination; and recently, dipyrone metabolites in carriers of the hepatitis B virus. In addition increased drug- and drug metabolite-related toxicity has been observed in virally infected cells. Pathogenetic mechanisms for the interaction between drugs and viruses are varied, and include biological mechanisms (often immunological) and changes in drug metabolism. The combined effects of chemical and biological exposure provide a unique model for the study of disease induction.