Grant: Operating Grant

Drug treatment is intended to provide patient therapy, but unfortunately drug treatment can also result in unexpected and harmful side-effects. Adverse drug reactions have been reported to cause 106 000 deaths per year in the US, and account for 2-6% of hospital admissions. The adverse drug reaction that I propose to study is drug-induced agranlulocytosis, a condition that causes patient's neutrophils (white blood cells) to drop to dangerously low levels. This condition will reduce a patient's capacity to combat infection, and could result in sepsis, and death. It has been proposed that myeloperoxidase, a neutrophil enzyme, can catalyze drug metabolism to form reactive metabolites that may cause this condition. It is not understood how such reactions may mediate agranulocytosis, however, I propose that some drugs will cause novel modifications to protein which can mediate the condition. The outcome of this research will aid in producing an animal model, which will allow further exploration of the mechanisms involved and methods to prevent this adverse drug reaction.