Pharamacology Flashcards
Allopurinol is most likely to precipitate methotrexate toxicity by which one of the following mechanisms?
Methotrexate competitively inhibits the enzyme folic acid reductase.
Methotrexate inhibits the reduction of folic acid and interferes with tissue cell reproduction. Its main effect is directed to the S phase of cell division. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, dermal epithelium, buccal and intestinal mucosa and cells of the urinary bladder are sensitive to the effects of methotrexate.
Patients must have relatively normal kidney function to excrete the drug adequately and avoid excessive toxicity.
Allopurinol inhibits xanthine oxidase, the enzyme which converts hypoxanthine to xanthine, and of xanthine to urate/uric acid. Because allopurinol decreases urate formation, it reduces uric acid concentrations in both body fluids and urine. Therapeutic effects therefore include gouty arthritis, prevention and treatment of acute uric acid nephropathy; reduced risk of renal impairment by urate/uric acid and prevention and dissolution of uric acid renal stones.
