MOA: 1. directly inhibits synthesis of UA by inhibition of XO
2. indirectly ↑ - FB mechanism → ↓ substrate required to produce UA
Indicated for the treatment of both overproducers and underexcreters. Treatment of choice for overproducers with tophi. Drug of choice in patients with gout and chronic kidney disease.
Allopurinol is an analog of hypoxanthine. It is a competitive antagonist of xanthine oxidase (XO). When allopurinol is acted upon by the same enzyme, alloxanthine is produced, also referred to as oxipurinol. This latter compound is an irreversible inhibitor of XO.
Excretion of allopurinol SIMILAR to uric acid (RENAL), therefore, uricosuric agents would increase the excretion of allopurinol, decreasing its activity.
Dose: Begin with 100mg up to 300mg. Usually not more but could go up to 800mg!
Increase incidence of acute attacks following initiating of treatment
Minor common side effects include GI (nausea, vomiting, diarrhea) and HA
Skin rash is also prevalent (2%) and can be very severe and often fatal (20
to 30% of the time). Altered liver function is common.
Allopurinol Hypersensitivity Syndrome: major concern - 0.1 to 0.4% - associated with
severe cutaneous reactions (Stevens-Johnson) or may include eosinophilia, hepatitis,
leukocytosis, fever and renal involvement. Mortality ¼ of all cases - Due to
accumulation of oxipurinol? Cellular immune response to allopurinol and oxipurinol??
Associated with abnormal renal function and increased levels of both compounds?