Pharmacodynamic pathways for drugs that lower uric acid levels

Unlike other animals, humans and apes have lost the ability to break down uric acid. High uric acid levels (hyperuricemia) can result in gout and kidney failure, and are a symptom of Tumor Lysis Syndrome experienced by some cancer patients.

Two new PharmGKB pathways describe the mechanism of action of drugs that lower uric acid levels to treat or prevent hyperuricemia, and outline the underlying genes involved. The pharmacogenetic associations behind adverse reactions to allopurinol (HLA-B*5801) and rasburicase (G6PD) are detailed.

Three treatment strategies for hyperuricemia/ gout exist:

1. Reduce the generation of uric acid: Allopurinol, Febuxostat

2. Increase the removal of uric acid: Rasburicase, Pegloticase

-> Covered in the PharmGKB Uric Acid-Lowering Drugs Pathway

3. Reduce the reabsorption of uric acid: Probenecid, Benzbromarone, Sulfinpyrazone

-> Covered in the PharmGKB Uricosurics Pathway