Drugs associated with gout

Drugs which can raise serum uric acid levels include:[5,6]

• cyclosporin
• ethambutol
• pyrazinamide
• cytotoxic chemotherapy
• (thiazide) diuretics
• valproates
• phenobarbital
• favipiravir

Uric acid metabolism

Uric acid is produced mainly in the liver (with some occurring in the small intestine) as a breakdown (catabolic) product of purine, particularly from nucleotides.[5,6]

Purine is a double-ringed heterocyclic structure of carbon and nitrogen with hydrogen and is the precursor of two of the nucleotide building blocks of DNA and RNA, adenine and guanine. Purines are also involved in modulating energy production and signal transmission, are part of the structure of some co-enzymes, and are used in platelets, muscles and neurotransmission.[9,10]

Purine:                                     Uric acid:

About two thirds of molecules containing purine are made in the body while the rest derive from the diet. Uric acid is produced from the breakdown of dietary purines or from the release of the nucleic acids from DNA and RNA in damaged, dying or dead cells or other endogenous sources of purine.[10,11,12]

Conversion of purine to uric acid via intermediaries includes inosine, hypoxanthine and then xanthine which is converted into uric acid by the enzyme xanthine oxidase, the target of a treatment option. Most of the uric acid is then filtered via the kidneys. Around 10% is eliminated in urine but most is reabsorbed.[6,10,12]