Xanthine Oxidase Inhibitors

Gout is caused by high uric acid (hyperuricemia) in the blood that leads to excess uric acid crystallizing in the joints causing swelling and pain. This is either caused by the over production of uric acid or under excretion by the kidneys. Uric acid is produced from the breakdown of the protein purine which is released when cells die or introduced from the food we eat.

Under normal conditions, uric acid is supposedly produced in enough quantities so as to be efficiently removed by fully-functioning kidneys. There are cases however when specific enzyme defects cause excessive production of uric acid. The enzyme that helps breakdown purine to uric acid is xanthine oxidase. Since xanthine oxidase makes the conversion of purine into uric acid happen, preventing its activity results to slow down of uric acid production. Such is the role of xanthine oxidase inhibitors.

Xanthine oxidase inhibitors come in two forms: purine analogues and others. Allopurinol, oxypurinol, tisopurine are purine analogues used in the treatment of gout. They work by mimicking the structure of metabolic purines. In other words they trick the body into thinking they are purines and therefore interferes in its conversion to uric acid. This results to slower and consequently lower production of uric acid.  Other xanthine oxidase inhibitors include febuxostat and inositols of which only febuxostat is so far used for the treatment of gout. In the case of febuxostat, it blocks xanthine oxidase active site preventing it from converting purine into uric acid.

Xanthine oxidase inhibitors like allopurinol and febuxostat are considered first-line therapy for gout. They form part of most conventional drug treatments for gout. Since they lower uric acid production they are not advised to be given during an acute gout attack as they may trigger additional flare-ups. They are given when pain and swelling has subsided usually from taking colchicine or non-steroidal anti-inflammatory drugs (NSAID’s).

Xanthine Oxidase Inhibitors – Side Effects

The most common adverse side-effects of xanthine oxidase inhibitors are skin rashes which maybe a sign of allergic reaction and gastrointestinal upsets like diarrhea, nausea and vomiting. It can also cause joint stiffness and swelling. In some cases it also causes altered liver functions. Nevertheless, xanthine oxidase inhibitors are usually well-tolerated by majority of gout patients.

There are also natural products known to inhibit xanthine oxidase in vitro. This includes three flavonoids occurring in many fruits and vegetables such as quercetin, myercetin and kaempferol. Of the three flavonoids, quercetin on its own or combined with other natural products found to be good for gout (for example cherry extract) is commonly used as natural food supplements.