|A.||Acute gouty arthritis|
Evidence of bone /joint damage
Allopurinol should not be started during an acute attack, as it can result in the sudden lowering of uric acid. Sudden changes in concentration may lead to further attacks of gouty arthritis.
Hypouricemic therapy in the form of allopurinol is usually indicated when :
Two or more acute attacks of gout
When gout is associated with tophi
Bone or joint damage
High serum uric acid level (>9.0 mg/dl)
Uric acid stones.
Treatment of acute gouty arthritis:
Chronic gout therapy
After the symptoms of acute gout subside, patients enter the intercritical period during which a decision must be made regarding the need for treatment with a urate-lowering medication. One important point to consider is that abrupt lowering of urate levels can precipitate an attack of acute gout during the intercritical period. Thus, these patients should receive prophylactic colchicine coverage irrespective of which urate-lowering medication is used.
The choice of urate-lowering medications is uricosuric drugs (which promote uric acid excretion) or xanthine oxidase inhibitors (which inhibit uric acid production)
Probenecid (uricosuric drug) inhibits the tubular reabsorption of filtered and secreted urate, thereby increasing urate excretion.
The ideal candidates for probenecid therapy are those with a 24-hour urine uric acid excretion of less than 800 mg in 24 hours, no history of nephrolithiasis, and good renal function (creatinine clearance >80 mL/min).
Allopurinol (a competitive inhibitor of the enzyme xanthine oxidase) is the most widely used antihyperuricemic agent.
The ideal candidates for allopurinol treatment are as follows:
Uric acid overproducers (24-h urinary uric acid excretion >800 mg on a general diet or >600 mg on a purine-restricted diet)
Patients with renal insufficiency, nephrolithiasis, or tophaceous gout
Patients at risk for developing uric acid nephropathy
(Hypersensitivity, Hepatotoxicity, bone marrow depression, and interstitial nephritis are rare but serious adverse effects of allopurinol).
Febuxostat (xanthine oxidase inhibitor)
Febuxostat should be reserved for use in people in whom allopurinol has failed due to intolerance or lack of efficacy. Febuxostat should be used with particular caution in patients with high cardiovascular risk.
Lesinurad (Zurampic) is the first selective uric acid reabsorption inhibitor (SURI) approved by the FDA.
It acts by inhibiting the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid. It also inhibits organic anion transporter 4 (OAT4), a uric acid transporter associated with diuretic-induced hyperuricemia.
Lesinurad must be coadministered with a xanthine oxidase inhibitor and is indicated for hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.
Pegloticase (Krystexxa) is a recombinant, pegylated, uric acid–specific enzyme that catalyzes the oxidation of uric acid to allantoin. It is approved for use in adults with chronic gout that is refractory to conventional therapy. It is administered by intravenous infusion.