Drug Therapy of Gout 1

Gout Recurrent inflammatory disorder Hyperuricemia Seen mainly in men Hyperuricemia Uric acid level greater than 7 mg/dL in men or greater than 6 mg/dL in women Uric acid crystals deposited in joints Episodes of severe joint pain (typically in large toe) Causes Excessive production of uric acid Impaired renal excretion of uric acid 2

Overview of Drug Therapy Short-term to relieve symptoms of attack Infrequent flare-ups (fewer than 3 times/yr) NSAIDs: first-line agents Glucocorticoids also used Long-term to lower blood levels of uric acid 3 or more times per year Uricosuric drugs 3

NSAIDs Agents of first choice for gouty arthritis Adverse effects Better tolerated and more predictable than colchicine Relief should be within 24 hours; swelling subsides over the next few days Adverse effects GI ulceration, decreased renal function, fluid retention, increased risk of cardiovascular events 4

NSAIDs Indomethacin (Indocin) Naproxen (Naprosyn) Diclofenac (Voltaren) 5

Glucocorticoids Highly effective in relieving pain Useful for patients who are hypersensitive to, are unresponsive to, or have medical conditions that contraindicate the use of NSAIDs Avoid in patients prone to hyperglycemia 6

Colchicine Anti-inflammatory agent Uses No longer the first-line drug Now reserved for patients who are unresponsive/intolerant to safer agents Uses Treats acute gouty attack Reduces incidences of attack Aborts an impending attack 7

Colchicine Mechanism of action Pharmacokinetics Adverse effects Gastrointestinal Myelosuppression Myopathy Drug interaction 8

Drug Therapy for Hyperuricemia Goals of therapy Promote dissolution of urate crystals Prevent new crystal formation Prevent disease progression Reduce the frequency of acute attacks Improve quality of life Note: Because these drugs have no analgesic or anti-inflammatory actions, they are not useful in an acute gouty attack 9

Drug Therapy for Hyperuricemia Allopurinol (Zyloprim) Inhibits uric acid formation Febuxostat (Uloric) Probenecid (Benemid) Increases uric acid excretion Sulfinpyrazone (Anturane) 10

Allopurinol (Zyloprim) Reduces blood levels of uric acid Uses Chronic tophaceous gout Hyperuricemia due to chemotherapy Adverse effects (generally well tolerated) Hypersensitivity syndrome Gastrointestinal effects Neurologic effects 11

Fig. 74–1. Reduction of uric acid formation by allopurinol. 12

Febuxostat (Uloric) Reduces blood levels of uric acid Uses Chronic tophaceous gout Adverse effects (uncommon) Liver function abnormalities Nausea Arthralgia Rash 13

Probenecid (Generic Only) Acts on renal tubules to inhibit reabsorption of uric acid Prevents formation of new tophi and helps existing tophi decrease May exacerbate acute episodes of gout Add indomethacin for relief Adverse effects Usually well tolerated, but mild GI effects occasionally occur; take with food Drug interactions 14