Chapter 74

1. Chapter 74 Drug Therapy of Gout

2. Gout • Recurrent inflammatory disorder • 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

3. 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

4. NSAIDs • Agents of first choice for gouty arthritis • 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

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

6. 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

7. Colchicine • Anti-inflammatory agent • 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

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

9. 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

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

11. 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

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

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

14. 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