1. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 74 Drug Therapy of Gout

2. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.5 NSAIDs  Indomethacin (Indocin)  Naproxen (Naprosyn)  Diclofenac (Voltaren)

6. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.8 Colchicine  Mechanism of action  Pharmacokinetics  Adverse effects  Gastrointestinal  Myelosuppression  Myopathy  Drug interaction

9. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.12 Fig. 74–1. Reduction of uric acid formation by allopurinol.

13. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.13 Febuxostat (Uloric)  Reduces blood levels of uric acid  Uses  Chronic tophaceous gout  Adverse effects (uncommon)  Liver function abnormalities  Nausea  Arthralgia  Rash

14. Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.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