Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 74 Drug Therapy of Gout
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
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
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.5 NSAIDs Indomethacin (Indocin) Naproxen (Naprosyn) Diclofenac (Voltaren)
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
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.8 Colchicine Mechanism of action Pharmacokinetics Adverse effects Gastrointestinal Myelosuppression Myopathy Drug interaction
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
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
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.12 Fig. 74–1. Reduction of uric acid formation by allopurinol.
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
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