1. Drug Therapy of Gout 1

2. 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

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 3

4. 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

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

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 6

7. 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

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

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 9

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

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 11

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

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

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 14