1. Gout Familial metabolic disease characterized by : Acute arthritis Uric acid stones in the kidneys Hyperuricemia

2. Treatment of gout Acute attack NSAID,s Colchicine Chronic gout Uricosuric agents Allopurinol

3. Colchicine Produces its anti-inflammatory effects by binding to the intracellular protein tubulin, preventing its polymerization leading to the inhibition of leukocyte migration into affected area. Inhibits the synthesis & release of leukotrienes.

4. Pharmacokinetics Given orally, rapidly absorbed from GIT. Partially metabolized and excreted in urine & part of the drug is recycled in the bile and is excreted unchanged in feces.

5. Clinical uses Selective for an acute attack of gouty arthritis,alleviating the pain within 12 hours. Prophylaxis of recurrent attacks of acute gout. In preventing attacks of acute Mediterranean fever. Hepatic cirrhosis.

6. Adverse effects Diarrhea is a common adverse effect. May cause nausea,vomiting,abdominal pain. Chronic use may cause, alopecia,bone marrow depression,peripheral neuritis, myopathy.

7. Acute intoxication Burning throat pain. Bloody diarrhea. Shock. Hematuria. Fatal ascending C.N.S.depression.

8. Contraindication & Precaution Contraindicated in pregnancy Should be used with caution in hepatic, renal or cardiovascular diseases.

9. NSAID,s Inhibits pain & inflammation. Inhibits urate crystal phagocytosis by decreasing the migration of granulocytes into the inflammatory area. ( Indomethacin is commonly used & it may replace colchicine. Aspirin in therapeutic doses is contraindicated as it compete with uric acid secretion in proximal tubule.

10. Uricosuric Agents Probenecid & Sulfinpyrazone They are weak organic acids. Sulfinpyrazone is a metabolite of phenylbutazone.

11. Pharmacokinetics Probenecid is reabsorbed by the renal tubules & slowly metabolized. Sulfinpyrazone & its active metabolite are excreted rapidly through kidney. The duration of their effect after oral administration is nearly the same.

12. Mechanism of action Uricosuric drugs ( probenecid, sulfinpyrazone, large dose of aspirin) block the active transport sites of the proximal tubules(middle segment ),so the net reabsorption of uric acid is decreased.

13. Clinical uses Chronic gout (urine volume should be maintained at a high level,and urinary pH kept alkaline ). Probenecid is a general inhibitor of the tubular secretion of organic acids, so it is used to prolong action of other weak organic acids as some antibiotics e.g. penicillin.

14. Adverse effects Gastrointestinal irritation,more with sulfinpyrazone. Allergic dermatitis, more with probenecid. Nephrotic syndrome with probenecid. Both of them rarely cause aplastic anaemia.

15. Allopurinol Inhibits synthesis of uric acid by inhibiting xanthine oxidase enzyme

16. Pharmacokinetics 80% absorbed after oral administration. Metabolized to active metabolite alloxanthine. Given once daily. Drug & its metabolite are excreted in the feces & urine.

17. Clinical uses Primary hyperuricemia of gout.. When probenecid or sulfinpyrazone can not be used. For recurrent renal stones.

18. Clinical uses In hyperuricemia secondary to renal disease or after treatment with chemotherapeutic agents. When serum urate levels are greatly elevated.

19. Adverse effects Acute attacks of gouty arthritis may occur during the first weeks of therapy. ( colchicine or NSAIDs should be administered concurrently ) G.I.T.( nausea, vomiting,diarrhea ). Peripheral neuritis, necrotizing vasculitis.

20. Adverse effects Hypersensitivity reactions especially allergic skin reaction in 3% of patients ). Bone marrow depression Hepatic toxicity and interstitial nephritis.

21. Drug interactions Allopurinol interferes with the metabolism of: chemotherapeutic agents as 6- mercaptopurines, cyclophosphamide& immunosuppressant azathioprine requring reduction the dosage of these drugs ( 75% ). Probenecid & oral anticoagulant