1. Gout

2. Gout: is a metabolic disorder characterized by
high blood level of uric acid. Urate is end product of purine metabolism.
The joint at the base of the big toe ( metatarsal-phalangeal joint) is affected.
Gout increases in those who eat a lot of meat.
At high levels, uric acid crystallizes and the crystals deposit in joints, tendons and surrounding tissues, resulting in an attack of gout.
It may result in  kidney stones.  

5. Gout and hyperuricemia depend on two processes:
1- over production of urate (due to excessive cell destruction ).
2- under excretion of urate (due to renal insufficiency ).

6. Drugs used in treatment and prevention of gout:- different mechanisms are included:- 1- Interfering with uric acid synthesis e.g. allopurinol (xanthine oxidase inhibitor). 2- Increasing uric acid excretion (Uricosuric agents) e.g. probenecid and sulfinpyrazone. 3- Inhibiting leukocyte entry into the affected joints e.g. colchicine. 4- NSAIDs.

7. Allopurinol
is a purine analog. It decrease the production of uric acid by competitively inhibiting xanthine oxidase. When xanthine oxidase is inhibited, the circulating xanthine and hypoxanthine are more soluble and less likely to precipitate. The drug is completely absorbed after oral dose

9. Side effects: -
It is well tolerated
Hypersensitivity including skin rash, nausea and diarrhea.
Acute attacks of gout may occur during the first weeks of treatment thus colchicine and NSAIDs should be added

11. Uricosuric agents( probenecid and sulfinpyrazone ):
probenecid :a general inhibitor of the tubular secretion of organic acids sulfinpyrazone : a derivative of Phenylbutazone )
MOA: They block the proximal tubular reabsorption of uric acid.
Probenecid is also block tubular secretion of penicillin, naproxen and indomethacin.
*During early therapy,high fluid intake is needed.They are well tolerated *Sulfinpyrazone is a contraindication in peptic ulcer.
*Fenofibrate is an antihyperlipidemic drug with uricosuric action.

12. Colchicine is an alkaloid, rapidly relieves the pain suffering and inflammation of an acute attacks of gout. Effective orally and t1/2 is 1 hr This rapid effect is of high benefit for diagnosis, it is more useful if taken within 24 hrs of onset of attack and It is useful in patients whom NSAIDs are contraindicated.

13. Mechanism of action: 1- It decreases granulocytes migration to the affected area, 2- It blocks cell division by binding to mitotic spindles 3-Inhibs the synthesis & release of leukotrienes.

14. Side effects: Nausea and vomiting abdominal pain diarrhea
aplastic anemia
alopecia and agranulocytosis.

15. Uses: 1- Gout 2- Recurrent hereditary polyserositis
Should be not used in pregnancy

16. Drugs regimen in gout: -
A- Treating acute gout: - It is treated with
1- colchicine to decrease movement of granulocytes into the affected area
2- NSAIDs to decrease pain and inflammation.
Aspirin is contraindicated because it compete with uric acid for the organic acid secretion mechanism in the proximal tubule of the kidney

17. B- Treating chronic gout: -
include using two lines: -
1- Uricosuric
2- Allopurinol

18. Drugs that precipitating gout: -
all diuretics ( except spironolactone ),
aspirin,
ethambutol,
pyrazinamide,
nicotinic acid and alcohol.

19. Thank you