Define gout Describe outlines of treatment Describe treatment of acute gouty arthritis Describe the mechanism of action clinical uses amp side effects of drugs used in acute attacks OBJECTIVES continue ID: 1037763
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1. GOUT
2. OBJECTIVESAt the end of lectures students should :Define gout Describe outlines of treatmentDescribe treatment of acute gouty arthritis Describe the mechanism of action , clinical uses & side effects of drugs used in acute attacks
3. OBJECTIVES ( continue)Classify drugs used in chronic treatmentDefine each group of drugs Describe the mechanism of action, clinical uses & side effects & drug interactions for drugs used in chronic treatment
4. Breakdown of product of the body’s purine (nucleic acid) metabolism.What is gout?
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7. What is the treatment of gout ?
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9. Non-pharmacologicTherapy
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11. DRUGS USED IN TEATMENT OF GOUTMost therapeutic strategies for gout involve lowering the uric acid level below the saturation point (<6 mg/dL), thus preventing the deposition of urate crystals. This can be accomplished by: interfering with uric acid synthesis with allopurinolincreasing uric acid excretion with probenecid or sulfinpyrazoneinhibiting leukocyte entry into the affected joint with colchicine,administration of NSAIDs
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13. NSAIDsdrugs of choice for young, healthy adults without any other serious medical conditionusually taken orally at their highest safe dosage as long as gout symptoms persist and for three or four days afterlow doses of NSAIDs may be used to prevent gout attacks, including in patients who are starting anti-hyperuricemic therapies.
14. 2. Colchicine
15. MECHANISM OF ACTIONS
16. PHARMACOKINETICSPHAPHARMACOKINETICS
17. THERAPEUTIC USES
18. Adverse effectsDiarrhea is a common adverse effect. May cause nausea, vomiting ,abdominal cramps.Chronic use may cause, alopecia, bone marrow depression, peripheral neuritis, myopathy.Also, affect fertility
19. Prevention of recurrent attackInhibition of uric acid synthesis AllopurinolUricosuric drugs- Probenacid - Sulfinpyrazone
20. Inhibition of uric acid synthesis
21. PharmacokineticsWell absorbed orallyBioavailability 53%Vd= 0.87l/kgLow protein bindingmetabolism is reported 76%. Renal Excretion accounts for 10% and plasma half life is 1.2 h
22. Severe tophaceous deposits (uric acid deposits in tissues)Therapeutic Uses
23. High serum uric acid in patients with impaired renal functions.
24. uric acid stones or nephropathy.
25. used to prevent increased uric acid levels in patients receiving cancer chemotherapy
26. ALLOPURINOL(SIDE EFFECTS AND DRUG INTERACTIONS)
27. Side Effects (most common)Prolong and exacerbationof an acute attack of gout
28. Maculopapular skin rash
29. nausea, diarrhea
30. Drug InteractionsWith oral anticoagulant: warfarin and dicumarolinhibits their metabolism
31. With anticancer :Reduce the metabolism of 6-mercaptopurineand azathioprine Requring reduction ofDosage up to 75%
32. With ampicillin :Increases frequencyof skin rashProlongs half life ofChlorpropamide both compete for excretion in renal tubule
33. FebuxostatIs a new oral non-purine xanthine oxidase (XO)inhibitor.Is structurally different from allopurinol& lacks purine ringMore selective and potent inhibitor of XO than allopurinol & has no effect on other enzymes involved in purine or pyrimidine metabolismWell absorbed orally ( 84%)Can be given with or without foodGiven orally once dailyMetabolized in liver & excreted in in the urine & faeces
34. ContinueMore effective than allopurinol in patients with impaired renal function; no dose adjustment is required in mild-to- moderate renal impairmentUsed for treatment of chronic hyperuricemia in gout patientsGiven to patients who do not tolerate allopurinol
35. Adverse effectsIncrease number of gout attacks during the first few months of treatmentIncrease level of liver enzymesNausea, DiarrheaHeadacheNumbness of arm or leg
36. Uricosuric drugs
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38. Uricosuric drugs ( probenecid, sulfinpyrazone, large dose of aspirin)decrease the reabsorption of uric acid & increase the amount excretedMechanism of action
39. Clinical usesChronic gout (urine volume should be maintained at a high level, and urinary pH kept alkaline ).Probenecid is used to prolong the action of some antibiotics e.g. penicillin.
40. Side effectsExacerbation of acute attackRisk of uric acid stoneGIT upsetAllergic rash
41. Contra-indicationPrevious urinary tract stoneImpaired renal functionRecent acute goutCo-administration of low dose aspirin
42. DRUG INTERACTIONS Aspirin can prevent probenecid from being fully effective
43. DRUG INTERACTIONS: Sulfinpyrazone can aggravate peptic ulcer disease Aspirin products can interfere with sulfinpyrazone's effectsSulfinpyrazone can enhance the action of certain diabetes medicines
44. Recombinant mammalian uricasePegloticaseIs a uric acid specific enzyme which is a recombinant modified mammalian uricase enzymeConverts uric acid to allantoinGiven I.V. peak decline in uric acid level within 24-72 hours
45. ContinueUsed for the treatment of chronic gout in adult patients refractory to conventional therapyAdverse effectsInfusion reactionsAnaphylaxisGout flareNephrolithiasisArthralgia, muscle spasmHeadache
46. SUMMARYGout is a form of arthritis that is characterized by sudden , severe attacks of pain, redness and tenderness.Gout is caused by deposits of uric acid crystals in a jointUric acid is a waste product formed from the breakdown of purines.
47. SUMMARY ( continue)Treatment of gout includes :Treatment of acute attacks Prevention of future attacksTreatment of chronic gout
48. SUMMARY (continue)Drugs used for acute attacks includes :NSAIDs ( selective or non-selective)Colchicine interfere with the migration of granulocytes to the site of inflammation & reduce the release and synthesis of leukotriensMain adverse effects includes :
49. SUMMARY ( continue)DiarrheaSkin rash Kidney, liver & CNS injuryDrugs used for chronic treatment includes :Uricosuric drugs that increase urinary excretion of uric acid
50. SUMMARY ( continue)Probenecid & sulfinpyrazoneTheir main adverse effects includes :Gastrointestinal problemsSkin rashesLeukopeniaAnti-hyperuricemic drugs that reduce the production of uric acid
51. SUMMARY ( continue)Allopurinol is an oxidase inhibitorUsed in patients with elevated blood uric acid levelOr in patients with tendency for renal stone formationIts main adverse effects includes :Gastric problems
52. SUMMARY ( continue)Skin rashesLeukopeniaThrombocytopeniaAllopurinol reduces the metabolism of some drugs including azathioprime , this needs reduction of the doses of these drugs up to 75%