1. GOUT

2. By
Prof. Azza El- Medany
Dr. Osama Yousf

3. OBJECTIVES At the end of lectures students should : Define gout
Describe outlines of treatment
Describe treatment of acute gouty arthritis
Describe the mechanism of action , clinical uses & side effects of drugs used in acute attacks

4. OBJECTIVES ( continue)
Classify drugs used in chronic treatment
Define each group of drugs
Describe the mechanism of action, clinical uses & side effects & drug interactions for drugs used in chronic treatment

5. Breakdown of product of the body’s purine (nucleic acid) metabolism.
What is gout?
High blood uric acid level
Acute arthritis
monosodium urate stone in kidney
♂>♀
Familial metabolic disease
Breakdown of product of the body’s purine (nucleic acid) metabolism.

6. etiology of raised uric acid level
Idiopathic decrease in uric acid excretion
(75%)
Increase uric acid production due to increased cell turn over (tumors), increase uric acid synthesis
High dietary purine intake
Impaired uric acid excretion secondary to thiazide diuretics, chronic Renal failure

9. Aaarrrgghhh!!

10. What is the treatment for gout ?

11. Clinical stages of Gout

12. Asymptomatic Stage Acute stage Intercritical stage Chronic stage 1 2 34
Chronic stage

13. ASYMPTOMATIC STAGE
urate levels rise in the blood, but produces no symptoms

14. ACUTE STAGE

15. INTERCRITICAL STAGE
symptom-free intervals between gout episodes. Most people have a second attack from six months to two years, while others are symptom-free for five to 10 years.

16. CHRONIC STAGE

17. Broad lines in treatment of gout
Non-pharmacologic
pharmacologic
Acute gouty arthritis
Chronic gout(long term treatment)

18. Non-pharmacologic Therapy

22. Control….

24. Acute gouty arthritis
NSAIDs
colchicine
corticosteroid

25. 1. NSAIDs

26. NSAIDs (Selective or non- selective )
Inhibit pain & inflammation.
Inhibit urate crystal phagocytosis by decreasing the migration of granulocytes into the inflammatory area.
They are commonly used now for treatment of acute attack or to prevent recurrent attacks with other drugs.
( Except aspirin & paracetamol)

27. 2. Colchicine

28. Basyir Bin Kamaruzaman (15)

29. OVERVIEW A plant alkaloid
A Selective drug effective only in gouty arthritis
Has No analgesic effects

30. MECHANISM OF ACTIONS
Binds to tubulin (microtubular protein ) disrupt cellular function ( migration of granulocytes to affected area
Inhibits the synthesis and release of leukotrienes & TNF-α
Blocks cell division by binding to mitotic spindles

31. PHARMACOKINETICS PHAPHARMACOKINETICS
Given orally, followed by rapid absorption from the GI tract
Reaches peak plasma levels within 2 hours
Excreted unchanged in the faeces & urine.
Should be used with caution in patients with renal impairment

32. Treatment for Mediterranean Fever
THERAPEUTIC USES
Treatment for Mediterranean Fever
Colchicine is used as prophylaxis to prevent recurrent attacks in more than 80 percent of patients.
The anti-inflammatory activity of colchicine is specific for gout, alleviating the pain within 12 hours

33. Adverse effects Severe diarrhea ( cause of its restriction in use )
Chronic use
alopecia, bone marrow depression, peripheral neuritis, myopathy.

34. Acute intoxication ( large doses)
Burning pain in throat
Bloody diarrhea
Shock
Hematuria
C.N.S. depression

35. Contraindication
pregnancy
Precaution
in hepatic , renal problems

36. 3. Corticosteroids

37. Chronic gout (long term treatment) 2-Increase excretion of uric acid
1-Inhibition of uric acid synthesis
2-Increase excretion of uric acid

38. Treatment of Refractory Gout
Mammalian uricase enzyme

39. Inhibition of uric acid synthesis

40. Xanthine Oxidase Inhibitors

41. Mechanism of action

42. ALLOPURINOL-Pharmacokinetics
Well absorbed orally (80% )
Metabolized in the liver to oxypurinol which is responsible for most of its urate-lowering effect
Given once daily.
Drug & its metabolite excreted through the kidney.
Dose adjustment is needed in renal impairment

43. Pharmacokinetics

44. Therapeutic Uses
Treatment of primary hyperuricemia

45. Hyperuricemia secondary to other conditions such as :

46. Impaired renal functions.

47. uric acid stones or nephropathy.

48. In patients receiving cancer chemotherapy

49. ALLOPURINOL SIDE EFFECTS & DRUG INTERACTIONS

50. Side Effects (most common)
exacerbation of
an acute attack of gout

51. Maculopopular skin rash

52. nausea, diarrhea

53. Side Effects (less common)
Body : fever, headache
CVS : vasculitis

54. Thrombocytopenia
Epistaxis

55. Potentiates its action
Drug Interactions
Inhibits metabolism of
oral anticoagulant:
( warfarin )
Potentiates its action

56. Inhibits metabolism of
anticancer drugs :
(6-mercaptopurine
& azathioprine )
So ,doses of anticancer
Must be reduced up to 75%

57. With ampicillin :
Increases frequency
of skin rash

58. Febuxostat Is a new oral non-purine xanthine oxidase (XO) inhibitor.
Is structurally different from allopurinol as it lacks purine ring
Selective and potent inhibitor of XO than allopurinol
Well absorbed orally ( 84%), given once daily
Can be given with or without food
Metabolized in liver & excreted in urine & feces
No dose adjustment is needed in renal impairment

59. Continue
Suitable than allopurinol in patients with impaired renal function as no dose adjustment is required .
Used for treatment of chronic hyperuricemia in gout patients
Given to patients who do not tolerate allopurinol

60. Adverse effects
Recurrent attacks of acute gout during the first few months of treatment
Increase level of liver enzymes
Nausea, Diarrhea
Headache
Numbness of arm or leg

61. DRUGS INCREASED EXCRETION OF URIC ACID

62. Uricosuric drugs

63. 1- Probenecid

64. 3- Large doses of aspirin ( more than 5g )
2- Sulfinpyrazone
3- Large doses of aspirin ( more than 5g )

65. Mechanism of action of uricosuric drugs
Block the active transport sites of the proximal tubules(middle segment ) causing :
reduction of
Uric acid
re-absorption
(uric acid excretion

66. Clinical uses
Chronic gout

67. Warning
Urine volume should be maintained at a high level, and urinary pH kept alkaline .

68. Adverse effects Acute attack of gout Risk of uric acid stone GIT upset
Allergic rash

69. ( continue)
Nephrotic syndrome ( probenecid)
Aplastic anemia ( rare )

70. DRUG INTERACTIONS
Probenecid prolong the action of some antibiotics as: penicillins

71. Contraindications
History of urinary tract stones
Impaired renal function
Recent acute gout attack
Administration of low doses of aspirin

72. Treatment of Refractory Gout
Mammalian uricase enzyme

73. Modified mammalian uricase enzyme
Pegloticase
Is a modified mammalian uricase enzyme
Converts uric acid to allantoin
Given I.V. Infusion peak decline in uric acid level within hours

74. Continue Adverse effects Infusion reactions Anaphylaxis Gout flare
Used for the treatment of gout in adult patients refractory to conventional therapy
Adverse effects
Infusion reactions
Anaphylaxis
Gout flare
Nephrolithiasis
Arthralgia, muscle spasm
Headache

75. THANK YOU