Drugs for the Gout and Rheumatic Arthritis

1. Drugs for Gout and RA
Dr. Saroj Suwal
The disease of kings" or “Rich man's disease"

2. Disorder of Purine metabolism
characterized by recurrent attacks of acute inflammatory arthritis –
a red, tender, hot, swollen joint. •
•
• caused by elevated levels of uric acid in the blood which crystallize
and are deposited in joints, tendons, and surrounding tissues.

3. Gout/Gouty Arthritis
• metabolic disorder characterized by
hyperuricaemia
• First MTP joint of the big toe is the
most commonly affected (~50% of
cases).
(chronic gout – Helix of the ear)
Uric acid 
• normal plasma urate 2–6 mg/dl).
• product of purine metabolism,

4. pathophysiology
•Uric acid high in
Blood
•Precipitates
•and
•deposits
• joints, kidney
and subcutaneous
tissue.

6. DRUGS FOR GOUT
ACUTE GOUT
• NSAIDS
• Colchicine
• Corticosteroids
CHRONIC GOUT
Uricosurics
• Probenecid
• Sulfinpyrazone
Synthesis Inhibitors
• Allopurinol
• Febuxostat

7. NSAIDS
• Naproxen, Piroxicam, Diclofenac, Indomethacin
or Etoricoxib
•STRON
G
NSAIDS
•inhibit
synthesi
s of
PGs
•inhibit
migration of
leucocytes
into the
inflamed
joint.
reduce
inflamm
ation in
gout.

8. COLCHICINE
• Plant alkaloid from Colchicum autumnale
• suppresses gouty inflammation.
• MOA:
• binds to protein tubulin and inhibits microtubule
formation, arresting granulocyte motility and
decreasing inflammation.
• alsoinhibits leukocyte chemotaxis, formation of
glycoprotein and phagocytosis.

9. Indication:
•Anti-inflammatory in Gout (NSAIDs alternative)
•Chondritis
•Prophylaxis of Gout
• Dose:
• 1mg starting and then 0.5mg 2-3 hourly until pain
reduces (total 3 doses/day)

10. Adverse effects
•Nausea, Vomiting, Abdominal Pain, Diarrhoea
•Myopathy, Neutropenia, Aplastic anaemia,
Alopecia (prolong use)
Contraindications
•Pregnancy
•Liver disease
•Renal disease
•Cardiovascular disease

11. CORTICOSTEROIDS
Cotricosteriods
Inhibit conversion of
phospholipids into
arachidonic acid
suppress inflamtion

12. Routes:
• Oral route
• Intraarticular route
• Intramuscular route
• Intravenous
Orally Prednisolone 40–60 mg may be given in one day,
followed by tapering doses over few weeks.

13. URICOSURICS:
drugs that promote renal clearance of uric acid by
inhibiting urate reabsorption.

14. PROBENECID
•Inhibits the
tubular
reabsorbtion of
urate,
•increasing the
urinary excretion
of uric acid
•decreasing serum
urate level.

15. Indications:
•Chronic Gout & Hyperuricemia
•Prolong the action of Penicillin Dose:
250-500mg BD

16. Adverse effect and contraindications
Adverse effects:
•Dyspepsia
•Hypersensitivity (Rashes)
•Gastric distress (Peptic ulcer)
Contraindications:
Should avoiide if creatinine clearance is less than 50
ml/min.

17. MOA:
Allopurinol is a purine analog which inhibits
the enzyme xanthine oxidase and reduces
ALLOPURINOL

18. Indications
• Hyperuricemia in Gout
• Hyperuricemia in Cancer or Renal diseases
• Kala-azar
Dose:
Start with 100 mg OD, gradually increase as
needed to
300 mg/day; maximum 600 mg/day

19. Adverse effects
• Hypersensitivity (rashes)
• Fever
• Muscle pain
Contraindications
• Pregnancy
• Lactation
• Hypersensiitivity

20. FEBUXOSTAT
MOA:
• is a nonpurine xanthine oxidase inhibitor
• reduces uric acid formation and decreases uric acid
levels in blood.

21. Indications:
• Chronic Gout
• Hyperuricemia Dose: 40-80mg OD
Adverse effects
• Liver damage
• Diarrhoea
• Nausea
• headache
Contraindications
Same as Allopurinol

22. an autoimmune disease in which
there is joint inflammation,
synovial proliferation and
destruction of articular cartilage.
RHEUMATOID ARTHRITIS (RA)

23. Immune
complexes
Composed of IgM
Activate complement
release cytokines
(mainly TNFα and IL-1)
which are chemotactic
for neutrophils.

24. The inflammatory cells secrete lysosomal enzymes
which damage cartilage and erode bone, while PGs
produced in the process cause vasodilatation and pain.

25. Goals of Therapy:
•Reduce pain, swelling and joint stiffness.
•Prevent articular cartilage damage and bony
erosions.
•Prevent deformity and preserve joint function.

26. Drugs for Rheumatoid Arthritis
 NSAIDS
 CORTICOSTEROIDS
 DMARDS- Disease Modifying
Antirheumatoid Drugs

27. Disease Modifying Antirheumatoid Drugs (DMARDS)
1.Immunosupressants:
Methotrexate, Azathioprene Cyclosporine
2.Sulphasalazine
3.Hydroxychloroquine
4.Leflunomide
5. TNFα inhibitors:
Etanercept,Infliximab Adalimumab
6. IL-1 antagonist:
Anakinra
Gold & Penicillamine are no longer used!

28. (DMARDS)
METHOTREXATE
Folic acid analog, Antimetabolite
MOA:
• inhibits biosynthesis and proliferation of DNA
and immune cells (T cell & B cell).
• inhibits cytokine production, chemotaxis and
cell-mediated immune reaction.

29. METHOTREXATEχ
Note:- Conversion of folic acid into its
active form, Tetrahydrofolic acid (TH4) is
essential for the synthesis of DNA and cell
proliferation.

30. Indications:
•First Choice
• alone or combination
•Psoriasis, Ankylosing spondylitis
•Immunosuppression and anti-
inflammatory
•Anticancer (Leukaemia, Breast
cancer, Carcinomas)
•Dose For Rheumatoid
Arthritis: 7.5-15 mg weekly

31. Adverse Effects:
• Bone marrow depression
• Leukopenia (Decrease WBC)
• Thrombocytopenia (↓ Platelets)
• Anaemia (Decrease RBC)
• Liver damage
• Renal failure
• Skin reactions
• Alopecia

32. Contraindications:
• Pregnancy
• Bone marrow, Liver And Renal
Impairment
• Ulcerative disorders

33. SULPHASALAZINE
MOA:
• Anti bacterial
• decreases IgA & IgM factors, suppresses T cell
response and
• has anti- inflammatory & immunosuppressive
actions.

35. HYDROXYCHLOROQUINE(HCQ)
given for long periods of 3-6 months.
• Supress lysosomal enzyme
• Reduce monocyte , IL 1
• Inhibit B lymphocyte and interfare
antigen processing
• Has free radical activity

36. Indications:
• Rheumatoid Arthritis
• Anti-malarial
Dose:
400 mg/day for 4–6 weeks, followed by 200 mg/day
for maintenance
Adverse effect
• Retinal damage
• IBS
• Graying of Hair

37. LEFLUNOMIDE
MOA:
• inhibits proliferation of stimulated
lymphocytes
• Active metabolite of leflunomide inhibits
dihydroorotate dehydrogenase and
pyrimidine synthesis in actively dividing cells
& antibody production by B-cells is
depressed.

38. Indications:
• Rheumatoid Arthritis
• Immunosuppression
Dose:
loading dose of 100 mg daily for 3 days
followed by 20 mg OD.
Adverse effects:
• Loss of hair
• Thrombocytopenia
• Leukopenia

39. BIOLOGICALS
TNFα inhibitors: Etanercept
Infliximab Adalimumab
MOA:
• inhibit cytokines, especially TNFα or IL-1
• are reserve drugs for severe refractory
disease.
• mainly suppress macrophage and T-cell
function.
• Thus inflammation in the joint regress and new
erosions are slowed.
IL-1 antagonist: Anakinra
Abatacept

40. Indications: (given s.c.)
Autoimmune diseases like RA,
inflammatory bowel
diseases, psoriasis, scleroderma, etc.

41. Thank you