1. What is Arthritis?
 There are 127 different kinds of
arthritis!
 Osteoarthritis: progressive
degeneration of joint cartilage.
Minor degree of inflammation.
 Rheumatoid arthritis: Severe
inflammation that involves many
joints and moves beyond
musculoskeletal system.
 Gout: Very painful form of
arthritis characterized by the
formation of uric acid crystals
and severe inflammation.

2. Rheumatoid arthritisChronic progressive, autoimmune disease in
which there is joint inflammation, synovial
proliferation, and destruction (crippling) of
articular cartilages with waxing and waning
course.
INFLAMMATORY MEDIATORS-
Cytokines
Interleukin 1
TNF-alpha

3. Autoimmune
IgM activates complements and release infl. Mediators
Neutrophil infiltration
Release of Lysosomal enzymes
PGs
Damage to cartilage, bone errosion
vasodilatation
edema & pain

7. • Diagnosis
–
–
–
•
Early diagnosis is the first step to easy control
History
Physical examination
Findings
1.Morning stiffness >1hour
2.Symetrical joint swelling for 6 weeks.
3.Swelling in 3 or more joint areas lasting for
6 weeks or more.
4.Rheumatoid nodule.
5.Positve RF.
6.Radiographic erosions.

8. The treatment approach:
1. Aims to reduce & possibly prevent damage to the joints & other
organs.
2. Relief of pain –primary aim.
3. Rx of pathology-
Arrest of disease process
- Modification of disease process
-
Nonpharmacological therapy:
o Traditional physical therapy includes-heat & cold therapy
o Motion exercises, Aerobic exercise with muscle strength.
Pharmacological therapy:
o NSAIDs
o DISEASE MODIFYING ANTIRHEUMATIC DRUGS
[DMARDs]
o Adjuvant: GLUCOCORTICOIDS

9. NSAIDs• Used in first; they afford symptomatic relief of
pain, swelling, morning stiffness, immobility.
• Donot arrest disease process.





Diclofenac sodium (75-100mg BD)
Ibuprofen
(200-400mg TDS)
Naproxen
(500mg single dose)
Aspirin
(3-5g/day)
Indomethacin
Special precautions
- Peptic
ulcer
-Bleeding disorder

10. DISEASE MODIFYING ANTIRHEUMATIC
DRUGS [DMARDs]
• Suppress the rheumatoid process i.e.
arrest the basic process of joint
destruction
• Bring about remission.
• Also called as SAARDs
»Contd.,

11. DMARDs
•
1.Methotrexate (Mtx.)
•
2. Agents used in mild disease or in combination with MTX.
•
•
•
•
3.Traditional DMARDs -(limited used currently)
•
•
•
•
Gold salts (Aurothiomalate sodium)…..X
d-Penicillamine………………………..X
Azathioprine
4. Biological agents
•
•
•
•
Hydroxychloroquine
Sulfasalazine
Minocycline
Cyclosporine
Infliximab
Leflunomide
Methoterxate, Azathioprine, Cyclosporine are IMMUNOSUPPRESANT
Leflunomide IMMUNO MODULATOR

12. METHOTREXATE (Mtx)
• An anti metabolite (inhibit dihydrofolate reductase)
inhibits folic acid synthesis.
• 1st line DMARD at present
• RA-Primary MOA is anti-inflammatory rather than
antimetabolites -Inhibit cytokine production, cell
mediated immune reaction, chemotaxis.
• Dose-7.5-10 mg oral weekly.
• Onset of symptom relief is relatively rapid –
preferred for initial treatment
»Contd.,

13. • PK- Oral BV of Mtx is variable, may effected by food
- Excretions is dec. in renal disease pt.
• S/E-GIT distress (parenteral therapy effective to reduce
30mg/wk. i.v, less expensive.)
-Oral ulcer
-Hair loss
-Pneumonia (dec. By use of FA)
-Dose dependent progressive liver damage

14. Hydroxychloroquine
• Antimalarial
• Antirheumatic-found to induce remission in 50% patients.
• MOA-inhibit inflammatory cells: monocytes interleukins,
B lymphocytes.
• RA- long periods
• Dose-200mg bd
• Combined with MTX.
• S/ERetinal damage
Corneal opacities
Neuropathy, Myopathy
Rash
Graying of hairs
Irritable bowel syndrome

15. Sulfasalazine
• Combination of sulphapyridine and 5 aminosalicylic
acid
• Inhibits generation of superoxides and cytokines by
the inflammatory cells.
• Efficacy is equal to chloroquine.
• 1-3g/day (3divided dose)
• Few adverse effect / good alternative for Mtx
Minocycline
• Group III broad spectrum antibiotic inhibit
arthritic inflammation.
• Used in com. With MTX.

16. Gold salts (Aurothiomalate sodium)
• Introduced in 1929.
• Gold is most effective agent for arresting
rheumatic process and preventing
involvement of additional joints.
• It reduce chemotaxis, phagocytosis,
macrophages and lysosomal activity and
inhibit cell mediated immunity
• Benefit - 4-6wks
• Starting dose10mg im/wk gradually inc. to
50mg/im/wk up to 1g.then maintain
50mg /im/ for few months.
»Contd.,

17. • PK:-Gold is heavily bound to plasma and
tissue proteins, specially in kidney, stay in
the body for years
• Toxicity:– Vasodilatation, postural hypotension
– Dermtitis, pruritic rash,
– Albuminuria
– Hepatitis, peripheral neuritis, pulmonary
fibrosis
– Eosinophilia , bone marrow suppression

18. D-Penicillamine
• Copper chelating agent
• Gold compound like action but less
efficacious.
• Toxicity is similar like gold
• Toxicity: Rash, Proteinurea, Kidney damage,
bone marrow depression
• Dose: Start with 125-250mg OD, then 250mg
BD.

19. Azathioprine
• Purine antimetabolite
• Potent suppressant of cell mediated
immunity
• Affect differentiation and function of T-cells
and natural killer cells
• Remission in RA is less but some cases
not responding to gold may respond to it.
• Given along with corticosteroid
• Dose: 2.5-5mg/kg/day

20. 4.Biological agents
Infliximab• Chimeric IgG1-kappa monoclonal antibody
• Anti TNF antibodies
• Binds to soluble, bound both the forms of TNF
and thus causes dose dependent neutralization
of TNF alpha.
• Useful in patients resistant to DMARDs and
Methotrexate.
• Given IV, half life 8-12 days.
• A/E: N,V,H and coughing.
other use-Crohn’s disease.
»Contd.,

21. Entanercept
• Dimer consisting of TNF receptor joined to Fc
domain of human IgG…..binds to TNFα & β.
• Given by SC route thrice a wk.
• Effective in juvenile RA where Infliximab is found
ineffective.
Levamisole
• Antihelminthic in a dose of 150 mg.
• MOA-unknown
• A/E- Agranulocytosis

22. Leflunomide:
• Recently introduced immunomodulator
• It inhibits proliferation of activated lymphocytes in
patients with active RA.
• Arthritic symptoms are suppressed and radiological
progression is retarded
• It is rapidly converted in the body to active
metabolite, which inhibits dihydroorotate
dehydrogenase and pyrimidine synthesis in actively
growing cells.
»Contd.,

23. • It is alternative for MTX or Sulfasalazine
• Dose: Loading dose of 100mg daily for
3days followed by 20mg OD (t1/2 2 wks)
• S/E: Elevation of liver enzymes, renal
impairment and teratogenic effect
23

24. • Adverse effects:- D, H, N, rashes, loss of
hair, thrombocytopenia, chest infection
• C/I:children, pregnant and lactating
women.

25. Corticosteriods
• Potent immunosuppressants and
antiinflammatory drugs.
• Inducted at any stage in RA.
• They do not arrest the rheumatoid process nor
prevent erosions.
• Long term use of corticosteroid carries serious
disadvantages.. Low dose 5-10mg
• High dose employed over short periods in cases
with severe systemic manifestations.