rheumatoid arthritis (vk)
DESCRIPTION
TRANSCRIPT
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.
Rheumatoid arthritis-
Chronic 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
Autoimmune
IgM activates complements and release infl. Mediators
Neutrophil infiltration
Release of Lysosomal enzymes PGs
Damage to cartilage, bone errosion
vasodilatationedema & pain
• 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.
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 therapyo Motion exercises, Aerobic exercise with muscle strength.
Pharmacological therapy:o NSAIDso DISEASE MODIFYING ANTIRHEUMATIC DRUGS
[DMARDs]o Adjuvant: GLUCOCORTICOIDS
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
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.,
DMARDs• 1.Methotrexate (Mtx.)
• 2. Agents used in mild disease or in combination with MTX.• Hydroxychloroquine • Sulfasalazine• Minocycline
• 3.Traditional DMARDs -(limited used currently)• Gold salts (Aurothiomalate sodium)…..X• d-Penicillamine………………………..X• Azathioprine
• 4. Biological agents • Cyclosporine Leflunomide• Infliximab
• Methoterxate, Azathioprine, Cyclosporine are IMMUNOSUPPRESANT• Leflunomide IMMUNO MODULATOR
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.,
• 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
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/E- Retinal damage Corneal opacities Neuropathy, Myopathy Rash
Graying of hairsIrritable bowel syndrome
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.
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.,
• 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
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.
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
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.
4.Biological agents
»Contd.,
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
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
• Adverse effects:- D, H, N, rashes, loss of
hair, thrombocytopenia, chest infection
• C/I:children, pregnant and lactating
women.
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.