Rheumatoid-Arthritis-lnmc

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By: drpankajmangal (98 month(s) ago)

hi gud morning madam. this ppt is awesom .u describe RA inbeautiful manner .plz send this ppt. to drpankajmangal@gmail.com thanks

By: drpankajmangal (98 month(s) ago)

hi gud morning madam. this ppt is awesom .u describe RA inbeautiful manner .plz send this ppt. to drpankajmangal@gmail.com thanks

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Rheumatoid arthritis:

Rheumatoid arthritis Dr.Reena verma

Slide 2:

Now the first thing to remember is that we are all too young to have arthritis and there are plenty of people out there willing to remind us of this when ever we forget. Obviously any aches you have are either just in your mind or due to “ growing pains ” (oh please let me stop growing then!). But don ’ t worry, once you pass the point of being considered too young, you can look forward to being told that “ everyone gets a touch of arthritis as they get older ” so it ’ s nothing to worry about

Rheumatoid arthritis:

Rheumatoid arthritis Chronic, systemic, inflammatory ,autoimmune disease predominantly affecting joints & periarticular tissues

etiology:

etiology Autoimmune disease: autoantibodies to Fc portion of IgG antibody are produced by B lymphocytes High titres of serum RA factor

Pathophysiology:

Pathophysiology Inflammation Synovial proliferation Joint tissue destruction

Principles of management :

Principles of management Rest to acutely inflamed joints Relief of pain & stiffness Reduction of inflammation Prevention of articular damage Preservation of joint function & muscle strength Improve general well being of patient

PHARMACOTHERAPY OF RHEUMATOID ARTHRITIS:

PHARMACOTHERAPY OF RHEUMATOID ARTHRITIS

Slide 13:

classification 1)Symptomatic drugs : NSAIDs 2)Disease modifying antirheumatic drugs(DMARDs/SAARDs) >immunosuppressants- methotrexate,azathioprine,cyclosporine >sulfasalazine >Chloroquine/hydroxychloroquine >leflunomide >gold,auranofin >d-penicillamine

Classification(cont.):

Classification(cont.) 3)Biologic response modifiers(BRM): > TNF α inhibitors:etanercept,infliximab,adalimumab >IL-1 antagonist-anakinra 4)Adjuvant drugs : Corticosteroids

Methotrexate:

Methotrexate DMARD of first choice & standard drug Immunosuppressant & antiinflammatory agent Dihydrofolate reductase inhibitor Inhibits cytokine production, chemotaxis & cell mediated immune reaction

methotrexate:

methotrexate Oral low dose (7.5-15 mg) weekly regimen Rapid onset of action ⇨ preferred for initial treatment Sustained & predictable response Variable oral bioavailability; affected by presence of food

methotrexate:

methotrexate Side effects : nodulosis, oral ulceration & GI upset >Prolonged courses: liver cirrhosis, ⇪ chest infection C/I- Pregnancy lactation liver disease active infection leucopenia & peptic ulcer methotrexate

azathioprine:

azathioprine Purine antimetabolite Azathioprine ↦ 6-mercaptopurine TPMT Suppressant of cell mediated immunity & inflammation Azathioprine + corticosteroids : Steroid sparing effect Not combined with methotrexate

Mycophenolate mofetil:

Mycophenolate mofetil Semisynthetic fungal antibiotic Active metabolite: Mycophenolic acid Inhibits B & T cell proliferation Inhibits inosine monophosphate dehydrogenase ⇨ reduces production of cytotoxic T cells Also interferes with leucocyte adhesion

sulfasalazine:

sulfasalazine Sulfapyridine + 5-amino salicylic acid Active moiety: sulfapyridine Suppresses generation of superoxide radicals & cytokine elaboration Used as second line drug in milder cases A/E : neutropenia/thrombocytopenia, hepatitis

Chloroquine hydroxychloroquine:

Chloroquine hydroxychloroquine Milder non erosive disease refractory to methotrexate/sulfasalazine Reduce monocyte IL-1 ⇛ inhibit B-lymphocytes; also interfere with antigen processing

Slide 23:

HYDROXYCHlOROQUINE IS PREFERRED prolonged usage : retinal damage & corneal opacity A/e : rashes, graying of hair, irritable bowel syndrome, myopathy & neuropathy hydroxychloroquine …

leflunomide:

leflunomide Similar in efficacy to Methotrexate Faster onset of action Symptomatic cure + retards radiological progression of disease Used as alternative to methotrexate Leflunomide + Methotrexate ⇛ ⇪ Hepatotoxicity Can be combined with Sulfasalazine

Leflunomide…:

Leflunomide … Leflunomide ⇛ active metabolite ⇨ inhibits dihydro-orotate dehydrogenase & pyrimidine synthesis in actively dividing cells Inhibits proliferation of activated lymphocytes in active RA Long t1/2= 2 weeks

Adverse effects of Leflunomide:

Adverse effects of Leflunomide Diarrhoea, headache, nausea, rashes, loss of hair, thrombocytopenia, leucopenia, chest infections, hepatic transaminases C/I: Pregnant, Lactating & children

gold:

gold Most effective agent to arrest rheumatoid process Reduces chemotaxis Phagocytosis macrophage & lysosomal activity monocyte differentiation inhibits cell mediated immunity Prevents joint destruction; induces bone healing

Gold…:

Gold… Highly cumulative drug; high toxicity A/E : postural hypotension , dermatitis, pruritic rashes, stomatitis, membranous glomerulonephropathy (albuminuria), hepatitis, peripheral neuritis, encephalopathy, pulmonary fibrosis & eosinophilia Salts used: Sodium aurothiomalate, aurothiosulfate, aurothioglucose

Auranofin:

Auranofin Orally active Bioavailability: 25% Lower efficacy Lower toxicity to skin, mucous membranes, kidney & bone marrow Main A/E : diarrhoea, abdominal cramps Rarely pruritis, taste disturbances, mild anaemia & alopecia

BIOLOGIC RESPONSE MODIFIERS:

BIOLOGIC RESPONSE MODIFIERS

TNF-alpha blockers:

TNF-alpha blockers INFLIXIMAB ADALIMUMAB ETANERCEPT

infliximab:

infliximab Chimeric monoclonal anti TNF antibody Binds to soluble + membrane bound TNF-alpha ⇨ dose dependent neutralisation ⇛ down regulation of macrophage & T cell functions ⇛ prevents release of cytokines

infliximab:

infliximab Distributed mostly in vascular compartment Terminal t 1/2 = 8-12 days Not metabolised by hepatic cytochrome P450 enzymes A/E: headache, nausea, rash & cough Can ppt URTI; activation of latent TB Antibodies may develop to infliximab

Infliximab:

Infliximab Given IV once in 2 months More beneficial when combined with methotrexate Sustained & consistent benefit even in DMARD & methotrexate resistant cases Also approved for Crohn’s disease, juvenile chronic arthritis, psoriatric arthritis, wegener’s granulomatosis & sarcoidosis

adalimumab:

adalimumab Recombinant human-anti-TNF monoclonal antibody Given SC T 1/2 = 9-14 days Similar actions as infliximab Lesser immunogenicity

etanercept:

etanercept Genetically engineered fusion protein Dimer: TNF receptor+ Fc domain of human IgG Binds to TNF alpha & also TNF beta (cytokine lymphotoxin alpha) Given SC twice a week Useful in RA including juvenile RA where infliximab is less effective

Interleukin-1 blocker-Anakinra:

Interleukin-1 blocker-Anakinra Used in combination with methotrexate in methotrexate resistant cases

Potential side effects:

Potential side effects Injection site reactions Infections & neutropenia Malignancy Immunogenicity Given Subcutaneously OD C/I: in case of infection Never to be combined with TNF alpha inhibitors

Toclizumab:

Toclizumab Humanized anti-interleukin 6 receptor agent that blocks the action of the inflammatory cytokine. Phase III trials worldwide Licensed in Japan as an orphan drug for treatment of Castleman's disease.

STATUS OF NEWER BIOLOGICS :

STATUS OF NEWER BIOLOGICS

Slide 43:

Rituximab: FDA-approved for lymphoma in 1997 Abatacept: - FDA-approved February, 2006 for - patients with moderately severe RA - inadequate response to > 1 DMARDs - use in combination with MTX UPDATE - FDA-approved December, 2005 for - patients with moderately severe RA - inadequate response to > 1 DMARDs - use as monotherapy or with DMARDs other than TNF antagonists or anakinra

Slide 44:

Rituximab: Mechanism of Action

Slide 45:

Abatacept modulates the immune response by binding to CD80/CD86 on an antigen-presenting cell (APC), such as a dendritic cell, thus preventing costimulatory binding of CD28 on naive T cells and attenuating T-cell activation. Abatacept: Mechanism of Action

Tenidap sodium:

Tenidap sodium IL-1 synthesis inhibitor

corticosteroids:

corticosteroids Potent immunosuppressant & antiinflammatory action Adjuvant drugs: symptomatic improvement + arrest rheumatoid process + delay bony erosions Low doses-Disadv: steroid dependency High doses over short periods for severe systemic manifestations

Indications for local intra-articular therapy:

Indications for local intra-articular therapy One or two joints : resistant in patients otherwise well controlled on medical therapy Patients with one active joint in whom oral NSAID are contraindicated Caution: Avoid injection more often than once in 3 months

Choice of drug therapy:

Choice of drug therapy Early treatment with DMARD ⇨ improves quality of life & long term outcome Aspirin/NSAID given initially for quick symptomatic relief Start concurrently DMARD-methotrexate, hydroxychloroquine, sulfasalazine If uncontrolled-combination of DMARD

Drug therapy…:

Drug therapy … Severe cases: steroids in large doses ⇨ tapered to maintenance doses Methotrexate (+folic acid) currently favored Relative rapid onset of action Maintains sustained improvement Relative safety High level of patient compliance

Slide 52:

Thank you

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