1. תרופות בשימוש בראומטולוגיה פרופ. משה טישלר מחלקה פנימית ב והשרות הראומטולוגי בי " ח אסף הרופא צריפין

2. NSAIDs Mechanism of action-inhibition of the enzyme cycloxygenase Mechanism of action-inhibition of the enzyme cycloxygenase Used for suprression of inflammation and control of pain in various rheumatic conditions Used for suprression of inflammation and control of pain in various rheumatic conditions Treatment does not change the course of disease Treatment does not change the course of disease

5. Prostaglandins/ thromboxane COX-2 inhibitors Arachidonic acid COX-1COX-2 NSAIDs X X Prostaglandins Primarily protect gastroduodenal mucosa Primarily support platelet function Primarily mediate inflammation, pain, and fever X Glucocorticoids X NSAIDs – מנגנון פעולה

10. Non-steroidal anti-inflammatory drugs Non-steroidal anti-inflammatory drugs NSAIDS are anti-inflammatory and analgesic NSAIDS are anti-inflammatory and analgesic do not modify the disease course do not modify the disease course GI side effects are common GI side effects are common take NSAIDS with food or proton pump inhibitors or use the new COX-2 group take NSAIDS with food or proton pump inhibitors or use the new COX-2 group monitor older patients closely (hypertension, congestive heart failure, diabetes, and renal insufficiency) monitor older patients closely (hypertension, congestive heart failure, diabetes, and renal insufficiency)

11. Corticosteroids in Rheumatic Diseases Low doses are used in RA to help control inflammation Low doses are used in RA to help control inflammation High doses are used to suppress disease activity in SLE with target organ involvement and various systemic vasculitides High doses are used to suppress disease activity in SLE with target organ involvement and various systemic vasculitides

14. Rheumatoid Arthritis glucocorticoids the most potent and rapidly acting anti-inflammatory agent the most potent and rapidly acting anti-inflammatory agent used as a bridge therapy until DMARDs become effective; local injection is efficacious and less toxic than DMARDs used as a bridge therapy until DMARDs become effective; local injection is efficacious and less toxic than DMARDs low dose systemic therapy, may slow the rate of joint damage, and is effective in refractory RA low dose systemic therapy, may slow the rate of joint damage, and is effective in refractory RA

15. Glucocorticoids Glucocorticoids Side effects Side effects osteoporosis, cushingoid state, hypertension, premature athersclerosis, infectionosteoporosis, cushingoid state, hypertension, premature athersclerosis, infection Reducing the risk of osteoporosis Reducing the risk of osteoporosis regular exercise, timely estrogen therapy, supplemental calcium and vitamin Dregular exercise, timely estrogen therapy, supplemental calcium and vitamin D calcitonin or biphosphonates in patients with low bone mass and refractory to hormone replacement therapycalcitonin or biphosphonates in patients with low bone mass and refractory to hormone replacement therapy

16. Intraarticular Therapy Use in RA to suppress local inflammation Use in RA to suppress local inflammation Use in RA to induce chemical synovectomy Use in RA to induce chemical synovectomy Use in Osteoarthritis to relieve pain Use in Osteoarthritis to relieve pain

18. Antimalarials Mechanism of action unknown Mechanism of action unknown Use in RA to control inflammation in mild disease or in combination with other drugs Use in RA to control inflammation in mild disease or in combination with other drugs Use in SLE to control arthritis and various skin manifestations Use in SLE to control arthritis and various skin manifestations Regular daily dosage between 200 and 400 mg Regular daily dosage between 200 and 400 mg

20. Gold Compounds in Rheumatic Diseases Mechanism of action unknown Mechanism of action unknown Used to treat Rheumatoid Arthritis Used to treat Rheumatoid Arthritis Can be used also in Psoriatic Arthritis Can be used also in Psoriatic Arthritis Intramuscular doses are 50 mg weekly for 3 months and then 50 mg monthly Intramuscular doses are 50 mg weekly for 3 months and then 50 mg monthly Oral gold is not used today Oral gold is not used today

23. Penicillamine Used for treatment of Rheumatoid Arthritis Used for treatment of Rheumatoid Arthritis Was used in the past for treatment of Systemic Sclerosis Was used in the past for treatment of Systemic Sclerosis Dosage range between 250 and 750 mg daily Dosage range between 250 and 750 mg daily

25. Sulfasalazine Mechanism of action unknown Mechanism of action unknown Used to suppress arthritis in Rheumatoid Arthritis, Psoriatic Arthritis and all Sero- negative Spondyloarthropaties Used to suppress arthritis in Rheumatoid Arthritis, Psoriatic Arthritis and all Sero- negative Spondyloarthropaties Daily dosage varies between 2 and 3 gr. Daily dosage varies between 2 and 3 gr.

30. Methotrexate Mechanism of action- folic acid antagonist Mechanism of action- folic acid antagonist in Rheumatoid Arthritis inhibits IL-1 in Rheumatoid Arthritis inhibits IL-1 Used most commonly in Rheumatoid Arthritis and Psoriatic Arthritis but also in other arthritides Used most commonly in Rheumatoid Arthritis and Psoriatic Arthritis but also in other arthritides Used also in Polymyositis/Dermatomyositis Used also in Polymyositis/Dermatomyositis Dosage ranges between 7.5 and 20 mg weekly Dosage ranges between 7.5 and 20 mg weekly

32. Leflunomide (Arava) Used to suppress arthritis in Rheumatoid Arthritis and Psoriatic Arthritis Used to suppress arthritis in Rheumatoid Arthritis and Psoriatic Arthritis Mechanism of action-inhibition of pyrimidine synthesis Mechanism of action-inhibition of pyrimidine synthesis Daily dosage 20 mg Daily dosage 20 mg Concentrations can be found in the body for 6 months after stopping treatment Concentrations can be found in the body for 6 months after stopping treatment

35. Immunosuppressive Medications Mechanism of action-suppression of the immune system Mechanism of action-suppression of the immune system Used for treatment of Rheumatoid Arthritis, SLE, and various vasculitides Used for treatment of Rheumatoid Arthritis, SLE, and various vasculitides Can be used also as steroid sparing agents Can be used also as steroid sparing agents Cyclophospamide is given in pulses for organ involvement in SLE and is also gives in vasculitis Cyclophospamide is given in pulses for organ involvement in SLE and is also gives in vasculitis Oral daily cyclophosphamide is given in Rheumatoid vasculitis Oral daily cyclophosphamide is given in Rheumatoid vasculitis

38. Minocycline Mechanism of action-inhibition of cartilage metaloproteinases ? Mechanism of action-inhibition of cartilage metaloproteinases ? Used in Rheumatoid Arthritis in combination with MTX Used in Rheumatoid Arthritis in combination with MTX

40. Biologic Treatment of Rheumatic Diseases Mechanism of action-targeted against proinflammatory cytokines Mechanism of action-targeted against proinflammatory cytokines Used for treatment of Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis Used for treatment of Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis

41. The Role of TNF-  in Arthritis

42. Cytokines – Receptor Interaction Adapted with permission from Choy EHS, Panayi GS. N Engl J Med. 2001;344:907-916. © 2001 Massachusetts Medical Society. All rights reserved. Inflammatory Cytokine Normal InteractionNeutralization of Cytokines Receptor Blockade Activation of Anti-inflammatory Pathways Cytokine Receptor Soluble Receptor Monoclonal Antibody Receptor Antagonist Anti- inflammatory Cytokine Suppression of Inflammatory Cytokines No Signal Inflammatory Signal

43. Comparison of Anti-TNF Agents Etanercept Infliximab Adalimumab Etanercept Infliximab Adalimumab TNF inhibitoryesyes yes TNF inhibitoryesyes yes Neutralize Soluble TNFyesyes yes Neutralize Soluble TNFyesyes yes Neutralize Cell-bound TNFyesyes yes Neutralize Cell-bound TNFyesyes yes Neutralizes LTyesno no Neutralizes LTyesno no Lyse TNF-Producing Cellsnoyes yes Lyse TNF-Producing Cellsnoyes yes Human originentirelypartially entirely Human originentirelypartially entirely Half-Life4.8 d9.5 d 12-14 d Half-Life4.8 d9.5 d 12-14 d Antibodies<5%13% <1% Antibodies<5%13% <1% Concomitant MTXOptionalRequired Optional Concomitant MTXOptionalRequired Optional DosageSQ,IV, SQ, DosageSQ,IV, SQ, bi-weeklyq4-8wks q2wks

44. Biologic DMARDs Side Effects Side Effects Local irritaion at the site of injection Local irritaion at the site of injection Upper respiratory tract infections Upper respiratory tract infections Tuberculosis Tuberculosis Increase in the incidence of autoantibodies Increase in the incidence of autoantibodies Lymphoma? Lymphoma?

45. IVIG Mechanism of action-probably blockage of receptors to antigens/autoantibodies Mechanism of action-probably blockage of receptors to antigens/autoantibodies Used for treatment of resistant Polymyositis/Dermatomyositis Used for treatment of resistant Polymyositis/Dermatomyositis Also used for various complications associated with SLE and other vasculotides Also used for various complications associated with SLE and other vasculotides

46. IVIG Side Effects Side Effects Headaches Headaches Acute Renal Failure Acute Renal Failure Acute Myocardial Infarction Acute Myocardial Infarction