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NSAIDs 1 st line of therapy in the medical management of RA.

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Presentation on theme: "NSAIDs 1 st line of therapy in the medical management of RA."— Presentation transcript:

1 NSAIDs 1 st line of therapy in the medical management of RA

2 Control the symptoms and signs of local inflammatory process Minimal effect on the progression of the disease i.e. Diclofenac sodium, naproxen sodium, etc.

3 COX-2 inhibitors – Suppresses COX that is involved in inflammation – Less damaging to the stomach – Associated with increased risk of cardiovascular events

4 GLUCOCORTICOIDS 2 nd line of therapy

5 Systemic GC therapy – Provide effective symptomatic therapy in patients with RA – Low dose PREDNISONE (<7.5 mg/dl) Useful additive therapy to control symptoms May retard the progression of bone erosions Initial course of low dose GC may have a long term protective effect against bone damage LOW DOSE GC + DMARD therapy (i.e. Methotrexate) can be beneficial in controlling sins and symptoms rapidly and affording long term retardation of bone erosion Source: Harrison’s Principles of Internal Medicine 17 th ed.

6 DMARDS (Disease-Modifying Anti-rheumatic Drugs) 3 rd line of therapy

7 Slows down the progression of joint destruction Slow acting because it may take 6 weeks to 6 months for it to become evident Methotrexate, azathioprine, penicillamine, hydroxychloroquine and chloroquine, organic gold compounds, sulfasalazine

8 Methotrexate DMARD of FIRST choice to treat RA Individuals with RF for development of bone erosions or persistent synovitis or >3months

9 MOA: – Inhibition of aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase and thymidylate synthetase, with secondary effects on polymorphonuclear chemotaxis

10 Pharmacokinetics – 70% absorbed after oral administration – Metabolized to a less active hydroxylated metabolite and both the parent compound and the metabolite are polyglutamated within cells where they stay for prolonged periods – Half-life: 6-9 hours – Increased in the presence of hydroxychloroquine – Excreted primarily in the urine

11 Indications – Dosing regimen: mg weekly, 30 or 35 mg weekly has an increased effect – Decreases the rate of appearance of new erosions – Juvenile chronic arthritis, ankylosing spondylitis, polymyositis, dermatomyositis, Wegener’s granulomatosis, giant cell arteritis, SLE and vasculitis Maximal improvement is observed after 6 months of therapy

12 Adverse Effects – Nausea and mucosal ulcers – most common – GI upset – Progressive dose-related hepatotoxicity (enzyme elevation) occurs frequently – Contraindicated in pregnancy Source: Basic and Clinical Pharmacology 10 th edition, 2007 by Katzung

13 BIOLOGICS 4 th line of therapy

14 Slows down progression of damage to articular structures Major impact on the signs and symptoms of RA

15 TNG-neutralizing agents – Infliximab, etanercept and adalimumab IL-1 neutralizing agents –Anakinra B-cell inhibitors – Rituximab Inhibition of T cell activation –Abatacept

16 ABATACEPT

17 MOA: – Costimulation modulator that inhibits the activation of T cells.

18 Pharmacokinetics – IV infusion – 3 doses (day 0, week 2 and week 4) initially – Followed by monthly infusions – Dose is based on body weight <60kg – 500mg kg – 750mg >100kg – 1000g – Half-life: days – Coadministration with methotrexate, NSAIDs and corticosteroids does not influence clearance of abatacept

19 Indications – Can be used as monotherapy or in combination with other DMARDs in patients with moderate to severe rheumatoid arthritis who have had an inadequate response to DMARDs or TNF antagonists. – Reduces the clinical signs and symptoms of rhematoid arthritis, slows the progression of damage to the joints, and improves the physical function of patients

20 Adverse Effects – Increased risk of upper respiratory tract – concomitant use with TNF antagonists is NOT recommended due to increased risk of infection Source: Basic and Clinical Pharmacology 10 th edition, 2007 by Katzung

21 IMMUNOSUPPRESSIVE THERAPY 5 th line of therapy

22 Azathioprine, leflunomide, cyclosporine and cyclophosphamide Effective in the treatment of RA and exerts therapeutic effects similar to DMARDs DMARDs > immunosuppressive agents Increase toxicities Reserved for patients who have failed DMARDs and biologics therapy Source: Harrison’s Principles of Internal Medicine 17 th ed.


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