1. Disease modified Anti-rheumatic drugs ( DMARD)

2. BY
PROF. AZZA EL-MEDANY
DR.
OSAMA YOUSIF

3. General Features & Conditions to use DMARD
Low doses are commonly used early in the course of the disease
Used when the disease is progressing & causing deformities or damage
Used when the inflammatory disease is not responding to NSAIDs
Can not repair the existing damage , but prevent further deformity
Have no analgesic effects
Slow onset their effects take from 6 weeks up to 6 months to be evident

4. General Clinical Uses Treatment of rheumatic disorders
Combination therapies are both safe & effective

5. Hydroxychloroquine Mechanism of action : Trapping free radicals
Suppression of T lymphocyte cells

6. Pharmacokinetics
Rapidly & completely absorbed following oral administration.
Penetrates into C.N.S. & Cross the placental barrier
Metabolized in liver

7. Adverse Effects Pruritus GIT upset Headaches Blurred vision
Discoloration of nail beds & mucous membranes
Irreversible retinal damage

8. Methotrexate Immunosuppressant drug
Used mainly as chemotherapy for cancer treatment
Doses of methotrexate as antirheumatic are much lower than those needed in cancer chemotherapy
Given once a week

9. Mechanism of action
Inhibition of T-Cells ( cell-mediated immune reactions)

10. Adverse Effects Nausea Cytopenia Mucosal ulceration Liver cirrhosis
Acute pneumonia
Mucosal ulceration

11. Biologic disease modifiers
Genetically engineered drugs that are used to modify imbalances of the immune system in autoimmune diseases.
(1)Block, or modify the activity of selected cells in the immune system.
(2)Blocking action of certain mediators that responsible for inflammatory conditions.

12. Classification of biologic disease modifiers
T-cell modulating drug ( abatacept )
B-cell cytotoxic agent ( rituximab )
Anti-IL-6 blocking agents (Tocilizumab)
TNF- α blocking agents ( infliximab)

13. Tocilizumab IL-6 receptor inhibitor
Blocks the activity of IL-6 mediated signaling
Half-life is dose dependent (11-13 days )
Given as monthly IV infusion
Used as monotherapy in adult with rheumatoid arthritis or in children over 2 years with systemic juvenile arthritis

14. Cont.
In combination with methotrexate or other non biologic anti-rheumatic drugs in patients with active rheumatoid arthritis

15. Side effects Severe infusion reactions
Serious infections ( bacterial, tuberculosis ,fungal
Increase cholesterol level
Increase liver enzymes
Decrease in WBCs
Blood tests will be used monthly for increase in cholesterol, liver enzymes & decrease in WBCs

16. Tumor necrosis factor –α
(TNF-α ) blocking agents

17. Infliximab
A chimeric antibody ( 25% mouse, % human)

18. Mechanism of action
Binds to human TNF-α resulting in inhibition of macrophage & T cell function

19. Infliximab Given as IV infusion over at least two hours
Half-Life 8-12 days
Given every 8 weeks regimen.
Elicits up to 62% incidence of human antichimeric antibodies.
Concurrent therapy with methotrexate decreases the incidence of human antichimeric antibodies
Contraindicated in patients with a history of tuberculosis

20. Upper respiratory tract infections Activation of latent tuberculosis
Pancytopenia
Adverse effects
Infections
Activation of latent tuberculosis
Infusion reactions

21. Comparison between NSAIDs & DMARDs
Slow onset of action used in chronic cases when deformity or damage is exciting
Arrest progression of the disease
Prevent formation of new deformity
Rapid onset of action used in acute cases to relief inflammation & pain
No effect
Can not stop formation of new deformity