Drugs used in rheumatoid arthritis DMARDS

Drugs used in the treatment of rheumatoid arthritis

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

3. General Features &
Conditions to use antirheumatic
Low doses are commonly used early in the course
of the disease
Used when the disease is progressing & causing
deformities
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 & efficacious

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. & traverse the placenta
Metabolized in liver

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

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. Nausea
Liver
cirrhosis
Mucosal
ulceratio
n
Acute
pneumonia
–like
syndrome
Adverse Effects
Cytopenia

11. Biologic disease modifiers
Genetically engineered drugs that are used to
modify imbalances of the immune system in
autoimmune diseases.
Some of these agents block, or modify the
activity of selected cells in the immune
system, while others –including tocilizumab
work by blocking certain messenger proteins
known as cytokines , that send signals
between those cells.

13. Classification of biologic disease
modifiers
T-cell modulating drug ( abatacept )
B-cell cytotoxic agent ( rituximab )
Anti-IL-6 receptor antibody ( tocilizumab)
TNF- blocking agents ( infliximab)

14. Tocilizumab
IL-6 receptor inhibitor
Binds to membrane IL-6 receptors ,blocking
the activity of IL-6 in mediating signals
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

15. Cont.
Can be given in combination with
methotrexate
or other non biologic anti-rheumatic drugs in
patients with active rheumatoid arthritis .

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

17. Drug Interaction
In combination of tocilizumab with some drugs
such as cyclosporine or warfarin
{IL-6 inhibits CYP450, this enzyme is essential for
the metabolism of cyclosporine or warfarin.
Tocilizumab which act as inhibitor for IL-
6 ,resulting in restoring the activity of the
enzyme }

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

19. Infliximab
A chimeric antibody ( 25%
mouse, 75% human)

20. Mechanism of action
Binds to human TNF-α resulting in inhibition
of its action as a mediator in inflammatory
diseases

21. 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 prevalence of human
antichimeric antibodies

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

23. Comparison between NSAIDs &
DMARDs
DMARDs NSAIDs
Slow onset of action used
in chronic cases when
deformity 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