Download L4-Anti-rheumatic dr..

BY
PROF.
AZZA EL-MEDANY
DR.
OSAMA YOUSIF
General Features &
Conditions to use antirheumatic
 Low doses are commonly used early in the course of
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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
General Clinical Uses
 Treatment of rheumatic disorders
 Combination therapies are both
safe & efficacious
Hydroxychloroquine
Mechanism of action :
 Trapping free radicals

Suppression of T lymphocyte cells
Pharmacokinetics
 Rapidly & completely absorbed following oral
administration.
 Penetrates into C.N.S. & traverse the placenta
 Metabolized in liver
Adverse Effects
Pruritus
GIT upset
Discoloration
of nail beds &
mucous
membranes
Headaches
Blurred
vision
Irreversible
retinal
damage
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
Mechanism of action
Inhibition of T-Cells ( cell-mediated immune
reactions)
Nausea
Liver
cirrhosis
Mucosal
ulceration
Cytopenia
Adverse Effects
Acute
pneumonia –
like
syndrome
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.
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)
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
Cont.
 Can be given in combination with methotrexate
or other non biologic anti-rheumatic drugs in
patients with active rheumatoid arthritis .
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
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 }
Tumor necrosis factor –α
(TNF-α ) blocking agents
Infliximab
A chimeric antibody ( 25% mouse,
75% human)
Mechanism of action
 Binds to human TNF-α resulting in inhibition of
its action as a mediator in inflammatory diseases
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
Upper
respiratory
tract infections
Pancytopenia
Adverse
effects
Activation of
latent
tuberculosis
Infections
Infusion
reactions
Comparison between NSAIDs &
DMARDs
DMARDs
 Slow onset of action used in
chronic cases when deformity
is exciting
 Arrest progression of the
NSAIDs
 Rapid onset of action used in
acute cases to relief
inflammation & pain
 No effect
disease
 Can not stop formation of
 Prevent formation of new
deformity
new deformity