by prof. azza el-medany dr. osama yousif general features & conditions to use antirheumatic low...
DESCRIPTION
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 evidentTRANSCRIPT
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BY
PROF.
AZZA EL-MEDANY
DR.
OSAMA YOUSIF
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General Features & Conditions to use antirheumatic Low doses are commonly used early in the
course of the diseaseUsed when the disease is progressing &
causing deformities Used when the inflammatory disease is not
responding to NSAIDsCan not repair the existing damage , but
prevent further deformityHave no analgesic effectsSlow onset their effects take from 6 weeks
up to 6 months to be evident
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General Clinical Uses
Treatment of rheumatic disorders
Combination therapies are both safe & efficacious
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Hydroxychloroquine Mechanism of action :
Trapping free radicals
Suppression of T lymphocyte cells
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PharmacokineticsRapidly & completely absorbed following
oral administration.
Penetrates into C.N.S. & traverse the placenta
Metabolized in liver
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Pruritus
GIT upset
Discoloration of nail beds & mucous membranes
Irreversible retinal damage
Adverse EffectsHeadaches
Blurred vision
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MethotrexateImmunosuppressant drugUsed mainly as chemotherapy for cancer
treatment
Doses of methotrexate as antirheumatic are much lower than those needed in cancer chemotherapy
Given once a week
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Mechanism of action
Inhibition of T-Cells ( cell-mediated immune reactions)
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Nausea
Liver cirrhosis
Mucosal ulceration
Acute pneumonia –like syndrome
Adverse Effects
Cytopenia
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Biologic disease modifiersGenetically 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.
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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)
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TocilizumabIL-6 receptor inhibitorBinds 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
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Cont.Can be given in combination with
methotrexate
or other non biologic anti-rheumatic drugs in
patients with active rheumatoid arthritis .
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Side effectsSevere infusion reactionsSerious infections ( bacterial,
tuberculosis ,fungal Increase in cholesterol levelIncrease in liver enzymesDecrease in WBCs
Blood tests will be used monthly for increase in cholesterol, liver enzymes & decrease in WBCs
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Drug InteractionIn 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 }
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Tumor necrosis factor –α
(TNF-α ) blocking agents
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Infliximab
A chimeric antibody ( 25% mouse, 75% human)
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Mechanism of actionBinds to human TNF-α resulting in
inhibition of its action as a mediator in inflammatory diseases
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InfliximabGiven as IV infusion over at least two
hoursHalf-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
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Adverse effects
Infections
Upper respiratory
tract infections
Activation of latent
tuberculosis
Pancytopenia
Infusion reactions
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Comparison between NSAIDs & DMARDs
DMARDs NSAIDsSlow 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