BY

PROF.

AZZA EL-MEDANY

DR.

OSAMA YOUSIF

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

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

PharmacokineticsRapidly & completely absorbed following

oral administration.

Penetrates into C.N.S. & traverse the placenta

Metabolized in liver

Pruritus

GIT upset

Discoloration of nail beds & mucous membranes

Irreversible retinal damage

Adverse EffectsHeadaches

Blurred vision

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

Mechanism of action

Inhibition of T-Cells ( cell-mediated immune reactions)

Nausea

Liver cirrhosis

Mucosal ulceration

Acute pneumonia –like syndrome

Adverse Effects

Cytopenia

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.

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)

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

Cont.Can be given in combination with

methotrexate

or other non biologic anti-rheumatic drugs in

patients with active rheumatoid arthritis .

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

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 }

Tumor necrosis factor –α

(TNF-α ) blocking agents

Infliximab

A chimeric antibody ( 25% mouse, 75% human)

Mechanism of actionBinds to human TNF-α resulting in

inhibition of its action as a mediator in inflammatory diseases

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

Adverse effects

Infections

Upper respiratory

tract infections

Activation of latent

tuberculosis

Pancytopenia

Infusion reactions

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