Antirheumatic drugs BY PROF AZZA ELMEDANY DR OSAMA

Anti-rheumatic drugs

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 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 : v Trapping free radicals v 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 v. 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.

In other words , some medicines directly affect the cells , and others block the communication between cells

Classification of biologic disease modifiers v. T-cell modulating drug ( abatacept ) v. B-cell cytotoxic agent ( rituximab ) v. Anti-IL-6 receptor antibody ( tocilizumab) v. 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 CYP 450, 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 NSAIDs Slow onset of action used in chronic cases when deformity is exciting Rapid onset of action used in acute cases to relief inflammation & pain Arrest progression of the disease No effect Prevent formation of new deformity Can not stop formation of new deformity