Disease –Modifying Antirheumatic drugs

Slow Acting Anti-inflammatory Drugs )

BY PROF.

AZZA EL-MEDANY

DR.

OSAMA YOUSF

OBJECTIVES

At the end of the lecture the students should

Define DMARDsDescribe the classification of this

group of drugsDescribe the general advantages &

criteria of this group of drugs Describe the general clinical uses

o Know some examples of drugs related to DMARDS.

o Describe the mechanism of action , specific clinical uses , adverse effects &

contraindications of individual drugs.

OBJECTIVES ( Continue)

General FeaturesLow doses are commonly used early in the course

of the diseaseUsed when the disease is progressing & causing

deformities ( they stop the progress of the disease )

Used when the inflammatory disease is not responding to NSAIDs

Can not repair the existing damage , but prevent further deformity

Have 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 :

Stabilization of lysosomal enzyme activity

Trapping free radicals

Suppression of T lymphocyte cells

PharmacokineticsRapidly & completely absorbed following

oral administration.

Has a very large volume of distribution

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

Metabolized in liver

ContinueSome metabolic products retain

antimalarial activity

Both parent drug & metabolites are excreted in the urine

The excretion rate is enhanced in acidic urine

Pruritius

GIT upset

Discoloration of nail beds & mucous membranes

Irreversible retinal damage

Adverse EffectsHeadaches

Blurred vision

MethotrexateImmunosuppressant drug

Response to methotrexate occurs sooner than for other slow acting drugs.

Doses of methotrexate are much lower than those needed in cancer chemotherapy

Given once a week

Mechanism of action

Inhibition of polymorphonuclear chemotaxis

Suppression of T lymphocyte Cells

Nausea

Liver cirrhosis

Mucosal ulceration

Acute pneumonia –like syndrome

Adverse Effects

Cytopenias

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 macrophage & T cell function

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 actionArrest progression of the

diseasePrevent formation of

new deformityUsed in chronic cases

when deformity is exciting

No analgesic effect

Rapid onset of actionNo effect Can not stop formation

of new deformityUsed in acute cases to

relief inflammation & pain

Analgesic effect

SUMMARYDMARDs are used mainly in chronic cases of

rheumatoid arthritis , when the disease is progresssing and forming deformity.

They do not remove the existing damage but prevent further formation of deformities.

They have no analgesic effect.

SUMMARY ( Continue)They are slow in onset needs weeks to

manifest their effects .

Hydroxychloroquine acts mainly through suppression of the activity of lysosomal enzymez and trapping free radicals .

Its main adverse effects is irreversible retinal damage & hepatic toxicity.

CONTINUEMethotrexate acts mainly through

suppression of phagocytic cells & T cells

Its adverse effects are bone marrow depression & mucosal ulceration

Infliximab is a chimeric TNF-α blocking agent.

Given with methotrexate to reduce antichimeric effect

CONTINUEIts main adverse effects are upper respiratory

tract infections & reactivation of latent TB,

CONTINUEMethotrexate acts mainly through

suppression of phagocytic cells &