DMARDs

DMARDs

Terminology
DMARDs stands for disease-modifying antirheumatic drugs. The term is given
because of the ability of the members of this heterogeneous group of drugs to
reverse joint damage ,an effect never seen with nonsteroidal anti-inflammatory
drugs- NSAIDs-.
This group is also called SAARDs which stands for slow acting antirheumatic
drugs because it takes 6 weeks to 6 months for their benefit to be apparent.

DMARDs agents

1-Methotrexate
2-Sulfasalazine
3-Cyclosporine
4-Infliximab & adalimomab
5-Etanerecept
6-Leflunomide
7-Gold compounds
8-Hydroxychloroquine
9-Penicillamine


DMARDs mechanisms of action
1-Methotrexate
It reduces the number of immune cells required to the inflammatory response.
2-Sulfasalazine
The sulfapyridine moiety appears to be more important than the
5-aminosalicylic acid component as antirheumatic.
3-Cyclosporine
It binds to T-lymphocyte`s immunophylline which leads finally to inhibition
of certain cytokines important in inflammation.
4-Infliximab & adalimomab
They are monoclonal antibodies that bind to and prevent the action of
TNF-alpha , a cytokine which plays a key role inflammation .
5-Etanerecept
A recombinant protein composed of two TNF receptors and acts as a decoy
decreasing the cellular actions of TNF-alfa
.6-Leflunomide
It inhibits dihydrooroate dehydrogense, an enzyme required by activated
lymphocytes for the synthesis of the pyrimidines needed for RNA synthesis.
7-Gold compounds
Gold compounds as auranofine(oral) and aurothioglucose (injectable) alter the
activity of macrophages,cells which play a central role in inflammation.They
also suppress the phagocytic activity by neutrophils (microhages) .
8-Hydroxychloroquine
It may interfer with activity of T-lymhocytes,decrease leucocyte chemotaxis
and other mechanisims.
9-Penicillamine
Its mechanisms of action is similar to that of .hydroxychloroquine


Clinical indications of DMARDs
1-Rhematoid arthritis (RA) not responding to other agents.
2-Lupus erythematosis
3-Juvenile RA
4-Sjögren syndrom
5-Other immunological diseases

Kinetics of DMARDs

-Oral

-Parenteral

-----Aurothioglucose-----Infliximab & adalimomab-----Etanerecept.

Toxicity of DMARDs (side effects)

DMARDs can cause severe or fatal toxicities
!-Methotrexate
.....Gastric
2-Sulfasalazine
.....GIT disturbances.....Leukopenia.....skin rash
3-Cyclosporine
.....Nephrotoxity.....Peipheral neuropthy.....Hypertension
4-Infliximab & adalimomab
.....Activation of latent TB.....Upper respiratoty tract infection.
5-Etanerecept
.....Injection site reactions
6-Leflunomide
.....Teratogecity.....GIT reactions.
7-Gold compounds
.....Diarhoea.....Hematologic abnormalities.....Dermatitis.
8.Hydroxychloroquine
.....GIT
9.Penicillamine
.....Git
abnormalities.....Proteinuria.