Sunday 7 / 12 / 2014
©Ali Kareem 2014-2015
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مكتب اشور لالستنساخ
DMARDs
Lecture 2
Total lectures NO. 26
Dr. Najeeb
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
-----Methotrexate-----Sulfasalazine-----Cyclosporine-----
Leflunomide-----Auranofine-----Hydroxychloroquine----
Penicillamine.
-Parenteral
-----Aurothioglucose-----Infliximab & adalimomab-----Etanerecept.
Toxicity of DMARDs (side effects)
DMARDs can cause severe or fatal toxicities
!-Methotrexate
.....Gastric irritation.....Hematotoxicity.....Teratogenicity
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 disturbances.....Hepatotoxicity.....Skin
reactions.
7-Gold compounds
.....Diarhoea.....Hematologic abnormalities.....Dermatitis.
8.Hydroxychloroquine
.....GIT
disturbances.....Rash.....Myopathy.....Neuropathy......ototoxicity.
9.Penicillamine
.....Git disturbances.....Dermatitis.....Hematological
abnormalities.....Proteinuria.