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-----Leflun
omide-----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......ototoxic
ity.
9.Penicillamine
.....Git disturbances.....Dermatitis.....Hematological
abnormalities.....Proteinuria.