Disease modifying anti rheumatic drugs DMARDs

Disease modifying anti rheumatic drugs DMARDs
Rheumatoid arthritis is a chronic ,systemic inflammatory disorder that many tissues and organs attacks ( specifically joints).
R.A is a form of autoimmunity .
The cause of which still completely unknown
Patients diagnosed with R.A:
Therapy initiation with DMARDs in addition NSAIDs and low dose of corticosteroids and physical therapy .
DMARDs rapidly help to stop the progression of disease at earlier stage.
No one of DMARDs is efficacious
And well tolerated , when inadequate response
Then we use anew DMARDs like
Leflunomide
Anakinra
Tumor necrosis factor inhibitors TNF e.g
Adalimumab ,Etanercept ,Infliximab
Methotrexate ( MTX)

Its an immunosuppressant drug used alone or in combination .
MTX slow erosion in joints, the response occurs
Within 3-6 months of starting treatment.
Other DMARDs can be added to MTX .
Doses of MTX is lower than those used in chemotherapy.
MTX given once a week
S.E of MTX = mucosal ulceration , nausea ,cytopenia ,cirrhosis , acute pneumonia like symp.
Leflunomide
Immunomodulatory agent that mainly causes cell arrest of lymphocytes by its action on dihydroorate dehydrogenase(DHODH).
Activated proliferating lymphocytes require
Constant DNA syn. To proliferate
Purine and pyrimidine are the building blocks of DNA and DHODH is necessary for pyrimidine
Syn.
Leflunomide reversible inhibitor of DHODH
It can be used alone or combined with MTX.
In the treatment R.A .
Leflunomide well absorbed after oral adminis.
kinetics
Extensively bound with albumin more 90%
T1/2 =14-18 days
Loading dose is necessary , rapidly metabolized to active metaboli.
Excretion in urine and feces
SE:
Headache ,diarrhea ,nausea , weight loss , allergic reaction ( flu like syndrome ),skin rash , alopecia and hypokalemia
Its a teratogenic agent
It contraindicated in pregnancy
Hydroxychloroquine
This drug used also in malaria treatment
And it used in R.A in combination with MTX .
The mechanism of action include inhibition of
Phospholipase A2 and platelets aggregation.
It may cause renal toxicity.
Sulfasalazine
Used for mild R.A in combination with hydroxy-
Chloroquine and MTX.
Onset of action =1-3 months
Associated with leucopenia
D- penicillamine
Analogue to cystein ,it slow progression of bone
Destruction and R.A .
Added to NSAIDs or glucocorticoid therapy
It causes serious S.E =blood dyscrasias or renal
Impairment .
Prolong uses causes nephritis ,aplastic anemia
Auranofin (GOLD SALTS
This drug is taken by macrophage and it suppress phagocytosis and lysosomal enzy.
This mechanism retards bone and articular destruction.
Benefit appear in 3-6 months.