Review of Pharmacology - 9E (2015)

Autacoids
Rheumatoid Arthritis
Rheumatoid arthritis (RA) is an autoimmune multisystem disease. NSAIDs are used to provide
symptomatic relief but exert no effect on the progression of the disease. Disease modifying anti
rheumatoid drugs (DMARDs) slow the progression of disease but act slowly (takes 6 weeks
to 6 months).
A. Corticosteroids
Low-dose corticosteroids can de used as a bridge therapy (until DMARDs start to work) or as
adjunctive therapy (with DMARDs) in rheumatoid arthritis
B. Synthetic DMARDs
1. Methotrexate
It is first choice DMARD and is used at much lower doses (7.5 mg weekly) than required in
cancer chemotherapy (30 mg daily).
Adverse effects of methotrexate
• Gastric irritation and stomatitis (most common)
• Pancytopenia
• Hepatotoxicity with fibrosis and cirrhosis Risk factors are:
v Chronic hepatitis
v Heavy alcohol consumption
v Diabetes mellitus
v Obesity
v Kidney disease
• Interstitial pneumonitis (Hypersensitivity reaction)
• Teratogenicity
• Increased risk of B-cell lymphomas
• Amoxycillin and probenecid increase risk of methotrexate toxicity
Methotrexate is first choice
DMARD
Leflunomide is a prodrug (converted
in the body to an active
metabolite) that inhibits the enzyme
dihydro orotate dehydrogenase.
General Autacoids Pharmacology
2. Sulfasalazine
It is metabolized to sulfapyridine and 5-aminosalicylic acid. Former is the active moiety in
RA and latter is useful for ulcerative colitis. It is used in patients when methotrexate is
contraindicated.
3. Leflunomide
It is a prodrug (converted in the body to an active metabolite) that inhibits the enzyme
dihydro orotate dehydrogenase. This enzyme is required for pyrimidine synthesis and thus
growth of B cells is arrested by leflunomide. Cholestyramine decreases its toxicity by enhancing
its clearance. It is faster acting (action is manifested in 4 weeks as compared to 3 months with
N
Teriflunomide is dihydro-orotate
dehydrogenase inhibitor (like
leflunomide). It is indicated for
relapsing-remitting multiple
sclerosis.
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