Drug Classification: Disease Modifying Antirheumatic Drugs (DMARD)

Methotrexate

Mechanism of Action:

Methotrexate is classified as an antimetabolite drug. It blocks DNA synthesis in proliferating cells by binding with and blocking the action of dihydrofolate reductase which enables regeneration of folate, a cofactor in the production of substrates for DNA and RNA synthesis. By this mechanism it prevents cell proliferation making it both immunosuppressant and cytotoxic.

Lecture and CAL materials:

Infliximab

UNDER REVIEW (September 2016)

Mechanism of Action:

Infliximab is an injectable antibody that blocks the effects of tumor necrosis factor alpha (TNF alpha). TNF alpha is a pro-inflammatory cytokine, a substance made by cells of the body which has an important role in promoting inflammation.

Lecture and CAL materials:

Azathioprine

Mechanism of Action:

Cytotoxic immunosuppressant- azathioprine is a prodrug. It is metabolized to its active form mercaptopurine, a purine analogue which inhibits DNA synthesis. Clonal proliferation of the immune response is thus inhibited&#059; may also inhibit cytokines and growth factors. Mercaptopurine is released slower from azathioprine and is more effective as an immunosuppressant. (mercaptopurine is more useful as an antineoplastic drug). Drug action is potentiated by allopurinol (gout medication-gout is caused by excessive purine degradation to uric acid) which inhibits xanthine oxidase. This enzyme acts to degrade azathioprine. The dosage of azathioprine should be reduced by 25% with concurrent use of allopurinol. Thiopurine methyltransferase (TMPT) is another enzyme that degrades azathioprine. Individuals homozygous for low TMPT are susceptible to myelosuppression (bone marrow suppression). See comments.

Lecture and CAL materials:

Sulfasalazine

UNDER REVIEW (September 2016)

Mechanism of Action:

An aminosalicylate drug that is a combination of a sulphonamide (an antibiotic) and 5-aminosalicylic acid (5-ASA, an aspirin derivative). Mode of action unknown: sulfasalazine is a prodrug, that is, it is not active in its ingested form but is broken down by bacteria in the colon into its two constituents: 5-aminosalicylic acid (5ASA), and sulfapyridine. There is some controversy as to which of these two products are responsible for the activity of sulfasalasine. It reduces cytokine production and inflammatory activity. The anti-inflammatory action of 5-ASA is at least in part mediated through modulation of the endocannabinoid system via elevation of anandamide levels – anandamide being an endogenous cannabinoid.

Lecture and CAL materials: