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Inflammatory bowel disease
Published in Michael JG Farthing, Anne B Ballinger, Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Elizabeth Carty, Anne B Ballinger
Azathioprine and 6-MP are metabolized to 6-thioinosinic acid, which is thought to achieve immunosuppression by incorporation into purine nucleotides, disrupting normal purine metabolism and therefore interfering with DNA and RNA synthesis and decreased numbers of B and T lymphocytes. Clinical response may take 3-6 months.
Pharmacology of Therapeutic Agents in Photomedicine
Published in Henry W. Lim, Nicholas A. Soter, Clinical Photomedicine, 2018
Ira C. Davis, Matthew J. Stiller, Jerome L. Shupack
Azathioprine (Fig. 4), a purine analogue, is well absorbed after oral intake, and is metabolized to 6-mercaptopurine, which is not cytotoxic, and to 6-thioinosinic acid and 6-thioguanylic acid which are cytotoxic (45). Conversion primarily by erythrocytes and the liver to inactive metabolites occurs within 10 hr. These metabolites are excreted in the urine. Azathioprine is metabolized by xanthine oxidase. Therefore concomitant allopurinol administration will increase azathioprine levels. Azathioprine inhibits DNA and RNA synthesis and mitoses by incorporating into nucleic acids. Both B- and T-lymphocyte immune responses are affected (43).
Use of synthetic and biologic DMARDs during pregnancy
Published in Expert Review of Clinical Immunology, 2019
Gustavo Guimarães Moreira Balbi, Vinicius Domingues, Gabriela Guimarães Moreira Balbi, Guilherme Ramires De Jesús, Roger Abramino Levy
Azathioprine is commonly prescribed for pregnant patients with SLE as steroid-sparing agent. This drug and its active metabolite, 6-mercaptopurine, are purine analogs that interfere with adenine and guanine nucleosides, inhibiting rapidly dividing cells like T lymphocytes [18]. Initial animal studies reported increased risk for congenital malformations in fetuses exposed to azathioprine [19], but this was not demonstrated in pregnant women [20], including in a recent prospective study [21]. Human fetuses are not capable of metabolizing azathioprine into thioinosinic acid, which is the determinant of azathioprine effect on dividing cells and probably the responsible for the teratogenicity in animals [22].
Immunosuppression in the Management of Presumed Non-infective Uveitis; Are We Sure What We are Treating? Notes on the Antimicrobial Properties of the Systemic Immunosuppressants
Published in Ocular Immunology and Inflammation, 2020
In 1953, Elion & Hitchings, working at Burroughs Wellcome in New York discovered 6-mercaptopurine, and although this is still used in cancer therapy, its pro-drug azathioprine was introduced in 1959 as an immunosuppressant. It is a purine antagonist; its metabolites thioinosinic acid and thioguanylic acid are purine analogues, and being incorporated into DNA cross-links during synthesis, prevent normal structure from developing.