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Pathway Description
Carbimazole Action Pathway
Homo sapiens
Drug Action Pathway
Carbimazole an imidazole antithyroid agent used for the treatment of hyperthyroidism and thyrotoxicosis. It is also used to prepare patients for thyroidectomy. Carbimazole is a prodrug, which is converted to methimazole in the gastrointestinal tract or after absorption into the blood. Methimazole enters the thyroid gland and is transported into thyroid follicle cells, where it inhibits the production of the thyroid hormones T3 (liothyronine) and T4 (thyroxine). Thyroid hormone synthesis begins with iodide being transported into the follicle cell, through the Na+/I- symporter, then into the follicle lumen through the pendrin transporter. Iodide is oxidized to iodine using thyroid peroxidase (TPO). TPO catalyzes the iodination of the tyrosine molecules in thyroglobulin to produce mono-iodinated tyrosine (MIT) and di-iodinated tyrosine (DIT). The thyroglobulin molecules enter the follicle lumen for this reaction via exocytosis. Coupling of MIT and DIT occurs, again using TPO. Coupling produces T3 and T4 molecules which are still attached to the thyroglobulin molecule. This complex goes through endocytosis to enter the follicle cell, where proteolysis of the thyroglobulin molecule occurs to release T3 and T4, amino acids, and MIT and DIT molecules which may not have been coupled. T3 and T4 are secreted from the thyroid gland into the blood where they can go exert their effects in other organs. The Amino acids can be used in protein synthesis to produce more thyroglobulin molecules, and MIT and DIT are metabolized by iodotyrosine deiodinase I, to produce iodide and tyrosine which can be recycled to be used in process of thyroid hormone synthesis again. Methimazole inhibits TPO, preventing iodide oxidation, the incorporation of iodine into tyrosine molecules and coupling of MIT and DIT, as a result, the production of T3 and T4 is decreased and less T3 and T4 are secreted from the follicle cell, reducing the concentration of thyroid hormones in the blood. Common side effects from taking carbimazole may include nausea, vomiting, diarrhea, dizziness, headaches, painful joints, itchy skin, rash and thinning hair. Serious side effects may include neutropenia, acute pancreatitis, liver damage, infections and hypoglycemia.
References
Carbimazole Pathway References
Ritter, James (2020). Rang and Dale’s Pharmacology (9th ed). The thyroid. Retrieved from: https://www-clinicalkey-com.login.ezproxy.library.ualberta.ca/#!/content/book/3-s2.0-B9780702074486000354?scrollTo=%23hl0000114
Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M: KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2021 Jan 8;49(D1):D545-D551. doi: 10.1093/nar/gkaa970.
Pubmed: 33125081
Wishart, D., Knox, C., Guo, A., Shrivastava, S., Hassanali, M., Stothard, P., . . . Woolsey, J. (2005, June). Carbimazole. Retrieved November 3, 2021, from https://go.drugbank.com/drugs/DB00389
NHS( n.d.). Carbimazole. Retrieved November 3, 2021 from: https://www.nhs.uk/medicines/carbimazole/
Singh G, Correa R: Methimazole
Pubmed: 31424807
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