Chemistry:Thiamazole

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Short description: Chemical compound
Thiamazole
Methimazole.svg
Thiamazole ball-and-stick.png
Clinical data
Trade namesTapazole, others
Other namesmethimazole (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa682464
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability93%
Protein bindingNone
MetabolismLiver
Elimination half-life5-6 hours
ExcretionKidney
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC4H6N2S
Molar mass114.17 g·mol−1
3D model (JSmol)
Melting point146 °C (295 °F)
Solubility in water275[1] mg/mL (20 °C)
  (verify)

Thiamazole, also known as methimazole, is a medication used to treat hyperthyroidism.[2] This includes Graves disease, toxic multinodular goiter, and thyrotoxic crisis.[2] It is taken by mouth.[2] Full effects may take a few weeks to occur.[3]

Common side effects include itchiness, hair loss, nausea, muscle pain, swelling, and abdominal pain.[2] Severe side effects may include low blood cell counts, liver failure, and vasculitis.[2] Use is not recommended during the first trimester of pregnancy due to the risk of congenital anomalies, but it may be used in the second trimester or third trimester.[4] It may be used during breastfeeding.[4] Those who developed significant side effects may also have problems with propylthiouracil.[2] Thiamazole is a cyclic thiourea derivative that works by decreasing the production of thyroid hormones.[2]

Thiamazole was approved for medical use in the United States in 1950.[2] It is on the World Health Organization's List of Essential Medicines.[5][6] It is available as a generic medication.[2] It is also available in Europe and Asia.[7] In 2020, it was the 206th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[8][9]

Medical uses

Thiamazole is a drug used to treat hyperthyroidism such as in Graves' disease, a condition that occurs when the thyroid gland begins to produce an excess of thyroid hormone. The drug may also be taken before thyroid surgery to lower thyroid hormone levels and minimize the effects of thyroid manipulation. Additionally, thiamazole is used in the veterinary setting to treat hyperthyroidism in cats.

Adverse effects

It is important to monitor any symptoms of fever or sore throat while taking thiamazole; this could indicate the development of agranulocytosis, an uncommon but severe side effect resulting from a drop in the white blood cell count (to be specific, neutropenia, a deficiency of neutrophils). A complete blood count (CBC) with differential is performed to confirm the suspicion, in which case the drug is discontinued.[10] Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) may increase recovery.

Other known side effects include:

  • skin rash
  • itching
  • abnormal hair loss
  • upset stomach
  • vomiting
  • loss of taste
  • abnormal sensations (tingling, prickling, burning, tightness, and pulling)
  • swelling
  • joint and muscle pain
  • drowsiness
  • dizziness
  • decreased platelet count (thrombocytopenia)
  • aplasia cutis congenita (prenatal exposure)
  • thyroid gland enlargement (prenatal exposure)
  • choanal atresia (prenatal exposure during the first trimester of pregnancy)
  • acute pancreatitis[11][12][13]

Interactions

Adverse effects may occur for individuals who:

  • Take anticoagulants ('blood thinners') such as warfarin (Coumadin), diabetes medications, digoxin (Lanoxin), theophylline (Theobid, Theo-Dur), and vitamins
  • Have ever had any blood disease, such as decreased white blood cells (leukopenia), decreased platelets (thrombocytopenia) or aplastic anemia, or liver disease (hepatitis, jaundice)

Mechanism of action

Thiamazole inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I−) to iodine (I2), hypoiodous acid (HOI), and enzyme linked hypoiodate (EOI), facilitating iodine's addition to tyrosine residues on the hormone precursor thyroglobulin, a necessary step in the synthesis of triiodothyronine (T3) and thyroxine (T4).[citation needed]

It does not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors such as perchlorate and thiocyanate.

A study has shown that it modulates secretion of CXCL10.[14]

Chemical properties

The cyclic thiourea derivative thiamazole is a white to matte brown crystalline powder with a characteristic odour. The boiling point is 280 °C (decomposition). Thiamazole is soluble in water, ethanol and chloroform, but hardly soluble in ether.[15]

Thiamazole acts as a free radical scavenger for radicals such as the hydroxyl radical (•OH) radical.[16] It is used as free radical scavenger in organic chemistry.[17]

Veterinary uses

Thiamazole is also indicated in cats to treat hyperthyroidism.[18]

References

  1. ↑ "DrugBank: Methimazole (DB00763)". drugbank.ca. http://www.drugbank.ca/drugs/DB00763. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "Methimazole Monograph for Professionals". American Society of Health-System Pharmacists. https://www.drugs.com/monograph/methimazole.html. 
  3. ↑ The Flesh and Bones of Medical Pharmacology E-Book. Elsevier Health Sciences. 2008. p. 74. ISBN 9780723437161. https://books.google.com/books?id=zFbsy-ugRhgC&pg=PA74. 
  4. ↑ 4.0 4.1 "Methimazole Use During Pregnancy". https://www.drugs.com/pregnancy/methimazole.html. 
  5. ↑ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  6. ↑ World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. 2021. WHO/MHP/HPS/EML/2021.02. 
  7. ↑ "Treatment of graves' disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation". The Journal of Clinical Endocrinology and Metabolism 97 (7): 2396–2403. July 2012. doi:10.1186/1756-6614-8-S1-A12. PMID 22547422. 
  8. ↑ "The Top 300 of 2020". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  9. ↑ "Methimazole - Drug Usage Statistics". https://clincalc.com/DrugStats/Drugs/Methimazole. 
  10. ↑ "Medical treatment of hyperthyroidism: state of the art". Experimental and Clinical Endocrinology & Diabetes 118 (10): 678–684. November 2010. doi:10.1055/s-0030-1253420. PMID 20496313. 
  11. ↑ "Methimazole Treatment and Risk of Acute Pancreatitis: A Population-based Cohort Study". The Journal of Clinical Endocrinology and Metabolism 105 (12): e4527–e4530. December 2020. doi:10.1210/clinem/dgaa544. PMID 32813014. 
  12. ↑ "Methimazole and risk of acute pancreatitis". The Lancet. Diabetes & Endocrinology 8 (3): 187–189. March 2020. doi:10.1016/s2213-8587(20)30025-5. PMID 32035032. 
  13. ↑ Pharmacovigilance Risk Assessment Committee (PRAC) (4 January 2019). "PRAC recommendations on signals". European Medicines Agency. https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendations-signals-adopted-26-29-november-2018-prac-meeting_en.pdf. 
  14. ↑ "Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes". The Journal of Endocrinology 195 (1): 145–155. October 2007. doi:10.1677/JOE-07-0240. PMID 17911406. 
  15. ↑ Entry on Thiamazol. at: Römpp Online. Georg Thieme Verlag, retrieved 10. November 2014.
  16. ↑ "Evidence for direct interactions between methimazole and free radicals". FEBS Letters 176 (2): 337–340. 1984-10-29. doi:10.1016/0014-5793(84)81192-8. 
  17. ↑ Inhibition of amine oxide, 2010-12-30, https://patents.google.com/patent/CN102741310B/en, retrieved 2019-04-14 
  18. ↑ "Managing hyperthyroidism in cats." by S Caney, Veterinary Times 2012 Vol.42 No.46 pp.12-15

External links



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