Methimazole

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Methimazole
Methimazole.svg
Thiamazole ball-and-stick.png
Systematic (IUPAC) name
1-methyl-3H-imidazole-2-thione
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682464
Pregnancy cat. D (US)
Legal status Prescription Only (S4) (AU) -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 93%
Protein binding None
Metabolism Hepatic
Half-life 5-6 hours
Excretion Renal
Identifiers
CAS number 60-56-0 YesY
ATC code H03BB02
PubChem CID 1349907
DrugBank DB00763
ChemSpider 1131173 YesY
UNII 554Z48XN5E YesY
KEGG D00401 YesY
ChEBI CHEBI:50673 YesY
ChEMBL CHEMBL1515 YesY
Chemical data
Formula C4H6N2S 
Mol. mass 114.17 g/mol
Physical data
Melt. point 146 °C (295 °F)
Solubility in water 275[1] mg/mL (20 °C)
 YesY (what is this?)  (verify)

Methimazole (also known as Tapazole or Thiamazole or MMI) is an antithyroid drug,[2] and part of the thioamide group. Like its counterpart propylthiouracil, a major side effect of treatment is agranulocytosis.

Indications[edit]

Methimazole is a drug used to treat hyperthyroidism, 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, Methimazole is used in the veterinary setting to treat hyperthyroidism in cats.

Mechanism of action[edit]

Methimazole inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I-) to iodine (I0), facilitating iodine's addition to tyrosine residues on the hormone precursor thyroglobulin, a necessary step in the synthesis of triiodothyronine (T3) and thyroxine (T4).

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.

It acts at CXCL10.[3]

Adverse effects[edit]

It is important to monitor any symptoms of fever or sore throat while taking methimazole; 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. 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 white blood cells
  • decreased platelet count (thrombocytopenia)
  • Aplasia cutis congenita (prenatal exposure)

Drug interactions[edit]

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)
  • Are pregnant, or going to become pregnant, or are breast-feeding.

Methimazole has been demonstrated to potently inhibit all CYP450 enzymes, meaning that the plasma concentration of all hepatically metabolized drugs will be significantly increased when taken with, or after, methimazole.[4] This must be considered when starting a patient on methimazole, increasing their dose, or starting a methimazole patient on another drug. Many drugs will need their doses lowered and dosing-time intervals increased when co-administered with methimazole. For some hepatically metabolized drugs with very low therapeutic indexes, co-administration with methimazole may not be possible at all.

See also[edit]

References[edit]

  1. ^ http://www.drugbank.ca/drugs/DB00763
  2. ^ Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N (June 2007). "Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease". The Journal of Clinical Endocrinology and Metabolism 92 (6): 2157–62. doi:10.1210/jc.2006-2135. PMID 17389704. 
  3. ^ Crescioli C, Cosmi L, Borgogni E, et al. (October 2007). "Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes". J. Endocrinol. 195 (1): 145–55. doi:10.1677/JOE-07-0240. PMID 17911406. 
  4. ^ Guo Z, Raeissi S, White RB, Stevens JC. Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. PMID 9172960.