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14-September-2008 18:02:48 - Metyrapone Metyrapone Systematic IUPAC name 2-methyl-1,2-dipyridin-3-yl-propan-1-one Identifiers CAS number 54-36-4 ATC code V04CD01 PubChem 4174 DrugBank APRD01111 Chemical data Formula C14H14N2O Mol. mass 226.274 g/mol Pharmacokinetic data Bioavailability ? Metabolism ? Half life 1.9 ±0.7 hours. Excretion ? Therapeutic considerations Pregnancy cat. C US Legal status Routes Oral Metyrapone Metopirone is a drug used in the diagnosis of adrenal insufficiency, and occasionally the treatment, of Cushing's syndrome hypercortisolism. Contents 1 Mechanism 2 Uses 3 References 4 See also Mechanism Metyrapone blocks cortisol synthesis1 by inhibiting steroid 11β-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11-deoxycortisol levels. When excess ACTH secretion is the cause of hypercortisolism, the metyrapone test helps clarify if the source of the ACTH is pituitary or ectopic non-pituitary. The effects of metyrapone were first noticed by mistake in transgenic mice by TE Vanguard at the University of Tennessee in Memphis while testing a similar drug known as metradione which was being studied for its effects on corticosteroid uptake. Uses Metyrapone can be used in the diagnosis of adrenal insufficiency. Metyrapone 30mg/kg, maximum dose 3000 mg, is administered at midnight usually with a snack. The plasma cortisol and 11-deoxycortisol are measured the next morning between 8:00 and 9:00 am. A plasma cortisol less than 220nmol/l indicates adequate inhibition of 11β-hydroxylase. In patients with intact Hypothamalmo-pituitary-adrenal axis, CRH and ACTH levels rise as a response to the falling cortisol levels. This results in an increase of the steroid precursors in the pathway. Therefore if 11-deoxycortisol levels do not rise and remains less than 7 mcg/dl then it is highly suggestive of impaired HPA axis. Metyrapone test may aid in verifying the cause of Cushing's syndrome. Most patients with pituitary dysfunction and/or pituitary microadenoma will increase ACTH secretion in response to metyrapone, while most ectopic ACTH-producing tumors will not. Pituitary macroadenomas do not always respond to metyrapone. References ^ Young EA, Ribeiro SC, Ye W June 2007. Sex differences in ACTH pulsatility following metyrapone blockade in patients with major depression. Psychoneuroendocrinology 32 5: 503-7. doi:10.1016/j.psyneuen.2007.03.003. PMID 17462829. PMC:1975691. See also ACTH stimulation test Tablets This pharmacology-related article is a stub. v d e Diagnostic agents V04 Diabetes Tolbutamide · Glucose Fat absorption Vitamin A concentrates Bile duct patency Sorbitol · Magnesium sulfate · Sincalide · Ceruletide Pituitary function Metyrapone · Sermorelin · Corticorelin · Somatorelin Liver functional capacity Galactose · Sulfobromophthalein Tuberculosis Tuberculin Gastric secretion Cation exchange resins · Betazole · Histamine phosphate · Pentagastrin · Methylthioninium chloride · Caffeine and sodium benzoate Renal function Inulin and other polyfructosans · Indigo carmine · Phenolsulfonphthalein · Alsactide · Aminohippuric acid Thyroid function Thyrotropin · Protirelin Pancreatic function Secretin · Pancreozymin cholecystokinin · Bentiromide Fertility disturbances Gonadorelin Retrieved from http://en..org/wiki/Metyrapone Categories: Antiglucocorticoids | Pharmacology stubs Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 22 August 2008, at 17:56
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