Metyrapone

Metronidazole — see also Imidazole, 1-(2-hydroxy-ethyl)-2-methyl-5-nitro-antiprotozoal activity, 1, 180 veterinary use, 1, 208 mode of action, 1, 208 Metyrapol metabolism, 1, 234 Metyrapone... 

Metyrapone human plasma/urine liq-liq extraction silica Chiralcel OJ UV 42... 

Figure 11.4 Chromatograms of plasma samples on a silica-chiralcel OJ coupled column system (a) plasma spiked with oxprenolol (internal standard) (b) plasma spiked with 040 p-g/ml metyrapone and 0.39 p-g/ml metyrapol (racemate) (c) plasma sample obtained after oral administration of 750 mg metaiypone. Peaks are as follows 1, metyrapone 2, metyrapol enantiomers 3, oxprenolol. Reprinted from Journal of Chromatography, 665, J. A. Chiarotto and I. W. Wainer, Determination of metyrapone and the enantiomers of its chfral metabolite metyrapol in human plasma and urine using coupled achfral-chfral liquid cltro-matography, pp. 147-154, copyright 1995, with permission from Elsevier Science.

J. A. Chiar otto and I. W. Wainer, Determination of metyrapone and the enantiomers of its chiral metabolite metyrapol in human plasma and urine using coupled achhal-chhal liquid cliromatogruphy , J. Chromatogr. 665 147-154 (1995). 

Metyrapone Acetylsalicylic acid Caraspirin calcium Acetylsalicylic acid chloride Benoryiate Phenprocoumon N-Acetylsulfanilyl chloride Sulfacytine Sulfamethoxazaole 3-Acetylthiomethyl propanoic acid Captopril... 

Williams PA, Cosine J, Vinkovic DM et al (2004) Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science 305 683-686... 

Overnight Administer metyrapone at Normal response is a Distinguishes between normal individuals and... 

The unstimulated serum cortisol and rapid ACTH stimulation tests are useful in the diagnosis of adrenal crisis (Table 42-2). The insulin tolerance test is contraindicated owing to preexisting hypoglycemia. The metyrapone test is also contraindicated because metyrapone inhibits cortisol production. 

Metyrapone synthesis. Inhibits 11 -hydroxylase. 750 mg/day than 600 mg/day). Generally well tolerated. patients with hyperlipidemia. Used in Cushing s disease, ectopic... 

Cassiano, N.M., Cass, Q.B., Degani, A.L.G., Wainer, I.W. (2002). Determination of the plasma levels of metyrapone and its enantiomeric metyrapol metabolites by direct plasma injection and multidimensional achiral-chiral chromatography. Chirality 14, 731-735. 

The answer is a. (Hardman, pp 1482—1483. Katzung, pp 673-674.) Metyrapone inhibits 11-hydroxylation of steroid precursors, which prevents formation of cortisone and cortisol. These precursors are then diverted into aldosterone and androgen production pathways, which explains the adverse effects of hirsutism and edema... 

Other tests that can help determine the etiology include the high-dose dexamethasone suppression test, plasma ACTH test, metyrapone stimulation test, corticotropin-releasing hormone stimulation test or inferior petrosal sinus sampling. 

Ectopic ACTH syndrome Surgery, chemotherapy. Metyrapone (Metopirone) 250-mg capsules 0.5-1 g/day, divided eveiy 4-6 hours 1-2 g/day, divided every 4-6 6 g/day... 

Metyrapone inhibits 11-hydroxylase activity, resulting in inhibition of cortisol synthesis. Initially, patients can demonstrate an increase in plasma ACTH concentrations because of a sudden drop in cortisol. This can cause an increase in androgenic and mineralocorticoid hormones resulting in hypertension, acne, and hirsutism. Nausea, vomiting, vertigo, headache, dizziness, abdominal discomfort, and allergic rash have been reported after oral administration. 

Combination therapy with metyrapone and aminoglutethimide appears more effective than either agent alone for various etiologies of Cushing s disease with fewer side effects and is useful for inoperable patients. 

Other tests include the insulin hypoglycemia test, the metyrapone test, and the corticotrophin-releasing hormone stimulation test. 

FIGURE 4.19 Structures of the CYP3A4 substrates, metyrapone and progesterone. 

A few typical examples of CBR-catalyzed reduction of xenobiotics include the reduction of the antipsychotic haloperidol (6), the P450 inhibitor metyrapone (6), the oral hypoglycemic acetohexamide (6), and the anticoagulant warfarin (7). 

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