Orimeten - General Information
An aromatase inhibitor that produces a state of "medical" adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Orimeten has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p454)
Pharmacology of Orimeten
Orimeten inhibits the enzymatic conversion of cholesterol to D5-pregnenolone, resulting in a decrease in the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens.
Orimeten for patients
Patients should be warned that drowsiness may occur and that they should not drive, operate potentially dangerous machinery, or engage in other activities that may become hazardous because of decreased alertness.
Patients should also be warned of the possibility of hypotension and its symptoms.
Cytadren accelerates the metabolism of dexamethasone; therefore, if glucocorticoid replacement is needed, hydrocortisone should be prescribed.
Aminoglutethimide diminishes the effect of coumarin and warfarin.
Cytadren is contraindicated in those patients with serious forms, and/or more severe manifestations, of hypersensitivity to glutethimide or aminoglutethimide.
Additional information about Orimeten
Orimeten Indication: For the suppression of adrenal function in selected patients with Cushing's syndrome, malignant neoplasm of the female breast, and carcinoma in situ of the breast.
Mechanism Of Action: Orimeten reduces the production of D5-pregnenolone and blocks several other steps in steroid synthesis, including the C-11, C-18, and C-21 hydroxylations and the hydroxylations required for the aromatization of androgens to estrogens, mediated through the binding of aminoglutethimide to cytochrome P-450 complexes. A decrease in adrenal secretion of cortisol is followed by an increased secretion of pituitary adrenocorticotropic hormone (ACTH), which will overcome the blockade of adrenocortical steroid synthesis by aminoglutethimide. The compensatory increase in ACTH secretion can be suppressed by the simultaneous administration of hydrocortisone. Since aminoglutethimide increases the rate of metabolism of dexamethasone but not that of hydrocortisone, the latter is preferred as the adrenal glucocorticoid replacement. Although aminoglutethimide inhibits the synthesis of thyroxine by the thyroid gland, the compensatory increase in thyroid-stimulating hormone (TSH) is frequently of sufficient magnitude to overcome the inhibition of thyroid synthesis due to aminoglutethimide. In spite of an increase in TSH, aminoglutethimide has not been associated with increased prolactin secretion.
Drug Interactions: Anisindione The agent decreases the anticoagulant effect
Dexamethasone Decreases the effect of dexamethasone
Dicumarol The agent decreases the anticoagulant effect
Acenocoumarol The agent decreases the anticoagulant effect
Warfarin The agent decreases the anticoagulant effect
Tamoxifen Decreases the effect of tamoxifen
Food Interactions: Take without regard to meals.
Generic Name: Aminoglutethimide
Synonyms: Dl-Aminoglutethimide; P-Aminoglutethimide
Drug Category: Antineoplastic Agents; Adrenergic Agents
Drug Type: Small Molecule; Approved
Absorption: Rapidly and completely absorbed from gastrointestinal tract. The bioavailability of tablets is equivalent to equal doses given as a solution.
Toxicity (Overdose): Oral LD50s (mg/kg): rats, 1800; dogs, >100. Intravenous LD50s (mg/kg): rats, 156; dogs, >100. Symptoms of overdose include respiratory depression, hypoventilation, hypotension, hypovolemic shock due to dehydration, somnolence, lethargy, coma, ataxia, dizziness, fatigue, nausea, and vomiting.
Protein Binding: 21-25%
Biotransformation: Hepatic. 34-54% of the administered dose is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as an N-acetyl derivative.
Half Life: 12.5 ± 1.6 hours
Dosage Forms of Orimeten: Tablet Oral
Chemical IUPAC Name: 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione
Chemical Formula: C13H16N2O2
Aminoglutethimide on Wikipedia: https://en.wikipedia.org/wiki/Aminoglutethimide
Organisms Affected: Humans and other mammals