Aminoglutethimide

Chemical name

3-(4-Аминофенил)-3-этил-2, 6-пиперидиндион

Gross

C13-H16-N2-O2

Characteristics

White or kremovo-bely crystalline powder. Rat in the water, it is readily soluble in most organic solvents.

Of drugs

The drugs-protivoopujolevoe (zitostaticescoe). Suppress fermentativoe make cholesterol pregnenolon and ingibiruet biosynthesis crust napochechnikov gluko- and mineralokortikoidov, estrogen and androgenov. Education steroids blocked at the level of gidrauxilirovania side chains of 11, 18 and 21 carbon atoms and flavoring first ring, the final synthesis of estrogen (contact zitohromom P450, oposredutm this process, and delays aromatazu). Compensatorno increases secretion ACTG; Oppressing biotransformatia androgenov in estrogena, minimizes tiroksina synthesis of the thyroid gland and compensatorno increases secretion tireotroponogo hormone. In patients with the syndrome Itsenko - Kushinga reduces the highest levels eye in the blood, and thus the severity symptoms. Reducyruet level of estrogen in the blood and suppresses their biosynthesis in neoplastic tissues, promotes regression of the tumor in women with gormonozawisimami malignant mammary gland in menopause. The most effective therapy for the progressive tumors, including in the advanced carcinoma prostate cancer, in the liturgy of soft tissue and bone. And protivosudorojnam Vlijaniem.posle intake of rapidly and completely absorbed, bioavailability - 92-98%. C_max achieved through 1-4 hours (an average of 1.5 hours). Linking plasma proteins (mostly with albuminom), 21-25%; Concentration in the blood cells in the 1,4-1,7 times higher plasma. The range of doses 125-1000 mg value of the equilibrium concentration in the blood is proportional to dose; At doses of 500 and 1000 mg a day, every day for 3 months values equilibrium concentrations of 4.5 and 9.5 µ g / ml, respectively. Metabolised mainly in the liver (oxidation and azetilirovanie aromatic amino) to inactive or low metabolites. Total plasma Cl-about 3.5 h, the volume of 76 litres T_1/2 -15-hours Write, unedited, and in the form of metabolites, mostly kidneys (97%) and jelchew (3-7%).

Indications

Gipercortitizm : syndrome Itsenko - Kushinga caused tumors (carcinoma, prostate adenoma, including the pre - and aftercare period amino korticosteroma) or giperplaziei crust napochechnikov, ectopicescoy products ACTG; Relapses after subtotalna adrenalektomii; Advanced breast cancer (with cancer) among women postmenopause, metasteziruty cancer prostate cancer (palliative treatment); Arterial hypertension (Integrated Management).

Contraindications

Hypersensitivity, incl. glutetimidu to; inducyruemaya porphyria, pregnancy, breast-feeding (at the time of treatment excluded), the children's age.

Side-Effects

Sluggish, drowsiness, insomnia or depression, inadequate response to external stressors sputannosti consciousness ataxy, headache, dizziness; Neutropenia, lakopenia, agranulozitos, thrombocytopenia, anemia (including Hemolytic), pancitopenia, reduced hemoglobin and gematokrita; Hypothyreosis crust napochechnikov until napochechnikova malnutrition; Hypothyroidism, furry and girsutizm (women), premature sexual development (for boys); Arterial gipotenzia (until collapse), tachycardia; nausea, vomiting, diarrhoea or constipation, anorexia, human liver functional tests including raising gamma-glutamintransferzy; holetsaticeski hepatitis, jaundice, a breach of kidney function; giponatriemia, giperkaliemia, hypoglycaemia, giperholesterinemia; fever, increased sweating; mialgia; skin rashes, dermatitis exfoliativei, syndrome Stevens-Johnson, Laiella syndrome; allergic, including anaphylactoidnye reaction, itching, urticaria, Kwinke swelling, allergic alveolitis, with eozinofilnami lung infiltratami et al.

Specific guidance

Proof of light and humidity.

Patient interaction

Hypnotics, tranquillisers, Tricyclic antidepressants, alcohol compound or modify the symptoms of acute overdose. Dioretiki giponatriemia added. Does (due to the activation of liver enzymes) biotransformatia glucocorticoids, oral anticoagulants, digitoksina, theofillina, medroksiprogesteron and oral gipoglikemicakih funds.

Overdosing

There is a decline of corticosteroid (respiratory depression, giperventilatia followed gipoventilaciei, gipotenzia, hypovolaemic shock, drowsiness, lethargy, ataxy, dizziness, a sense of fatigue, muscle weakness, coma, nausea, vomiting; Loss of sodium and water, giponatriemia, gipohloremia, giperkaliemia, hypoglycaemia). Treatment : washing stomach, and the oppression of breath-rooms, IVL, in gipovolemii and hypotension - rehydration (500 ml of plasma, blood plazmozamenitelei), then at / in the adrenaline 10 mg in 500 ml izotoniceski solution of sodium chloride, in the development of symptoms deficit glucocorticoids in / in cefuroxim hydrocortisone (100 mg hydrocortisone sodium succinate 500 ml izotoniceski solution of sodium chloride), and 50 ml of 40% glucose solution for 3 h, and then in / hydrocortisone in 10 ml per hour consistently to be able to separate reception hydrocortisone inside. Answers gemoperfuzia or dialysis (with severe intoxication).

Precautions

Selection dose recommended in the hospital. Be wary appointed to the human liver and kidneys, children. Before implementing the presence of pregnancy. During the period of treatment to control AD functional status napochechnikov crust, the thyroid gland and every two weeks, especially in the first two or three months, the cells of peripheral blood. In napochechnikova gipofunktion arising during the treatment, or in stressful situations (surgery, trauma, acute illness, etc.), shall be glukokortikoida (hydrocortisone). In developing human blood and suspicion of allergic Muhin therapy overturned. The skin rashes, especially at the beginning of treatment, require temporary suspension of treatment. Patients warned of the need during the course refrain from activities potentially hazardous activities that require increased attention and psychomotor speed reactions, that the use of alcohol, to renounce the use of hormonal contraceptives.

Dosing and Administration

Inside, at the time of delivery. Dose set individually depending on the disease and the patient. Adults : syndrome Itsenko - Kushinga-250 mg 2-3 times (napochechnikov adenoma), 2-4 times (napochechnikov carcinoma), 4-7 times (ectopica products ACTG) a day. In metasteziruuschem breast cancer for women and cancer metasteziruuschem prostate gland of 125 mg twice a day (usually 8-9 hours and 16-18 hours), a four times a day at intervals of not less than 6900, under constant review (preferably monitoring) of the plasma hydrocortisone, to achieve the desired level of napochechnikova supression; depending on the level of dose hydrocortisone gradually increased to 250 mg weekly intervals of 1-2 weeks until easy to dose (less than or equal to 1 g / day); maximum dose of 2 g per day.

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