Дексаметазон химические свойства, назначение, производство
Описание
The activity of dexamethasone, as
measured by glycogen deposition, is 20 times greater than that of hydrocortisone. It has five times the
anti-inflammatory activity of prednisolone. Clinical data indicate that this compound has seven times the
antirheumatic potency of prednisolone. It is roughly 30 times more potent than hydrocortisone. Its
pharmacokinetics are presented in Table 33.3. Routes of metabolism for dexamethasone are similar to those for
prednisolone, with its primary 6β-hydroxy metabolite being recovered in urine. Dexamethasone sodium
phosphate is the water-soluble sodium salt of the 21-phosphate ester, with an IV half-life of less than 10
minutes because of rapid hydrolysis by plasma phosphatases. Peak plasma levels for dexamethasone
usually are attained in approximately 10 to 20 minutes following its IV administered dose. A similar reaction
occurs when the phosphate ester is applied topically or by inhalation.
Химические свойства
White or almost white, crystalline powder.
Использование
Dexamethasone is used for the same indications as all corticosteroids; however, it
exhibits a significantly more powerful anti-inflammatory and anti-allergic action.
It is used for circulatory collapse—shock during or after surgical operations, trauma,
blood loss, myocardial infarction, and burns. It is also used in severe infections—toxemia,
vascular collapse in meningococcosis, septicemia, diphtheria, typhoid fever, and peritonitis.
It is used in severe allergic conditions—asthmatic status, laryngeal edema, severe anaphylactic
reactions to medicinal drugs, and pyrogenic reactions.
Показания
Cushing’s disease is defined as hypercortisolism due to
chronic overproduction of corticotrophin by a corticotroph
adenoma. Cortisol’s lack of suppressibility during
the administration of low doses of dexamethasone
but suppressibility during high-dose dexamethasone is
the key diagnostic finding in 99% of the patients with
Cushing’s disease. This contrasts with the lack of glucocorticoid
suppressibility typically found in patients with
corticotrophin-independent hypercortisolism (Cushing’s
syndrome). A judicious selection of the available tests
may be necessary to obtain an accurate diagnosis in patients
with Cushing’s syndrome.
Общее описание
Dexamethasone, 9-fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione,is the 16 -isomer of betamethasone.
Dexamethasone acetate, USP (21-acetate)
Dexamethasone sodium phosphate, USP (21-sodiumphosphate).
Реакции воздуха и воды
Insoluble in water.
Профиль реактивности
Dexamethasone may be sensitive to prolonged exposure to light. Dexamethasone is incompatible with strong oxidizers, strong acids, acid chlorides and acid anhydrides. Oxidation may occur with bases.
Пожароопасность
Flash point data for Dexamethasone are not available; however, Dexamethasone is probably combustible.
Биологическая активность
Glucocorticoid; anti-inflammatory. Reduces levels of activated NF- κ B in immature dendritic cells (DCs) and inhibits differentiation into mature DCs.
Фармаколо?гия
Dexamethasone is a corticosteroid with high glucocorticoid activity and
virtually no mineralocorticoid activity. I ts mechanism of action as an
antiemetic is unknown, but it is possible that either direct genomic or
indirect non-genomic effects on 5-HT3 and GABAA receptors contribute to its
antiemetic activity. Many of the original studies were carried out using 8–
10mg of dexamethasone phosphate, but smaller doses (2.5–4mg) provide
equal antiemetic efficacy with minimal risk of adverse effects. Concerns
relating to adrenal suppression and other steroid-induced adverse effects
(including increased risk of bleeding) after a single dose of dexamethasone
remain largely unfounded. O ne of the most unpleasant adverse effects of
dexamethasone involves intense perineal stimulation after rapid i.v.
injection.
Фармакокине?тика
The activity of dexamethasone, as
measured by glycogen deposition, is 20 times greater than that of hydrocortisone. It has five times the
anti-inflammatory activity of prednisolone. Clinical data indicate that this compound has seven times the
antirheumatic potency of prednisolone. It is roughly 30 times more potent than hydrocortisone. Its
pharmacokinetics are presented in Table 33.3. Routes of metabolism for dexamethasone are similar to those for
prednisolone, with its primary 6β-hydroxy metabolite being recovered in urine. Dexamethasone sodium
phosphate is the water-soluble sodium salt of the 21-phosphate ester, with an IV half-life of less than 10
minutes because of rapid hydrolysis by plasma phosphatases. Peak plasma levels for dexamethasone
usually are attained in approximately 10 to 20 minutes following its IV administered dose. A similar reaction
occurs when the phosphate ester is applied topically or by inhalation.
Профиль безопасности
Poison by intraperitoneal and subcutaneous routes. An experimental teratogen. Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits toxic fumes of F-.
Методы очистки
Dexamethasone has been recrystallised from Et2O or small volumes of EtOAc. Its solubility in H2O is 10 mg/100mL at 25o; and is freely soluble in Me2CO, EtOH and CHCl3. [Arth et al. J Am Chem Soc 80 3161 1958; for the -methyl isomer see Taub et al. J Am Chem Soc 82 4025 1960, see Beilstein 8 IV 3501.]
Дексаметазон препаратная продукция и сырье
сырьё
препарат