メチラポン 化學(xué)特性,用途語,生産方法
効能
診斷補(bǔ)助薬 (下垂體機(jī)能判定)
商品名
メトピロン (セオリアファーマ)
使用
Metyrapone acts as a glucocorticoid synthesis inhibitor, maintaining stress-hormone levels.
生物活性
Cytochrome P450 inhibitor. Blocks glucocorticoid synthesis via inhibition of steroid 11- β hydroxylase (CYP11B1) activity (IC 50 = 7.83 μ M). Also inhibits CYP3A4 and cytochrome P450-mediated ω / ω -1 hydroxylase activity.
作用機(jī)序
Metyrapone (Metopirone) produces its primary pharmacological
effect by inhibiting 11-β-hydroxylase,
thereby causing diminished production and release of
cortisol. The resulting reduction in the negative feedback
of cortisol on the hypothalamus and pituitary
causes an increase in corticotrophin release and in the
secretion of precursor 11-deoxysteroids.
臨床応用
Metyrapone is used in the differential diagnosis of both
adrenocortical insufficiency and Cushing’s syndrome
(hypercortisolism). The drug tests the functional competence
of the hypothalamic–pituitary axis when the
adrenals are able to respond to corticotrophin; that is,
when primary adrenal insufficiency has been ruled out.
After metyrapone administration, a patient with a
disease of pituitary origin cannot achieve a compensatory
increase in the urinary excretion of 17-hydroxycorticosteroids
or 11-deoxysteroids. Moreover, if pituitary
corticotrophin is suppressed by an autonomously secreting
adrenal carcinoma, there will be no increase in response
to metyrapone. On the other hand, if pituitary
corticotrophin secretion is maintained, as occurs in adrenal
hyperplasia, the inhibition of corticoid synthesis produced
by metyrapone will stimulate corticotrophin secretion
and the release of metabolites of precursor urinary
steroids, which can be measured as 17-hydroxycorticosteroids.
Metyrapone is now used less frequently in the
differential diagnosis of Cushing’s syndrome because of
the ability to measure plasma corticotrophin directly.
The steroid-inhibiting properties of metyrapone
have also been used in the treatment of Cushing’s syndrome,
and it remains one of the more effective drugs
used to treat this syndrome. However, the compensatory
rise in corticotrophin levels in response to falling
cortisol levels tends to maintain adrenal activity.This requires
that glucocorticoids be administered concomitantly
to suppress hypothalamic–pituitary activity.
Although metyrapone interferes with 11β- and 18-
hydroxylation reactions and thereby inhibits aldosterone
synthesis, it may not cause mineralocorticoid deficiency
because of the compensatory increased production
of 11-desoxycorticosterone.
副作用
Side effects associated with the use of metyrapone include
gastrointestinal distress, dizziness, headache, sedation,
and allergic rash. The drug should not be used in
cases of adrenocortical insufficiency or when hypersensitivity
reactions can be expected. When administered
to pregnant women during the second or third trimesters,
the drug may impair steroid biosynthesis in the
fetus. Because metyrapone is relatively nontoxic, it is
used in combination therapy with the more toxic aminoglutethimide
to reduce its dosage.
メチラポン 上流と下流の製品情報(bào)
原材料
準(zhǔn)備製品