1-ヒドラジノフタラジン 化学特性,用途語,生産方法
用途
血管拡張薬 降圧薬
効能
血圧降下薬, 血管拡張薬
説明
Cross-reactions between hydrazine derivatives occur. Hydralazine may sometimes cause flushing and reversible Lupus erythematosis
化学的特性
Yiellow Solid
使用
Hydralazine is a non-nucleoside analog that inhibits DNA methylation and reactivates the expression of tumor suppressor genes. Non-selective MAO-A/B inhibitor; semicarbazide-sensitive amine oxidase inhibitor. Antihypertensive.
定義
ChEBI: The 1-hydrazino derivative of phthalazine; a direct-acting vasodilator that is used as an antihypertensive agent.
生物学の機能
The vasodilation produced by hydralazine (Apresoline)
depends in part on the presence of an intact blood vessel
endothelium. This implies that hydralazine causes
the release of nitric oxide, which acts on the vascular
smooth muscle to cause relaxation. In addition, hydralazine
may produce vasodilation by activating K
+
channels.
接触アレルゲン
Hydralazine is a hydrazine derivative used as a antihypertensive
drug. Skin rashes have been described during
treatment. Exposure occurs mainly in the pharmaceutical
industry. Cross-sensitivity is frequent with hydrazine,
which is considered to be a potent sensitizer.
作用機序
Hydralazine exhibits an antihypertensive effect by directly relaxing smooth muscles of the
vessels. It has an effect on arterial vessels while having a minimal effect on venous vessels.
As a result, resistance of peripheral vessels decreases, and blood pressure is reduced
(diastolic more than systolic).
It does not have a substantial effect on nonvascular smooth musculature or cardiac tissues.
Homeostatic circulatory reflexes remain natural, and the resulting hypotension activates cardiovascular
reflexes, which are expressed as an increase of heart work, power, and volume
of cardiac output. Therefore, it is most effectively used in combination with β-blockers.
薬理学
Hydralazine produces widespread but apparently not
uniform vasodilation; that is, vascular resistance is decreased
more in cerebral, coronary, renal, and splanchnic
beds than in skeletal muscle and skin. Renal blood
flow and ultimately glomerular filtration rate may be
slightly increased after acute treatment with hydralazine.
However, after several days of therapy, the
renal blood flow is usually no different from that before
drug use.
In therapeutic doses, hydralazine produces little effect
on nonvascular smooth muscle or on the heart. Its
pharmacological actions are largely confined to vascular
smooth muscle and occur predominantly on the arterial
side of the circulation; venous capacitance is much less
affected. Because cardiovascular reflexes and venous capacitance
are not affected by hydralazine, postural hypotension
is not a clinical concern. Hydralazine treatment
does, however, result in an increase in cardiac
output.This action is brought about by the combined effects
of a reflex increase in sympathetic stimulation of the
heart, an increase in plasma renin, and salt and water retention.
These effects limit the hypotensive usefulness of
hydralazine to such an extent that it is rarely used alone.
臨床応用
Hydralazine is generally reserved for moderately hypertensive
ambulatory patients whose blood pressure is
not well controlled either by diuretics or by drugs that
interfere with the sympathetic nervous system. It is almost
always administered in combination with a diuretic
(to prevent Na
+ retention) and a β-blocker, such
as propranolol (to attenuate the effects of reflex cardiac
stimulation and hyperreninemia). The triple combination
of a diuretic, β-blocker, and hydralazine constitutes
a unique hemodynamic approach to the treatment of hypertension,
since three of the chief determinants of
blood pressure are affected: cardiac output (β-blocker),plasma volume (diuretic), and peripheral vascular resistance
(hydralazine).
Although hydralazine is available for intravenous
administration and has been used in the past for hypertensive
emergencies, it is not generally employed for
this purpose. The onset of action after intravenous injection
is relatively slow, and its actions are somewhat
unpredictable in comparison with those of several other
vasodilators.
副作用
Most side effects associated with hydralazine administration
are due to vasodilation and the reflex hemodynamic
changes that occur in response to vasodilation.
These side effects include headache, flushing, nasal congestion,
tachycardia, and palpitations. More serious
manifestations include myocardial ischemia and heart
failure. These untoward effects of hydralazine are
greatly attenuated when the drug is administered in
conjunction with a β-blocker.
When administered chronically in high doses, hydralazine
may produce a rheumatoidlike state that
when fully developed, resembles disseminated lupus
erythematosus.
純化方法
It crystallises from MeOH. UV: max 656nm at pH ~11. It complexes with Bi3+ , Zn2+ , Fe2+ and Co2+ .
1-ヒドラジノフタラジン 上流と下流の製品情報
原材料
準備製品