Гидралазин

Описание

Cross-reactions between hydrazine derivatives occur. Hydralazine may sometimes cause flushing and reversible Lupus erythematosis

Химические свойства

Yiellow Solid

Использование

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.

Определение

ChEBI: The 1-hydrazino derivative of phthalazine; a direct-acting vasodilator that is used as an antihypertensive agent.

Биологические функции

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.

Контактные аллергены

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.

Механизм действия

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.

Фармаколо?гия

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.

Клиническое использование

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.

Побочные эффекты

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.

Методы очистки

It crystallises from MeOH. UV: max 656nm at pH ~11. It complexes with Bi3+ , Zn2+ , Fe2+ and Co2+ .