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Tuesday, March 10, 2015

Hydralazine (apresoline) is a direct-acting smooth muscle relaxant used to treat hypertension by acting as a vasodilator primarily in arteries and arterioles. By relaxing vascular smooth muscle, vasodilators act to decrease peripheral resistance, thereby lowering blood pressure and decreasing afterload.

However, this only has a short term effect on blood pressure, as the system will reset to the previous, high blood pressure necessary to maintain pressure in the kidney necessary for natriuresis. The long-term effect of antihypertensive drugs comes from their effects on the pressure natriuresis curve. It belongs to the hydrazinophthalazine class of drugs.

It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

Medical use



Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex sympathetic stimulation of the heart (the baroreceptor reflex). The sympathetic stimulation may increase heart rate and cardiac output, and in patients with coronary artery disease may cause angina pectoris or myocardial infarction. Hydralazine may also increase plasma renin concentration, resulting in fluid retention. To prevent these undesirable side effects, hydralazine is usually prescribed in combination with a beta-blocker (e.g., propranolol) and a diuretic. In the UK, labetalol tends to be the first-line beta-blocker.

Hydralazine is used to treat severe hypertension, but again, it is not a first-line therapy for essential hypertension. However, hydralazine is the first-line therapy for hypertension in pregnancy, with methyldopa. It has also been used successfully as a treatment for myelodysplastic syndrome in its capacity as a DNA methyltransferase inhibitor.

Hydralazine is commonly used in combination with isosorbide dinitrate for the treatment of congestive heart failure in self-identified African American populations. This preparation, BiDil, was the first race-based prescription drug.

Side effects



Very common (>10% frequency) side effects include:

  • Headache
  • High heart rate
  • Palpitations

Common (1-10% frequency) side effects include:

Uncommon (0.1-1% frequency) side effects include:

Rare (<0.1% frequency) side effects include:

Contraindications

Contraindications include:

Interactions

It may potentiate the antihypertensive effects of:

Drugs subject to a strong first-pass effect such as beta-blockers may increase the bioavailability of hydralazine. Epinephrine (adrenaline)'s heart rate-accelerating effects are increased by hydralazine, hence may lead to toxicity.

Mechanism of action



Hydralazine binds to and activates gated potassium channels on vascular smooth muscle. The result is an efflux of potassium and a subsequent hyperpolarization of the cell. This prevents calcium-mediated activation and constriction of the smooth muscle, resulting in vasodilation. However, this induced vasodilation triggers the baroreflex resulting in tachycardia and vasoconstriction. Hydralazine is, therefore, not a great candidate for control of hypertension alone. It is often coadministered with a beta blocker to mitigate the effects of the baroreflex.

Hydralazine requires the endothelium to provide nitric oxide, thus only causes vasodilation in vivo with functional endothelium. Hydralazine will not cause vasodilation in vitro in an isolated blood vessel.

Activation of hypoxia-inducible factors has been suggested as a mechanism.

See also



  • Cadralazine
  • Dihydralazine
  • Endralazine
  • Sodium nitroprusside

References





 
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