Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 46 Vasodilators

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Vasodilation  Can be produced with a variety of drugs  Some act primarily on veins or arterioles, and some act on both types of vessels  Wide variety of therapeutic applications

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Concepts in Vasodilator Pharmacology  Selectivity of vasodilatory effects  Selective dilation of arterioles  Hydralazine  Selective dilation of veins  Nitroglycerin  Dilate arterioles and veins  Prazosin

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hemodynamic Effects  Drugs that dilate resistance vessels (arterioles) cause a decrease in cardiac afterload  Drugs that dilate capacitance vessels (veins) reduce the force with which blood is returned to the heart, thus reducing preload

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Overview of Therapeutic Uses  Principal indications  Essential hypertension  Hypertensive crisis  Angina pectoris  Heart failure  Myocardial infarction  Pheochromocytoma  Peripheral vascular disease  Pulmonary arterial hypertension  Production of controlled hypotension during surgery

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Vasodilators  Adverse effects related to vasodilation  Postural hypotension  Reflex tachycardia  Expansion of blood volume

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hydralazine (Apresoline)  Selective dilation of arterioles  Mechanism is unknown  Postural hypotension is minimal  Therapeutic uses  Essential hypertension  Hypertensive crisis  Heart failure

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Hydralazine (Apresoline)  Adverse effects  Reflex tachycardia  Increased blood volume  Systemic lupus erythematosus–like syndrome  Headache, dizziness, weakness, and fatigue  Drug interactions  Other antihypertensive agents  Avoid excessive hypotension  Combined with beta blocker to protect against reflex tachycardia and diuretics to prevent sodium and water retention and expansion of blood volume

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Minoxidil (Loniten)  Selective dilation of arterioles  More intense dilation than hydralazine, but causes more severe adverse reactions  Used for severe hypertension that is unresponsive to safer drugs  Adverse effects  Reflex tachycardia  Sodium and water retention  Hypertrichosis  Pericardial effusion  Other

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Sodium Nitroprusside (Nitropress)  Fastest-acting antihypertensive agent  Causes venous and arteriolar dilation  Administration: IV infusion  Onset: immediate (BP returns to pretreatment level in minutes when stopped)  Used for hypertensive emergencies  Adverse effects  Excessive hypotension  Cyanide poisoning  Thiocyanate toxicity

11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fig. 46–1. Structure and metabolism of sodium nitroprusside.

12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Other Vasodilators  Angiotensin-converting enzyme (ACE) inhibitors  Angiotensin II receptor antagonists  Direct renin inhibitors  Organic nitrates  Calcium channel blockers  Sympatholytics  Alpha-adrenergic blocking agents  Ganglionic blocking agents  Adrenergic neuron blocking agents  Centrally acting agents  Nesiritide  Drugs for pulmonary arterial hypertension