Image for Cardiovascular Pharmacology Concepts, Richard E Klabunde PhD

Cardiovascular Pharmacology Concepts

Richard E. Klabunde, PhD

Clinical Disorders:

Therapeutic Classes:

Mechanism Classes:


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Click here for information on Cardiovascular Physiology Concepts, 2nd edition, a textbook published by Lippincott Williams & Wilkins (2011)

 

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Click here for information on Normal and Abnormal Blood Pressure, a textbook published by Richard E. Klabunde (2013)

 



Potassium-Channel Openers

General Pharmacology

Potassium-channel openers are drugs that activate (open) ATP-sensitive K+-channels in vascular smooth muscle. Opening these channels hyperpolarizes the smooth muscle, which closes voltage-gated calcium channels and decreases intracellular calcium. With less calcium available to combine with calmodulin, there is less activation of myosin light chain kinase and phosphorylation of myosin light chains (click here for details). This leads to relaxation and vasodilation. Because small arteries and arterioles normally have a high degree of smooth muscle tone, these drugs are particular effective in dilating these resistance vessels, decreasing systemic vascular resistance, and lowering arterial pressure. The fall in arterial pressure leads to reflex cardiac stimulation (baroreceptor-mediated tachycardia).

Therapeutic Indications

Being effective arterial dilators, potassium-channel openers are used in the treatment of hypertension. These drugs are not first-line therapy for hypertension because of their side effects, and therefore they are relegated to treating refractory, severe hypertension. They are generally used in conjunction with a beta-blocker and diuretic to attenuate the reflex tachycardia and retention of sodium and fluid, respectively.

Specific Drugs

Although several potassium-channel openers have been used in research for many years, only one, minoxidil, is approved for use in humans for treating hypertension. (Go to www.rxlist.com for detailed information on minoxidil)

Side Effects and Contraindications

Common side effects to minoxidil include headaches, flushing and reflex tachycardia. The potent vasodilator actions of minoxidil can lead to fluid retention and edema formation. Reflex cardiac stimulation can precipitate angina in patients with coronary artery disease. Minoxidil produces T wave changes in a high percentage (~60%) of patients under chronic treatment. One of the most noted side effects of minoxidil is hypertrichosis, a thickening and enhanced pigmentation of body hair, and therefore this drug is more commonly used for treating baldness.

DISCLAIMER: These materials are for educational purposes only, and are not a source of medical decision-making advice.