michigan hypertension core curriculum - State of Michigan

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 leading to vessel relaxation and vasodilation. Because small
arteries and arterioles normally have a high degree of smooth muscle tone, minoxidil is particularly
effective in dilating these resistance vessels, decreasing systemic vascular resistance, and lowering
arterial pressure. There can be a dramatic drop in arterial pressure leading to reflex cardiac stimulation
(baroreceptor-mediated tachycardia). 15
Toxicity/Adverse Effects:
Common side-effects of hydralazine include diarrhea, reflex tachycardia, headache, anorexia,
nausea, vomiting, depression and palpitations. Additionally, hydralazine has been associated with a
drug-induced lupus syndrome, which resolves when the drug is stopped.
Minoxidil causes sodium and water retention, possibly new or worsening pleural and pericardial
effusions, aggravation of myocardial ischemia and/or left ventricular hypertrophy, flushing and reflex
tachycardia, and T wave changes on EKG. Additionally, hypertrichosis, a side effect first noticed in
patients when minoxidil was introduced in the early 1980s, has been considered a favorable effect by
some making topical minoxidil now one of the top treatments available for male pattern baldness. This
side effect limits the acceptance of minoxidil in female patients. 16
Preparations and Doses:
Hydralazine (Apresoline) 25–100 mg PO BID
Minoxidil (Loniten) 2.5–80 mg PO BI
Central Adrenergic Inhibitors
Like the direct vasodilators, the central adrenergic inhibitors are useful adjuncts in the treatment
of hypertension but are not considered first line agents because of their CNS effects, in particular.
They tend to be useful and effective in hypertensive patients with renal disease because they do not
compromise renal function.
This class of drugs includes clonidine, guanabenz, guanfacine, and α-methyldopa. Of these,
clonidine is the most commonly used and has particular utility in that it can be applied transdermally
200 Hypertension Core Curriculum