michigan hypertension core curriculum - State of Michigan

once per week as a patch; thus, it may be useful for non-adherent patients (e.g., those with dementia).
Alpha-methyldopa is, as mentioned above, along with hydralazine, one of two preferred agents for the
treatment of hypertension in pregnancy due to lack of demonstrated harmful effects on the developing
fetus.
Pharmacology:
Clonidine, guanabenz and guanfacine are structurally related compounds and have similar
antihypertensive profiles. These agents stimulate α2-adrenergic receptors in the brain stem and reduce
sympathetic outflow to the peripheral vasculature, thus lowering systemic arterial resistance and heart
rate. Because they have a central action, they are more likely than other anti-hypertensives to produce
drowsiness, lethargy, and depression. 17
Alpha methyldopa is a structural analog of dopa and functions as a pro-drug. After
administration, α-methyldopa is converted to α-methynorepinephrine, which then serves as the α2-
adrenoceptor agonist in the medulla to decrease sympathetic outflow.
Reserpine is an old, centrally acting drug that depletes synaptic stores of noradrenaline and
other catecholamines. The long duration of action is a desirable characteristic in anti-hypertensive
agents. Low doses of reserpine can be used very effectively to lower BP with a low-risk of depression
seen at higher doses. Nasal stuffiness is the most commonly encountered side effect.
Toxicity/Adverse Effects:
Side effects of the centrally acting alpha 2 adrenoceptor agonists include sedation, dry mouth,
bradycardia, orthostatic hypotension, and impotence. Constipation, nausea and gastric upset are
also associated with the sympatholytic effects of these drugs. Fluid retention and edema is also a
problem with chronic therapy; therefore, they are typically administered concurrently with a diuretic. Of
particular note, sudden discontinuation of clonidine can lead to rebound crescendo hypertension, which
results from excessive sympathetic activity. The tendency towards significant rebound of hypertension
quality makes the oral formulation of clonidine less appealing for routine use, though, as noted, the
transdermal formulation does have its advantages in certain patient populations. These agents should
not be used with concurrent beta blockade.
Preparations and Dosages:
NKFM & MDCH 201