Pharm: anti-HTN alpha blockers, sympatholytics, and vasodilators

What are the selective alpha-1 receptor blockers?

prazosin, terazosin, and doxazosin

What are the nonselective alpha blockers?

phenoxybenzamine and phentolamine

Which alpha blocker has once daily dosing? (a positive)

terazosin

which alpha blocker has CYP3A4 metabolism?

doxazosin

Which nonselective alpha blocker is IV?

phentolamine

it has a short onset and short duration of action (good for crisis)

What are the effects of blocking alpha-1 receptors?

decreased BP, preload, and venous return to the heart (becuase of the decreased peripheral resistnce vie vasodilation)

compensatory Na and water retention in kidneys (bc of the decrease in MAP)

orthostatic hypotension (blocking contraction of vessels leads to venous pooling)

alpha blockers should be taken with a ____. Why?

diuretic; to counteract the compensatory Na and water retention via the kidneys

What drug(s) are associated with orthostatic hypotension and the “first dose effect”? How do we mitigate this?

the alpha-1 selective blockers; the first dose should be small and taken at bedtime to reduce risk of falling

What drug(s) do we use to treat mild-moderate HTN as an add-on therapy as well as to treat urinary retention due to benign prostatic hyperplasia (improves urine flow)

selective alpha-1 blockers (prazosin, terazosin, and doxazosin)

What drug(s) do we use to treat pheochromocytoma to ocunteract HTN/sweating due to excessive catecholamine release?

phenoxybenzamine (irreversible blocker)

What drug(s) do we use to manage extravasation of vasopressors, reversal of local anesthesia (dental work), and diagnosis of pheochromocytoma?

phentolamine (competitve antag)

What drug(s) are known to cause reflex tachycardia?

nonselective alpha blockers (phenoxybenzamine and phentolamine)

What drug(s) AE include miosis, nasal stuffiness, and intraoperative floppy iris?

alpha blockers

What are the alpha-2 adrenergic receptor agonists (not antags)?

clonidine and methyldopa

Which anti-HTN agent is a substrate of COMT?

methyldopa

Which anti-HTN agent is available in many forms including: oral tablet, extended release capsule, once weekly tansdermal patch, and solution for epidural injection?

clonidine

What is the MOA of alpha-2 agonists?

they either activate postsynaptic or presysnaptic alpha-2 receptors

overall: decreased sympathetic tine and increase parasymp tone which lowers BP and decreases HR and myocardial contractility

What is another proposed mechanism of clonidine?

it may bind to imidazoline receptors in addition to its alpha-2 receptors

Explain renal blood flow and GFR and how it is affected by alpha-2 agonists

sensitivity to baroreceptor regulation is maintains so renal blood flow and GFR are essentially unchanged

What drug is known as a “false transmitter” and why

methyldope; it gets converted inside the presynaptic vessicles from methyldopa to methyldopamine then finally to methylnorepinephrine which gets release by the vessicle instead of NE (thus “false transmitter”)

Which alpha-2 agonist is used in the management of HTN in pregnancy?

methyldopa

What drug(s) therapeutic uses includes refractory add on for HTN, pain management, ADHD, glaucoma, menopause, and substance abuse withdrawal?

clonidine (pain management = epidural)

What drug(s) are contraindicated in pts iwth cardiovascular disease (bradycardia, coronary insufficiency, recent MI and conduction distrurbances)?

alpha-2 agonists (clonidine and methyldopa)

What are the 5 most common AEs of the alpha-2 agonists? (clonidine and methyldopa)

bradycardia, sedation, drowsiness, mental depression (can’t think clearly), and constipation

What drug(s) is it very important to taper and why?

alpha-2 agonists (like clonidine)

sudden d/c leads to catehcolamine surge and rebound HTN

explain how to stop medications if a pt is taking clonidine and a beta-blocker

withdraw the beta-bocker several days before the clonidine (clonidine first would lead to unopposed vasoconstriction)

What are the oral direct vasodilators?

hydralazine and minoxidil

Whcih direct vasodialtor is both oral and parenteral?

hydralazine

What are the parenteral direct vasodilators?

hydralazine, nitroprusside, and fenoldopam

Which drug is taken up by RBCs and converted to NO and cyanide, so there is possiblity of cyanide toxicity from saturating the rhodanese?

nitroprusside

Which drug’s AE include cyanide toxicity? How can we reverse it?

nitroprusside; antidotes: hydroxocobalamin or sodium nitrite + sodium thiosulfate

Which drug has a metabolite, thiocyanate, that may accumulate in pts with renal failure

nitroprusside

Which drug can cause pts to develop antinuclear abs and lupus-like syndrome? Why does this occur?

hydralazine; slow acetylators (NAT2) or too high of a dose

Which drug can lead to inadequate levels and an inadequate response to the drug if the pt is a rapid acetylator?

hydralazine

Of the direct vasodilators, which ones act on what?

hydralazine, minoxidil, and fenoldopam: dilates only arterioles

nitroprusside: dilates both arterioles and venous vessels

Of the direct vasodilators, which one acts specifically on peripheral arterioles?

fenoldopam

Which drug’s MOA: opening of K(atp) channels in smooth muscle membranes of arterioles leading to hyperpolarization and relaxation of smooth muscle

minoxidil

Which drug’s MOA: activates guanylyl cyclase to increase cellular cGMP leading to smooth muscle relaxation

nitroprusside

Which drug’s MOA: dopamine D1 agonist leading to relaxation of vascular smooth muscle and natriuresis and diuresis

fenoldopam

Which drug(s) do not cause rthostatic hypotension or sexual dysfunction because the sympathetic reflexes are intact?

the direct vasodilators

Vasodilators are given with other anti-HTN agents. What are they and why?

they are give with diuretics (to counteract the Na and water retention) and with beta blockers (to counteract the tachycardia)

What drug is given with nitrate to pts with heart failure with reduced ejection fraction?

hydralazine

Which direct vasodilator is used for hpertensive emergency in pregnancy or postpartum?

hydralazine

Which drug is used as a last line therapy to tx severe HTN?

minoxidil

Which drug is used for acute HTN, acute decompensated heart failure, and controlled hypotension during surgery?

nitroprusside

Which drug can be used to tx HTN in pediatric pts and pts with renal compromise? also used for up to 48 hrs to tx severe HTN

fenoldopam

Which drug’s unique AE include increased intraocular pressure and should be avoided in pts with glaucoma?

fenoldopam

Which drug’s unique AE/therapeutic use is hypertrichosis (hair growth)

minoxidil (can be an AE or used topically for male pattern baldness)

What are the 8 common AEs of the direct vasodilators?

HA, nausea, anorexia, palpitations, sweating, flushing, reflex tachycardia, and salt and water retention

remember the BBs and diuretics should be co-admin to counteract these compensatory responses