Centrally Acting alpha2 Agonists
Activating $\alpha_2$ receptors on vascular smooth muscle causes vasoconstriction, but activating presynaptic $\alpha_2$ receptors in this central location inhibits sympathetic outflow and causes vasodilation
What is the brainstem (or central nervous system)?
Unlike hydralazine and minoxidil which dilate only arterioles, sodium nitroprusside is classified as a nonselective vasodilator because it dilates both of these vessel types
What are arterioles AND venules?
Mineralocorticoid receptor antagonists (MRAs) like spironolactone are unique among all diuretic classes because they do not require this condition to exert their pharmacological effect
What is access to the tubular lumen?
Selective $\alpha_1$ blockers like doxazosin, prazosin, and terazosin reduce blood pressure with significantly less of this compensatory cardiac effect compared to non-selective blockers
What is reflex tachycardia?
Methyldopa is a prodrug converted sequentially by aromatic L-amino acid decarboxylase and dopamine $\beta$-hydroxylase into this active metabolite that stimulates central presynaptic $\alpha_2$ receptors
What is $\alpha$-methylnorepinephrine?
Oral hydralazine undergoes extensive first-pass N-acetylation, resulting in a low oral bioavailability of 16% in fast acetylators compared to this percentage in slow acetylators
What is 35%?
Unlike spironolactone which causes gynecomastia in ~10% of patients, eplerenone is eliminated primarily via this CYP enzyme into inactive metabolites and rarely causes endocrine side effects
What is CYP3A4?
Extracted from the root of Rauwolfia serpentina, this historic, now-discontinued sympatholytic agent lowers blood pressure by irreversibly blocking VMAT
What is Reserpine?
Despite having a short elimination half-life of about 2 hours, methyldopa can be dosed once or twice daily because its peak clinical effect is delayed for this long
What is 6 to 8 hours?
Systemic minoxidil acts as a $K_{ATP}$ channel opener in vascular smooth muscle, but it must first be activated by this hepatic enzyme
What is hepatic sulfotransferase (converting it to minoxidil N-O sulfate)?
Amiloride and triamterene reduce potassium excretion by directly blocking these specific ion channels in the principal cells of the late DCT and collecting duct
What are Epithelial Sodium Channels (ENaC)?
Metyrosine is not useful for essential hypertension, but is indicated for the preoperative management of this catecholamine-secreting adrenal medulla tumor
What is pheochromocytoma?
A major clinical limitation of clonidine in hypertension therapy is the paucity of information regarding its efficacy in reducing this long-term risk
What is the risk of cardiovascular consequences of hypertension?
Hydralazine is no longer a first-line agent due to its adverse effect profile, most notably this severe autoimmune toxicity that resembles serum sickness, vasculitis, and glomerulonephritis
What is Drug-Induced Lupus Syndrome?
Beyond preventing diuretic-induced hypokalemia, amiloride is specifically indicated to treat this inherited form of hypertension caused by ENaC hyperactivity
What is Liddle Syndrome?
Metyrosine reduces endogenous norepinephrine levels by 35% to 80% through competitive inhibition of this rate-limiting enzyme
What is tyrosine hydroxylase?
Abrupt withdrawal of oral clonidine at daily doses greater than 0.3 mg can trigger severe rebound hypertension accompanied by these four specific signs of sympathetic overactivity
What are nervousness, sweating, increased heart rate (tachycardia), and tremors?
Minoxidil should never be used alone; it must be co-administered with a diuretic, a sympatholytic (e.g., $\beta$-blocker), and an inhibitor of this system to prevent cardiac remodeling
What is the Renin-Angiotensin System (RAS)?
Triamterene can precipitate acute renal failure when combined with this specific NSAID, and can also form kidney stones due to its low urinary solubility
What is indomethacin?
The first dose of an $\alpha_1$-selective receptor blocker can produce a severe orthostatic hypotensive response that may result in this acute clinical complication
What is syncope (fainting)?