Antihypertensive Drugs

Correct Answer

B — Angiotensin converting enzyme inhibitors

Rationale

Captopril is an angiotensin converting enzyme inhibitor, the prototype agent of this class. Thiazide diuretics include hydrochlorothiazide. Calcium channel blockers include amlodipine and verapamil. Beta-adrenergic receptor antagonists include metoprolol and propranolol.

Correct Answer

A — Loop diuretics

Rationale

Furosemide is the prototype loop diuretic. Loop diuretics act in the thick ascending limb of the loop of Henle, where they block the sodium-potassium-2 chloride cotransporter and produce the most potent natriuresis of any diuretic class. Thiazide diuretics such as hydrochlorothiazide act in the distal convoluted tubule. Potassium-sparing diuretics include amiloride and triamterene, which block sodium channels in the collecting duct. Aldosterone antagonists such as spironolactone competitively block mineralocorticoid receptors in the collecting duct.

Correct Answer

C — Aldosterone antagonist

Rationale

Spironolactone competitively blocks mineralocorticoid receptors in the renal collecting duct, antagonizing aldosterone's effects on sodium reabsorption and potassium excretion. It is therefore classified as an aldosterone antagonist (and more broadly as a potassium-sparing diuretic). Loop diuretics such as furosemide act at the thick ascending limb. Beta-adrenergic receptor antagonists such as metoprolol reduce heart rate and renin release. Alpha-1 adrenergic receptor antagonists such as prazosin reduce arteriolar tone.

Correct Answer

D — Centrally acting alpha-2 adrenergic receptor agonist

Rationale

Clonidine acts centrally in the brainstem to stimulate alpha-2 adrenergic receptors, which reduces sympathetic outflow to the heart and peripheral vasculature. It is therefore classified as a centrally acting alpha-2 adrenergic receptor agonist. Alpha-1 adrenergic receptor antagonists such as prazosin act peripherally on vascular smooth muscle. Direct arteriolar vasodilators such as hydralazine relax arteriolar smooth muscle directly. Angiotensin receptor blockers such as losartan block angiotensin II type 1 receptors.

Correct Answer

B — Direct arteriolar vasodilators

Rationale

Hydralazine directly relaxes arteriolar smooth muscle by a mechanism that involves increased cyclic guanosine monophosphate production, reducing total peripheral resistance. It acts directly on the vessel wall rather than through a receptor or enzyme. Alpha-1 adrenergic receptor antagonists such as prazosin block receptor-mediated vasoconstriction. Calcium channel blockers prevent voltage-gated calcium entry into vascular smooth muscle. Angiotensin converting enzyme inhibitors reduce angiotensin II production.

Correct Answer

A — Selective beta-1 adrenergic receptor antagonist

Rationale

Metoprolol is a selective beta-1 adrenergic receptor antagonist, also called a cardioselective beta-blocker. Propranolol is the prototype nonselective beta-adrenergic receptor antagonist. Prazosin is a selective alpha-1 adrenergic receptor antagonist. Clonidine is a centrally acting alpha-2 adrenergic receptor agonist.

Correct Answer

C — Reduced renal perfusion pressure, decreased sodium delivery to the macula densa, and beta-1 adrenergic receptor stimulation

Rationale

Juxtaglomerular cells release renin in response to three distinct signals: a fall in renal perfusion pressure detected by stretch-sensitive baroreceptors in the afferent arteriole, decreased sodium chloride delivery to the macula densa cells of the distal tubule, and direct beta-1 adrenergic receptor stimulation from sympathetic nervous system activation. This three-pathway architecture explains how beta-blockers reduce renin release and thus lower blood pressure partly through renin-angiotensin-aldosterone system suppression. Elevated sodium delivery, increased perfusion pressure, and elevated angiotensin II all suppress renin release through negative feedback.

Correct Answer

D — Arteriolar vasoconstriction, aldosterone release, increased sympathetic activity, and vascular remodeling

Rationale

Angiotensin II acting at angiotensin II type 1 receptors produces four clinically important effects: vasoconstriction of arterioles (raising total peripheral resistance and blood pressure directly), stimulation of aldosterone release from the adrenal cortex (increasing sodium retention and volume), amplification of sympathetic nervous system activity (further raising cardiac output and vascular tone), and promotion of vascular and myocardial remodeling over time (contributing to target organ damage). These four effects explain why angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce blood pressure through multiple simultaneous mechanisms and provide organ protection beyond blood pressure lowering alone.

Correct Answer

A — Accumulation of bradykinin in the airway due to reduced enzymatic degradation

Rationale

Angiotensin converting enzyme normally degrades bradykinin, a potent inflammatory peptide. When angiotensin converting enzyme is inhibited, bradykinin accumulates in airway tissues where it stimulates sensory nerve fibers and produces a dry, non-productive cough. This effect is class-wide — it occurs with all angiotensin converting enzyme inhibitors — and is the most common reason patients discontinue this drug class. Angiotensin receptor blockers do not inhibit angiotensin converting enzyme and therefore do not cause this cough, making them the preferred alternative in patients who develop this adverse effect.

Correct Answer

B — Sodium reabsorption and potassium excretion

Rationale

Aldosterone binds mineralocorticoid receptors in principal cells of the renal collecting duct and upregulates sodium channels on the luminal membrane along with the sodium-potassium adenosine triphosphatase pump on the basolateral membrane. The net result is sodium reabsorption (expanding plasma volume) coupled with potassium excretion (producing hypokalemia with excess aldosterone). This paired effect explains why primary aldosteronism — characterized by autonomous aldosterone secretion — presents with hypertension and hypokalemia, and why spironolactone (an aldosterone antagonist) is both antihypertensive and potassium-sparing.

Correct Answer

C — Reduced heart rate, reduced myocardial contractility, and decreased renin release from juxtaglomerular cells

Rationale

Beta-adrenergic receptor antagonists lower blood pressure through three simultaneous mechanisms. Blockade of cardiac beta-1 receptors reduces heart rate (negative chronotropy) and myocardial contractility (negative inotropy), lowering cardiac output. Blockade of beta-1 receptors on juxtaglomerular cells in the kidney reduces renin release, which in turn reduces angiotensin II production and aldosterone secretion — suppressing both vasoconstriction and volume expansion. These combined effects make beta-blockers particularly effective in patients with sympathetic overactivation, such as younger hypertensive patients with high resting heart rates.

Correct Answer

D — They force sodium excretion pharmacologically, reducing plasma volume and shifting the blood pressure operating point downward

Rationale

In hypertension, the pressure-natriuresis relationship is reset: the kidney requires a higher blood pressure to excrete the same sodium load. This resetting is driven by renin-angiotensin-aldosterone system and sympathetic nervous system activation, which increase tubular sodium reabsorption. Diuretics override this reset by directly blocking sodium transporters at specific tubular segments — producing natriuresis regardless of blood pressure level. As plasma volume falls, cardiac output decreases and blood pressure is reduced to a new, lower operating point. This mechanism explains why diuretics are particularly effective in volume-dependent and sodium-sensitive forms of hypertension.

Correct Answer

A — Aldosterone upregulates collecting duct sodium channels and basolateral sodium-potassium pumps, driving potassium into the tubular lumen for excretion

Rationale

Aldosterone increases the number of epithelial sodium channels on the luminal membrane and sodium-potassium adenosine triphosphatase pumps on the basolateral membrane of principal cells in the collecting duct. As more sodium enters the cell from the tubular lumen, the electrochemical gradient favoring potassium secretion into the lumen increases. The result is enhanced potassium excretion in the urine. In primary aldosteronism, this process runs autonomously regardless of volume status, producing the characteristic combination of sodium retention (hypertension, volume expansion) and potassium wasting (hypokalemia). Aldosterone acts in the collecting duct, not the proximal tubule, and does not affect the sodium-potassium-2 chloride cotransporter located in the loop of Henle.

Correct Answer

B — Angiotensin II normally maintains efferent arteriolar tone to preserve glomerular filtration pressure; its loss causes filtration to collapse

Rationale

In bilateral renal artery stenosis, reduced perfusion pressure in both kidneys drives compensatory elevation of angiotensin II, which constricts the efferent arteriole (the vessel carrying blood away from the glomerular capillary tuft) to maintain intraglomerular pressure and filtration rate. When an angiotensin converting enzyme inhibitor removes this angiotensin II-dependent support, the efferent arteriole dilates, intraglomerular pressure falls, and glomerular filtration rate drops precipitously. This is the mechanism behind the clinical warning that angiotensin converting enzyme inhibitors and angiotensin receptor blockers are contraindicated in bilateral renal artery stenosis. With unilateral stenosis, the contralateral kidney compensates, and the risk is substantially lower.

Correct Answer

D — Autonomous aldosterone secretion promotes sodium reabsorption in the renal collecting duct, expanding plasma volume

Rationale

The clinical picture — hypertension with hypokalemia, suppressed renin, and an elevated aldosterone-to-renin ratio — is the classic presentation of primary aldosteronism (autonomous aldosterone excess from an adrenal adenoma or bilateral adrenal hyperplasia). In this condition, aldosterone acts on mineralocorticoid receptors in the collecting duct to promote sodium reabsorption and potassium excretion regardless of volume status. The resulting sodium retention expands plasma volume and raises blood pressure. Renin is suppressed because the volume expansion removes the normal stimulus for renin release. Catecholamine excess (pheochromocytoma) would present with episodic symptoms and elevated plasma metanephrines (breakdown products of epinephrine and norepinephrine), not suppressed renin. Renovascular disease drives renin up, not down.

Correct Answer

C — The drug removes angiotensin II-mediated efferent arteriolar constriction, which was the only mechanism maintaining adequate filtration pressure across both stenosed kidneys

Rationale

With bilateral renal artery stenosis, blood flow to both kidneys is reduced. Angiotensin II compensates by constricting the efferent arteriole (the vessel leaving the glomerular capillary tuft), raising intraglomerular pressure to maintain a filtration rate sufficient for survival. An angiotensin converting enzyme inhibitor blocks angiotensin II production, dilating the efferent arteriole and collapsing the filtration pressure. Because both kidneys are affected, no compensating kidney is available. The result is a sharp, often reversible fall in glomerular filtration rate seen as a rise in serum creatinine. This is the mechanistic basis for the contraindication. Bradykinin accumulation causes cough, not glomerular injury.

Correct Answer

A — Episodic mass release of catecholamines causes intense arteriolar vasoconstriction and increased cardiac output simultaneously

Rationale

This presentation describes a pheochromocytoma — a catecholamine-secreting tumor of the adrenal medulla or sympathetic ganglia. The episodic triad of headache, diaphoresis, and palpitations, combined with dramatic episodic blood pressure surges and elevated plasma metanephrines, is characteristic. The mechanism of hypertension is catecholamine-driven: epinephrine and norepinephrine released in massive bursts stimulate alpha-1 receptors in arteriolar walls (causing intense vasoconstriction and raising total peripheral resistance) and beta-1 receptors in the heart (raising heart rate and contractility and thereby increasing cardiac output). Both limbs of the blood pressure equation — cardiac output and total peripheral resistance — rise simultaneously. The episodic pattern reflects intermittent tumor secretion, distinguishing this from the sustained elevation of primary aldosteronism or renovascular hypertension.

Correct Answer

B — Age-related loss of arterial wall compliance causes early return of the reflected pulse wave, augmenting systolic pressure while diastolic pressure remains stable or falls

Rationale

Isolated systolic hypertension — defined as systolic blood pressure at or above 140 millimeters of mercury with diastolic pressure below 90 — is the dominant pattern of hypertension in adults over 60 and is caused by age-related arterial stiffening. In a young person with compliant arteries, the pulse wave generated by each cardiac contraction travels to the periphery and returns (reflected wave) during diastole, reinforcing diastolic pressure. As the aorta stiffens with age, pulse wave velocity increases, and the reflected wave returns earlier — during late systole rather than diastole. This augments systolic pressure while leaving diastolic pressure unchanged or reduced. The result is a wide pulse pressure (the difference between systolic and diastolic readings). This pattern carries significant cardiovascular risk and should not be dismissed as a normal consequence of aging.