Other Antihypertensives

Name: Other Antihypertensives — Cardiovascular pharmacology
Creator: LearnDrugs

Verified · Oct 2026

Each drug is best learned by where it interrupts blood-pressure control — the vascular alpha-1 receptor, the brainstem, the vascular smooth-muscle cell, or renin — because that site predicts its signature problem: first-dose syncope, rebound hypertension, reflex tachycardia with fluid retention, cyanide, or fetal toxicity.

Nursing view → administration, monitoring and patient teaching

Compare: Antihypertensives compared — mechanism and drug choice →

Drugs

prazosin Minipress

doxazosin Cardura

terazosin —

clonidine Catapres-TTS

methyldopa —

hydralazine —

minoxidil —

nitroprusside —

aliskiren Tekturna

Mechanism

Alpha-1 blockers antagonize vascular (and prostatic) alpha-1 receptors → vasodilation. Central alpha-2 agonists stimulate brainstem alpha-2 receptors → reduced sympathetic outflow. Direct vasodilators relax arterial smooth muscle directly (nitroprusside via nitric oxide, releasing cyanide). The direct renin inhibitor aliskiren lowers plasma renin activity, blocking conversion of angiotensinogen to angiotensin I.

Alpha-1 blockade: arterioles, the prostate and the iris

Alpha-1 receptors on vascular smooth muscle mediate catecholamine vasoconstriction. Prazosin, doxazosin and terazosin are quinazoline, competitive alpha-1 antagonists: blocking norepinephrine at the receptor lowers systemic vascular resistance. Because they spare alpha-2 receptors, the presynaptic brake on norepinephrine release stays intact, so tachycardia and tremor are less common than with nonselective alpha-blockers.

Alpha-1 receptors are dense in the prostatic stroma, capsule and bladder neck, where they set the dynamic (smooth-muscle tone) part of BPH obstruction; blockade lowers urethral resistance, while the static enlargement is untouched. They also sit on the iris dilator muscle, which links the class to intraoperative floppy iris syndrome.

The three differ mainly in half-life: prazosin about 2–3 hours, terazosin about 12 hours and doxazosin about 22 hours.

Central sympatholytics: clonidine and methyldopa

Clonidine, an imidazoline, stimulates alpha-2 (and imidazoline) receptors in the brainstem — in the nucleus tractus solitarii it excites a pathway that inhibits excitatory cardiovascular neurons — so sympathetic outflow falls, along with peripheral and renal vascular resistance, heart rate and blood pressure. Postural reflexes stay intact, so orthostatic symptoms are mild and infrequent, and plasma renin activity and catecholamine excretion also fall.

Methyldopa is a prodrug: it is metabolized to alpha-methylnorepinephrine, which lowers arterial pressure by stimulating central inhibitory alpha-adrenergic receptors (false neurotransmission and lower plasma renin activity may contribute). Cardiac output and renal blood flow are maintained.

Stopping clonidine abruptly releases the brake: nervousness, agitation, headache and tremor are followed by a rapid rise in blood pressure with high plasma catecholamines. The risk is greater after higher doses or when a beta-blocker is continued, because the beta-blockade leaves alpha-adrenergic vasoconstriction unopposed.

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Clonidine and methyldopa’s metabolite both act on central alpha-2 receptors; abrupt withdrawal removes the brake.

Direct arteriolar vasodilators and the reflex they provoke

Hydralazine relaxes arteriolar smooth muscle by interfering with intracellular calcium — it is thought to inhibit IP3-induced calcium release from the sarcoplasmic reticulum and myosin phosphorylation. Because it dilates arterioles far more than veins, postural hypotension is minimal.

Minoxidil opens ATP-sensitive potassium channels, relaxing vascular smooth muscle and lowering peripheral resistance. It does not interfere with vasomotor reflexes, so it does not cause orthostatic hypotension.

The fall in resistance sets off reflex sympathetic discharge — faster heart rate, higher stroke volume and cardiac output — and renin release from the juxtaglomerular cells; angiotensin II and aldosterone then retain sodium and water. That is why both drugs are paired with a beta-blocker and a diuretic, and why angina can worsen as myocardial oxygen demand rises.

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Direct vasodilators trigger a reflex that a beta-blocker and a diuretic are added to blunt.

Nitroprusside: nitric oxide in, cyanide out

Sodium nitroprusside is ferrous iron complexed with nitric oxide and cyanide groups. Reacting with hemoglobin and sulfhydryl groups, it releases NO, which raises cGMP in vascular smooth muscle and relaxes both arteries and veins — afterload and preload fall together. The effect starts within a minute or two and fades almost as fast after the infusion stops (circulatory half-life about 2 minutes).

The same reaction with hemoglobin yields cyanmethemoglobin and free cyanide. Methemoglobin buffers some cyanide; mitochondrial rhodanese converts the rest to thiocyanate, a step limited by the supply of sulfur donors, especially thiosulfate. Except during brief or low-rate infusions, cyanide is produced faster than it is cleared. Thiocyanate leaves through the kidney (half-life about 3 days, doubled or tripled in renal failure).

Free cyanide binds the iron of cytochrome c oxidase and stops oxidative phosphorylation: cells turn to anaerobic metabolism (lactic acidosis), and because tissues cannot use oxygen, venous blood stays oxygen-rich.

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Nitroprusside releases nitric oxide for vasodilation and cyanide that must be detoxified.

Aliskiren: renin itself as the target

Renin, released from the juxtaglomerular cells, is the rate-limiting enzyme of the renin–angiotensin–aldosterone system: it cleaves angiotensinogen to angiotensin I (the rest of the cascade is drawn on the ACE-inhibitor page). Aliskiren inhibits renin directly, lowering plasma renin activity (PRA).

Every RAAS blocker removes angiotensin II’s negative feedback, so renin concentration rises. With ACE inhibitors and ARBs this shows up as higher PRA; with aliskiren the extra renin is itself inhibited, so PRA, angiotensin I and angiotensin II all fall.

It shares the class hazards of RAAS drugs: hyperkalemia, acute renal failure in kidneys that depend on the RAAS (renal artery stenosis, severe heart failure, volume depletion), and fetal renal toxicity. It is poorly absorbed (bioavailability about 2.5%), and a high-fat meal cuts absorption substantially.

Comparing the drugs

Site of action and signature problem

Drug	Site of action	Signature problem	Remember
Prazosin	Vascular α1 (competitive)	First-dose syncope	Shortest half-life (2–3 h)
Doxazosin	Vascular and prostatic α1	First-dose syncope; floppy iris	CYP3A4 substrate; half-life about 22 h
Terazosin	Vascular and prostatic α1	First-dose syncope (highest risk in the first 7 days)	Restarting after a break acts like a first dose
Clonidine	Brainstem α2 / imidazoline agonist	Rebound hypertension on abrupt stop	Dry mouth, drowsiness; patch levels persist about 8 h after removal
Methyldopa	Central α2, via α-methylnorepinephrine	Coombs-positive hemolytic anemia; hepatitis	Improved fetal outcome in published pregnancy reports
Hydralazine	Arteriolar smooth muscle (calcium handling)	Drug-induced lupus	Slow acetylators (NAT2) at higher risk
Minoxidil	K-ATP channel opener	Fluid retention, pericardial effusion; hypertrichosis	Given with a beta-blocker and a loop diuretic
Nitroprusside	NO donor → cGMP (arteries and veins)	Cyanide and thiocyanate toxicity	IV only; effect gone within minutes
Aliskiren	Renin (direct inhibitor)	Fetal toxicity; hyperkalemia	No ACE inhibitor or ARB in diabetes

Pharmacokinetics at a glance

Drug	Half-life	Elimination	Watch
Prazosin	2–3 h	Hepatic (CYP450)	Longer in renal failure and heart failure
Doxazosin	About 22 h	Hepatic (mainly CYP3A4); mostly fecal	Strong CYP3A inhibitors
Terazosin	About 12 h	Mostly as metabolites (about 40% urine, 60% feces)	Renal impairment has no significant effect
Clonidine	12–16 h (up to 41 h in severe renal impairment)	About half renal, unchanged	Patch: steady state in 3 days, slow decline after removal
Methyldopa	105 min (BP effect 12–24 h)	Renal (about 70% of the absorbed drug)	Removed by dialysis
Hydralazine	3–7 h	Hepatic acetylation; metabolites in urine	Plasma levels vary widely (acetylator status)
Minoxidil	About 4 h (BP effect about 75 h)	Glucuronidation; urine	Not protein-bound; removed by hemodialysis
Nitroprusside	About 2 min	Reaction with hemoglobin → cyanide → thiocyanate (renal)	Thiocyanate half-life about 3 days
Aliskiren	About 24 h (accumulation)	About one-fourth of the absorbed dose as parent drug in urine; CYP3A4	Bioavailability about 2.5%; high-fat meals

Methyldopa and minoxidil act far longer than their plasma half-lives suggest.

Pharmacokinetics

Alpha-1 blockers: half-life sets the first-dose risk window — prazosin, doxazosin, terazosin: Terazosin is essentially completely absorbed with little first-pass metabolism and a half-life of about 12 hours; its first-dose syncope risk is greatest in the first 7 days and returns when therapy is interrupted for several days and restarted. Doxazosin is extensively metabolized in the liver (mainly CYP3A4) with a terminal half-life of about 22 hours.
Clonidine patch: slow on, slow off — clonidine: The transdermal system delivers clonidine at a roughly constant rate for 7 days (absolute bioavailability about 60%); therapeutic levels take 2–3 days to appear. After removal, levels persist for about 8 hours and then decline slowly over several days. The elimination half-life lengthens to as much as 41 hours in severe renal impairment.
Methyldopa: short half-life, removed by dialysis — methyldopa: The plasma half-life is 105 minutes, but a smooth BP response takes 12–24 hours to develop and BP returns to baseline 24–48 hours after withdrawal. About 70% of the absorbed drug is excreted in urine, renal clearance falls in renal insufficiency, and hypertension can recur after dialysis because the drug is removed.
Hydralazine: polymorphic acetylation — hydralazine: Hydralazine is rapidly absorbed, has a half-life of 3–7 hours and undergoes extensive hepatic metabolism, including polymorphic acetylation. Plasma levels vary widely between people: slow acetylators generally have higher levels.
Minoxidil: effect outlasts the drug — minoxidil: Minoxidil is at least 90% absorbed and has an average plasma half-life of 4.2 hours, but a single dose lowers BP for about 75 hours. About 90% is metabolized, mainly by glucuronide conjugation; it is not protein-bound, does not cross the blood–brain barrier, and can be removed by hemodialysis.
Nitroprusside: a 2-minute drug with a 3-day metabolite — nitroprusside: Nitroprusside is cleared from the circulation within minutes by reaction with hemoglobin. Its cyanide is converted to thiocyanate, which the kidneys clear with a half-life of about 3 days — doubled or tripled in renal failure — so thiocyanate toxicity is a risk of prolonged infusions and renal failure.
Aliskiren: poor and food-sensitive absorption — aliskiren: Bioavailability is about 2.5%, the accumulation half-life about 24 hours, and steady state takes 7–8 days. A high-fat meal lowers AUC by 71% and peak concentration by 85%. About one-fourth of the absorbed dose appears unchanged in urine, and CYP3A4 appears to be the main metabolizing enzyme.

Pharmacogenomics

NAT2 (acetylator status) hydralazine

Hydralazine is listed in the FDA biomarker table for NAT (clinical pharmacology), and CPIC has a level-A guideline for NAT2 and hydralazine. Poor (slow) metabolizers are predicted to have higher hydralazine levels — more effect but also more adverse effects, including drug-induced lupus — while rapid and intermediate metabolizers are predicted to have lower levels and efficacy. The label notes that slow acetylators need lower doses to control BP.

Uses & drug choice

Resistant/add-on hypertension; hypertensive emergency (IV nitroprusside)
Oral minoxidil only for severe hypertension that causes symptoms or target-organ damage and is not controlled by a diuretic plus two other drugs
Doxazosin and terazosin for symptomatic BPH (both also treat hypertension); prazosin and doxazosin off-label for PTSD-related nightmares
Methyldopa for hypertension in pregnancy (safe in pregnancy; a preferred option with labetalol and long-acting nifedipine)
Hydralazine for hypertension in eclampsia (one of the first-line options; given IV when the patient is unconscious)
Clonidine for ADHD in children
Off-label: clonidine for Tourette tics and for opioid, benzodiazepine or alcohol withdrawal

Hypertension with symptomatic BPH → Doxazosin or terazosin

Both are labeled for BPH and hypertension: blocking prostatic and bladder-neck alpha-1 receptors eases the dynamic obstruction while vascular blockade lowers resistance. Prazosin is labeled for hypertension only.

Chronic hypertension in pregnancy → Methyldopa — never aliskiren

Published reports of methyldopa in all trimesters suggest fetal harm is remote, with improved fetal outcomes in controlled studies. Aliskiren carries a boxed fetal-toxicity warning, like every drug acting directly on the renin–angiotensin system.

Hypertensive emergency needing minute-to-minute titration → IV nitroprusside, with continuous BP monitoring

Onset within 1–2 minutes and offset almost as fast; it lowers both preload and afterload. Cyanide risk limits rate and duration, and it is not used for compensatory hypertension (aortic coarctation, arteriovenous shunt).

Severe hypertension with target-organ damage despite a diuretic plus two other drugs → Oral minoxidil, with a beta-blocker and a loop diuretic

Its K-ATP channel opening is powerful, but the reflex tachycardia and salt and water retention must be blocked — the label requires the companions.

Diabetes, already on an ACE inhibitor or ARB, BP still high → Do not add aliskiren

Contraindicated: dual RAS blockade in diabetes raises the risk of renal impairment, hyperkalemia and hypotension, and aliskiren has not improved renal or cardiovascular outcomes in type 2 diabetes.

Hypertension while pheochromocytoma is being evaluated → Avoid methyldopa and minoxidil

Methyldopa fluoresces like catecholamines and falsely raises urinary catecholamine results; minoxidil is contraindicated in pheochromocytoma because its BP drop may stimulate catecholamine secretion from the tumor.

Adverse effects

Common

Dizziness and hypotension, often orthostatic (oral minoxidil itself does not cause orthostasis); dry mouth & sedation (clonidine, methyldopa); reflex tachycardia, headache, edema (vasodilators); hypertrichosis (minoxidil); diarrhea (aliskiren).

Serious

First-dose syncope (alpha-1 blockers); rebound hypertension if clonidine stopped abruptly; hydralazine lupus-like syndrome; nitroprusside cyanide toxicity.

Coombs-positive hemolytic anemia and liver injury (methyldopa)

Methyldopa can cause a positive direct Coombs test (10–20% on prolonged therapy) that rarely progresses to hemolytic anemia, and liver injury (fever, abnormal liver tests or jaundice; rarely fatal hepatic necrosis).

Angioedema, hyperkalemia and renal impairment (aliskiren)

Aliskiren can cause angioedema or anaphylaxis at any time and, like other RAAS drugs, can raise potassium and impair renal function.

■ Boxed warning · oral minoxidil

Can cause pericardial effusion (occasionally tamponade) and worsen angina — reserved for hypertension not controlled by a diuretic plus two other drugs.

■ Boxed warning · fetal toxicity (aliskiren)

Drugs acting directly on the renin–angiotensin system can injure or kill the fetus — stop aliskiren as soon as pregnancy is detected.

First-dose syncope (alpha-1 blockers): Blocking alpha-1 receptors removes catecholamine vasoconstriction, and syncope is believed to reflect an excessive postural hypotensive effect; occasionally a bout of supraventricular tachycardia precedes it, and hemodilution may contribute. The risk is greatest in the first 7 days and returns after a dose increase or a restart.
Intraoperative floppy iris syndrome (alpha-1 blockers): Alpha-1 receptors drive the iris dilator muscle; long-term blockade can cause dilator dysfunction or atrophy, so the iris billows, prolapses toward the incisions and constricts despite mydriatics. Stopping the drug before surgery does not appear to help.
Rebound hypertension (clonidine): Chronic central alpha-2 stimulation suppresses sympathetic outflow; abrupt withdrawal lets it rebound, with elevated plasma catecholamines and a rapid BP rise. A continued beta-blocker leaves alpha-mediated vasoconstriction unopposed and makes it worse.
Reflex tachycardia, fluid retention and angina (hydralazine, minoxidil): Arteriolar dilation drops resistance; baroreflex sympathetic discharge raises heart rate and cardiac output and drives renin secretion, so angiotensin II and aldosterone retain sodium. Higher heart rate and output raise myocardial oxygen demand, which can unmask angina.
Drug-induced lupus (hydralazine): Risk rises with greater cumulative exposure, female sex, slow acetylation and immunogenetic variants such as HLA-DR4. Antihistone antibodies are present in more than 95% of hydralazine-induced cases, whereas anti-dsDNA is generally absent.
Coombs-positive hemolytic anemia (methyldopa): With prolonged therapy the red cell becomes coated with IgG, giving a positive direct Coombs test in 10–20% of patients; rarely this progresses to hemolytic anemia. The Coombs test may stay positive for weeks to months after the drug is stopped.
Hypertrichosis (minoxidil): Minoxidil acts on potassium channels in hair follicles as well as vessels, dilating the arterioles around follicles and prolonging the anagen (growth) phase — the same action that makes topical minoxidil a hair-loss treatment.
Hyperkalemia, renal failure and fetal toxicity (aliskiren): Like other RAAS drugs it lowers angiotensin II and aldosterone; kidneys whose filtration depends on the RAAS can fail, potassium rises, and in the second and third trimesters reduced fetal renal function causes oligohydramnios and neonatal renal failure.

Toxicity & antidote

Cyanide: metabolic acidosis, hypoxemia, bradycardia, confusion and seizures; venous blood may look arterial. Acidosis can lag dangerous cyanide levels by more than an hour, so suspicion alone justifies treatment. Stop the infusion. The label’s regimen gives sodium nitrite to turn some hemoglobin into methemoglobin (which binds cyanide) and then sodium thiosulfate as the sulfur donor for conversion to thiocyanate; hydroxocobalamin binds cyanide directly (forming cyanocobalamin). Hemodialysis removes thiocyanate but not cyanide.

Thiocyanate: with renal failure or infusions longer than about 3 days, tinnitus, abdominal pain, weakness and confusion can progress to seizures and coma. Methemoglobinemia is rarer and needs large amounts of nitroprusside.

Clonidine overdose: an early rise in BP (likely from peripheral alpha-2 stimulation causing vasoconstriction) is followed by hypotension, bradycardia, respiratory depression, hypothermia, miosis, drowsiness and, in large overdoses, conduction defects, apnea, coma and seizures. There is no specific antidote: atropine for bradycardia, fluids or vasopressors for hypotension, and naloxone as a possible adjunct.

Interactions

Strong CYP3A inhibitors (doxazosin)

Raise doxazosin exposure — monitor blood pressure and for symptoms of hypotension.

Ferrous sulfate or ferrous gluconate (methyldopa)

Lower methyldopa bioavailability and can weaken BP control — co-administration is not recommended.

Lithium (methyldopa)

Monitor carefully for lithium toxicity.

ACE inhibitors or ARBs (aliskiren)

Dual RAS blockade: more hypotension, hyperkalemia and renal-function changes, usually with no added benefit — contraindicated in diabetes and generally avoided, especially with CrCl < 60 mL/min.

Cyclosporine or itraconazole (aliskiren)

Significantly raise aliskiren levels — avoid.

NSAIDs, including COX-2 inhibitors (aliskiren)

Can worsen renal function, even to acute renal failure, in older, volume-depleted or renally impaired patients, and blunt the BP effect — monitor renal function.

Potassium supplements or potassium-sparing diuretics (aliskiren)

Add to the hyperkalemia risk — monitor potassium.

High-fat meals (aliskiren)

Substantially decrease absorption — take aliskiren the same way relative to meals every day.

Contraindications

Concurrent PDE5 inhibitors (alpha-1 blockers) use caution — Additive vasodilation causes severe hypotension.
Abrupt discontinuation of clonidine — Causes rebound hypertensive crisis — must be tapered.
Hydralazine with coronary artery disease, mitral valvular rheumatic heart disease, or hydralazine allergy — Labeled contraindications for hydralazine tablets.
Nitroprusside at the maximum rate for more than 10 minutes — The boxed warning says a maximum-rate infusion should never last more than 10 minutes — stop it if BP is not controlled; cyanide can reach toxic, potentially lethal levels.
Nitroprusside with hepatic/renal impairment or prolonged infusion use caution — Cyanide/thiocyanate accumulation causes toxicity — limit duration and monitor.
Nitroprusside for compensatory hypertension (aortic coarctation, AV shunt), for lowering BP in surgery with poor cerebral circulation or in moribund emergency-surgery patients, with Leber’s optic atrophy or tobacco amblyopia, or for high-output heart failure — Labeled contraindications; the optic-atrophy and amblyopia patients have unusually high cyanide/thiocyanate ratios.
Methyldopa with active liver disease (acute hepatitis, active cirrhosis), a past methyldopa-related liver disorder, or an MAO inhibitor — Labeled contraindications for methyldopa, which can itself cause hepatitis and, rarely, fatal hepatic necrosis.
Minoxidil with pheochromocytoma — Its blood-pressure-lowering action may stimulate catecholamine secretion from the tumor (labeled contraindication).
Aliskiren with an ACE inhibitor or ARB in a patient with diabetes, or in a child under 2 — Labeled contraindications: dual RAS blockade in diabetes raises the risk of renal impairment, hyperkalemia and hypotension; juvenile animal studies showed high aliskiren exposures from immature transporters and enzymes.

High-yield

Positive direct Coombs test after months on an antihypertensive Methyldopa (IgG-coated red cells; rarely hemolytic anemia)

Arthralgia, serositis and antihistone antibodies on an arteriolar vasodilator Hydralazine-induced lupus — slow acetylators (NAT2) at higher risk

Lactic acidosis and oxygen-rich venous blood during a prolonged IV vasodilator infusion Nitroprusside cyanide toxicity (cytochrome c oxidase blocked)

Tinnitus and confusion after days of nitroprusside in renal failure Thiocyanate toxicity

K-ATP channel opener used orally for resistant hypertension and topically for hair loss Minoxidil

Rapid BP rise with tremor and agitation after abruptly stopping a central agent Clonidine withdrawal (rebound catecholamine surge)

Billowing iris and progressive miosis during cataract surgery Alpha-1 blocker — intraoperative floppy iris syndrome

Prodrug whose metabolite stimulates central alpha-2 receptors Methyldopa → alpha-methylnorepinephrine

Antihypertensive that lowers plasma renin activity even as renin concentration rises Aliskiren (direct renin inhibitor)

Falsely high urinary catecholamines in a pheochromocytoma workup Methyldopa (fluorescence interference)

Receptor, Brainstem, Muscle, Enzyme

Receptor — the alpha-1 blockers (-azosin): first-dose syncope, floppy iris
Brainstem — clonidine and methyldopa: rebound when clonidine stops; Coombs-positive anemia with methyldopa
Muscle — hydralazine, minoxidil, nitroprusside: reflex tachycardia and fluid retention; lupus, hair, cyanide
Enzyme — aliskiren on renin: fetal toxicity, hyperkalemia, no ACE inhibitor or ARB in diabetes

The site of action predicts the signature problem.

Nitroprusside: NO in, CN out

NO — nitric oxide raises cGMP and dilates arteries and veins within minutes
CN — cyanide is buffered by methemoglobin and turned into thiocyanate by rhodanese with thiosulfate; thiocyanate needs the kidneys

Antidotes follow the chemistry: nitrite (more methemoglobin), thiosulfate (more sulfur), hydroxocobalamin (binds cyanide).

Practice questions

Q1A 64-year-old man in the ICU has received an IV nitroprusside infusion at a high rate for many hours for a hypertensive emergency. He becomes confused, his serum lactate climbs, and a central venous blood gas shows an unexpectedly high oxygen saturation.

What is the mechanism of his deterioration?

A.Excess cGMP causing refractory vasodilation
B.Thiocyanate accumulation from renal failure
C.Reflex sympathetic activation from the BP drop
D.Methemoglobin formation impairing oxygen delivery
E.Cyanide binding cytochrome c oxidase and blocking oxidative phosphorylation

Show answer

E. Cyanide binding cytochrome c oxidase and blocking oxidative phosphorylation — Nitroprusside reacts with hemoglobin to release cyanide; once methemoglobin buffering and thiosulfate-dependent conversion to thiocyanate are overwhelmed, free cyanide binds cytochrome c oxidase. Cells switch to anaerobic metabolism (lactic acidosis) and cannot extract oxygen, so venous blood stays oxygen-rich. Thiocyanate toxicity is slower (days, renal failure) and presents with tinnitus and confusion; methemoglobinemia needs very large amounts.

Q2A 61-year-old woman who has taken hydralazine for hypertension for over a year develops fever, arthralgias and pleuritic chest pain. Her ANA and antihistone antibodies are positive; anti-dsDNA is negative.

Which patient characteristic most increased her risk?

A.CYP2D6 ultrarapid metabolism
B.Slow (poor-metabolizer) NAT2 acetylator status
C.HLA-B*58:01 carriage
D.G6PD deficiency
E.Rapid NAT2 acetylator status

Show answer

B. Slow (poor-metabolizer) NAT2 acetylator status — Hydralazine undergoes polymorphic acetylation. Slow acetylators (NAT2 poor metabolizers) have higher hydralazine levels and are predicted by CPIC to have more adverse effects, including drug-induced lupus; female sex and cumulative exposure add risk. Antihistone antibodies are present in more than 95% of hydralazine-induced cases, while anti-dsDNA is usually absent.

Q3A 57-year-old man taking clonidine and metoprolol for hypertension runs out of both medications while traveling. Two days later he presents with headache, tremor, agitation and a blood pressure of 224/122 mm Hg.

What best explains this presentation?

A.Beta-blocker withdrawal causing a fall in cardiac output
B.Activation of the renin–angiotensin system by the metoprolol
C.Clonidine’s peripheral alpha-2 agonism increasing vascular tone
D.Loss of central alpha-2 suppression of sympathetic outflow, with a catecholamine surge
E.Hypertensive encephalopathy from undiagnosed pheochromocytoma

Show answer

D. Loss of central alpha-2 suppression of sympathetic outflow, with a catecholamine surge — Clonidine lowers BP by stimulating brainstem alpha-2 receptors and reducing sympathetic outflow. Abrupt withdrawal releases that brake: nervousness, agitation, headache and tremor with a rapid BP rise and high plasma catecholamines. The risk is greater when a beta-blocker is involved, which is why the beta-blocker is withdrawn several days before clonidine is tapered.

Q4A 29-year-old woman at 32 weeks’ gestation has taken methyldopa for chronic hypertension since early pregnancy. Before an urgent cesarean delivery, the blood bank reports a positive direct Coombs test; her hemoglobin is normal and the indirect Coombs test is negative.

What explains the positive test?

A.IgG coating of her red cells induced by methyldopa
B.Alloimmunization against fetal Rh antigens
C.Methyldopa-induced bone marrow suppression
D.Complement activation by a cold agglutinin
E.Interference of methyldopa with the reagent’s fluorescence

Show answer

A. IgG coating of her red cells induced by methyldopa — With prolonged methyldopa therapy, 10–20% of patients develop a positive direct Coombs test as the red cells become coated with IgG. Without hemolytic anemia, usually only the direct test is positive, which does not interfere with typing or cross-matching; both direct and indirect tests are done before transfusion. Methyldopa’s fluorescence interferes with urinary catecholamine tests, not the Coombs test.

Q5A 66-year-old man with severe hypertension and chronic kidney disease, uncontrolled on a thiazide and two other drugs, is started on oral minoxidil alone because of intolerance to other agents. Two weeks later his resting pulse has risen by 25 beats/min, he has gained 3 kg, and his ankles are swollen.

What should have been given with minoxidil, and why?

A.Epinephrine, to support blood pressure and heart rate
B.An ACE inhibitor, to prevent hypertrichosis
C.A beta-blocker and a loop diuretic, to blunt reflex tachycardia and renin-driven salt and water retention
D.Clonidine, to prevent orthostatic hypotension
E.A beta-blocker alone, because minoxidil does not cause fluid retention

Show answer

C. A beta-blocker and a loop diuretic, to blunt reflex tachycardia and renin-driven salt and water retention — Minoxidil opens K-ATP channels and lowers peripheral resistance, which triggers sympathetic, vagal-inhibitory and renal homeostatic responses: faster heart rate and output, more renin and salt and water retention. The label requires a beta-blocker (or other sympathetic suppressant) and usually a loop diuretic. Minoxidil itself does not cause orthostatic hypotension. Without a diuretic it retains several hundred milliequivalents of salt, with the matching water, within a few days, so a beta-blocker alone is not enough. Its hypertrichosis has no endocrine explanation and stops only when minoxidil is discontinued, so an ACE inhibitor would not prevent it, and sympathomimetics such as epinephrine are avoided because of their excessive cardiac stimulation.

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By LearnDrugs

Educational summary for medical students. Always verify against current prescribing information and guidelines. Not medical advice.