Nitrates, Hydralazine

Foundations and mechanisms

Haemodynamic rationale

Nitrates and hydralazine are vasodilators whose clinical effects are best understood through ventricular wall stress and vascular capacitance/resistance. Myocardial oxygen demand is driven principally by heart rate, contractility and systolic wall tension; by the law of Laplace, wall stress is proportional to intraventricular pressure and radius and inversely proportional to wall thickness. Venodilatation reduces venous return, end-diastolic volume and ventricular radius, thereby reducing preload and myocardial oxygen consumption. Arteriolar dilatation reduces systemic vascular resistance and afterload, increasing forward stroke volume where contractile reserve exists, but may provoke reflex sympathetic activation.

In anaesthetic and critical care practice these distinctions are essential: organic nitrates are predominantly venodilators at low doses, whereas hydralazine is a predominantly arteriolar vasodilator. Both may lower arterial pressure, but they do so with different effects on filling pressure, cardiac output, heart rate and coronary perfusion pressure.

Organic nitrates and nitrovasodilators

Organic nitrates include glyceryl trinitrate, isosorbide dinitrate and isosorbide mononitrate. Sodium nitroprusside is not an organic nitrate, but is commonly considered with nitrates as a direct nitric oxide donor and potent balanced vasodilator.

Drug	Usual dose	Onset	Elimination half-life	Dominant haemodynamic effect
Glyceryl trinitrate, sublingual	300–600 micrograms; repeat every 5 min if required	1–3 min	1–4 min	Venodilatation; coronary vasodilatation
Glyceryl trinitrate, intravenous	5–200 micrograms/min titrated to effect	1–2 min	1–4 min	Preload reduction; afterload reduction at higher doses
Isosorbide dinitrate	5 mg sublingual; 10–40 mg oral	2–5 min sublingual	Approximately 1 h	Venodilatation; active metabolites
Isosorbide mononitrate	10–20 mg twice daily or modified-release 30–120 mg daily	30–60 min oral	4–6 h	Longer-acting venodilatation
Sodium nitroprusside	0.3–10 micrograms/kg/min IV	Seconds	Plasma half-life approximately 2 min	Balanced arterial and venous vasodilatation

Nitrates undergo enzymatic bioactivation to nitric oxide or related S-nitrosothiols. Glyceryl trinitrate is bioactivated principally by mitochondrial aldehyde dehydrogenase-2. Nitric oxide activates soluble guanylate cyclase in vascular smooth muscle, increasing cyclic guanosine monophosphate. cGMP activates protein kinase G, which reduces intracellular calcium availability, enhances myosin light-chain phosphatase activity and causes dephosphorylation of myosin light chains. The result is vascular smooth muscle relaxation.

The venous circulation is more sensitive than the arterial circulation to organic nitrates. At low concentrations there is venodilatation, reduced central venous pressure, reduced pulmonary capillary wedge pressure and reduced left ventricular end-diastolic pressure. With increasing dose there is arteriolar dilatation, reduced systolic blood pressure and potential reflex tachycardia. Nitrates also dilate large epicardial coronary arteries and relieve coronary vasospasm; they do not reliably dilate small resistance vessels in ischaemic territories and may worsen hypotension if coronary perfusion pressure falls.

Tolerance and interactions

Nitrate tolerance develops within 24–48 h of continuous exposure and reflects impaired bioactivation, oxidative stress, neurohumoral counter-regulation, plasma volume expansion and thiol depletion. Clinically, a nitrate-free interval of approximately 10–12 h per day is used for chronic therapy. Acute tachyphylaxis is relevant during prolonged intravenous GTN infusions in critical care.

PDE-5 inhibitors prevent cGMP degradation and markedly potentiate nitrate-induced vasodilatation. Nitrates are contraindicated after sildenafil or vardenafil within 24 h and tadalafil within 48 h; longer avoidance may be prudent in renal or hepatic impairment. Severe hypotension is particularly likely in preload-dependent states such as right ventricular infarction, severe aortic stenosis, hypovolaemia and hypertrophic obstructive cardiomyopathy.

Hydralazine

Hydralazine is a direct arteriolar vasodilator with minimal direct venous effect. Its precise molecular mechanism is incompletely defined, but clinically relevant mechanisms include reduction of intracellular calcium release from the sarcoplasmic reticulum, interference with inositol trisphosphate-mediated calcium signalling, potassium-channel-mediated hyperpolarisation and possible stimulation of endothelial nitric oxide pathways. The net effect is relaxation of resistance arterioles, reduced systemic vascular resistance and reduced afterload.

Parameter	Hydralazine
IV dose	5–10 mg slow IV; repeat every 20–30 min according to response
Oral dose	25 mg twice daily initially; usual maintenance 50–100 mg twice or three times daily
Onset after IV dose	5–20 min
Duration	2–6 h, often longer than plasma concentration predicts
Half-life	Approximately 2–8 h; affected by acetylator status
Metabolism	Hepatic acetylation and hydroxylation; renal excretion of metabolites

Because hydralazine selectively reduces arteriolar tone, arterial pressure falls with little reduction in venous return. Baroreceptor-mediated sympathetic activation increases heart rate, myocardial contractility and renin release; plasma volume expansion may occur with continued use. Consequently, hydralazine is commonly combined with a beta-blocker and diuretic in chronic hypertension. It may increase myocardial oxygen consumption and is relatively unattractive in active coronary ischaemia unless heart rate is controlled.

In obstetric practice, hydralazine remains a recognised intravenous option for severe hypertension, typically defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg, alongside labetalol and nifedipine in contemporary guidelines. Its delayed and variable peak effect compared with agents such as labetalol is a frequent examination point.

Mechanistic comparison

Feature	Nitrates	Hydralazine
Primary vascular site	Venous capacitance vessels; arteries at higher dose	Arteriolar resistance vessels
Second messenger	NO–soluble guanylate cyclase–cGMP–PKG	Reduced intracellular calcium signalling; possible NO contribution
Preload	Markedly reduced	Little direct reduction
Afterload	Reduced at moderate to high dose	Markedly reduced
Reflex tachycardia	Variable; more with hypotension	Common and mechanistically expected
Key pharmacological limitation	Tolerance; PDE-5 inhibitor interaction; preload dependence	Unpredictable duration; sympathetic activation; lupus-like syndrome with chronic use

Clinical assessment and investigations

Clinical presentations prompting consideration of nitrates or hydralazine

Nitrates and hydralazine are encountered in anaesthetic practice as vasodilators used for myocardial ischaemia, acute heart failure, hypertensive emergencies, controlled hypotension, and obstetric hypertension. Assessment must identify the dominant haemodynamic abnormality: excess preload, excess afterload, coronary vasospasm, fixed outflow obstruction, or distributive/volume-depleted hypotension. This distinction is essential because nitrates predominantly reduce venous return at low doses and arterial tone at higher doses, whereas hydralazine is a direct arteriolar vasodilator with reflex sympathetic activation and little venodilator effect.

Clinical scenario	Typical findings	Relevance to drug choice
Acute coronary syndrome or perioperative myocardial ischaemia	Chest pain, ST depression/elevation, new wall-motion abnormality, troponin rise above 99th percentile	GTN reduces LV wall stress and coronary spasm; avoid if hypotensive or RV infarction suspected
Acute cardiogenic pulmonary oedema	Severe dyspnoea, crackles, hypoxaemia, hypertension, CXR alveolar oedema, raised BNP/NT-proBNP	High-dose nitrates useful when systolic BP is usually >110 mmHg; reduce preload and afterload rapidly
Hypertensive emergency	Usually BP >180/120 mmHg with acute organ injury: encephalopathy, ACS, pulmonary oedema, AKI, aortic dissection	Use titratable IV agents; hydralazine has unpredictable duration and is mainly reserved for pregnancy-related severe hypertension
Severe hypertension in pregnancy/pre-eclampsia	BP ≥160 systolic or ≥110 diastolic; headache, visual symptoms, epigastric pain, thrombocytopenia, transaminitis, proteinuria	IV hydralazine is guideline-supported, but labetalol or nifedipine are often alternatives
Heart failure with reduced ejection fraction intolerant of ACEI/ARB/ARNI	Reduced LVEF, congestion, raised natriuretic peptides, renal dysfunction or hyperkalaemia limiting RAAS blockade	Hydralazine plus isosorbide dinitrate improves outcomes in selected groups, notably Black patients with persistent symptoms

Focused assessment before administration

Initial assessment should include haemodynamic trend rather than an isolated blood pressure reading: heart rate, rhythm, pulse pressure, capillary refill, urine output, temperature, level of consciousness, oxygenation, and evidence of pulmonary or systemic congestion. In the anaesthetised patient, invasive arterial pressure monitoring is preferred when continuous nitrate infusion or IV hydralazine is used for unstable hypertension, because abrupt preload or afterload reduction may cause myocardial or cerebral hypoperfusion.

Contraindications to nitrates must be actively sought. These include systolic BP <90 mmHg or MAP <65 mmHg, severe bradycardia or tachycardia with instability, suspected right ventricular infarction, severe aortic stenosis, hypertrophic obstructive cardiomyopathy, raised intracranial pressure where cerebral perfusion is precarious, and recent phosphodiesterase-5 inhibitor exposure. Recommended nitrate avoidance intervals are approximately 24 hours after sildenafil or vardenafil and 48 hours after tadalafil, due to synergistic cyclic GMP-mediated vasodilatation and refractory hypotension.

Hydralazine assessment should focus on states in which reflex tachycardia and increased cardiac output are undesirable, such as active myocardial ischaemia, aortic dissection, severe tachyarrhythmia, and high sympathetic tone. Chronic use requires enquiry for drug-induced lupus, arthralgia, fever, pleuritic pain, rash, neuropathy, and constitutional symptoms; risk increases with higher cumulative exposure, slow acetylator phenotype, female sex, and doses commonly exceeding 100–200 mg/day.

Differential diagnosis

Problem	Important differentials	Discriminating investigations
Chest pain or intraoperative ischaemia	ACS, coronary spasm, anaemia, hypoxaemia, tachyarrhythmia, pulmonary embolism, aortic dissection, oesophageal causes	12-lead ECG, serial high-sensitivity troponin, Hb, ABG, D-dimer/CTPA if appropriate, CT aortogram
Acute dyspnoea with hypertension	Cardiogenic pulmonary oedema, asthma/COPD, PE, aspiration, ARDS, sepsis	CXR, lung ultrasound B-lines, echocardiography, BNP/NT-proBNP, ABG, lactate
Severe perioperative hypertension	Pain, hypoxia, hypercarbia, bladder distension, emergence, raised ICP, phaeochromocytoma, pre-eclampsia, MAOI/sympathomimetic interaction	ETCO2, ABG, analgesic depth, urinary catheter, neurological assessment, urinalysis, catecholamine testing later if indicated
Cyanosis or low SpO2 despite adequate PaO2	Methaemoglobinaemia, dyshemoglobinaemia, probe artefact, severe shock	Co-oximetry; methaemoglobin normally <1–2%, symptoms usually >20–30%

Investigations and interpretation

A 12-lead ECG is mandatory in suspected ACS or nitrate-responsive chest pain. STEMI criteria are new ST elevation at the J point in two contiguous leads: generally ≥1 mm, with V2–V3 thresholds of ≥2.5 mm in men <40 years, ≥2.0 mm in men ≥40 years, and ≥1.5 mm in women. ST depression ≥0.5 mm in contiguous leads supports ischaemia. High-sensitivity troponin should be interpreted using assay-specific 99th percentile upper reference limits and dynamic change; perioperative myocardial injury may be clinically silent and requires correlation with haemodynamics and ECG.

Bedside echocardiography is highly informative before vasodilator therapy: assess LV systolic function, regional wall-motion abnormality, RV dilatation or infarction, pericardial tamponade, dynamic LV outflow obstruction, and severe valvular stenosis. Nitrates may precipitate profound hypotension in preload-dependent RV failure or fixed/dynamic outflow obstruction. Lung ultrasound showing diffuse bilateral B-lines supports pulmonary oedema; CXR may show alveolar oedema, cardiomegaly, pleural effusions, or alternative diagnoses.

Laboratory assessment should include FBC, U&E, creatinine, magnesium, coagulation profile when ACS or obstetric disease is suspected, LFTs, glucose, and ABG/VBG with lactate. In acute heart failure, BNP <100 pg/mL or NT-proBNP <300 pg/mL makes heart failure unlikely in acute dyspnoea, although renal failure, age, obesity, and atrial fibrillation affect interpretation. In pre-eclampsia, proteinuria is defined as urine protein:creatinine ratio ≥30 mg/mmol or 24-hour protein ≥300 mg; severe features include platelets <100 × 10⁹/L, creatinine >90 micromol/L or doubling from baseline, ALT/AST elevation, pulmonary oedema, or neurological symptoms.

Therapeutic thresholds relevant to assessment

For hypertensive emergency, contemporary guidance recommends controlled reduction of MAP by no more than 20–25% in the first hour, then to approximately 160/100 mmHg over 2–6 hours, avoiding precipitous falls. Exceptions include aortic dissection, where the target is systolic BP <120 mmHg and heart rate <60 beats/min within about 20 minutes using beta-blockade before vasodilatation. In ACS, nitrates are appropriate for ongoing pain, hypertension, or pulmonary congestion provided systolic BP is >90 mmHg and there is no contraindication. In severe pregnancy hypertension, treatment is generally indicated at BP ≥160/110 mmHg, aiming initially for approximately 140–150/90–100 mmHg to reduce maternal stroke risk while preserving uteroplacental perfusion.

Management, pharmacology and procedures

Clinical use and haemodynamic objectives

Nitrates and hydralazine are vasodilators used to manipulate preload, afterload and coronary perfusion. In peri-operative and critical care practice, treatment should be goal-directed: relieve myocardial ischaemia, reduce pulmonary congestion, or control severe hypertension while maintaining organ perfusion. Excessive blood pressure reduction is harmful; in hypertensive emergencies a typical target is reduction of mean arterial pressure by no more than 20–25% in the first hour, then to approximately 160/100 mmHg over 2–6 hours unless aortic dissection or eclampsia mandates faster control.

Nitrates: acute and chronic management

Glyceryl trinitrate (GTN) is the principal acute nitrate. It is converted enzymatically, predominantly via mitochondrial aldehyde dehydrogenase, to nitric oxide, activating soluble guanylate cyclase, increasing cyclic GMP and causing myosin light-chain dephosphorylation. Venodilatation predominates at low doses, reducing venous return, left ventricular end-diastolic pressure and wall stress; higher doses dilate arteries and epicardial coronary vessels. This explains its utility in angina, acute pulmonary oedema with hypertension, peri-operative myocardial ischaemia and controlled hypotension.

Drug	Typical dose	Onset/duration	Key points
GTN sublingual tablet/spray	300–600 micrograms SL, or 400 micrograms spray; repeat every 5 min to 3 doses	Onset 1–3 min; duration 20–30 min	First-line symptomatic relief of angina; sit patient down because syncope may occur
GTN intravenous infusion	Start 5–10 micrograms/min; titrate every 3–5 min; usual range 10–200 micrograms/min	Onset 1–2 min; plasma half-life 1–4 min	Use non-PVC giving sets where possible; continuous arterial pressure monitoring for high-dose use
Isosorbide dinitrate	10–40 mg orally 2–3 times daily; IV preparations vary by institution	Oral onset 20–60 min; duration 4–6 h	Active metabolites include isosorbide-5-mononitrate
Isosorbide mononitrate	20 mg twice daily, or modified-release 30–120 mg once daily	Bioavailability nearly 100%; half-life 4–5 h	Preferred long-term nitrate; schedule nitrate-free interval

In acute coronary syndromes, nitrates improve pain and haemodynamics but do not reduce mortality; antiplatelet therapy, anticoagulation, statins and revascularisation determine prognosis. Avoid nitrates in systolic blood pressure <90 mmHg, marked bradycardia or tachycardia with instability, right ventricular infarction, severe aortic stenosis, hypertrophic obstructive cardiomyopathy, raised intracranial pressure, and recent phosphodiesterase-5 inhibitor exposure: sildenafil or vardenafil within 24 hours, tadalafil within 48 hours. Concomitant riociguat is contraindicated.

Tolerance develops within 24–48 hours of continuous exposure due to sulphydryl depletion, neurohormonal activation and oxidative stress. Long-term therapy therefore requires a daily nitrate-free interval of 10–12 hours, accepting possible early-morning angina. Adverse effects are dose-related headache, flushing, hypotension, reflex tachycardia, syncope and, rarely, methaemoglobinaemia at very high doses or prolonged exposure. Abrupt withdrawal may precipitate rebound angina.

Hydralazine: acute and chronic management

Hydralazine is a direct arteriolar vasodilator with minimal venodilating activity. It reduces systemic vascular resistance and afterload, increasing stroke volume when ventricular function is impaired, but provokes baroreceptor-mediated tachycardia, increased renin release and sodium-water retention. Mechanisms include interference with intracellular calcium handling, potassium-channel effects and nitric oxide-related pathways, but its precise molecular target remains incompletely defined.

Setting	Regimen	Monitoring and cautions
Severe hypertension in pregnancy/pre-eclampsia	5–10 mg IV slowly; repeat every 20–30 min according to response, or infusion 0.5–10 mg/h	Aim usually <150/100 mmHg while avoiding maternal hypotension and uteroplacental hypoperfusion
Peri-operative or ward hypertension	5–10 mg IV; repeat cautiously; effect may last 2–6 h	Less titratable than GTN, labetalol or nicardipine; avoid in active myocardial ischaemia
Chronic resistant hypertension	25 mg twice daily or three times daily; titrate to 50–100 mg three times daily; usual maximum 200 mg/day	Combine with beta-blocker and diuretic to limit tachycardia and fluid retention
HFrEF with nitrate combination	Isosorbide dinitrate 20 mg plus hydralazine 37.5 mg three times daily; titrate to 40 mg/75 mg three times daily	Indicated when ACEi/ARB/ARNI not tolerated, and as add-on in selected Black patients with persistent symptoms

Hydralazine has oral bioavailability of approximately 25–50% because of first-pass acetylation; slow acetylators have higher exposure and greater toxicity risk. The plasma half-life is approximately 2–8 hours, but antihypertensive effects persist longer due to vascular binding. It crosses the placenta and is widely used in obstetric hypertensive emergencies, although contemporary guidance often also supports labetalol or nifedipine depending on context.

In heart failure, the nitrate–hydralazine combination has outcome data. V-HeFT I showed mortality benefit versus placebo in men with chronic heart failure, while A-HeFT demonstrated a 43% relative reduction in mortality and fewer first hospitalisations when fixed-dose isosorbide dinitrate/hydralazine was added to standard therapy in self-identified Black patients with NYHA III–IV HFrEF. Current ACC/AHA/HFSA and ESC guidance reserves it for patients intolerant of renin–angiotensin system inhibition or as add-on therapy in selected persistently symptomatic patients.

Procedural and safety considerations

Intravenous vasodilator therapy requires large-bore reliable access, frequent non-invasive blood pressure measurement or invasive arterial monitoring when rapid titration is required, continuous ECG monitoring in ischaemic patients, and assessment of urine output, lactate and mental status as markers of perfusion. GTN infusions may adsorb to polyvinyl chloride tubing, causing under-delivery; glass bottles or low-adsorption giving sets reduce this problem. Hydralazine should be avoided as sole therapy in coronary disease or aortic dissection because reflex tachycardia and increased contractility may worsen myocardial oxygen demand or shear stress.

Follow-up after chronic therapy should assess blood pressure, angina frequency, heart failure symptoms, adherence to nitrate-free intervals, headache limiting compliance, and drug interactions. Hydralazine monitoring should include full blood count and antinuclear antibody testing if symptoms suggest drug-induced lupus. Lupus-like syndrome is dose- and duration-related, more common in slow acetylators, women and at doses above 200 mg/day; features include arthralgia, fever, serositis and positive ANA or anti-histone antibodies. Other complications include peripheral neuropathy, fluid retention, tachyarrhythmias and rare blood dyscrasias.

Exam controversies and advanced synthesis

Guideline positioning: where nitrates and hydralazine actually sit

Nitrates and hydralazine are often described simplistically as “vasodilators”, but examination answers should distinguish their haemodynamic niche. Organic nitrates predominantly reduce preload via venodilatation at low doses, with arterial/coronary effects at higher doses; hydralazine is a predominantly direct arteriolar vasodilator with little venodilator effect. This distinction predicts both therapeutic use and complications under anaesthesia.

Clinical setting	Nitrates	Hydralazine	Exam controversy/pitfall
Acute coronary syndrome/angina	GTN sublingual 300–600 micrograms; IV 5–200 micrograms/min titrated	Generally avoided	Nitrates relieve pain/ischaemia but do not reduce mortality in routine ACS; avoid in RV infarction, severe AS, hypotension, recent PDE-5 inhibitor use.
Acute pulmonary oedema with hypertension	First-line vasodilator if SBP usually >110 mmHg; high-dose IV GTN may be required	Not preferred acutely	Venodilatation reduces LV filling pressure rapidly; diuretics are not the immediate haemodynamic treatment in “flash” pulmonary oedema.
Hypertensive emergency	Useful in myocardial ischaemia/pulmonary oedema	Selected use, especially pregnancy; slow titration difficult	Hydralazine has unpredictable onset/duration and reflex tachycardia; labetalol/nicardipine often preferred outside obstetrics.
Chronic HFrEF	Isosorbide dinitrate combined with hydralazine	Combined with nitrate	Benefit is in combination, not hydralazine monotherapy; especially relevant where ACEi/ARB/ARNI not tolerated and in selected Black patients.

Trials and evidence that commonly surface in viva discussion

The major heart failure evidence for this pair comes from vasodilator trials rather than anaesthetic studies. In V-HeFT I, hydralazine plus isosorbide dinitrate reduced mortality compared with placebo in men with chronic heart failure, although subsequent ACE inhibitor data were stronger. V-HeFT II showed enalapril superior to hydralazine–isosorbide dinitrate for survival. The modern landmark is A-HeFT, in self-identified Black patients with NYHA III–IV HFrEF already receiving standard therapy: fixed-dose isosorbide dinitrate/hydralazine significantly reduced mortality by approximately 43% and first hospitalisation for heart failure by approximately 33%; the trial was stopped early. Current HF guidelines therefore position hydralazine–nitrate therapy as add-on therapy in symptomatic HFrEF in this group, and as an alternative when renin–angiotensin system inhibitors are contraindicated, for example renal dysfunction, hyperkalaemia or angio-oedema.

For ACS, historical large trials such as ISIS-4 and GISSI-3 did not show a clear mortality benefit for routine nitrate therapy. Thus, in exams, nitrates are anti-ischaemic and haemodynamic agents, not disease-modifying mortality drugs. They are indicated for symptom relief, hypertension and pulmonary congestion, provided there is no haemodynamic contraindication.

Dose, kinetics and “anaesthetic relevance”

Drug	Typical acute dose	Onset/duration	Key viva points
Glyceryl trinitrate, sublingual	300–600 micrograms, repeat every 5 min up to 3 doses	Onset 1–3 min; duration 20–30 min; plasma half-life about 1–4 min	Marked first-pass metabolism; useful for acute angina; headache and hypotension common.
GTN infusion	Start 5–10 micrograms/min; titrate commonly to 20–200 micrograms/min	Immediate titratability	Adsorbed by PVC giving dose loss; use appropriate giving sets where possible. Tolerance may occur within 24 h.
Sodium nitroprusside	0.3–10 micrograms/kg/min	Seconds; duration 1–2 min	Not a nitrate but often compared; balanced arterial/venous dilator; cyanide/thiocyanate toxicity risk, especially prolonged high-dose infusion or renal/hepatic failure.
Hydralazine IV	5–10 mg slow IV, repeat after 20–30 min; obstetric regimens often 5 mg IV increments	Onset 5–20 min; duration 2–6 h; half-life about 2–8 h	Unpredictable and prolonged; reflex tachycardia, increased renin, fluid retention; lupus-like syndrome with chronic use.
Hydralazine oral	25–100 mg two to four times daily; maximum commonly 300 mg/day	Variable bioavailability due to acetylation	Slow acetylators have greater exposure and higher adverse effect risk.

Controversies and contraindications: high-yield pitfalls

• Right ventricular infarction: nitrates can precipitate profound hypotension by reducing preload to a preload-dependent RV. Suspect with inferior MI, raised JVP and clear lungs; confirm with right-sided ECG leads.
• Fixed outflow obstruction: severe aortic stenosis or hypertrophic obstructive cardiomyopathy may decompensate with vasodilatation because cardiac output cannot increase appropriately. Nitrates are not absolutely impossible in all cases, but require extreme caution, invasive monitoring and titration.
• PDE-5 inhibitors: sildenafil and vardenafil generally require avoidance of nitrates for at least 24 h; tadalafil for at least 48 h, longer with renal/hepatic dysfunction. The mechanism is synergistic cGMP accumulation causing refractory hypotension.
• Intracranial pathology: nitrates and hydralazine may increase cerebral blood volume via vasodilatation and can increase intracranial pressure; avoid abrupt reductions in MAP where cerebral perfusion pressure is marginal.
• MetHb: organic nitrates rarely cause clinically significant methaemoglobinaemia, but risk increases with large doses or co-oxidants. Treat symptomatic cases with methylene blue 1–2 mg/kg IV, avoiding or using caution in G6PD deficiency.
• Hydralazine in ischaemic heart disease: reflex sympathetic activation increases heart rate, contractility and myocardial oxygen demand; it may worsen angina unless combined with beta-blockade and adequate coronary perfusion pressure.

Viva-level integration

A robust answer integrates receptor-level pharmacology with perioperative haemodynamics. Nitrates are prodrugs generating nitric oxide, activating soluble guanylate cyclase, increasing cGMP and dephosphorylating myosin light chains. Hydralazine’s mechanism is less completely defined, involving arteriolar smooth muscle hyperpolarisation, reduced intracellular calcium availability and NO-related effects; it is not simply “NO donor pharmacology”. Therefore, GTN reduces pulmonary capillary wedge pressure and myocardial wall stress quickly, whereas hydralazine reduces systemic vascular resistance and afterload but may increase cardiac output at the cost of tachycardia.

In the FRCA oral, avoid claiming that nitrates “improve coronary perfusion” unconditionally. They dilate large epicardial vessels and relieve spasm, but systemic hypotension and tachycardia may reduce diastolic perfusion pressure. Similarly, do not choose hydralazine for rapidly titratable intraoperative hypertension in an unstable patient; its long and variable effect makes it inferior to agents such as remifentanil, labetalol, nicardipine or GTN depending on the cause. The safest synthesis is: select the vasodilator according to preload, afterload, coronary perfusion, ventricular dependence, and titratability, not according to the generic label “antihypertensive”.