Nitroglycerin
Indications
| Indication | Formulation | Population | Status |
|---|---|---|---|
| Acute relief or acute prophylaxis of angina pectoris due to coronary artery disease | Sublingual tablets · Lingual spray | Adults with stable or unstable angina | FDA Approved |
| Prevention (prophylaxis) of angina pectoris due to coronary artery disease | Topical 2% ointment · Transdermal patch | Adults with chronic stable angina | FDA Approved |
| Peri-operative hypertension | IV injection (5 mg/mL) | Adults in surgical/peri-anaesthesia setting | FDA Approved |
| Control of congestive heart failure in the setting of acute myocardial infarction | IV injection | Adults with HF complicating acute MI | FDA Approved |
| Angina pectoris not responsive to sublingual nitroglycerin and beta-blockers | IV injection | Adults with refractory ischaemic chest pain | FDA Approved |
| Induction of intra-operative hypotension | IV injection | Adults requiring controlled hypotension during anaesthesia | FDA Approved |
| Moderate-to-severe pain associated with chronic anal fissure | Rectal ointment 0.4% (Rectiv) | Adults | FDA Approved (2011) |
Nitroglycerin is one of the oldest cardiovascular drugs in continuous clinical use — its anti-anginal effect was first described in 1879 and modern formulations remain a first-line therapy for the symptomatic relief of myocardial ischaemia. Its principal therapeutic effect is venodilation, which reduces preload and ventricular wall stress; at higher doses it also dilates conductance arteries (including epicardial coronaries) and modestly reduces afterload. Heart rate and contractility are not directly affected, but reflex tachycardia is common with rapid blood-pressure reduction.
The clinical decision is rarely whether to use nitroglycerin but which formulation. Sublingual tablets and lingual spray are reserved for acute attacks: they have an onset of 1–3 minutes and are titratable by repeat dosing. The IV preparation provides minute-by-minute haemodynamic control for peri-operative hypertension, refractory ischaemia, and hypertensive acute heart failure. Topical ointment and transdermal patches are used only for chronic prophylaxis — their slow onset makes them inappropriate for acute attacks and a daily nitrate-free interval is essential to prevent tolerance. The rectal ointment (Rectiv 0.4%) is FDA-approved for chronic anal fissure and is the only formulation with a non-cardiovascular indication.
Acute coronary syndrome (NSTEMI/STEMI) — ongoing ischaemic chest pain. Per the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR chest pain guideline and the 2020 ESC NSTE-ACS guideline (Class I, Level C): sublingual nitroglycerin 0.3–0.4 mg every 5 minutes for up to 3 doses, with IV nitroglycerin if pain persists or for accompanying hypertension or heart failure. Evidence quality: high (long-standing standard of care).
Acute decompensated heart failure (ADHF) with elevated filling pressures and adequate blood pressure. Per the 2022 AHA/ACC/HFSA HF guideline: IV nitroglycerin may be considered as an adjunct to diuretic therapy for relief of dyspnoea in hospitalised ADHF without symptomatic hypotension. Evidence quality: moderate (no mortality benefit demonstrated in randomised trials).
Hypertensive emergency, particularly with acute pulmonary oedema or coronary ischaemia. IV infusion 10–200 mcg/min (or higher with high-dose bolus protocols in sympathetic crashing acute pulmonary oedema, “SCAPE”). Evidence quality: moderate.
Coronary artery vasospasm (variant/Prinzmetal angina, including cocaine-associated chest pain) — sublingual or IV. Evidence quality: high for vasospasm, moderate for cocaine.
Intracoronary administration during PCI for no-reflow phenomenon. 100–200 mcg intracoronary boluses. Evidence quality: moderate.
Esophageal spasm and biliary colic — short-term symptomatic relief. Evidence quality: low.
Uterine relaxation (retained placenta, breech extraction, fetal extraction during caesarean) — anaesthesia setting. Evidence quality: low–moderate.
Dosing
Nitroglycerin dosing is route-specific and titrated to clinical effect. The same active ingredient produces dramatically different pharmacokinetics across formulations — from the ~1-minute onset of sublingual administration to the slow steady-state release of a 24-hour patch. The two universal principles are: (1) use the lowest effective dose (excessive use accelerates tolerance); and (2) build a daily nitrate-free interval of at least 10–12 hours into any chronic regimen.
Sublingual Tablets (Nitrostat 0.3, 0.4, 0.6 mg)
| Indication | Dose | Schedule | Notes |
|---|---|---|---|
| Acute relief of an angina attack | 0.3–0.6 mg SL | One tablet at first sign of attack; may repeat every 5 minutes; maximum 3 tablets in 15 minutes | Sit before taking. If chest pain not relieved or worsens after 3 doses, call emergency services Per Nitrostat PI |
| Acute prophylaxis (anticipated anginal trigger) | 0.3–0.6 mg SL | 5–10 minutes before activity expected to provoke angina | Single dose; do not use as scheduled prophylaxis |
Lingual Spray (Nitromist, NitroQuick spray — 400 mcg/spray)
| Indication | Dose | Schedule | Notes |
|---|---|---|---|
| Acute relief of an angina attack | 1–2 sprays (0.4–0.8 mg) on or under the tongue | May repeat every 5 minutes; maximum 3 sprays in 15 minutes | Do not inhale or swallow. Do not shake the canister Useful when xerostomia limits SL tablet absorption |
| Acute prophylaxis | 1–2 sprays | 5–10 minutes before anticipated trigger | Single use; sit during administration |
Intravenous Injection (5 mg/mL concentrate; standard premixed dilutions 100, 200, 400 mcg/mL in D5W or 0.9% saline)
| Indication | Starting Dose | Titration | Typical Range |
|---|---|---|---|
| Per PI: peri-operative hypertension, CHF in setting of acute MI, refractory angina, induction of intra-operative hypotension | 5 mcg/min via non-PVC tubing Or 25 mcg/min if PVC tubing used (PVC absorbs 20–60% of dose) | Increase by 5 mcg/min every 3–5 minutes up to 20 mcg/min; if no response, increment by 10 then 20 mcg/min | 5–200 mcg/min (titrate to BP, symptoms) |
| Acute coronary syndromes / refractory ischaemic chest pain (off-label dosing range) | 10–20 mcg/min | Increase by 5–10 mcg/min every 3–5 minutes | 10–200 mcg/min Hold for SBP <90 mmHg or symptomatic hypotension |
| Acute decompensated heart failure (off-label) | 10–20 mcg/min | Aggressive titration in 5–10 mcg/min steps every 3–5 minutes | Up to 400 mcg/min per ACLS reference; ≥200 mcg/min often required |
| Sympathetic crashing acute pulmonary oedema (SCAPE) — off-label, emergency setting | High-dose IV bolus 0.4–2 mg every 3–5 min (case-series literature; up to 16 mg reported) | Concomitant infusion typically initiated | Use only in monitored ED/ICU settings with arterial-line BP monitoring; specialist input recommended |
PVC tubing absorbs 20–60% of nitroglycerin (per the IV nitroglycerin PI). Use glass bottles and non-PVC (polyolefin or polyethylene) administration sets where possible. If PVC tubing must be used, the labelling notes that the published starting dose of ~25 mcg/min reflects PVC delivery. Some in-line filters also adsorb nitroglycerin and should be avoided.
Do not mix with any other medication in the same infusion. Do not co-infuse through the same line as blood — pseudoagglutination and haemolysis may occur.
Always use an infusion pump. Continuous BP monitoring (preferably arterial line for higher doses) is required.
Topical 2% Ointment (Nitro-Bid)
| Indication | Starting Dose | Titration | Maximum / Range |
|---|---|---|---|
| Prevention of chronic angina due to CAD | ½ inch (~7.5 mg) on rising + ½ inch 6 hours later | Increase by ½ inch every 6 hours as needed | Range ½–2 inches (7.5–30 mg) per application Apply to dry, hairless trunk; rotate sites; allow ≥10–12 h nitrate-free interval at night |
Transdermal Patch (Nitro-Dur, Minitran — 0.1, 0.2, 0.4, 0.6, 0.8 mg/h)
| Indication | Starting Dose | Titration | Maximum / Range |
|---|---|---|---|
| Prevention of chronic angina due to CAD | 0.2–0.4 mg/h patch applied once daily | Wear for 12–14 hours daily, then remove for a 10–12 hour nitrate-free interval | Up to 0.8 mg/h Apply to dry, hairless upper arm or trunk; rotate sites. Remove before defibrillation, MRI, electrocautery |
Rectal Ointment 0.4% (Rectiv)
| Indication | Dose | Schedule | Notes |
|---|---|---|---|
| Moderate-to-severe pain from chronic anal fissure | 1 inch (375 mg ointment ≈ 1.5 mg nitroglycerin) intra-anally | Every 12 hours for up to 3 weeks | Use a finger cot or disposable glove. Headache is the dose-limiting adverse effect. Same systemic interactions as cardiovascular formulations apply Per Rectiv PI |
Special Populations
| Population | Recommendation | Notes |
|---|---|---|
| Renal impairment | No specific adjustment | Pharmacokinetic data limited; titrate to clinical response |
| Hepatic impairment | Use cautiously; no specific adjustment | Dinitrate metabolites cleared more slowly; tolerance may develop differently |
| Older adults | Start at the low end of the dosing range | Greater frequency of decreased hepatic, renal, or cardiac function and concomitant disease |
| Pediatric patients | Safety and effectiveness not established | Per Nitrostat PI. Off-label paediatric IV use exists in critical care |
Tolerance is real and rapid. Continuous nitrate exposure produces near-complete loss of haemodynamic effect within 24–48 hours. The IV nitroglycerin PI explicitly notes that continuous IV infusion lost almost all of its haemodynamic effect by 48 hours in one careful study, while patients receiving infusions for only 12 of every 24 hours showed no similar attenuation. Always plan for an interruption — either an intermittent IV strategy, scheduled patch removal at night, or skipped doses of ointment.
Use the lowest effective dose for acute attacks. The Nitrostat PI advises that “only the smallest dose required for effective relief of the acute angina attack should be used.” Excess use accelerates tolerance and increases adverse effects without proportional benefit.
The “3-and-call” rule for SL. Patients should be counselled that if chest pain is unrelieved after 3 SL doses (15 minutes), they should call emergency services rather than continue self-administration — chest pain refractory to nitroglycerin may represent acute MI requiring reperfusion.
Long-acting nitrates blunt SL response. Patients on chronic ointment, patch, or oral isosorbide mononitrate may have reduced acute SL nitroglycerin efficacy. Document this in the chart.
Pharmacology
Mechanism of Action
Nitroglycerin is a prodrug. Inside vascular smooth muscle, it undergoes bioactivation — predominantly by mitochondrial aldehyde dehydrogenase (ALDH-2) — to release nitric oxide (NO). NO activates soluble guanylate cyclase, increasing intracellular cyclic GMP, which leads to dephosphorylation of myosin light chains and smooth-muscle relaxation. The principal pharmacological action is relaxation of vascular smooth muscle. At low doses the effect is selective for capacitance veins, reducing preload, ventricular wall stress, and myocardial oxygen demand — the dominant antianginal mechanism. At higher doses, conductance arteries (including epicardial coronary arteries and collateral vessels) and arterioles dilate, redistributing coronary flow toward ischaemic subendocardium, reducing afterload, and lowering systemic blood pressure. Heart rate is not directly affected, but baroreceptor-mediated reflex tachycardia is common with rapid blood-pressure reduction.
The mechanism of nitrate tolerance remains incompletely defined but appears to involve depletion of mitochondrial sulfhydryl groups and inactivation of ALDH-2, increased oxidative stress (superoxide and peroxynitrite generation that uncouples downstream signalling), and neurohormonal counter-regulation (volume retention, sympathetic activation). All of these contribute to attenuation of effect during continuous exposure and recovery during a nitrate-free interval. Methaemoglobinaemia — clinically significant at high doses or in G6PD deficiency — reflects nitrite-mediated oxidation of haemoglobin iron from Fe²⁺ to Fe³⁺, which cannot bind oxygen.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption (sublingual) | Rapid: vasodilatory effect onset 1–3 min, max ~5 min, duration ≥25 min. Mean Tmax ~6–7 minutes. Cmax and AUC dose-proportional 0.3–0.6 mg. Absolute bioavailability ~40% (variable with mucosal hydration) | Counsel patients to avoid eating, drinking, or chewing tobacco during dissolution. Dry mouth (e.g., from beta-blockers, anticholinergics) impairs absorption — consider lingual spray. |
| Absorption (other routes) | IV: instantaneous (no absorption phase). Topical ointment: onset ~30 min, duration 4–8 h. Transdermal patch: steady-state delivery over 24 h. Oral: extensive first-pass metabolism (oral bioavailability <1%) — no oral immediate-release tablets are marketed | Route selection drives clinical use: SL/IV for acute, ointment/patch for chronic prophylaxis. Patches must be removed for ≥10–12 h daily to prevent tolerance. |
| Distribution | Volume of distribution ~3 L/kg; ~60% plasma protein binding | Crosses placenta and likely breast milk, but human lactation data are absent. |
| Metabolism | Primarily hepatic via mitochondrial aldehyde dehydrogenase-2 (ALDH-2) and glutathione-S-transferase to 1,2- and 1,3-glyceryl dinitrates and inorganic nitrite. Also metabolised in erythrocytes and vascular smooth muscle. Dinitrate metabolites have ~10× longer half-lives but ~10× lower vasodilator activity | ALDH-2 polymorphisms (common in East Asian populations) reduce activation and antianginal efficacy. Mitochondrial sulfhydryl-group depletion contributes to nitrate tolerance during continuous exposure. |
| Elimination | Plasma half-life ~1–4 minutes (very short — drives need for continuous IV infusion or sustained-release transdermal/topical formulations). Metabolites excreted predominantly in urine | Effects of IV infusion dissipate within 3–5 minutes after stopping — useful for titration in unstable patients. Conversely, sublingual or IV must be redosed frequently for persistent effect. |
Side Effects
The adverse-effect profile of nitroglycerin reflects its pharmacology directly. Headache (a vasodilator effect on cerebral and meningeal vessels) is universal, often dose-limiting at first, and partially abates with continued use. Hypotension and reflex tachycardia are common and may be severe in volume-depleted, hypotensive, or right-ventricular-infarction patients. Methaemoglobinaemia and tolerance are the two distinctive class effects requiring specific recognition. Adverse-event rates vary by formulation; the rates below are taken from product labelling for the SL tablet (Nitrostat) where available.
| Adverse Effect | Frequency | Clinical Note |
|---|---|---|
| Headache | Very common; dose-related | Per Nitrostat PI: dose-related headaches, especially at the start of therapy, may be severe and persist but usually subside with continued use. Treat with paracetamol; do not discontinue solely for headache if drug is otherwise effective. |
| Adverse Effect | Frequency | Clinical Note |
|---|---|---|
| Dizziness | Common (>2% per PI) | Usually orthostatic. Patients should sit when dosing SL/spray. Hold dose if symptomatic on standing. |
| Paraesthesia | Common (>2% per PI) | Rarely treatment-limiting; resolves on discontinuation. |
| Hypotension / orthostasis | Common | May be accompanied by paradoxical bradycardia and worsened angina (per PI). Severe in volume depletion, RV infarction, severe aortic/mitral stenosis, constrictive pericarditis. |
| Flushing | Common | Cutaneous vasodilation; benign and self-limited. |
| Nausea / vomiting | Common | Often a marker of severe hypotension; reassess BP. |
| Tachycardia (reflex) | Common | Baroreceptor response to BP reduction. Beta-blocker co-therapy attenuates this in chronic angina. |
| Local reactions (transdermal/topical) | Common | Erythema or pruritus at application site; rotate application sites. |
Note: Frequency categories above reflect sublingual nitroglycerin labelling. Dose-related headache is the dominant adverse effect across all formulations and is often more pronounced with continuous formulations (ointment, patch, IV infusion) than with intermittent SL dosing.
| Adverse Effect | Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Severe hypotension / shock | Uncommon — but life-threatening in volume-depleted patients, RV infarction, or with PDE-5 inhibitor co-administration | Within minutes of dose | Stop infusion / wash off ointment / remove patch. Trendelenburg position, IV crystalloid bolus, vasopressors (phenylephrine, norepinephrine) if persistent. Avoid in suspected RV infarction. |
| Methaemoglobinaemia | Rare — reported with moderate doses of organic nitrates (per IV nitroglycerin PI) | Cumulative dose-related; G6PD deficiency increases risk | Suspect when SpO₂/PaO₂ discordance or “chocolate-brown” blood. Confirm with co-oximetry. Discontinue nitroglycerin. Treat with methylene blue 1–2 mg/kg IV if not reversed (per IV PI Section 5). |
| Paradoxical bradycardia with hypotension | Uncommon (Bezold–Jarisch reflex) | Acute, with rapid BP reduction | Discontinue nitroglycerin; place supine; IV fluids; atropine 0.5–1 mg if symptomatic. |
| Increased intracranial pressure | Avoid in cerebral haemorrhage / TBI | Acute, dose-related | Per PI: contraindicated in patients with possible increased intracranial pressure (e.g., cerebral haemorrhage or traumatic brain injury). Discontinue immediately if used. |
| Heparin resistance | Drug interaction — IV nitroglycerin specifically | During concurrent IV nitroglycerin and heparin | Per IV PI: may interfere with anticoagulant effect of heparin. Monitor aPTT closely; may need higher heparin doses; aPTT may rebound after nitroglycerin discontinuation — anticipate need to reduce heparin. |
| Tolerance / loss of efficacy | Universal with continuous exposure >24–48 h | Within 24 hours of continuous infusion or 24-h patch wear | Build in a daily nitrate-free interval (≥10–12 h). If acute escalating doses fail to control angina/HF symptoms, consider tolerance and switch agent or interrupt therapy. |
| Allergic / hypersensitivity reactions | Extremely rare (per IV PI) | Any time | Discontinue; standard hypersensitivity management. |
| Rebound ischaemia / coronary spasm on abrupt withdrawal | Reported with chronic high-dose IV or industrial nitrate exposure | Hours to days after discontinuation | Wean rather than abruptly stop chronic IV infusion. Per PI: chest pain, acute MI, and even sudden death have occurred during temporary withdrawal of nitrates from industrial workers. |
Nitrate overdose causes severe hypotension (with reflex tachycardia or paradoxical bradycardia), persistent throbbing headache, vertigo, palpitations, visual disturbance, flushing followed by cold/cyanotic skin, nausea, vomiting, and methaemoglobinaemia. There is no specific antidote. Management is supportive: stop the nitrate, elevate the lower extremities, give IV crystalloid, and use vasopressors (phenylephrine preferred) if hypotension is unresponsive. Avoid epinephrine — it may worsen hypotension via β2-mediated vasodilation. Treat methaemoglobinaemia with methylene blue 1–2 mg/kg IV.
In acute inferior MI with right ventricular involvement, preload is critical for maintaining cardiac output through a stunned right ventricle. Even small doses of sublingual or IV nitroglycerin can precipitate profound hypotension by reducing RV filling. Always obtain a 12-lead ECG (and right-sided leads V4R when inferior MI is suspected) before administering nitrates in the acute coronary syndrome setting; if RV infarction is present or suspected, withhold nitrates and prioritise volume resuscitation.
Drug Interactions
The most clinically important nitroglycerin interactions are pharmacodynamic — additive vasodilation (catastrophic with PDE-5 inhibitors and riociguat) or antagonism (heparin and ergot alkaloids). Nitroglycerin itself is not a meaningful CYP substrate, inhibitor, or inducer, so true pharmacokinetic interactions are limited.
Monitoring
Monitoring is dominated by haemodynamic parameters (blood pressure and heart rate) and symptom response. The intensity of monitoring scales sharply with the route — chronic outpatient transdermal use requires periodic clinic visits, while IV infusion requires continuous BP monitoring (preferably arterial-line at higher doses).
-
Blood pressure
IV: continuous (arterial-line preferred >100 mcg/min). SL: before and ~5 min after dose. Chronic: every visit
Routine Hold or reduce dose if SBP <90 mmHg or symptomatic hypotension. Per ACLS: do not administer to patients with SBP <90 mmHg. Be especially cautious in inferior MI (assess for RV involvement first). -
Heart rate
IV: continuous. SL: with each dose. Chronic: every visit
Routine Reflex tachycardia is common; paradoxical bradycardia (Bezold–Jarisch) can occur with rapid BP fall. Tachycardia may worsen myocardial oxygen demand — consider co-administered beta-blocker in CAD. -
12-lead ECG
Baseline in any acute presentation; with new symptoms
Routine Critical to identify inferior MI with possible RV involvement (right-sided leads V4R) before nitrate administration. Document response to nitroglycerin in ACS — but do not use response/non-response as a diagnostic for cardiac vs non-cardiac chest pain. -
Symptom relief
Within 5 minutes of each acute dose; daily for chronic prophylaxis
Routine SL: chest pain unrelieved after 3 doses (15 min) requires emergency evaluation. Chronic: angina frequency/severity is the primary efficacy endpoint. -
Methaemoglobin level
Trigger-based: SpO₂/PaO₂ discordance; cyanosis with normal PaO₂; high-dose IV use
Trigger-based Co-oximetry. “Chocolate-brown” arterial blood is suggestive. Treat with methylene blue 1–2 mg/kg IV (avoid in G6PD deficiency — use ascorbic acid instead). -
Headache severity
Each visit during chronic use
Routine Often subsides with continued use. If persistent and limiting, dose reduction or formulation change may help; tolerance correlates with reduced efficacy as well. -
aPTT (when on concurrent IV heparin)
Frequent during co-infusion and after nitroglycerin discontinuation
Trigger-based Per IV nitroglycerin PI: nitroglycerin may interfere with the anticoagulant effect of heparin. Anticipate need to reduce heparin dose when nitroglycerin is stopped (rebound aPTT prolongation). -
Tolerance assessment
After 24–48 hours of continuous IV infusion or with chronic outpatient regimens
Trigger-based Escalating doses with diminishing effect suggests tolerance. Build in nitrate-free interval (≥10–12 h daily) for outpatient regimens; consider intermittent IV strategy in hospital. -
Skin (transdermal/topical)
Each visit
Routine Inspect application sites for erythema, dermatitis, irritation. Rotate sites. -
Patch removal before procedures
Pre-procedure
Trigger-based Remove transdermal patch before defibrillation, cardioversion, MRI, or electrocautery — metallic backing may cause arc burns. Document removal in chart.
Contraindications & Cautions
Absolute Contraindications (per Nitrostat / IV nitroglycerin PIs)
- Concomitant use of phosphodiesterase-5 inhibitors — sildenafil, tadalafil, vardenafil, avanafil. Risk of life-threatening hypotension. Allow appropriate washout (24 h sildenafil/vardenafil; 48 h tadalafil; 12 h avanafil) before nitrate use.
- Concomitant use of soluble guanylate cyclase stimulators — riociguat.
- Severe anaemia — large doses of nitroglycerin may cause oxidation of haemoglobin to methaemoglobin and could exacerbate anaemia.
- Increased intracranial pressure — cerebral haemorrhage, traumatic brain injury, recent neurosurgery.
- Hypersensitivity to nitroglycerin, other nitrates or nitrites, or any excipient.
- Acute circulatory failure or shock — including cardiogenic shock and severe hypovolaemia.
Warnings and Precautions — Use with Caution
- Right ventricular infarction — preload-dependence; even small doses can precipitate profound hypotension. Obtain right-sided ECG leads (V4R) in inferior MI before nitrate use.
- Hypertrophic cardiomyopathy (per PI) — nitrate therapy may aggravate the angina caused by HCM.
- Severe aortic or mitral stenosis — preload reduction may produce severe hypotension.
- Constrictive pericarditis or cardiac tamponade — preload-dependent state.
- Volume depletion or pre-existing hypotension — start at lowest dose; ensure euvolaemia first.
- Pregnancy — limited human data; animal studies show no adverse developmental effects at >64× human dose. Use only if benefit clearly outweighs risk; obstetric use (e.g., uterine relaxation) is off-label and short-term.
- Lactation — not studied; presence in human milk unknown. Consider risks and benefits.
- Pediatric patients — safety and effectiveness not established (per Nitrostat PI).
- G6PD deficiency — increased risk of methaemoglobinaemia at higher cumulative doses.
- Tolerance — universal with continuous exposure; build in nitrate-free interval.
- Long-acting nitrates may blunt acute SL response (per Nitrostat PI).
Nitroglycerin does not carry a boxed warning. The four principal labelled contraindications across formulations are: (1) concomitant PDE-5 inhibitor or sGC stimulator — risk of fatal hypotension; (2) severe anaemia — methaemoglobinaemia risk; (3) increased intracranial pressure — risk of cerebral haemorrhage; and (4) hypersensitivity to nitrates. The IV product additionally contraindicates use in acute circulatory failure and shock.
The most clinically catastrophic real-world interaction remains co-administration with PDE-5 inhibitors, particularly in emergency-department patients presenting with chest pain. Always ask explicitly about erectile-dysfunction or pulmonary-arterial-hypertension medications (sildenafil is sold under both Viagra and Revatio brand names) before any nitroglycerin administration.
Patient Counselling
Purpose of Therapy
Nitroglycerin relaxes blood vessels, particularly the veins, which reduces how hard the heart has to work and improves blood flow through the coronary arteries. Sublingual tablets and the lingual spray are short-acting medicines used to treat chest pain when it occurs (or just before activity that the patient knows tends to bring it on). Patches and ointment are used regularly to prevent chest pain from happening. The IV form is used in hospital under close monitoring. Patients should understand that nitroglycerin only treats symptoms — it does not cure coronary disease, and the medications that improve survival (aspirin, statins, ACE-i/ARB, beta-blockers when indicated) should be continued.
How to Take
Sublingual tablets: sit down. Place one tablet under the tongue or between the cheek and gum and let it dissolve — do not chew, crush, or swallow. A burning or tingling sensation is normal but does not indicate that the tablet is working. If chest pain is not relieved after 5 minutes, take a second tablet; after another 5 minutes a third may be taken. If chest pain has not gone away 5 minutes after the third tablet, call emergency services (911 / local emergency number). Do not drive yourself.
Lingual spray: sit down. Spray 1–2 sprays on or under the tongue and close the mouth. Do not inhale the spray. Do not swallow for 5–10 seconds. Repeat up to a total of 3 sprays in 15 minutes. Same rule for emergency call after 3 doses.
Patches and ointment are taken on a schedule, with a daily nitrate-free period (typically overnight). They will not help an attack that is already occurring — sublingual tablets or spray must be available for acute episodes.
Sources
- NITROSTAT (nitroglycerin) sublingual tablets — full prescribing information. Pfizer, Inc. FDA label PDF Primary US labelling for sublingual tablets (Initial US Approval 1981); source for indications, dosing, contraindications, pharmacokinetics, and adverse-event categories used throughout this monograph.
- Nitroglycerin Injection 5 mg/mL — full prescribing information. American Regent / Baxter. DailyMed label Primary source for IV nitroglycerin indications, dosing, PVC tubing absorption (20–60% loss), heparin interaction, methaemoglobinaemia management, and tolerance data.
- Nitroglycerin in 5% Dextrose Injection — full prescribing information. FDA label PDF Premixed IV preparation labelling — confirms standard infusion concentrations and dose ranges.
- RECTIV (nitroglycerin 0.4%) rectal ointment — full prescribing information. FDA label PDF FDA approval document (June 2011) for chronic anal fissure indication.
- NITRO-DUR (nitroglycerin transdermal system) — full prescribing information. Merck. FDA label PDF Source for transdermal patch dosing, nitrate-free interval requirement, and application/removal counselling.
- NITRO-BID (nitroglycerin 2% topical ointment) — full prescribing information. DailyMed label Source for topical ointment dosing range (½–2 inches; 7.5–30 mg per application).
- Boden WE, Padala SK, Cabral KP, Buschmann IR, Sidhu MS. Role of short-acting nitroglycerin in the management of ischemic heart disease. Drug Des Devel Ther. 2015;9:4793–4805. doi:10.2147/DDDT.S79116 Comprehensive review of pharmacology, formulations, and clinical use across angina and ACS settings.
- Münzel T, Daiber A, Gori T. Nitrate therapy: new aspects concerning molecular action and tolerance. Circulation. 2011;123(19):2132–2144. doi:10.1161/CIRCULATIONAHA.110.981407 Authoritative reference on the molecular mechanisms of nitrate bioactivation (ALDH-2) and tolerance.
- Houston KE, Levine BJ, Wilson JK, Mitchell BL, Caputo C, Boll J. Nitroglycerin Use in the Emergency Department: Current Perspectives. Open Access Emerg Med. 2022;14:327–334. doi:10.2147/OAEM.S340513 Modern review covering high-dose IV nitroglycerin in sympathetic crashing acute pulmonary oedema (SCAPE) and emerging ED practice.
- Nashed M, Frishman WH. Nitrates: A Review. StatPearls [Internet]. NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK482382/ Standard educational reference covering MOA, formulations, indications, and adverse effects.
- Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain. J Am Coll Cardiol. 2021;78(22):e187–e285. doi:10.1016/j.jacc.2021.07.053 Current US chest-pain evaluation guideline; recommends sublingual nitroglycerin for ongoing ischaemic pain in NSTEMI/STEMI; specifically notes that response to nitroglycerin should not be used as a diagnostic test for cardiac chest pain.
- Collet JP, Thiele H, Barbato E, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42(14):1289–1367. doi:10.1093/eurheartj/ehaa575 European guideline; sublingual or IV nitrates Class I, Level C in patients with ongoing ischaemic symptoms; IV nitrates for uncontrolled hypertension or signs of heart failure.
- Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Am Coll Cardiol. 2022;79(17):e263–e421. doi:10.1016/j.jacc.2021.12.012 Current US heart-failure guideline; IV nitroglycerin may be considered as adjunct to diuretic for relief of dyspnoea in ADHF without symptomatic hypotension.
- Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease. J Am Coll Cardiol. 2023;82(9):833–955. doi:10.1016/j.jacc.2023.04.003 Current chronic coronary disease guideline; recommends sublingual nitroglycerin or spray for immediate short-term relief of angina, with long-acting nitrates as one option for chronic prophylaxis.
- Chen Z, Foster MW, Zhang J, et al. An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation. Proc Natl Acad Sci USA. 2005;102(34):12159–12164. doi:10.1073/pnas.0503723102 Foundational paper identifying ALDH-2 as the principal mitochondrial enzyme responsible for nitroglycerin bioactivation to nitric oxide.
- Marsh N, Marsh A. A short history of nitroglycerine and nitric oxide in pharmacology and physiology. Clin Exp Pharmacol Physiol. 2000;27(4):313–319. doi:10.1046/j.1440-1681.2000.03240.x Historical review tracing nitroglycerin from its 19th-century discovery through modern NO biology.