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Bedside Snapshot

Organic nitrate that converts to nitric oxide (NO) and causes potent venodilation and moderate arterial dilation → decreased preload, decreased myocardial O₂ demand, and improved coronary blood flow.

  • Prehospital/EMS: Sublingual (SL) nitroglycerin is used for suspected ACS-related chest pain and acute pulmonary edema in hemodynamically stable patients with adequate blood pressure
  • ED/ICU: IV nitroglycerin infusion used for ongoing ischemic chest pain, hypertensive emergencies (especially with ACS or pulmonary edema), and acute decompensated heart failure with elevated BP
  • Onset: SL within 1–3 minutes; IV within 1–2 minutes
  • Duration: SL ~20–30 minutes; IV effects dissipate within 3–5 minutes after stopping infusion
  • Typical EMS dose: 0.4 mg SL every 5 minutes up to 3 doses (if SBP ≥90–100 mmHg)
  • Typical IV starting dose: 5–20 mcg/min, titrated to effect (range 10–200 mcg/min)
  • Major limitations: Hypotension, headache, reflex tachycardia; tolerance with continuous high-dose infusion; contraindicated with recent phosphodiesterase-5 inhibitor use
Brand & Generic Names
  • Generic Name: Nitroglycerin (glyceryl trinitrate)
  • Brand Names: Nitrostat, Nitro-Dur, Nitro-Bid, NitroMist, Nitronal, various generics
Medication Class

Organic nitrate; venodilator and coronary vasodilator; antianginal, preload reducer, antihypertensive

Pharmacology

Mechanism of Action:

  • Nitroglycerin is converted to nitric oxide (NO) in vascular smooth muscle cells via mitochondrial aldehyde dehydrogenase and other enzymatic pathways
  • NO activates guanylate cyclase → increased cyclic GMP → dephosphorylation of myosin light chains → relaxation of vascular smooth muscle
  • Venous dilation predominates at low doses → increased venous capacitance and decreased preload, which reduces LV wall stress and myocardial oxygen consumption
  • At higher doses, arterial dilation and coronary vasodilation occur, reducing afterload and improving coronary perfusion, particularly in areas supplied by collateral vessels
  • Also dilates large epicardial coronary arteries and can relieve vasospastic (Prinzmetal) angina

Pharmacokinetics:

  • Sublingual (SL): Rapid absorption via oral mucosa; onset within 1–3 minutes; peak effect 5–10 minutes; duration ~20–30 minutes
  • Intravenous (IV): Onset within 1–2 minutes; effects dissipate within 3–5 minutes after stopping infusion due to rapid metabolism
  • Metabolism: Extensive first-pass hepatic metabolism when swallowed; IV and SL bypass majority of first-pass initially. Metabolized to dinitrate and mononitrate metabolites (some active)
  • Elimination: Half-life of parent nitroglycerin is ~1–4 minutes; clinical effect duration depends on ongoing delivery (SL, IV, topical)
  • Buccal/lingual sprays: Behave similarly to SL tablets with rapid onset through the oral mucosa
Indications

Sublingual (EMS / ED):

  • Suspected acute coronary syndrome (angina, NSTEMI/STEMI) with chest discomfort and adequate blood pressure
  • Acute pulmonary edema / hypertensive cardiogenic pulmonary edema with adequate blood pressure

IV (ED / ICU):

  • Ongoing ischemic chest pain despite SL nitro in ACS (including STEMI/NSTEMI) when BP allows
  • Hypertensive emergency with ACS, acute pulmonary edema, or afterload-sensitive LV dysfunction
  • Controlled BP reduction perioperatively or in critical care when rapid titration is needed
Dosing & Administration

Available Forms:

  • Sublingual tablets: typically 0.3 mg, 0.4 mg, or 0.6 mg (U.S. crews most often carry 0.4 mg)
  • Metered-dose spray (lingual): commonly 0.4 mg per spray for SL or lingual administration
  • IV solution (concentrated): e.g., 50 mg in 10 mL vial (5 mg/mL) or 25 mg/5 mL; must be diluted in D5W or NS to appropriate infusion concentration (e.g., 50 mg in 250 mL → 200 mcg/mL)
  • Topical/patch formulations exist for chronic angina but are not commonly titrated in acute ED/ICU resuscitation

Sublingual Nitroglycerin Dosing (Adult, EMS/ED):

Scenario Typical Dose Frequency Notes
Suspected ACS chest pain (hemodynamically stable) 0.4 mg SL tablet or spray Every 5 minutes up to 3 doses Give only if SBP ≥90–100 mmHg, no RV infarct, no recent PDE-5 use
Acute pulmonary edema with hypertension 0.4 mg SL tablet or spray Every 5 minutes as BP allows Often while preparing IV infusion in ED; some aggressive EMS protocols use repeated SL if SBP very high
Blood pressure threshold (general EMS practice) Avoid if SBP <90–100 mmHg or symptomatic hypotension; re-check BP before each dose; use greater caution in elderly or preload-dependent patients
Contraindicated: recent PDE-5 inhibitor use Sildenafil/vardenafil within 24 hours; tadalafil within 48 hours → Do not give nitroglycerin (risk of profound, refractory hypotension)

IV Nitroglycerin Dosing (Adult, ED/ICU):

Indication Starting Dose Titration Targets / Notes
ACS with ongoing chest pain (hemodynamically stable) 5–10 mcg/min IV infusion Increase by 5–10 mcg/min every 3–5 min Titrate to pain relief or BP reduction; typical range 10–100 mcg/min
Hypertensive emergency with ACS or pulmonary edema 10–20 mcg/min IV Increase by 10–20 mcg/min every 3–5 min May require 50–200 mcg/min; some protocols go higher with invasive monitoring
Acute pulmonary edema (severe, hypertensive) Initial 20–40 mcg/min IV Titrate aggressively q3–5 min Goal: rapid preload/afterload reduction while maintaining SBP >90–100 mmHg
Perioperative BP control 5–10 mcg/min IV Titrate in 5–10 mcg/min increments Goal-driven BP reduction under anesthesia/ICU monitoring
Usual maximum range Typically 200 mcg/min; some critically ill patients may need more with invasive monitoring. Prolonged high-dose infusions increase risk of tolerance and toxicity
Weaning / tolerance Gradual down-titration as ischemia/edema resolve; watch for recurrence of chest pain or dyspnea. Tolerance can develop after 24–48 h; consider alternative agents
Contraindications

Contraindications:

  • Hypotension (SBP <90–100 mmHg) or significant symptomatic hypotension
  • Right ventricular infarction (preload-dependent state) – nitro can cause severe hypotension; require careful echo/RV evaluation and cardiology input
  • Severe aortic stenosis or hypertrophic obstructive cardiomyopathy (fixed outflow obstruction) – risk of syncope and severe hypotension
  • Use of phosphodiesterase-5 inhibitors for erectile dysfunction or pulmonary hypertension: sildenafil or vardenafil within 24 hours; tadalafil within 48 hours
  • Known hypersensitivity to nitroglycerin or other organic nitrates

Major Precautions:

  • Recent inferior STEMI with suspected RV involvement: obtain right-sided leads or echo; avoid or use very cautious dosing if RV infarct present
  • Volume depletion, anemia, or autonomic dysfunction can exaggerate hypotensive response
  • Closed-angle glaucoma and increased intracranial pressure historically listed as precautions; clinical relevance is limited but use clinical judgment
  • Continuous IV infusions beyond 24–48 hours may lead to tolerance; escalating doses with diminishing response should prompt evaluation for alternative therapies
  • Headache is extremely common; in ICU/ED this is often a sign the drug is working but can be limiting in awake patients
Critical Warning: NEVER give nitroglycerin to patients who have taken phosphodiesterase-5 inhibitors (sildenafil/vardenafil within 24h, tadalafil within 48h). Risk of profound, refractory hypotension.
Adverse Effects

Common:

  • Headache, flushing
  • Lightheadedness, dizziness
  • Reflex tachycardia, palpitations
  • Nausea

Serious:

  • Severe hypotension, syncope, cardiovascular collapse
  • Worsening ischemia in patients who are highly preload-dependent (e.g., RV infarct, severe AS)
  • Methemoglobinemia with very high doses or prolonged high-dose infusion (rare)
  • Rebound ischemia if abruptly discontinued in patients reliant on coronary vasodilation
Special Populations

Right Ventricular Infarction:

  • RV infarct is highly preload-dependent
  • Nitroglycerin can cause severe hypotension and cardiovascular collapse
  • Obtain right-sided ECG leads (V4R) or echo if inferior STEMI suspected
  • If RV involvement confirmed, avoid nitroglycerin or use with extreme caution under cardiology guidance

Elderly Patients:

  • More susceptible to hypotension and orthostatic effects
  • Use lower starting doses and titrate more slowly
  • Greater risk of falls and syncope

Volume Depletion:

  • Hypovolemia increases risk of severe hypotension
  • Consider fluid resuscitation before or concurrently with nitroglycerin
  • Monitor BP closely with each dose

Pregnancy & Lactation:

  • Generally considered safe in pregnancy when indicated for maternal condition
  • Use for acute coronary syndrome or hypertensive emergency when benefits outweigh risks
  • Limited data on excretion in breast milk; generally considered compatible
Monitoring

Clinical Monitoring:

  • Blood pressure and heart rate before each SL dose in EMS; continuous or frequent monitoring during IV infusion
  • Continuous ECG monitoring in ACS, pulmonary edema, or any nitro infusion; watch for ischemic changes and arrhythmias
  • Symptoms of chest pain and dyspnea as clinical endpoints for titration
  • Signs of hypotension: dizziness, syncope, altered mental status, cool clammy skin, decreased urine output
  • In prolonged high-dose infusions: consider periodic methemoglobin level if unexplained hypoxia or cyanosis appears
Clinical Pearls
EMS Critical Check: For EMS, verify BP and recent PDE-5 inhibitor use before EVERY SL dose; don't give nitro to a hypotensive or preload-dependent inferior/RV MI.
Pulmonary Edema: In acute pulmonary edema with hypertension, nitro (SL then IV) is often more immediately effective than diuretics for symptom relief because it rapidly decreases preload and afterload.
Non-Specific Relief: Chest pain relief from nitro is NOT specific for ACS—esophageal spasm and other causes can also improve; always interpret in clinical context.
Tolerance Consideration: If escalating IV nitro doses yield diminishing returns, consider nitrate tolerance and alternative agents (e.g., nicardipine, nitroprusside, ACE inhibitors, or non-nitrate vasodilators per cardiology/ICU guidance).
Patient Education: Educate patients discharged with SL nitro on proper use: sit down before taking, place under tongue, do not chew, call EMS if chest pain not relieved after 1 dose and persists after 5 minutes.
References
  • 1. Lexicomp. (2025). Nitroglycerin: Drug information. Wolters Kluwer.
  • 2. Amsterdam, E. A., Wenger, N. K., Brindis, R. G., et al. (2014). 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes. Journal of the American College of Cardiology, 64(24), e139–e228. https://doi.org/10.1016/j.jacc.2014.09.017
  • 3. O'Gara, P. T., Kushner, F. G., Ascheim, D. D., et al. (2013). 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. Circulation, 127(4), e362–e425. https://doi.org/10.1161/CIR.0b013e3182742cf6
  • 4. Farkas, J. (2023). Acute coronary syndrome (IBCC). EMCrit Project. https://emcrit.org/ibcc/acs/
  • 5. EMCrit Project. (2023). Pulmonary edema (IBCC). https://emcrit.org/ibcc/pulm-edema/
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