Vasodilator · Nitrate · Antihypertensive
Nitroglycerin
Also called NTG
Indications
- ACS chest pain not relieved by sublingual nitroglycerin and beta-blockers
- Heart failure and pulmonary congestion complicating acute MI
- Hypertensive pulmonary edema or acute heart failure without MI (off-label)
- Perioperative hypertension
- Controlled hypotension during surgery
- Uterine relaxation for retained placenta (off-label)
- Ointment for vasopressor extravasation (off-label)
Dosing
Nitroglycerin drip card and mL/h converterStart: 5–10 mcg/min. Flash pulmonary edema with SBP 160 or more (SCAPE): high dose, starting at 100 mcg/min with NIV (CAEP 2025)
Mechanism of action
Nitroglycerin is a prodrug: in vascular smooth muscle, mitochondrial aldehyde dehydrogenase 2 (ALDH2) and other enzymes denitrate it to release nitric oxide. NO binds the heme of soluble guanylyl cyclase and raises cGMP, which activates protein kinase G to lower cytosolic calcium and activate myosin light-chain phosphatase, relaxing the muscle. Veins respond at lower concentrations than arteries, so low doses mainly cut preload and higher doses also dilate arterioles and coronaries; continuous exposure blunts this pathway (tolerance).
Pharmacology
- Cardiovascular: venodilation lowers preload, LVEDP and wedge pressure, cutting oxygen demand; higher doses lower SVR and BP
- Cardiovascular: dilates epicardial coronaries and collaterals and relieves spasm; reflex tachycardia, or paradoxical bradycardia with hypotension
- Respiratory: lowers PA pressure but blunts hypoxic pulmonary vasoconstriction, so PaO₂ can fall
- CNS: cerebral and meningeal vasodilation causes headache and can raise ICP
- Other: relaxes esophageal, biliary and uterine smooth muscle
Pharmacokinetics
| Onset | IV: 1–2 min. Sublingual: 1–3 min, peak by 5 min |
|---|---|
| Duration | IV: minutes after stopping. Sublingual: at least 25 min |
| Half-life | About 3 min; dinitrate metabolites 32–36 min |
| Distribution | Vd about 3 L/kg |
| Protein binding | About 60% |
| Metabolism | Denitration in liver, red cells and vessel walls to 1,2- and 1,3-dinitroglycerin (about 2% and 10% as active), then mononitrates and glycerol |
| Clearance | Close to 1 L/kg/min, above liver blood flow |
| Elimination | Urine as nitrate metabolites; glycerol ends as CO₂ |
| Tolerance | Continuous dosing loses effect, often within a day; 10–12 h nitrate-free intervals restore it |
| Routes | IV, sublingual tablet or spray (about 40% bioavailable), ointment, patch, oral and intracoronary |
Chemistry
- Glyceryl trinitrate: a nitrate ester of glycerol, not a true nitro compound; MW 227
- Small, uncharged (no ionizable group) and lipid soluble, so it crosses mucosa and skin
- Volatile and explosive when pure; tablets lose potency outside the capped original glass bottle
- Premixed 0.1, 0.2 or 0.4 mg/mL in D5W in glass bottles (pH 3–5); 5 mg/mL vials hold 30% alcohol and 30% propylene glycol and need dilution
- Migrates into PVC: only 20–60% reached patients through PVC sets in studies; with non-PVC tubing, doses learned on PVC run high
Adverse effects and cautions
In the one-pagers
- ACS and STEMIInitial medications: Typical adult doses for exam study; follow your institution's or agency's protocols. EMTs: aspirin and assisting with the patient's own nitroglycerin.
- Aortic Dissection and Hypertensive EmergencyIV antihypertensives: Nitroglycerin: 5–200 mcg/min: Best for ACS and pulmonary edema; headache
- Heart FailureDecompensated HF and shock: Warm-wet: Most common: IV loop diuretic; vasodilator (nitroglycerin, nitroprusside) if BP allows
- Vasopressors and InotropesLines, extravasation and titration: Extravasation: stop the infusion, aspirate, remove the catheter, mark and elevate. For catecholamines or phenylephrine, infiltrate phentolamine 5–10 mg in 10–15 mL saline subcutaneously as soon as possible (label: within 12 h). Alternatives: terbutaline or topical nitroglycerin.
- After Cardiac SurgeryHemodynamics, low output and vasoplegia: Afterload: hypertension strains suture lines and raises bleeding; use nicardipine, clevidipine or nitroprusside, or nitroglycerin when ischemia or radial spasm is the worry. After mitral repair for regurgitation the LV loses its low-pressure outlet into the atrium and tolerates afterload poorly.
- ED Triage and ESIDecision point A: lifesaving intervention now: Medications: Naloxone, dextrose, epinephrine, atropine, adenosine, dopamine: Aspirin, IV nitroglycerin, antibiotics, heparin, analgesics
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In the algorithms
Other vasodilator drugs
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Sources
- FDA label: Nitroglycerin in 5% Dextrose (2016)
- FDA label: Nitrostat (2023)
- Chen 2002 (ALDH2, PNAS)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.