Nitroglycerin
Nitrostat · Nitro-Bid
Organic nitrate / nitric oxide donor / vasodilator
Metabolized to nitric oxide (NO) in vascular smooth muscle → activates guanylyl cyclase → ↑cGMP → smooth muscle relaxation. PREFERENTIAL VENOUS dilation (low doses) → reduces preload (decreases LV wall stress, ↓myocardial O₂ demand). Higher doses → arterial dilation, including coronary arteries (↑coronary perfusion in non-stenotic vessels).
Indications
- •Angina/MI (chronic, acute)
- •Acute LV failure / pulmonary edema
- •Controlled hypotension intraop (rare modern use)
- •Coronary vasospasm (Prinzmetal)
- •Esophageal achalasia (acute relaxation of lower esophageal sphincter)
- •Pulmonary hypertension acute management
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Sublingual angina | 0.4 mg SL q5min × 3 | — |
| Continuous infusion (acute MI, HF, controlled hypotension) | 5-200 mcg/min IV titrated to target | — |
| Bolus IV (esophageal spasm, sphincter relaxation) | 50-200 mcg IV | — |
| Topical paste | 1-2 inches q4-6h chronic | — |
Pharmacokinetics
Onset 1-3 min IV. Half-life 1-3 min (very short). Hepatic metabolism via glutathione + organic nitrate reductase. Tachyphylaxis develops within 24 h continuous infusion (sulfhydryl depletion) — drug-free interval needed for chronic use.
Hemodynamic effects
↓Preload (dominant low dose), ↓afterload (high dose), reflex tachycardia possible, may lower coronary perfusion pressure (if MAP drops disproportionately). At low/moderate dose: improves coronary supply > increases demand.
Side effects
- !Hypotension (additive with other antihypertensives)
- !Headache (universal — common reason for non-compliance)
- !Methemoglobinemia (rare, with very high cumulative doses)
- !Tachyphylaxis with continuous infusion >24 h
- !Reflex tachycardia
Contraindications
- ×Hypotension (already low BP)
- ×Severe aortic stenosis (preload reduction → severe hypotension)
- ×Right ventricular MI (preload-dependent state)
- ×Concurrent PDE5 inhibitor (sildenafil, tadalafil) — severe hypotension within 24-48 h of use
- ×Increased ICP (cerebral vasodilation)
- ×Constrictive pericarditis (preload-dependent)
Clinical pearls
- ★FIRST-LINE for myocardial ischemia + acute LV failure — preload reduction often resolves both.
- ★PDE5 inhibitor (sildenafil, tadalafil) within 24 h: avoid nitroglycerin — severe refractory hypotension via additive cGMP elevation.
- ★INFERIOR/RV MI: AVOID — preload-dependent state, NTG drops preload → severe hypotension. Use cautiously.
- ★Controlled hypotension: nicardipine + esmolol preferred over NTG in modern practice (NTG tachyphylaxis + tachycardia limit titration).
- ★Concentration: standard intraop infusion 100 mcg/mL (50 mg in 500 mL D5W). Start 10-20 mcg/min, titrate to target. Avoid PVC tubing — NTG adsorbs (use polyolefin/polyethylene tubing).
- ★Esophageal spasm or sphincter relaxation: 50-200 mcg IV bolus rapidly relaxes (ENT useful adjunct for vocal cord adduction during awake fiberoptic too).