Glyceryl trinitrate

Why this drug is interesting

GTN is given more often than almost anything else in an emergency department, frequently by ambulance crews before arrival, and its mechanism is widely misremembered. It is not primarily a coronary vasodilator. At clinical doses its dominant effect is venodilatation, which reduces venous return and therefore preload.

That single fact does most of the explanatory work. It is why GTN is transformative in acute pulmonary oedema — the failing ventricle is unloaded. It is why relief of chest pain after GTN says nothing useful about whether the pain is cardiac. And it is why every catastrophic GTN event happens in a patient whose cardiac output was preload-dependent: the under-filled, the severely stenotic, the right ventricular infarct.

Pharmacology

Mechanism

GTN is metabolised to nitric oxide, which activates guanylate cyclase in vascular smooth muscle, raising cyclic GMP and producing relaxation. The effect is dose-dependent and vessel-selective:

Kinetics

Onset, sublingual

1–3 minutes

Onset, IV

Within 1–2 minutes

Half-life

1–4 minutes — extremely short

Metabolism

Extensive hepatic first-pass, which is why there is no useful oral immediate-release form

Implication

An infusion is titratable minute by minute and reverses quickly when stopped

Indications and dosing

Licensed indications

• Unresponsive congestive heart failure, including secondary to acute myocardial infarction
• Acute left-sided heart failure and acute myocardial infarction
• Refractory unstable angina
• Control of hypertensive episodes during cardiac surgery, and induction of controlled hypotension for surgery

The overall recommended range is 10–200 micrograms/min, with up to 400 micrograms/min occasionally needed during surgical procedures. Give by infusion pump or syringe pump — never by bolus injection — with close haemodynamic monitoring throughout.¹

Sublingual

400–800 micrograms sublingually (one or two sprays, or a tablet) is the usual first step in the department, repeated as tolerated while an infusion is prepared.

Acute pulmonary oedema and SCAPE

Contraindications — the section that matters

Other contraindications

• Acute circulatory failure — shock, collapse
• Cardiogenic shock, unless a sufficient end-diastolic pressure is maintained
• Uncorrected hypovolaemia and hypotensive shock
• Aortic or mitral stenosis
• Hypertrophic obstructive cardiomyopathy
• Constrictive pericarditis and cardiac tamponade
• Conditions associated with raised intracranial pressure
• Severe anaemia

The SmPC adds that reducing systolic blood pressure below 90 mmHg must be avoided in low-filling-pressure states, and that concurrent alcohol potentiates the hypotensive effect.¹

Adverse effects

• Headache — very common, dose-related, and the commonest reason patients stop taking nitrates
• Hypotension, sometimes with reflex tachycardia
• Flushing, dizziness, light-headedness
• Syncope, particularly on standing after a sublingual dose
• Nausea and vomiting
• Tolerance with continued exposure
• Rarely, methaemoglobinaemia with very high or prolonged dosing

Practical points

• GTN adsorbs onto PVC — use the giving set specified for the preparation, or the delivered dose will be lower than the pump reports
• Check the blood pressure before, and frequently during, titration
• Stop the infusion if the systolic falls below the agreed floor; the short half-life means recovery is usually rapid, and legs-up plus fluid will manage most episodes

Critical appraisal

1. GTN improves symptoms without evidence of improved survival in acute coronary syndromes. The large ISIS-4 and GISSI-3 trials found no mortality benefit from routine nitrate therapy in myocardial infarction. Its role in ACS is symptomatic relief and management of hypertension or pulmonary congestion — not prognostic.
2. In acute heart failure the physiological case is strong and the trial evidence is weaker than expected. Vasodilatation clearly makes sense mechanistically and clinically, but randomised trials of nitrate strategies in acute heart failure have generally not demonstrated mortality benefit. That may reflect trial design and heterogeneous populations as much as absence of effect.
3. High-dose GTN in SCAPE is supported mainly by physiological reasoning and observational experience, not by randomised evidence. It is widely practised and probably right, and it should be described as what it is rather than presented as established.
4. The nitrate response as a diagnostic test should be actively unlearned. It persists in clinical documentation and handover language despite consistent evidence against it, and it leads to both over- and under-estimation of cardiac risk.
5. The PDE5 interaction is well known and still missed, principally because the history is not taken. The failure is one of asking, not of knowledge.

References

1. 1
   Glyceryl Trinitrate 1 mg/ml solution for infusion — Summary of Product Characteristics. electronic Medicines Compendium. Sections 4.1–4.4. Verified 20 Aug 2026.
2. 2
   Glyceryl trinitrate — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk
3. 3
   ISIS-4 Collaborative Group. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet 1995;345(8951):669–85.
4. 4
   GISSI-3 Investigators. Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet 1994;343(8906):1115–22.
5. 5
   Henrikson CA, Howell EE, Bush DE, et al. Chest pain relief by nitroglycerin does not predict active coronary artery disease. Ann Intern Med 2003;139(12):979–86.
6. 6
   McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42(36):3599–3726.
7. 7
   NICE NG185. Acute coronary syndromes. National Institute for Health and Care Excellence.