Glyceryl trinitrate (GTN)

Generic Name

Glyceryl trinitrate

Also Known As

Nitroglycerin

Trinitrin

1,2,3-Trinitroxypropane

Brand Names

Nitrolingual

Nitrostat

Nitromint

Nitro-Bid

Rectogesic

Transiderm-Nitro

Nitro-Dur

Minitran

Available in multiple formulations: sublingual tablets, buccal sprays, ointments, transdermal patches, intravenous solution, rectal ointment

Drug Class

Organic nitrate

Vasodilator

Anti-anginal agent

Mechanism of Action

GTN is converted enzymatically into nitric oxide (NO), a potent endogenous vasodilator

NO activates guanylate cyclase in vascular smooth muscle leading to increased levels of cyclic GMP

Elevated cGMP causes dephosphorylation of myosin light chains resulting in smooth muscle relaxation

Predominantly causes venodilation, reducing preload and myocardial oxygen demand

At higher doses, GTN also dilates arterial vessels, decreasing afterload

Relieves coronary vasospasm and improves subendocardial perfusion

Also reduces esophageal tone in rectal or esophageal use

Indications

Relief and prevention of angina pectoris (chronic stable, variant, and unstable angina)

Acute coronary syndrome (ACS)

Hypertensive emergencies (IV GTN)

Acute decompensated heart failure

Perioperative blood pressure control

Anal fissures (topical rectal ointment)

Off-label: esophageal spasm, pulmonary hypertension (limited), Raynaud’s phenomenon (topical)

Dosage and Administration

Sublingual Tablets

0.3 mg, 0.5 mg, or 0.6 mg placed under tongue during angina attack

May repeat every 5 minutes up to 3 doses within 15 minutes

If no relief after first dose, seek emergency care

Sublingual Spray

400 micrograms/spray

1–2 sprays under the tongue at angina onset

May repeat at 5-minute intervals (max 3 sprays in 15 minutes)

Transdermal Patches

5 mg to 15 mg released over 24 hours

Apply to hairless area of chest or upper arm

Used for angina prophylaxis

Apply patch daily and remove after 12–14 hours to prevent tolerance

Topical Ointment (e.g. Nitro-Bid 2%)

Measured in inches (e.g. 1–2 inches) on dosing paper

Applied to chest or upper arm every 6–8 hours

Used in angina prevention and heart failure

Rectal Ointment (e.g. Rectogesic 0.2%)

Apply ~1.5 cm to anal canal every 12 hours

Indicated for chronic anal fissures

Intravenous Infusion

Used in acute heart failure, hypertensive crisis, or unstable angina

Initial rate: 5 mcg/min, titrate by 5 mcg/min every 3–5 min

Max rate often ~200 mcg/min

Administer via infusion pump with glass container (polyvinyl chloride absorbs GTN)

Pediatric Use

Not routinely used in children except under specialist care

Geriatric Use

Initiate at lower doses due to increased sensitivity to hypotensive effects

Pharmacokinetics

Bioavailability low due to first-pass metabolism (oral forms rarely used)

Onset:

– Sublingual tablets/spray: 1–3 min

– Ointment: 15–60 min

– Patch: 30–60 min

– IV: immediate

Duration:

– Sublingual: 30–60 min

– Patch: up to 24 hours

Metabolized by liver and vascular tissue

Half-life: 1–4 minutes

Excreted via urine

Contraindications

Hypersensitivity to nitrates

Concurrent use of phosphodiesterase type 5 (PDE5) inhibitors (e.g. sildenafil, tadalafil, vardenafil)

Severe hypotension (SBP <90 mmHg)

Marked anemia

Increased intracranial pressure

Pericardial tamponade or restrictive cardiomyopathy

Constrictive pericarditis

Closed-angle glaucoma (topical formulations)

Shock or uncorrected hypovolemia

Warnings and Precautions

May cause significant hypotension, syncope, or reflex tachycardia

Develops tolerance with continuous exposure — nitrate-free interval required (typically 10–14 hours/day)

Abrupt withdrawal after prolonged use may worsen angina

May cause rebound hypertension (IV withdrawal)

Increased intracranial pressure with cerebral trauma

May worsen hypoxemia in patients with lung disease (impaired V/Q matching)

Headache is dose-dependent and may limit adherence

Use with caution in aortic/mitral stenosis due to risk of hypotension

Adverse Effects

Very Common

Headache (can be severe and persistent)

Flushing

Postural hypotension

Common

Dizziness

Reflex tachycardia

Palpitations

Nausea

Vomiting

Dermatitis (topical use)

Uncommon to Rare

Severe hypotension

Syncope

Paradoxical bradycardia

Methemoglobinemia (at very high doses)

Allergic skin reactions

Contact dermatitis with patches or ointment

Blurred vision (rare)

Pregnancy and Lactation

Pregnancy Category

Not officially classified in many regions

Limited data but not associated with major fetal risk

May be used if clinically necessary (e.g. heart failure, angina) under close monitoring

Lactation

Excreted in breast milk in low amounts

Use cautiously during breastfeeding

Drug Interactions

Phosphodiesterase Inhibitors (PDE5)

Sildenafil, tadalafil, vardenafil

Contraindicated — risk of profound hypotension, syncope, or MI

Other Antihypertensives

Beta-blockers, calcium channel blockers, ACE inhibitors

Additive hypotensive effect

Monitor blood pressure closely

Alcohol

May intensify vasodilation and hypotension

Avoid alcohol consumption

Ergot Alkaloids

May antagonize vasodilatory effects

Avoid concurrent use

Heparin

IV GTN may reduce heparin efficacy

Monitor aPTT and adjust heparin dose

Tricyclic Antidepressants/Antipsychotics

May increase postural hypotension

Monitoring Parameters

Relief of angina symptoms

Blood pressure and heart rate

Tolerance development — consider drug-free intervals

Headache severity (may require analgesia or dose adjustment)

Skin site irritation with patches

Signs of hypotension or syncope

ECG monitoring for IV use

Tolerance and adherence in chronic use

Counseling Points

Sit or lie down when taking sublingual GTN to avoid fainting

Place sublingual tablet under tongue; do not swallow or chew

If angina not relieved after 1 dose, seek emergency help after 5 minutes

Store sublingual tablets in original container; replace every 6 months

Avoid alcohol during therapy

Do not use erectile dysfunction drugs while on GTN

Rotate patch sites to avoid skin irritation

Remove patch at night to prevent tolerance

May cause headache; usually improves with continued use

Comparative Notes

GTN vs Isosorbide Mononitrate/Dinitrate

GTN is shorter-acting and used for acute angina

Isosorbide compounds are longer-acting and used for angina prophylaxis

GTN vs Beta-Blockers

GTN provides acute relief

Beta-blockers reduce heart rate and are more suitable for long-term angina control

GTN vs CCBs (e.g., amlodipine)

GTN works quickly but transiently

CCBs provide sustained anti-anginal effect and are used in vasospastic angina

Legal and Regulatory Status

Prescription-only for all injectable and patch forms

Sublingual forms often available OTC in emergency kits

Included in WHO Essential Medicines List