ADMINISTRATION ROUTES:
IV, Sublingual, Transdermal
ALTERNATIVE NAMES:
DBL Glyceryl Trinitrate, GTN, Glytrin, Nitronal, Nitrolingual, Nitroderm
ICU INDICATIONS:
- Afterload reduction by peripheral vasodilation
- Treatment of hypertension
- Treatment of angina
PRESENTATION AND ADMINISTRATION:
IV:
DBL Glyceryl Trinitrate solution for injection contains 50 mg in 10 mL.
Store the undiluted product at room temperature and protect from light.
Other strengths of glyceryl trinitrate exist: check strength carefully.
Add 50 mg (10 mL) of glyceryl trinitrate to 40 mL of compatible fluid in a syringe to make a final volume of 50 mg in 50 mL (1 mg/mL).
For adults this solution can be administered via a peripheral or central line.
For children this solution must be administered via a central line.
Compatible with the following IV fluids: Sodium chloride 0.9%, glucose 5%.
Use a dedicated line: do NOT mix with other medicines. Use a syringe pump and a low-sorbing giving set (e.g. PB-G40720) to reduce absorption of glyceryl trinitrate into the plastic. If a PVC set is used, titrate the dose and rate to effect - higher rates may be required.
Consider fill volume of the IV cannula: start infusion at a higher rate initially (e.g. 2 mL/hr for 15 min), then reduce to starting dose as outlined below.
Transdermal:
Nitroderm TTS 5 mg/24 hours (25 mg) and 10 mg/24 hours (50 mg) patches
Apply once daily to chest or upper arm for 12-18 hours (brand dependent) followed by a 6-12 hour nitrate-free period (usually overnight).
Sublingual spray:
Glytrin spray 400 microgram/dose
Nitrolingual pump spray 400 microgram/dose
DOSAGE:
IV infusion:
Begin at 0.6 mL/hr (10 microgram/min)
Increase every 3 - 5 minutes to effect
For acute pulmonary oedema associated with severe hypertension:
Begin at 1.2 mL/hr (20 microgram/min)
Increase every 3 - 5 minutes to effect
Usual infusion dose range:
0 - 12 mL/h (0 - 200 mcg/min)
In some cases (refractory hypertension or angina) rates of up to 24 mL/hr (400 microgram/min) may be used.
Nitrate tolerance occurs within 24-48 hours of continuous administration. Aim to transition to an oral agent or change to a different intravenous agent as soon as possible.
Transdermal:
Begin with 5 mg/24 hours patch.
Can increase patch dose or add additional patch to max two 10 mg/24 hours patches
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose as in normal renal function
DOSAGE IN PAEDIATRICS:
IV infusion:
For children < 30 kg
3 mg/kg in 50 mL glucose 5% at 0.5 - 5 mL/hr (0.5 - 5 microgram/kg/min)
For children ≥ 30kg
3 mg/kg in 100 mL glucose 5% at 1 - 10 mL/hr (0.5 - 5 microgram/kg/min)
CLINICAL PHARMACOLOGY:
The principal pharmacologic action of glyceryl trinitrate is relaxation of vascular smooth muscle, producing a vasodilator effect on both peripheral arteries and veins with more prominent effects on the latter. Dilation of the postcapillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure (preload). Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (afterload).
CONTRAINDICATIONS:
- Known hypersensitivity to glyceryl trinitrate or other nitrates
- Hypotention (SBP<90)
- Cardiogenic shock
- Heart valve stenosis
- Hypovolaemia
- Hypertrophic cardiomyopathy
- Raised intracranial pressure (e.g. cerebral haemorrhage/head trauma)
- Constrictive pericarditis
- Tamponade
- Severe anaemia and arterial hypoxemia
- Concomitant administration with phosphodiesterase-5 inhibitors (e.g. sildenafil, tadalafil)
WARNINGS:
Occasionally, high dose GTN may worsen oxygenation due to increased shunting
PRECAUTIONS:
General:
GTN may lead to severe hypotension in patients with haemodynamically significant aortic stenosis
Laboratory Tests:
No tests in addition to routine ICU tests are required
Drug/Laboratory Test Interactions:
None of note
IMPORTANT DRUG INTERACTIONS IN ICU:
Amplification of the vasodilatory effects of glyceryl trinitrate by sildenafil can result in severe hypotension.
Additive effects may be observed when glyceryl trinitrate is combined with other antihypertensives.
Ethanol intoxication has been reported with high doses as the solution contains ethanol as an excipient. For some preparations, a 5 mL ampoule of glycerine trinitrate may contain ethanol equivalent to 27 mL of wine. This should be considered if administering glceryl trinitrate to patients at higher risk of ethanol-related adverse effects, including pregnant or breast-feedin women, patients with liver disease, alcoholism, or epilepsy.
ADVERSE REACTIONS:
General:
Allergic reactions
Cardiovascular System:
Reflex tachycardia, paradoxical bradycardia, hypotension, syncope, rebound hypertension, palpitations, peripheral oedema, flushing
Gastrointestinal System:
Nausea, vomiting, abdominal pain
Central Nervous System:
Headache, dizziness, fainting, restlessness paresthesia (sublingual spray)
Haematological System:
Methaemoglobinaemia