Glyceryl trinitrate (GTN), also known as nitroglycerin, was first synthesized in 1847 by the Italian chemist Ascanio Sobrero, who discovered it as a highly explosive compound. In the 1860s, Alfred Nobel developed its use in explosives such as dynamite. Later, in the 1870s, its medicinal value was discovered when it was found to relieve chest pain by dilating blood vessels. In 1879, Dr. William Murrell introduced it for treating angina pectoris, marking its entry into clinical medicine. Since then, GTN has remained an important drug in cardiology for the treatment of angina and other heart-related conditions.
BRAND NAMES
GTN Sorbitrate
GTN-Sorbitrate-CR
Monit GTN
Monit GTN CR
Angispan
Angispan TR
Nitrostat
Nitrolingual
MECHANISM OF ACTION
Glyceryl trinitrate is an organic nitrate vasodilator that works by releasing nitric oxide (NO) in vascular smooth muscle cells. Nitric oxide activates the enzyme guanylate cyclase, which increases the level of cyclic guanosine monophosphate (cGMP).
PHARMACOKINETICS
Absorption:
GTN is well absorbed through mucous membranes and skin. Sublingual administration provides rapid absorption and quick onset of action, while oral forms undergo significant first-pass metabolism, reducing their effectiveness.
Distribution:
After absorption, GTN is rapidly distributed throughout the body. It has a short duration in plasma due to fast metabolism and does not accumulate significantly in tissues.
Metabolism:
GTN is extensively metabolized in the liver and vascular tissues by enzymes that convert it into active metabolites and release nitric oxide. This rapid metabolism is responsible for its short duration of action, especially in sublingual form.
Elimination:
The inactive metabolites of GTN are mainly excreted through the kidneys in urine. The drug itself has a very short plasma half-life, usually only a few minutes.
PHARMACODYNAMICS
Glyceryl trinitrate acts by releasing nitric oxide (NO), which activates guanylate cyclase and increases cGMP in vascular smooth muscle. This causes relaxation of blood vessels, mainly veins, leading to reduced venous return (preload) and decreased cardiac workload. At higher doses, it also dilates arteries, reducing afterload and improving coronary blood flow. Overall, it decreases myocardial oxygen demand and relieves angina pain.
ADMINISTRATION
Glyceryl trinitrate is given in different forms based on need. Sublingual tablets or spray are used for quick relief of angina. Transdermal patches provide long-term prevention. Intravenous infusion is used in emergencies like heart failure or myocardial infarction in hospitals. Oral and topical forms are used for maintenance therapy.
DOSAGE AND STRENGTH
Glyceryl trinitrate is available in different strengths depending on the route. Sublingual tablets are usually 0.3–0.6 mg for quick relief of angina, while sublingual spray delivers about 0.4 mg per dose. Transdermal patches are available in 0.2, 0.4, and 0.6 mg/hour for long-term use. IV infusion starts at 5–10 micrograms/min and is adjusted as needed. Topical ointment is used in 0.2%–2% strength.
DRUG INTERACTIONS
Glyceryl trinitrate shows important interactions with other drugs, especially those that also lower blood pressure. It can cause severe hypotension when used with PDE5 inhibitors like sildenafil, tadalafil, or vardenafil. Its effect is also enhanced by other antihypertensive drugs such as beta-blockers, calcium channel blockers, and diuretics, increasing the risk of low blood pressure.
FOOD INTERACTIONS
Glyceryl trinitrate has no significant direct food interactions, but alcohol should be avoided because it can enhance vasodilation and cause severe hypotension, dizziness, or fainting. Heavy or high-fat meals may slightly delay the onset of oral forms, but they do not markedly affect sublingual or spray forms
CONTRAINDICATIONS
Glyceryl trinitrate is contraindicated in patients with severe hypotension, shock, or marked anemia, as it can further reduce blood pressure and oxygen delivery. It should not be used in patients taking PDE5 inhibitors (such as sildenafil, tadalafil, or vardenafil) due to the risk of life-threatening hypotension.
SIDE EFFECTS
Headache: The most common side effect, often described as throbbing.
Dizziness/Lightheadedness: Particularly when standing up quickly, caused by a sudden drop in blood pressure.
Facial Flushing: A feeling of warmth or redness in the face.
Rapid Heart Rate (Palpitations): The heart may beat faster to compensate for lowered blood pressure
OVER DOSE
Overdose of glyceryl trinitrate causes severe hypotension, dizziness, headache, flushing, and tachycardia due to excessive vasodilation. In severe cases, it may lead to collapse or shock. Treatment includes stopping the drug, giving IV fluids, supportive care, and vasopressors if needed.
TOXICITY
Glyceryl trinitrate toxicity mainly results from excessive vasodilation leading to severe hypotension, headache, dizziness, flushing, tachycardia, and syncope. In high doses, it may cause collapse, shock, and reduced organ perfusion. Rarely, prolonged exposure can lead to methemoglobinemia, which reduces oxygen delivery in the blood. Management is mainly supportive with stopping the drug, giving IV fluids, and treating symptoms.
