Nitroglycerin

Nobel's patent for nitroglycerin

Synthesis of nitroglycerin

Nitroglycerin

Nitroglycerin (C3H5N3O9), also known as glyceryl trinitrate (GTN), is a chemical compound used for the management and treatment of angina pectoris, heart failure, and myocardial infarction. It is a potent vasodilator, expanding blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload.

History

Nitroglycerin was first synthesized in 1847 by Italian chemist Ascanio Sobrero by adding glycerol to a mixture of nitric and sulfuric acid. Initially, its explosive properties were of more interest, but by the late 19th century, its therapeutic potential for angina was discovered by William Murrell, marking the beginning of its medical use.

Pharmacology

Nitroglycerin works by releasing nitric oxide (NO), which relaxes smooth muscle cells in the blood vessel walls, primarily in the veins, arteries, and large coronary arteries. This process, known as vasodilation, leads to a decrease in venous return and arterial pressure, reducing the heart's workload and oxygen demand.

Mechanism of Action

Upon administration, nitroglycerin is converted to nitric oxide (NO), a signaling molecule that activates guanylate cyclase in smooth muscle cells. This activation increases cyclic guanosine monophosphate (cGMP) levels, leading to smooth muscle relaxation and vasodilation.

Administration

Nitroglycerin can be administered in several forms, including sublingual tablets, transdermal patches, topical ointments, and intravenous infusions. The choice of administration depends on the condition being treated, the required speed of onset, and the duration of action needed.

Clinical Uses

Nitroglycerin is primarily used in the management of:

• Angina Pectoris: To relieve or prevent chest pain caused by heart disease.
• Acute Coronary Syndrome: As part of the treatment regimen.
• Congestive Heart Failure: To improve symptoms by reducing cardiac preload and afterload.
• Controlled Hypotension: In surgical settings to reduce bleeding.

Side Effects

Common side effects include headache, dizziness, and hypotension. Orthostatic hypotension can occur, leading to an increased risk of falls, especially in the elderly. Tolerance to nitroglycerin can develop with long-term use, necessitating a nitrate-free period to restore sensitivity.

Contraindications

Nitroglycerin should not be used in patients with severe anemia, closed-angle glaucoma, or those taking phosphodiesterase inhibitors (e.g., sildenafil), as the combination can lead to severe hypotension.

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