Glycerol trinitrate

Glycerol trinitrate or nitroglycerin is a vasodilating agent used to prevent and treat hypertension, angina pectoris (chest tightness), chest pain, acute heart failure in patients with myocardial infarction, and pain caused by anal fissures.

The active ingredient is available in spray form, intravenous form, (sustained-release) tablet form, ointment form, and transdermal form. The latter is applied directly to the skin to prevent acute attacks of angina. The intravenous form is used off-label in emergency situations (cocaine-induced coronary spasm, hypertension emergencies, acute exacerbations of congestive heart failure).

Pharmacodynamics

The mechanism of action of glycerol trinitrate is based on relaxation of vascular smooth muscle, causing dilation of arteries and veins. As a result, blood pressure is lowered.
Durch die mitochondriale Aldehyddehydrogenase wird Glyceroltrinitrat in Stickstoffmonoxid gewandelt, welches das Enzym Guanylatzyklase aktiviert. Daraufhin wird das zyklische Guanosin-3‘,5‘-monophosphat synthetisiert und eine Kaskade von Proteinkinase-abhängigen Phosphorylierungsereignissen in den glatten Muskelzellen aktiviert. Durch die anschließende Dephosphorylierung der Myosinkette der Muskulatur wird eine Entspannung verursacht und ein erhöhter Blutfluss in den Venen und Arterien des Herzgewebes ermöglicht.

Pharmacokinetics

Glycerol trinitrate is rapidly absorbed and reaches the highest plasma concentration after only 4.4 minutes after administration, which is why it is often used in emergency situations. After sublingual administration, bioavailability is 40% and protein binding in plasma is approximately 60%. The drug is degraded to glycerol and carbon via several metabolizations.

Interactions

Glycerol trinitrate should not be used concomitantly with sildenafil, vardenafil, and tadalafil because concomitant administration can often cause an increased drop in blood pressure and a slowed heart rate, which can be fatal.

Side effects

Common side effects on initial use or when the dose is increased are a noticeable drop in blood pressure with symptoms such as dizziness, lightheadedness, and a reflex acceleration of the heartbeat. In addition, headache, heat sensation, and flushing (facial flushing) may occur.

Toxicological data

LD50 (rat, oral): 105 mg/kg
LD50 (Ratte, intravenös): 23,2 mg/kg