Glycerol nitrate

Glycerol nitrate (GTN) is an active ingredient from the family of nitrovasodilators (organic nitrate), a group of drugs that are broken down in the smooth muscle of the vessels of the large and small circulation and the draining urinary and biliary tracts, thereby releasing NO (NO donors). Nitrovasodilators are basic therapeutics for coronary heart disease. The average half-life of glycerol nitrate is about 0.04h.

Glycerol trinitrate is a very fast but short-acting nitrate, which is therefore well suited for the treatment of an acute attack. After application in the oral cavity, it is effective within seconds to minutes. The dilatation of veins and vessels reduces the preload of the heart (lowering the end-diastolic pressure). This improves the blood flow in the coronary vessels during diastole. Only in high, non-therapeutic doses do nitrates also have a slight arterial dilating effect.

• Acute treatment and prevention of angina pectoris (stage of coronary heart disease CHD caused by coronary sclerosis). Distally of this constriction, hypoxia of the heart muscle tissue occurs, which manifests itself in the classic symptoms of angina pectoris such as a feeling of pressure on the chest, severe pain possibly with radiations into the left arm, stomach, lower jaw and back, cold sweat and nausea. Glycerol trinitrate can be used acutely or as a preventive measure if an exposure is imminent which is expected to trigger an attack of angina pectoris.
• Acute left heart failure
• Coronary spasms (special form of angina pectoris, they are called Prinzmetal angina after their discoverer)
• Acute heart attack

• Headaches
• Blood pressure drop
• Flush
• Skin irritation
• Tolerance development

• Acute circulatory failure
• Cardiogenic shock
• Heart valve stenosis
• Pronounced hypotension
• Pregnancy and lactation

Nitroderm® TTS 5 membrane patch; Nitroderm® TTS patch; Nitrolingual® infusion solution

All therapeutically applied nitrovasodilators develop their antiischemic efficacy uniformly via the same mechanism. They release radical NO (nitric oxide), albeit via different bioactivation pathways. This corresponds to the physiologically released "Endothelium Derived Relaxing Factor" (EDRF) in healthy tissue. NO has the greatest relaxation effect where there is the greatest lack of physiological NO. Apparently there is an inverse correlation between the amount of NO formed, which is normally necessary for dilation, and the reaction to organic nitro compounds. Improvement of myocardial function and increase of oxygen supply to poorly perfused parts of the myocardium. NO activates guanylate cyclase. This increases the intracellular content of cGMP. This in turn lowers the cytosolic calcium concentration and thus causes the smooth muscle cells to relax. It is important to note that in vessels with altered endothelium, e.g. in arteriosclerosis, the release of EDRF is disturbed.

Tolerance development: All nitrate compounds from which nitric oxide (NO) is released enzymatically with the help of aldehyde dehydrogenase-2 are subject to tolerance development (glycerol trinitrate, ISDN, ISMN). This tolerance decreases very quickly after settling. In most cases a nitrate-free interval of 6-8 h is sufficient. The effectiveness in acute application is therefore not impaired.

NO is not released enzymatically from molsidomine but only after hepatic hydrolysis. It is suitable for bridging the nitrate pause of the other preparations. After longer therapy it should be skimmed out, rebound effects are possible. There are cross tolerances to the other nitrate compounds.

1. Graefe KH et al Pharma with effects on the vascular system In: Graefe KH et al (Eds) Pharmacology and Toxicology. Georg Thieme Publisher Stuttgart S.177-181
2. Speeches J (1990) Molsidomine. Blood Vessels 27:282-294