Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Norgine Pharmaceuticals Limited, Norgine House, Widewater place, Moorhall Road, Harefield, Middlesex, U89 6NS, UK
Pharmacotherapeutic group: Vasodilators used in Cardiac Diseases, organic nitrates
ATC Code: C01DA02
The main pharmacological activity of organic nitrates is the relaxation of smooth vascular muscles. The systemic vasodilation induces an increase of venous capacitance. Venous return is reduced. Ventricular volume, filling pressures and diastolic wall tension are diminished (preload reduction).
A diminished ventricular radius and reduced wall tension, lower myocardial energy and oxygen consumption, respectively.
The dilation of the large arteries near the heart leads to a decrease in both the systemic (reduction of afterload) and the pulmonary vascular resistance. In addition, this relieves the myocardium and lowers oxygen demands.
By dilating the large epicardial coronary arteries, glyceryl trinitrate enhances blood supply to the myocardium, improving its pump function and increasing the oxygen supply.
At molecular level, nitrates form nitric oxide (NO), which corresponds to the physical EDRF (endothelium derived relaxing factor). EDRF mediated production of cyclic guanosine monophosphate (CGMP) leads to relaxation of smooth muscle cells.
The transdermal absorption of glyceryl trinitrate circumvents the extensive hepatic first pass metabolism so the bioavailability is about 70% of that achieved after i.v. administration.
The steady-state concentration in the plasma depends on the patch dosage and the corresponding rate of absorption. At a rate of absorption of 0.4 mg/h, the steady-state concentration is about 0.2 µg/l on average. Plasma protein binding is about 60%.
Glyceryl trinitrate is metabolized to 1,2- and 1,3-dinitroglycerols. The dinitrates exert less vasodilatory activity than glyceryl trinitrate. The contribution to the overall effect is not known. The dinitrates are further metabolized to inactive mononitrates, glyceryl and carbon dioxide. The metabolism of glyceryl trinitrate, which is effected in the liver, but also in many other cells, e.g. the red blood cells, includes the separation of one or more nitrate groups.
The elimination half-life of glyceryl trinitrate is 2-4 min. In addition to the metabolism of glyceryl trinitrate, there is a renal excretion of the catabolites.
Glyceryl trinitrate is a well-known active substance, established for more than a hundred years. Thus new preclinical studies have not been carried out with Deponit 5.
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