Haemodynamics and plasma concentrations following sublingual GTN and intravenous, or inhaled, isosorbide dinitrate.

Abstract

CF44XN1 We measured plasma nitrate levels and haemodynamics following sublingual glyceryl trinitrate (GTN) (0.5 mg), or isosorbide dinitrate (ISDN) administered intravenously (0.5 mg) or by inhalation (1.25 mg) in 23 patients undergoing cardiac catheterisation for investigation of chest pain. 2 Peak levels were detected at 90 s and 5 min following intravenous and inhaled ISDN respectively and at 3 min following sublingual GTN. 3 Intravenous and inhaled ISDN produced similar plasma levels at 30 s and both were significantly greater than following sublingual GTN. 4 Plasma levels were maintained for longer following inhaled ISDN than intravenous ISDN or sublingual GTN. 5 Haemodynamic responses were qualitatively similar following each treatment; reduction in pulmonary vascular resistance and pressure and left ventricular end diastolic pressure occurred in each group. Heart rate, cardiac output and LV dP/dt.P-1 remained unchanged. 6 Maximal haemodynamic responses were greater following ISDN than GTN, with little difference between the two preparations of ISDN. 7 Haemodynamic responses were more sustained following inhaled ISDN than following sublingual GTN or intravenous ISDN, the latter two being similar in this respect. 8 These findings suggest that inhaled ISDN may provide more rapid and sustained relief from angina than sublingual GTN.

Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway

“…Our study is in agreement with previous reports that showed that GTN exposure in cultured endothelial cells leads to the accumulation of citrulline, indicative of nitric oxide synthase activation [8]. It also concurs with other studies that demonstrated that the rapid action of GTN is coincident with its peak concentrations in the plasma rather than with its lower nitrate metabolites [23,24]. Further support to the idea that eNOS intermediates nitroglycerin-induced vasodilation is found in early reports showing the endothelium dependence of GTN effects in animals and human patients [9,10,12].…”

Physiology of Angina and Its Alleviation With Nitroglycerin

“…However, the majority of the hemodynamic effects would be expected to have occurred within the first 2 minutes of administration. 33 …”

Investigation of the effects of physiological and vasodilation‐induced autonomic activation on the QTc Interval in healthy male subjects

“…(iii) Physical exercise involved running on the spot for 100 steps and an ECG was recorded when subjects were lying supine immediately after the exercise. After a further 45‐min supine rest, subjects were given a 0.5‐mg GTN tablet sublingually and remained supine for 3 min, when an ECG was recorded, corresponding to T max for sublingual GTN [13]. They were then asked to stand for 3 min when an ECG was recorded, after which they remained supine for the remainder of the study.…”