A study was carried out to assess the efficacy of a new transdermal preparation of glyceryl trinitrate (Transiderm-Nitro 5) in the 24 hour prophylaxis of angina and to determine the duration of effect of a single patch application. Twelve men with chronic stable angina were studied in a randomised, placebo controlled, double blind trial. By serial treadmill exercise testing a therapeutic effect was shown at three hours; the exercise time to angina and to 1 mm ST segment depression and the total exercise time were all significantly increased. At 24, 48, and 72 hours, however, no therapeutic effect was observed. Recent studies have shown a similar lack of effect at 24 hours for various forms of transdermal delivery systems. It is suggested that this lack of effect is due to the rapid onset of tolerance probably as a result of the constancy of blood concentrations obtained by this method of administration.

https://heart.bmj.com/content/heartjnl/53/6/631.full.pdf

Efficacy of transdermal glyceryl trinitrate in the treatment of chronic stable angina pectoris.

Comparative vasodilator effects of nitroglycerin, pentaerythritol trinitrate and biometabolites, and other organic nitrates

Nitroglycerin-(NTG)-induced headache and dilatation of the radial artery were followed in a double blind, randomized, placebo-controlled, cross-over study in 6 healthy volunteers. NTG 0.5 μg · kg−1 · min−1 or saline were infused IV for 7 h, and subsequently the infusion rate was doubled for 10 min. The radial artery diameter was measured repeatedly with high frequency ultrasound and pain was scored using a 10 point verbal scale. After 5 min of NTG infusion both headache and the arterial diameter differed significantly from baseline, and no further significant change occurred. The intensity of the headache was mild to medium (median headache score 3, range 1–7). The mean dilatation of the radial artery was 36%. The dilatation in each individual, was stable over time, both during NTG and placebo, and it did not change with the double infusion rate. The headache score in each individual was more fluctuan. No tolerance either to the NTG-induced headache or arterial dilatation was observed.

Lack of tolerance of headache and radial artery diameter during a 7 hour intravenous infusion of nitroglycerin

Independent of the route of nitroglycerin administration, substantial amounts of 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl dinitrate (1,3-GDN) metabolites accumulate in humans. Thus far their pharmacologic activity in comparison to nitroglycerin in humans is unknown. To compare the venodilatory potency of nitroglycerin and of 1,2-GDN and 1,3-GDN in vivo, cumulative dose-response curves were established in nine healthy volunteers by use of the dorsal hand vein compliance technique. Separated by a washout period, two of the three venodilators were infused in randomized order after preconstriction with phenylephrine. Values for maximum vasodilation were similar for all compounds: nitroglycerin, 109%; 1,2-GDN, 100%; and 1,3-GDN, 106%. The respective values for the dose rate exerting 50% of maximum vasodilation were 5.1, 43, and 60 ng/min, indicating that the dinitrates were about 10 times less potent than nitroglycerin (p < 0.001) but not significantly different from each other. The findings support the hypothesis that activity of nitroglycerin metabolites is related to the number of nitrate groups in the molecule and are in agreement with lower dinitrate potencies found in animal experiments.

M G Bogaert

Papers

Cardiovascular effects of glyceryldinitrates as compared to glyceryltrinitrate.