Nitrate therapy is the oldest treatment modality for angina pectoris. The clinical effects of nitrates have been considered to be predominantly related to peripheral actions; systemic vasodilation and a decrease in systemic vascular resistance, reducing the preload and afterload of the heart. These drugs are readily absorbed across mucosal surfaces. Long acting nitrates are avilable in sublingual, buccal, oral and topical delivery systems. The topical forms include NTG paste and transdermal patches. Long acting nitrates have a duration of action of 2 to 24 hours, depending on the preparation used. The transdermal patches provide the longest duration of activity with less pronounced effects.
In order to determine the efficacy and duration of action of transdermal NTG and sublingual NTG, we performed the following trial : After ligating the left anterior descending coronary arteries of cats, we observed the ECG for changes in the ST segments, and for the development of arrhythmias. When compared with controls, administration of sublingual nitroglycerin produced an increase in the time needed for development of a 0.5mm elevation of the ST segment (60 13 sec vs. 44 11 sec), a decrease in the peak elevation of the ST segment (6.6 2.8mm vs. 7.9 t 3.2mm), a shorter duration of ST elevation (115 f 28 sec vs. 161 45 sec.), and a decrease in the number of arrhythmias (5 t 2 vs. 10 2). By contrast, administration of transdermal NTG showed significant effects when compared with controls only at certain lengths of time following administration, and these effects were less than those obtained with sublingual nitroglycerin. Specifically, there was an increase in the time needed for development of a 0.5mm elevation of the ST segment at 4 and 6 hours following administration (54 12 sec. and 52 f 11 sec. vs. 44 f 11 for the control), a decrease in the peak ST segment elevation at 4 and 6 hours (7.1 2.4mm and 7.3 t 2.1mm vs. 7.9 3.2mm) a shortened duration of ST segment elevation at 2, 4, and 6 hours (149 t 39 sec, 124 24 sec, 136 32 sec vs. 161 45 sec) and a decreased number of arrhythmias at 4 and 6 hours (6 3, 7 2 vs. 10 2).
It was suggested that these results were the basis of the experiment to overcome the tolerance of transdermal nitropatch.
|