Trainsdermal nitroglycerin in angina pectoris

Intermittent Nitrate Therapy for Prior Myocardial Infarction Does Not Induce Rebound Angina nor Reduce Cardiac Events.

“…Since the late 1980's, intermittent treatment has been advocated in Western countries as a means of avoiding nitrate tolerance (4, 5, 21). In particular, after continuous therapy with transdermal glyceryl trinitrate was begun in the USAand found to be ineffective (22), the usefulness of a "patch-off period was proposed for transdermal patch treatment (4,5,8,21). Moreover, beneficial effects of intermittent administration were also reported for oral ISDN (7,23) and ISMN (7,10,15).…”

Therapy for Angina Pectoris Secondary to Coronary Disease

“…Tolerance is reported with all forms of nitroglycerin. Tolerance to antianginal effects develops rapidly in humans during long-term, 4 times daily therapy with ISDN and continuous therapy with nitroglycerin patches (Crean et al, 1984;James et al, 1985;Parker & Fung, 1984;Reichek et al, 1984). The putative mechanism of tolerance is drug-induced generation of superoxide anions in the affected vessels, leading to impaired biotransformation and decreased responsiveness to nitric oxide (Gori & Parker, 2004).…”

Update on nitrate tolerance.

“…The failure to demonstrate tolerance in these studies is difficult to explain in view of the many observations that have been made during the past decade showing rapid development of partial or complete tolerance during sustained nitrate therapy. Thus, studies from North America and Europe have clearly documented the rapid development of partial or complete tolerance to both the haemodynamic and anti-ischaemic effects during sustained nitrate therapy (Cowan et al, 1987;Crean et al, 1984;Parker & Fung, 1984;Rudolph et al, 1983;Thadani et al, 1980) With oral ISDN, the initial beneficial effects are dramatically reduced in magnitude and duration when the medications are given four times daily with the last dose late in the evening (Thadani et al, 1982). In this study in which doses of ISDN from 15 to 120 mg were initially given acutely, treadmill exercise time to the development of angina was prolonged for 8 h. During subsequent four times daily therapy, the effects persisted for only 2 h and the magnitude of the response was markedly reduced.…”

“…In this study in which doses of ISDN from 15 to 120 mg were initially given acutely, treadmill exercise time to the development of angina was prolonged for 8 h. During subsequent four times daily therapy, the effects persisted for only 2 h and the magnitude of the response was markedly reduced. With transdermal (Cowa'n et al, 1987;Parker & Fung, 1984) and intravenous GTN (Packer et al, 1987), complete tolerance occurs during short periods of continuous administration. This has been most clearly documented in the transdermal iOTN co-operative study carried out in North America (Transdermal Nitroglycerin Cooperative Study, 1991).…”

“…Studies with transdermal GTN before this had included small numbers of patients and provided conflicting results. The majority of studies showed short duration of effects during acute dosing (Parker & Fung, 1984;Reichek et al, 1984) and little or no effect during sustained once-daily therapy (Parker & Fung, 1984), however some studies indicated prolonged effects even during sustained daily patch application (Kapoor et al, 1985;Thompson, 1983). The transdermal GTN co-operative study involved 562 patients and showed an increase in exercise tolerance 4 h after the initial GTN patch application delivering 15 mg 24 h-1, but after 24 h there was no effect, indicating the rapid development of tolerance.…”