Nitroglycerin

The beneficial effects of ISDN are reduced following long-term treatment with the drug through a process known as tolerance. Controlled studies have shown that using intravenous and oral N-acetyl cysteine (NAC) reverses or prevents tolerance to nitrates. Another controlled study revealed that intravenous NAC enhanced the beneficial effects of ISDN on heart function. Therefore, people taking isosorbide dinitrate might benefit from supplemental NAC.

Vitamin C may help maintain the blood vessel dilation response to nitroglycerin. A double-blind study found that individuals taking 2 grams of vitamin C three times per day did not tend to develop nitroglycerin tolerance over time compared to those taking placebo. In another controlled clinical trial, similar protection was achieved with 500 mg three times daily.

People using long-acting nitroglycerin can avoid tolerance with a ten- to twelve-hour hour nitroglycerin-free period every day. People taking long-acting nitroglycerin should ask their prescribing doctor or pharmacist about preventing nitroglycerin tolerance.

Continuous nitroglycerin use leads to development of nitroglycerin tolerance and loss of effectiveness. Intravenous (iv) N-acetyl cysteine (NAC), during short-term studies of people receiving continuous nitroglycerin, was reported to reverse nitroglycerin tolerance. In a double-blind study of patients with unstable angina, transdermal nitroglycerin plus oral NAC (600 mg three times per day) was associated with fewer failures of medical treatment than placebo, NAC, or nitroglycerin alone. However, when combined with nitroglycerin use, NAC has led to intolerable headaches. In two double-blind, randomized trials of angina patients treated with transdermal nitroglycerin, oral NAC 200 mg or 400 mg three times per day failed to prevent nitroglycerin tolerance.