Combined use of nitroglycerin and N-acetylcysteine in the management of unstable angina pectoris.
The vasodilator effects of nitroglycerin (NTG) are mediated via activation of guanylate cyclase; this process is believed to require the availability of free sulfhydryl groups. Previous studies in man have shown that the sulfhydryl donor N-acetylcysteine (NAC) potentiates the systemic and coronary vasodilator effects of NTG. Furthermore, interaction of NTG and NAC may lead to the formation of S-nitroso-NAC, which strongly inhibits platelet aggregation. The effects of intravenous NTG combined with intravenous NAC (5 g 6 hourly) were compared with those of intravenous NTG alone in a double-blind trial in 46 patients with severe unstable angina pectoris unresponsive to conventional treatment, which included calcium antagonists and cutaneous nitrates in all but one patient. Treatment with NTG/NAC (24 patients) and that with NTG alone (22 patients) was associated with a similar frequency of episodes of chest pain and of increments in NTG infusion rate for pain control (10 vs 17; p = NS). The NTG/NAC group had a significantly lower incidence of acute myocardial infarction than the NTG/placebo group (three vs 10 patients; p = .013). Symptomatic hypotension occurred frequently in the NTG/NAC group (seven vs 0 patients; p = .006). Lactate-pyruvate ratios and venous NTG concentrations were not significantly affected by NAC. Subsequently, another 20 consecutive patients were treated with intravenous NTG and continuously infused NAC (10 g/day). Seven remained pain free during the first 24 hr of NTG infusion; 11 required increments in NTG infusion rate for pain control. Acute myocardial infarction occurred in one patient, while none developed symptomatic hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)
D000111:Acetylcysteine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy*; D000789:Angina, Unstable / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D005996:Nitroglycerin / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D012307:Risk Factors
D005996:Nitroglycerin; D000111:Acetylcysteine