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By Adam Schneeweiss MD, Marija Weiss DSc (auth.)

Nitrates were for a few years the cornerstone of cardiovascular treatment for numerous symptoms. not just have nitrates stood the attempt of time for therapy of persistent solid angina pectoris, however the symptoms for them have markedly ex­ panded. They now comprise all types of angina pectoris and myocardial ischemia, congestive center failure and hypertensive emergencies. The important results of nitrates in some of these stipulations consequence from their vasodilatory homes, however it remains to be doubtful even if the critical or peripheral results predominate within the thera­ peutic mechanism. lately nitrates were proven to satisfy an important requirement for every and each drug - to minimize mortality. a wide scale examine published that isosorbide dinitrate, mixed with hydralazine, decreased long term mortality by way of 28% in sufferers with congestive middle failure. This discovering will surely stimulate examine on nitrates, and it would be anticipated that curiosity in those medications will markedly elevate. The essentially used nitrates in scientific perform are nitroglycerin and the com­ plex natural nitrates, more often than not isosorbide dinitrate. The natural mononitrates are actually less than medical research, and isosorbide-5-mononitrate (IS-5-MN) seems to be specifically promising.

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Other investigators have more experience with intravenous nitroglycerin. Page et al [72] studied the effect of intravenous nitroglycerin in 67 patients with severe unstable angina, treated for 2-29 days with titrated doses. One-third of the patients had Prinzmetal's variant angina. Clinical condition improved in 95% of the patients and complete suppression of symptoms was observed in 63%. Intravenous nitroglycerin was used alone in 25% of the patients and together with beta-blockers in 50% of the patients.

These differences apply also to ISDN. IS-5-MN may be even more effective if the preliminary findings that it decreases systemic vascular resistance less than other nitrates are confirmed~ If nitrate monotherapy does not completely abolish symptoms and/or signs of ischemia in unstable angina, other antianginal agents should be added. The combination with calcium antagonists is very effective. In cases of unstable angina not related to coronary spasm beta-blockers may also be added. Their use in vasospastic angina is controversial, as it has been suggested that they may aggravate the spasm (due to unopposed coronary alpha-adrenergic stimulation).

2. Does Tolerance to the Antianginal Effect of ISDN Develop During Chronic Therapy? As every clinician knows from his experience, ISDN is effective over years of treatment and without development of tolerance in many patients. This is supported by most clinical studies performed specifically to evaluate this aspect. However, some studies, and mainly those of Parker and coworkers [93, 101], suggest the development of at least partial attenuation of the antianginal effect of oral ISDN during chronic treatment.

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