title: [Characteristics of angina pectoris therapy with nitrates].
abstract: Nitrates have been periodically controversial since their introduction in 1867 as a treatment for angina pectoris. The goal of this synopsis is to delineate the special and unchanged high ranking of nitrates in the treatment of angina pectoris with particular consideration to the dosage and dosage intervals. The anti-anginal/anti-ischemic effect of nitrates originates predominantly from the preload reduction induced by venous dilation; additionally, an accompanying coronary dilation can be of assistance. The special role of the preload reduction differentiates nitrates from beta blockers and calcium antagonists. But the initial positive anti-anginal/anti-ischemic effect can be lost under long-term treatment due to nitrate tolerance. This development of tolerance has been demonstrated for oral, intravenous and transdermal administration. Various mechanisms have been held accountable for this complex occurrence: exhaustion of the thiol pool, neurohumoral counter-regulation, and recently, an overproduction of free radicals. Nitrate tolerance has mean-while been recognized as a relevant clinical problem. The key to avoidance of nitrate tolerance lies in the interval therapy recommended by Stewart as early as 1905: it concludes that continual, 24-hour protection by nitrates alone is impossible. The ideal compromise between avoiding the development of tolerance and an optimal anti-ischemic protection, the duration of which should be as long as possible, demonstrates that approximately 12 hours of protection are clinically possible. As we showed in 1983, the administration of a single, high dose of slow-release ISDN effects this compromise. Asymmetric dosage intervals that guarantee the maintenance of anti-anginal/anti-ischemic nitrate effect may be alternatively used. A 12-hour patch-free interval is generally recommended for treatment with nitrate patches. Similarly, a 12-hour infusion-free period has been recommended for intravenous nitrate administration in patients with stable angina pectoris. In patients with unstable angina pectoris, the situation is more complex-probably due to the anti-platelet effect of nitrates. As has been the practice in the past, nitrates are to be the basic treatment of angina pectoris; as opposed to nifedipine, nitrates lead to a decrease in end-diastolic volume primarily through preload reduction. Nitrates have been documented to be highly effective in treating angina pectoris and myocardial ischemia; they demonstrate a high rate of "responders". Nitrates are the physiological substitute treatment of atherosclerotic vessels with EDRF-deficiency; they improve hemodynamics in the presence of congestive heart failure. Nitrates inhibit platelets in vivo and are standard medication for PTCA as well as other coronary interventions. They demonstrate only few untoward effects and are inexpensive.
authors.affiliation: Kardiologische Gemeinschaftspraxis, München.
authors.forename: S
authors.initials: S
authors.lastname: Silber
mesh_terms: D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009566:Nitrates / Q000009:adverse effects / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D009566:Nitrates; D014665:Vasodilator Agents
vernacular_title: Besonderheiten der Angina-pectoris-Therapie mit Nitraten.