Nitroglycerin hemodynamic effects

Tolerance to nitrates is defined as the reduction in hemodynamic effect or the requirement for higher doses to achieve a persistent effect with continuous use in the face of constant plasma concentrations [15]. Nitrate tolerance was first described for nitroglycerin in 1888 [36] it occurs with all organic nitrates, albeit to different extents. For reasons that are not understood, PETN appears to be the least susceptible to the development of tolerance. No, or much less, tolerance is observed with nitrite esters, such as amyl nitrite [37], molsidomine, and sodium nitroprusside. Earlier investigations suggested that a depletion of intracellular thiols is involved in tolerance development [17], but this has not been substantiated in later studies [38, 39]. As with organic nitrate bioactivation, the precise mechanism(s) involved in nitrate tolerance remain(s) unknown, but it is likely to be complex and multifactorial. Two principal... 

Marchionni N, Schneeweiss A, Di Bari M, Ferrucci L, Moschi G, Salani B et al. Age-related hemodynamic effects of intravenous nitroglycerin for acnte myocardial infarction and left ventricular failure. Am J Cardiol... 

Which of the following hemodynamic effects of nitroglycerin are primarily responsible for the beneficial results observed in patients with secondary angina ... 

Nitroglycerin should be initiated at a dose of 5 to 10 mcg/min (0.1 mcg/kg per minute) and increased every 5 to 10 minutes as necessary and tolerated. Hypotension and an excessive decrease in PAOP are important dose-limiting side effects. Maintenance doses usually vary from 35 to 200 mcg/min (0.5 to 3 mcg/kg per minute), although doses over 1000 mcg/min (15 mcg/kg per minute) have been used in rare cases. Tolerance to the hemodynamic effects of nitroglycerin may develop over 12 to 72 hours of continuous administration, but some patients have a sustained response. Neither nitroglycerin nor nitroprusside should be used in the presence of elevated intracranial pressure because either may worsen cerebral edema in this setting. 

Abrams, J. (1985). Hemodynamic effects of nitroglycerin and long-acting nitrates. Am. Heart J. no, 216-224. 

Bauer, J. A., and Fung, H.-L. (1991). Differential hemodynamic effects and tolerance properties of nitroglycerin and an S-nitrosothiol in experimental heart failure. /. Pharmacol. Exp. Ther. 256, 249-254. 

Leier, C. V., Bambach, D., Thompson, M. J., Cattaneo, S. M., Goldberg, R. J., and Unverferth, D. V. (1981a). Central and regional hemodynamic effects of intravenous isosorbide dinitrate, nitroglycerin, and nitroprusside in patients with congestive heart failure. Am. J. Cardiol. 48, 1115-1123. 

Kupari M, Heikkila J, Ylikahri R. Does alcohol intensify the hemodynamic effects of nitroglycerin Clin Cardiol (1984) 7, 382-6. 

Kubo SH, Fox SC, Prida XE, Cody RJ. Combined hemodynamic effects of nifedipine and nitroglycerin in congestive heart failure.(1985) 110, 1032-4. 

Continuous infusions of nitroglycerin should be initiated at a dose of 5 to 10 mcg/minute and increased every 5 to 10 minutes until symptomatic or hemodynamic improvement. Effective doses range from 35 to 200 mcg/minute. The most common adverse events reported are headache, dose-related hypotension, and tachycardia. A limitation to nitroglycerin s use is the development of tachyphylaxis, or tolerance to its effects,... 

As mentioned above, headache and other symptoms observed by people working with explosives disappeared upon maintained exposure [6]. The development of tolerance was first reported by Stewart in 1888 [48], soon after nitroglycerin was introduced into clinical practice. Tolerance is defined as the loss of hemodynamic and anti-anginal effects during continued therapy [16]. Flaherty has proposed the term attenuation instead of tolerance, since complete loss of anti-ischemic effects has rarely been observed and patients continue to respond to elevated doses [13] however, the term tolerance is generally accepted. 

Nitroglycerin may be applied topically (2% ointment). Its hemodynamic and benehcial effects appear as early as 15 minntes after application and last np to 4 hours. Nitroglycerin ointment may be especially nsefnl for the... 

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