Effectiveness of Isosorbide Dinitrate and Nitroglycerin in Relieving Angina Pectoris

Abstract

To the Editor: In their interesting report entitled “Effectiveness of Isosorbide Dinitrate and Nitroglycerin in Relieving Angina Pectoris During Uninterrupted Exercise” (Chest 67:640-646, 1975), Kattus and associates clearly demonstrated that the action of sublingually administered nitroglycerin is more rapid than that of isosorbide dinitrate (chewed and retained in the mouth) in onset and time required for relief of anginal pain. The time difference in the effect of the two preparations could have been yet more significant if nitroglycerin had been administered in the same way as isosorbide dinitrate, ie, chewing the tablet first and keeping it in the mouth, which could result in a faster absorption. Tutored by Dr. G. Howitt, I studied tachycardia induced by nitroglycerin (glyceryl trinitrate) as a “model” to assess the time course of the drug's effect in man following different modes of administration.1Matos L Glyceryl trinitrate-induced tachycardia, as a single “model” to estimate the time course of the drug's effect in man after different modes of administration, thesis. University of Manchester, Manchester, England1969Google Scholar This method fell short in providing information about the antianginal effect of the drug; the tachycardia is a reflex phenomenon, but it is a very consistent effect or side effect of nitroglycerin. This reflex action seems to emerge with no delay when a sufficient amount of the drug has been absorbed to produce its real clinical effect. For the sake of the precise monitoring of heart rate, the mean rates were obtained for groups of 15 beats on the electrocardiogram by a digitized processing of the R-R intervals and by a computerized evaluation of the results. The onset of the positive chronotropic action was chosen by the time of the first three consecutive points which exceeded the main baseline rate on the heart-rate curve by more than 2 SD. The fastest onset of action occurred after chewing the 0.5-mg tablet of nitroglycerin (54 ± 44 seconds, mean ± SD). The onset of action happened significantly later following sublingual administration (149 ± 125 seconds; P < 0.05). Pharmacopeias of different countries, eg, those of the United Kingdom2British Pharmacopoeia 1973. Pharmaceutical Press of London, London1973: 220Google Scholar, 3Martindale W Extra Pharmacopoeia. 26th ed. Pharmaceutical Press of London, London1972: 751Google Scholar and the United States,4United States Pharmacopeia (18th revision). Mack Publishing Co, Easton, Pa1970: 451Google Scholar recommend sublingual administration of nitroglycerin, and widely used pharmacologic5Osol A Pratt R Altschule MD The United States Dispensatory and Physician's Pharmacology. 26th ed. JB Lippincott Co, Philadelphia1967: 762Google Scholar, 6Goodman LS Gilman A The Pharmacological Basis of Therapeutics. 4th ed. Macmillan Publishing Co, Inc, New York1970: 751Google Scholar and medical7Beeson PB McDermott W Textbook of Medicine. 14th ed. WB Saunders Co, Philadelphia2015: 1003Google Scholar textbooks also give the same advice for its application. The difference between the onset of action following sublingual administration or chewing of the tablet can only be measured in seconds, but in the case of anginal attack, every second is important to ensure the earliest possible relief. For a faster absorption, it seems to be advisable to chew not only isosorbide dinitrate but also nitroglycerin tablets, in order to obtain results as quickly as possible. Effectiveness of Isosorbide Dinitrate and Nitroglycerin in Relieving Angina PectorisCHESTVol. 70Issue 1PreviewTo the Editor: Full-Text PDF