Ascanio Sobrero initially synthesized nitroglycerin, which Alfred Nobel used to produce dynamite. People soon learned that it is an effective treatment for angina pectoris and heart disease. In 1879, W. Murrel became the first to report that ingesting a 1% nitroglycerin solution alleviated angina and prevented further attacks. However, experts were unaware of how this medicine operated for decades. Articles published there in the late 1970s and the early 1980s demonstrated that nitric oxide promotes blood channel dilation (Joyner, 2018). It was believed that NO is responsible for the biological characteristics of nitroglycerin. Still, nobody knew precisely how nitroglycerin is activated in the body.
Chen Z. and colleagues discovered the enzyme responsible for this mechanism a year ago. They have dubbed this mitochondrial enzyme aldehyde dehydrogenase. Since its discovery 130 years ago, much has been known regarding nitroglycerin’s chemistry, biotransformation, and mechanism of action. This study seeks to provide a concise summary of this knowledge. Nitric oxide was identified at the end of the 20th century as a significant intermediary in the heart and blood vessels (Vanhoutte, 2018). For their contribution to this discovery, Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad received the Nobel Prize in 1998.
Nitric oxide inhibits the regeneration of smooth muscle cells. This is an essential aspect as to how coronary artery disease and restenosis constrict blood arteries. Nitric oxide(NO) could either cause or prevent cell death, depending on the type of cell. NO was revealed to prevent the apoptosis-related mortality of endothelial cell (Paone et al., 2019). This may prevent against some cardiovascular illnesses. NO oxide was revealed to be responsible for the creation of ecSOD, which may assist to explain why it functions as an antioxidant. NO also contributes to the creation of ferritin. The binding of ferritin to iron II inhibits the Fenton reaction. These results demonstrate how nitric oxide donations can be utilized in medicine.
Understanding how nitroglycerin functions in the body took some time. First, it was found that this mechanism involves thiols or molecules containing sulfhydryls. Radicals like nitric oxide do not stay very long. A portion of the NO produced by the cells immediately interacts with thiols to form nitrosothiols. People believe that one of the most crucial methods for storing NO is through S-nitrosothiols. The biotransformation of nitroglycerin produces various quantities and ratios of 1,2-glyceryl dinitrate, 1,3-glyceryl dinitrate, and NO depending on the tissue, cell, and dose (or S-nitrosothiols). It wasn’t until 2002 that the precise mechanics of this process were clarified, thanks to the discovery of an enzyme called nitroglycerin reductase that quickens this reaction (Gutierrez Cisneros, Bloemen & Mignon 2021). The name given to this enzyme from the mitochondria is aldehyde dehydrogenase (mtALDH).
As soon as nitroglycerin became administered for the first time in a clinical environment, it became evident that long-term usage of this medicine resulted to addiction (Knuuti & Revenco, 2020). The principal reason limiting the effectiveness of nitrate therapy for long-term angina pectoris, congestive heart failure, and acute myocardial infarction is the degradation of nitroglycerin’s hemodynamic and antiaggregatory properties over time. In the past, there have been two major groups of theories regarding how nitrate tolerance functions. According to the “dispositional” (“metabolic” or “end-organ tolerance”) theory, the weakening effects of organic nitrates are due to the decreased biotransformation of nitrates.
Interprofessional team members who work with patients who take nitroglycerin, such as clinicians, cardiology specialists, primary care providers, pharmacists, internists, and nursing staff, should be fully aware of the drug’s indications and contraindications, as well as its possible side effects. Overall, nitroglycerin is safe, and the levels don’t need to be checked. If someone takes too much nitroglycerin, it may be necessary to watch their vital signs to determine how it affects their blood flow. It is best to monitor your blood pressure, heart rate, breathing rate, and oxygen saturation. Pharmacists can help the team by keeping an eye out for interactions between drugs. Nitroglycerin is a category C drug for pregnant women, and it should be used with care by women who are breastfeeding. Currently, no one knows if nitroglycerin is found in breast milk. Nitroglycerine therapy will have better results and fewer side effects if professionals collaborate and share information.
References
Gutierrez Cisneros, C., Bloemen, V., & Mignon, A. (2021). Synthetic, natural, and semisynthetic polymer carriers for controlled nitric oxide release in dermal applications: A review.Polymers, 13(5),760.
Joyner, M. J. (2018). Nitric oxide, normal science, and lessons learned by a marginally prepared mind. Perspectives in Biology and Medicine, 61(2), 191-200.
Knuuti, J., & Revenco, V. (2020). 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes.European heart journal, 41(5), 407-477.
Paone, S., Baxter, A. A., Hulett, M. D., & Poon, I. K. (2019). Endothelial cell apoptosis and the role of endothelial cell-derived extracellular vesicles in the progression of atherosclerosis. Cellular and Molecular Life Sciences, 76(6), 1093-1106.
Vanhoutte, P. M. (2018). Nitric oxide: From good to bad. Annals of Vascular Diseases, ra-17.