Nitroglycerin , also known as glyceryl trinitrate ( GTN ), is a drug used for heart failure, high blood pressure, and for treating and preventing the chest pain due to insufficient blood flow to the heart (angina) or due to cocaine. These include chest pain due to a heart attack. This is taken by mouth, under the tongue, applied to the skin, or by injection into the blood vessels.
Common side effects include headache and low blood pressure. Low blood pressure can be severe. It is unclear whether the use in pregnancy is safe for the baby. It should not be used in conjunction with drugs in the sildenafil family (PDE5 inhibitor) because of the risk of low blood pressure. Nitroglycerin is present in the family of nitrate drugs. Although it is not entirely clear how it works, it is believed to function by dilating blood vessels.
Nitroglycerin was written around 1846 and began to be used medically in 1878. It is a List of Essential Medicines of the World Health Organization, the most effective and safe medicines needed in the health system. Wholesale costs in developing countries in 2014 are US $ 0.06-0,22 per dose by mouth. The drug nitroglycerin (GTN) is a dilute form of the same chemical used as an explosive, nitroglycerin. Dilution makes it not explosive.
Video Nitroglycerin (drug)
Medical use
Nitroglycerin is used for the treatment of angina, acute myocardial infarction, severe hypertension, and acute coronary artery spasm.
Angina
GTN is useful in reducing angina attacks, perhaps more than reversing angina once started, by increasing NO blood concentration, also called endothelial relaxation factor, before NO structure as responsible agent is known. This led to the development of transdermal patches of glyceryl trinitrate, providing a 24-hour release. However, the effectiveness of glyceryl trinitrate is limited by the development of tolerance/tachyphylaxis within 2-3 weeks of ongoing use. Continuous delivery and absorption (such as those provided by daily pills and especially skin patches) accelerate the tolerance onset and limit the usefulness of agents. Thus, glyceryl trinitrate works best when used only in short-term, pulse doses. Glyceryl trinitrate is useful for acute myocardial infarction (heart attack) and pulmonary edema, again working best when used rapidly, within minutes of symptom onset, as a pulse dose. It can also be administered as a sublingual or buccal dose in tablet form placed under the tongue or spray into the mouth for the treatment of angina attacks.
Other uses
The provisional evidence demonstrates the efficacy of glyceryl trinitrate in the treatment of various tendinopathies, both in pain management and the acceleration of soft tissue repair.
GTN is also used in the treatment of anal fissures, although usually at much lower concentrations than those used for the treatment of angina.
Tolerance
After long-term use for chronic conditions, nitrate tolerance - tolerance to agents such as GTN - can develop in patients, reducing their effectiveness. Tolerance is defined as the loss of symptomatic and hemodynamic effects of GTN and/or the need for higher doses of the drug to achieve the same effect, and was first described shortly after the introduction of GTN in cardiovascular therapy. Studies have shown that nitrate tolerance is associated with vascular disorders that have the potential to worsen the patient's prognosis. These include endothelial and autonomic dysfunction.
The nitrate tolerance mechanism has been studied for the past 30 years, and several hypotheses to explain tolerance have been offered, including:
- expansion of plasma volume;
- GTN transformation disturbance to NO or related species;
- opposition to GTN vasodilation through neurohormonal activation; and
- oxidative stress.
Recent evidence suggests that the production of oxygen-free radicals that destroy GTN can cause a number of disorders, including those described above, so the hypothesis of oxidative stress may represent a unifying principle.
Maps Nitroglycerin (drug)
Bad events
Glyceryl trinitrate can cause severe hypotension, bradycardia, and severe headaches that require analgesic intervention to relieve pain, a painful trait that can have a negative effect on patient compliance.
GTN can also cause severe hypotension, circulatory collapse, and death when used in conjunction with vasodilator drugs used for erectile dysfunction, such as sildenafil, tadalafil, and vardenafil.
The transdermal GTN patch must be removed before defibrillation due to the risk of explosion and/or burns, but investigations have concluded that the GTN patch explosion during defibrillation is due to voltage breakage involving the metal mesh in some patches.
Action mechanism
GTN is a prodrug to be symbolized, with anion nitrite or related species further reduced to produce active active nitric oxide (NO). Organic nitrates that undergo two steps in the body are called nitrovasodilators, and denitration and reduction occur through various mechanisms. The mechanism by which the nitrates produce NO is widely disputed. Some believe that organic nitrate produces NO by reacting with the sulfhydryl group, while others believe that enzymes such as glutathione S-transferase, cytochrome P450 (CYP), and xanthine oxidoreductase are the main sources of bioactivation GTN. In recent years, much evidence has been produced that supports the conclusion that clinically relevant denitration and reduction produce 1,2-glyceryl dinitrate (GDN) and NO, and that this reaction is catalyzed by mitochondrial aldehyde dehydrogenase (ALDH2 or mtALDH). ).
The NO produced by this process is a strong driving force guanylyl cyclase (GC) by a heme-dependent mechanism; This activation results in the formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). Among other roles, cGMP serves as a substrate for the cGMP-dependent protein kinase which activates light chain myosin phosphatase. Thus, NO production from exogenous sources such as GTN increases cGMP levels in the cells, and stimulates myosin defos- phorylation, leading to relaxation of smooth muscle cells in the blood vessels.
History
It was known almost since the time of GTN's first synthesis by Ascanio Sobrero in 1846 that handling and tasting nitroglycerin can cause intense sudden headaches, which exhibit vasodilation effects (as suggested by Sobrero). Constantine Hering developed a nitroglycerin form in 1847 and advocated for its dose as the treatment of a number of diseases; However, its use as a special treatment for blood pressure and chest pain is not included in between.
After Thomas Brunton's discovery that amyl nitrite can be used to treat chest pain, William Murrell experimented with the use of nitroglycerin to reduce angina pectoris and reduce blood pressure, and showed that the accompanying headache occurred as a result of an overdose. Murrell began treating patients with small doses of GTN in 1878, and the substance was widely adopted after he published the results in The Lancet in 1879.
The medical establishment uses the name "glyceryl trinitrate" or "trinitrin" to avoid worrying patients, due to the general consciousness that nitroglycerin is explosive.
Overdose can produce methemoglobinemia.
References
Further reading
- Ferreira, Julio C.B. & amp; Mochly-Rosen, Daria (2012). "Use of Nitroglycerin in Patients with Myocardial Infarction: Risks and Benefits" (review) . Journal of Circulation . 76 (1): 15-21. doi: 10.1253/circj.cj-11-1133. PMCÃ, 3527093 . PMID 22040938 . Retrieved March 30, 2017 . CS1 maint: Using the author parameters (links)
- Lundberg, Jon O.; Weitzberg, Eddie & amp; Gladwin, Mark T. (2008). "Path of Nitric Oxide Nitric Oxide in Physiology and Therapeutics" (review) . Nature Reviews Drug Discovery . 7 (2): 156-167. doi: 10.1038/nrd2466. ISSNÃ, 1474-1776 . Retrieved March 30, 2017 . (Subscription required ( help )) . CS1 maint: Using the author parameter (link)
- Marsh N, Marsh A. (2000). "A brief history of nitroglycerin and nitric oxide in pharmacology and physiology". Clin Exp Pharmacol Physiol . 27 (4): 313-9. doi: 10.1046/j.1440-1681.2000.03240.x. PMID 10779131.
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