Nitroglycerin (medication)
intravenous | |
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Pharmacokinetic data | |
Bioavailability | <1% |
Metabolism | liver (rapid), red blood cells, vascular wall |
Elimination half-life | 3 minutes |
Excretion | In urine, in bile |
Identifiers | |
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JSmol) | |
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Nitroglycerin, also known as glyceryl trinitrate (GTN), is a
Side effects and mechanism
Common side effects include
History, society and culture
Nitroglycerin was written about as early as 1846[5][6] and came into medical use in 1878.[7][8][9] The drug nitroglycerin is a dilute form of the same chemical used as the explosive, nitroglycerin.[9] Dilution makes it non-explosive.[9] In 2021, it was the 174th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[10][11]
Medical uses
Nitroglycerin is used for the treatment of angina,
Angina
Glyceryl trinitrate is useful in decreasing angina attacks, perhaps more so than reversing angina once started, by supplementing blood concentrations of NO, also called endothelium-derived relaxing factor, before the structure of NO as the responsible agent was known. This led to the development of transdermal patches of glyceryl trinitrate, providing 24-hour release.[13] However, the effectiveness of glyceryl trinitrate is limited by development of tolerance/tachyphylaxis within 2–3 weeks of sustained use. Continuous administration and absorption (such as provided by daily pills and especially skin patches) accelerate onset of tolerance and limit the usefulness of the agent. Thus, glyceryl trinitrate works best when used only in short-term, pulse dosing. Glyceryl trinitrate is useful for myocardial infarction (heart attack) and pulmonary edema, again working best if used quickly, within a few minutes of symptom onset, as a pulse dose. [citation needed]It may also be given as a sublingual or buccal dose in the form of a tablet placed under the tongue or a spray into the mouth for the treatment of an angina attack.[14]
Other uses
Tentative evidence indicates efficacy of glyceryl trinitrate in the treatment of various tendinopathies, both in pain management and acceleration of soft tissue repair.[15][16][17][18][19]
Glyceryl trinitrate is also used in the treatment of anal fissures, though usually at a much lower concentration than that used for angina treatment.[2]
Glyceryl trinitrate has been used to decrease pain associated with dysmenorrhea.[3]
Glyceryl trinitrate was once researched for the prevention and treatment of osteoporosis; however, the researcher Sophie Jamal was found to have falsified the findings, sparking one of the largest scientific misconduct cases in Canada.[20]
Tolerance
After long-term use for chronic conditions,
The mechanisms of nitrate tolerance have been investigated over the last 30 years, and several hypotheses to explain tolerance have been offered, including:
- plasma volume expansion
- impaired transformation of glyceryl trinitrate into NO or related species
- counteraction of glyceryl trinitrate vasodilation by neurohormonal activation[23]
- oxidative stress[24][full citation needed]
Adverse events
Glyceryl trinitrate can cause severe
Glyceryl trinitrate also can cause severe hypotension, circulatory collapse, and death if used together with vasodilator drugs that are used for erectile dysfunction, such as sildenafil, tadalafil, and vardenafil.[25]
Glyceryl trinitrate transdermal patches should be removed before
Mechanism of action
Glyceryl trinitrate is a
The NO produced by this process is a potent activator of
History
It was known almost from the time of the first synthesis of glyceryl trinitrate by Ascanio Sobrero in 1846 that handling and tasting of nitroglycerin could cause sudden intense headaches,[5][6] which suggested a vasodilation effect (as suggested by Sobrero).[28] Constantine Hering developed a form of nitroglycerin in 1847 and advocated for its dosing as a treatment of a number of diseases; however, its use as a specific treatment for blood pressure and chest pain was not among these. This is primarily due to his deep rooted focus in homeopathy.[29][30]
Following
The medical establishment used the name "glyceryl trinitrate" or "trinitrin" to avoid alarming patients, because of a general awareness that nitroglycerin was explosive.[31][verification needed]
Overdoses may generate methemoglobinemia.[32]
References
- ^ a b c d e f g h i j "Nitroglycerin". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
- ^ S2CID 46984485.
- ^ PMID 12196860.
- ^ a b Sobrero A (1847). "Sur plusieur composés détonants produits avec l'acide nitrique et le sucre, la dextrine, la lactine, la mannite et la glycérine" [On several detonating compounds produced with nitric acid and sugar, dextrin, lactose, mannitol, and glycerine]. Comptes Rendus (in French). 24: 247–248. From p. 248: "Il faut toutefois être sur ses gardes en faissant cet essai, car il suffit d'en tenir une très-petite quantité (ce qu'on peut en prendre en y mouillant légèrement le bout du petit doigt) sur la langue pour en éprouver une migraine assez forte pendant pleusieurs heures. Cette action sur le corps humain a été constatée par plusieurs personnes dans mon laboratoire, et je l'ai éprouvée plusieurs fois sur moi-même avant que je fusse certain qu'elle a des propriétés toxiques." (It is always necessary to be on one's guard when making this test, for it suffices to take a very small quantity of it (which one can take by lightly wetting, in it, the tip of the little finger) on [one's] tongue in order to feel a quite strong headache for several hours. This action on the human body has been confirmed by several persons in my laboratory, and I tested it several times on myself before I was certain that it has toxic properties.)
- ^ a b Sobrero A (1849). "Sopra alcuni nuovi composti fulminanti ottenuti col mezzo dell'azione dell'acido nitrico sulle sostante organiche vegetali" [On some new explosive products obtained by the action of nitric acid on some vegetable organic substances]. Memorie della Reale Accademia delle Scienze di Torino. 2nd series (in Italian). 10: 195–201. From p. 198: " … basta il tenere una gocciolina di Piroglicerina sulla lingua, senza inghiottirla, perchè si provi tosto un violento dolore di capo, quale è quello di una forte emicrania, accompagnato da pulsazioni interne assai penose: nello stesso tempo provasi debolezza alle estremità inferiori. Questo effetto sentii io più volte, ed il provarono il signor prof. Valerico Cauda prepartore della mia scuola, ed altre persone ehe tentarono l'esperimento." ( … it suffices to hold a droplet of Piroglicerina [i.e., Sabrero's name for nitroglycerin] on [one's] tongue, without swallowing it, because one soon feels a violent pain in the head, which is a strong headache, accompanied by very painful internal throbbings; at the same time one would feel weakness in the lower extremities. This effect I felt many times, and it was felt by Prof. Valerico Cauda, who prepares lecture demonstrations at my school, and [by] other people who tried the experiment.)
- ^ PMC 5901592.
- ISBN 9783527607495. Archivedfrom the original on 20 December 2016.
- ^ ISBN 9783527326693. Archivedfrom the original on 20 December 2016.
- ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
- ^ "Nitroglycerin - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
- PMID 18522770. Retrieved 23 November 2016.
- ^ "Nitro-Dur - FDA prescribing information, side effects and uses". drugs.com. Archived from the original on 1 April 2017. Retrieved 31 March 2017.
- ^ "Nitroclycerin Oral Route and Sublingual Route". www.mayoclinic.org.
- S2CID 26907571.
- PMID 18446422.
- PMID 30035035.
- PMID 22244067.
- PMID 20684913.
- PMID 27551032.
- ^ Nakamura et al.[full citation needed]
- ^ Gori et al.[full citation needed]
- ^ Such activation is suggested to cause sympathetic activation, and release of vasoconstrictors such as endothelin and angiotensin II.
- ^ Hypothesis of Munzel et al. (1995).[full citation needed]
- ^ "Phosphodiesterase Inhibitors". CV Pharmacology. Archived from the original on 13 June 2017. Retrieved 3 April 2017.
- ^ Scientific Committee on Occupational Exposure Limits (May 2008). Recommendation From the Scientific Committee on Occupational Exposure Limits for Glycerol Trinitrate (Nitroglycerin) [SCOEL/SUM/147] (Report). The Hague, NDL: Sociaal-Economische Raad. Archived from the original on 3 March 2016. Retrieved 30 March 2017.
- PMID 9715773.
- ^ (Sobrero, 1849), pp. 198–199. On pages 198–199, Sobrero describes the results of administering nitroglycerin to a puppy, a mouse, and a guinea pig. After giving (orally) several centigrams of nitroglycerin to a puppy, the animal vomited, and within 7-8 minutes, it ceased to breath. Sobrero managed to revive it, but it convulsed. "L'apertura del suo corpo non diede a scorgere alterazione veruna al ventricolo. I vasi de cervello erano pieni di sangue, come rigonfii di sangue erano l'orocchietta destra de cuore e specialmente la vena cava superiore." (The opening of its body did not reveal any deterioration of the ventricle. The vessels of the brain were full of blood; similarly swollen with blood were the right auricle of the heart and especially the superior vena cava.) Administering nitroglycerin to a mouse and a guinea pig produced similar results.
- ^ Hering C (1849). "Glonoine, a new medicine for headache, &c". American Journal of Homoeopathy. 4 (1): 3–5. Note: Hering renamed nitroglycerine "glonoine".
- PMID 2866851. See pp. 22–23.
- ]
- PMID 3917597.
Further reading
- Ferreira JC, Mochly-Rosen D (2012). "Nitroglycerin use in myocardial infarction patients". Circulation Journal. 76 (1): 15–21. PMID 22040938.
- Lundberg JO, Weitzberg E, Gladwin MT (February 2008). "The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics". Nature Reviews. Drug Discovery. 7 (2): 156–67. S2CID 5141850.
- Marsh N, Marsh A (April 2000). "A short history of nitroglycerine and nitric oxide in pharmacology and physiology". Clinical and Experimental Pharmacology & Physiology. 27 (4): 313–9. S2CID 12897126.