Nitroglycerin (medication): Difference between revisions

{{Short description|Medication}}

{{For|the undiluted form used as an explosive|Nitroglycerin}}

{{Use dmy dates|date=August 2021}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

| verifiedrevid = 457794822

| image2 = Nitrogylcerin (3D ball-and-stick model).png

| drug_name = Nitroglycerin

<!-- Clinical data -->

| tradename = Nitrol, others

| Drugs.com = {{Drugs.com|monograph|nitroglycerin}}

| pregnancy_category =

| routes_of_administration = [[Sublingual]], [[transdermal]], [[by mouth]], [[intravenous]]

| ATC_prefix = C01

| ATC_suffix = DA02

| ATC_supplemental = {{ATC|C05|AE01}}

| legal_US = Rx-only

| legal_UK = P

| legal_status =

<!-- Pharmacokinetic data -->

| protein_bound =

| metabolism = liver (rapid), red blood cells, vascular wall

| excretion = In urine, in bile

<!-- Identifiers -->

| IUPHAR_ligand = 7053

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEMBL_Ref = {{ebicite|correct|EBI}}

<!-- Chemical data -->

| IUPAC_name = 1,3-dinitrooxypropan-2-yl nitrate; [3-(nitrooxy)-2-[(nitrooxy)methyl]propyl] nitrate; 1,2,3-trinitroxy propane

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

<!-- Definition and medical uses -->

'''Nitroglycerin''', also known as '''glyceryl trinitrate''' ('''GTN'''), is a [[vasodilator]] used for [[heart failure]], high blood pressure ([[hypertension]]), [[anal fissures]], [[dysmenorrhea|painful periods]], and to treat and prevent chest pain caused by decreased blood flow to the heart ([[angina]]) or due to the recreational use of [[cocaine]].<ref name=AHFS2016/><ref name=Fen2006>{{cite journal |vauthors = Fenton C, Wellington K, Easthope SE |title = 0.4% nitroglycerin ointment: in the treatment of chronic anal fissure pain |journal = Drugs |volume = 66 |issue = 3 |pages = 343–9 |date = 2006 |pmid = 16526822 |doi = 10.2165/00003495-200666030-00006 |s2cid = 46984485 }}</ref><ref name=Mor2002>{{cite journal |vauthors = Morgan PJ, Kung R, Tarshis J |title = Nitroglycerin as a uterine relaxant: a systematic review |journal = Journal of Obstetrics and Gynaecology Canada |volume = 24 |issue = 5 |pages = 403–9 |date = May 2002 |pmid = 12196860 |doi = 10.1016/S1701-2163(16)30403-0 }}</ref><ref name="Nav">{{cite journal |vauthors = O'Leary ME, Hancox JC |title = Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias |journal = British Journal of Clinical Pharmacology |volume = 69 |issue = 5 |pages = 427–42 |date = May 2010 |pmid = 20573078 |pmc = 2856043 |doi = 10.1111/j.1365-2125.2010.03629.x }}</ref> This includes chest pain from a [[myocardial infarction|heart attack]].<ref name=AHFS2016/> It is taken [[Oral administration|by mouth]], [[sublingual administration|under the tongue]], applied to the skin, or by [[intravenous|injection into a vein]].<ref name=AHFS2016>{{cite web |title=Nitroglycerin |url=https://www.drugs.com/monograph/nitroglycerin.html |publisher=The American Society of Health-System Pharmacists |access-date=8 December 2016 |url-status=live |archive-url=https://web.archive.org/web/20161221004220/https://www.drugs.com/monograph/nitroglycerin.html |archive-date=21 December 2016}}</ref>

Common side effects include [[headache]] and low blood pressure.<ref name=AHFS2016/> The low blood pressure can be severe.<ref name=AHFS2016/> It is unclear if use in [[pregnancy]] is safe for the fetus.<ref name=AHFS2016/> It should not be used together with medications within the [[PDE5 inhibitor]] family such as [[sildenafil]] due to the risk of low blood pressure.<ref name=AHFS2016/> Nitroglycerin is in the [[nitrate (pharmacology)|nitrate]] family of medications.<ref name=AHFS2016/> While it is not entirely clear how it works, it is believed to function by [[vasodilation|dilating blood vessels]].<ref name=AHFS2016/>

Nitroglycerin was written about as early as 1846<ref name =AS1847/><ref name= AS1849/> and came into medical use in 1878.<ref name=WM1879/><ref name=Fis2006>{{cite book |vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=454 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA454 |language=en |url-status=live |archive-url=https://web.archive.org/web/20161220113902/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA454 |archive-date=20 December 2016}}</ref><ref name=Rav2011>{{cite book |vauthors = Ravina E |title=The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs |date=2011 |publisher=John Wiley & Sons |isbn=9783527326693 |page=153 |url=https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA153 |url-status=live |archive-url=https://web.archive.org/web/20161220120205/https://books.google.ca/books?id=iDNy0XxGqT8C&pg=PA153 |archive-date=20 December 2016}}</ref> The drug nitroglycerin is a dilute form of the same chemical used as the explosive, [[nitroglycerin]].<ref name=Rav2011/> Dilution makes it non-explosive.<ref name=Rav2011/> In 2021, it was the 174th most commonly prescribed medication in the United States, with more than 2{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Nitroglycerin - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Nitroglycerin | access-date = 14 January 2024}}</ref>

[[File:Nitro.JPG|thumb|Three different forms of nitroglycerin: intravenous, sublingual spray, and the nitroglycerin patch.]]

Nitroglycerin is used for the treatment of angina, [[acute myocardial infarction]], severe hypertension, and acute [[coronary artery spasm]]s.<ref name=AHFS2016/><ref name="Yasue2008">{{cite journal |vauthors = Yasue H, Nakagawa H, Itoh T, Harada E, Mizuno Y |title = Coronary artery spasm--clinical features, diagnosis, pathogenesis, and treatment |journal = Journal of Cardiology |volume = 51 |issue = 1 |pages = 2–17 |date = February 2008 |pmid = 18522770 |doi = 10.1016/j.jjcc.2008.01.001 |url = http://www.journal-of-cardiology.com/article/S0914-5087(08)00002-6/fulltext |access-date = 23 November 2016 |doi-access = free }}</ref> It may be administered [[Intravenous therapy|intravenously]], as a [[Sublingual administration|sublingual spray]], or as a [[Dermal patch|patch applied to the skin]].

===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.<ref>{{cite web |url=https://www.drugs.com/pro/nitro-dur.html |title=Nitro-Dur - FDA prescribing information, side effects and uses |work=drugs.com |access-date=31 March 2017 |url-status=live |archive-url=https://web.archive.org/web/20170401055025/https://www.drugs.com/pro/nitro-dur.html |archive-date=1 April 2017}}</ref> 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|date=March 2017}}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.<ref>{{cite web |url=https://www.mayoclinic.org/drugs-supplements/nitroglycerin-oral-route-sublingual-route/proper-use/drg-20072863 |title= Nitroclycerin Oral Route and Sublingual Route |website=www.mayoclinic.org}}</ref>

===Other uses===

Tentative evidence indicates efficacy of glyceryl trinitrate in the treatment of various [[Tendinopathy|tendinopathies]], both in pain management and acceleration of soft tissue repair.<ref>{{cite journal |vauthors = Goldin M, Malanga GA |title = Tendinopathy: a review of the pathophysiology and evidence for treatment |journal = The Physician and Sportsmedicine |volume = 41 |issue = 3 |pages = 36–49 |date = September 2013 |pmid = 24113701 |doi=10.3810/psm.2013.09.2019 |s2cid = 26907571}}</ref><ref>{{cite journal |vauthors = Andres BM, Murrell GA |title = Treatment of tendinopathy: what works, what does not, and what is on the horizon |journal = Clinical Orthopaedics and Related Research |volume = 466 |issue = 7 |pages = 1539–54 |date = July 2008 |pmid = 18446422 |pmc = 2505250 |doi = 10.1007/s11999-008-0260-1}}</ref><ref>{{cite journal |vauthors = Assem Y, Arora M |title = Glyceryl trinitrate patches-An alternative treatment for shoulder impingement syndrome |journal = Journal of Orthopaedic Translation |volume = 3 |issue = 1 |pages = 12–20 |date = January 2015 |pmid = 30035035 |pmc = 5982354 |doi = 10.1016/j.jot.2014.11.001}}</ref><ref>{{cite journal |vauthors = Bokhari AR, Murrell GA |title = The role of nitric oxide in tendon healing |journal = Journal of Shoulder and Elbow Surgery |volume = 21 |issue = 2 |pages = 238–44 |date = February 2012 |pmid = 22244067 |doi = 10.1016/j.jse.2011.11.001 }}</ref><ref>{{cite journal |vauthors = Gambito ED, Gonzalez-Suarez CB, Oquiñena TI, Agbayani RB |title = Evidence on the effectiveness of topical nitroglycerin in the treatment of tendinopathies: a systematic review and meta-analysis |journal = Archives of Physical Medicine and Rehabilitation |volume = 91 |issue = 8 |pages = 1291–305 |date = August 2010 |pmid = 20684913 |doi = 10.1016/j.apmr.2010.02.008 }}</ref>

Glyceryl trinitrate is also used in the treatment of [[anal fissure]]s, though usually at a much lower concentration than that used for angina treatment.<ref name=Fen2006/>

Glyceryl trinitrate has been used to decrease pain associated with [[dysmenorrhea]].<ref name=Mor2002/>

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.<ref name="ncbi">{{cite journal |title=Misconduct saga rattles bone scientists |journal=Canadian Medical Association Journal |last=Shuchman |first=Miriam |date=20 September 2016 |volume=188 |issue=13 |pages=938–939 |doi=10.1503/cmaj.109-5314 |pmid=27551032 |pmc=5026510 |doi-access=free}}</ref>

===Tolerance===

After long-term use for chronic conditions, [[nitrate tolerance]]—tolerance to agents such as glyceryl trinitrate— may develop in a patient, reducing its effectiveness. Tolerance is defined as the loss of symptomatic and hemodynamic effects of glyceryl trinitrate and/or the need for higher doses of the drug to achieve the same effects,{{citation needed|date=March 2017}} and was first described soon after the introduction of glyceryl trinitrate in cardiovascular therapy. Studies have shown{{citation needed|date=March 2023}} that nitrate tolerance is associated with vascular abnormalities which have the potential to worsen patients' prognosis.<ref>Nakamura et al.{{full citation needed|date=March 2017}}</ref>{{full citation needed|date=March 2017}} These include endothelial and autonomic dysfunction.<ref>Gori et al.{{full citation needed|date=March 2017}}</ref>{{full citation needed|date=March 2017}}

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<ref>Such activation is suggested to cause sympathetic activation, and release of vasoconstrictors such as endothelin and angiotensin II.</ref>

# oxidative stress<ref>Hypothesis of Munzel et al. (1995).{{full citation needed|date=March 2017}}</ref>{{full citation needed|date=March 2017}}

==Adverse events==

Glyceryl trinitrate can cause severe [[hypotension]], [[reflex tachycardia]], and severe headaches that necessitate analgesic<!-- (very rarely up to morphine)--> intervention for pain relief, the painful nature of which can have a marked negative effect on patient [[Compliance (medicine)|compliance]].

Glyceryl trinitrate also can cause severe hypotension, circulatory collapse, and death if used together with [[Vasodilation|vasodilator]] drugs that are used for [[erectile dysfunction]], such as [[sildenafil]], [[tadalafil]], and [[vardenafil]].<ref>{{cite web |title=Phosphodiesterase Inhibitors |url=http://www.cvpharmacology.com/vasodilator/PDEI |website=CV Pharmacology |access-date=3 April 2017 |url-status=live |archive-url=https://web.archive.org/web/20170613122156/http://cvpharmacology.com/vasodilator/PDEI |archive-date=13 June 2017}}</ref>

Glyceryl trinitrate transdermal patches should be removed before [[defibrillation]] due to the risk of explosion and/or burns,<ref>{{cite report |author = Scientific Committee on Occupational Exposure Limits |date = May 2008 |title = Recommendation From the Scientific Committee on Occupational Exposure Limits for Glycerol Trinitrate (Nitroglycerin) [SCOEL/SUM/147] |location = The Hague, NDL |publisher = Sociaal-Economische Raad |url = http://www.ser.nl/nl/grenswaarden/~/media/Files/Internet/Grenswaarden/SCOEL/GSW524_SCOEL_Prov147Nitroglycerine.ashx |access-date = 30 March 2017 |url-status = live |archive-url = https://web.archive.org/web/20160303183933/http://www.ser.nl/nl/grenswaarden/~/media/Files/Internet/Grenswaarden/SCOEL/GSW524_SCOEL_Prov147Nitroglycerine.ashx |archive-date = 3 March 2016 }}</ref>{{verification needed|date=March 2017}}{{better source needed|date=March 2017}} but investigations have concluded that glyceryl trinitrate patch explosions during defibrillation were due to the [[breakdown voltage]] of the metal mesh in some patches.<ref>{{cite journal |vauthors = Liddle R, Richmond W |title = Investigation into voltage breakdown in glyceryl trinitrate patches |journal = Resuscitation |volume = 37 |issue = 3 |pages = 145–8 |date = June 1998 |pmid = 9715773 |doi = 10.1016/S0300-9572(98)00059-8 }}</ref>{{primary source inline|date=March 2017}}

Glyceryl trinitrate is a [[prodrug]] which must be [[Denitration|denitrated]], with the [[nitrite]] anion or a related species further [[Redox|reduced]] to produce the active metabolite [[nitric oxide]] (NO). Organic [[nitrates]] that undergo these two steps within the body are called [[nitrovasodilators]], and the denitration and reduction occur via a variety of mechanisms. The mechanism by which such nitrates produce NO is widely disputed. Some believe{{weasel inline|date=March 2017}} that organic nitrates produce NO by reacting with [[sulfhydryl]] groups, while others believe that enzymes such as [[glutathione S-transferase]]s, [[cytochrome P450]] (CYP), and [[xanthine oxidoreductase]] are the primary source of glyceryl trinitrate bioactivation. In recent years,{{when|date=March 2017}} a great deal of evidence has been produced{{citation needed|date=November 2018}} that supports the conclusion that glyceryl trinitrate's clinically relevant denitration and reduction produce 1,2-glyceryl dinitrate (GDN) and NO, and that this reaction is catalysed by mitochondrial [[aldehyde dehydrogenase]] (ALDH2 or mtALDH).

The NO produced by this process is a potent activator of [[guanylyl cyclase]] (GC) by [[heme]]-dependent mechanisms; this activation results in formation of [[cyclic guanosine monophosphate]] (cGMP) from [[guanosine triphosphate]] (GTP). Among other roles, cGMP serves as a substrate for a [[cGMP-dependent protein kinase]] that activates [[myosin light chain phosphatase]].{{clarify|date=March 2017}} Thus, production of NO from exogenous sources such as glyceryl trinitrate increases the level of [[Cyclic guanosine monophosphate|cGMP]] within the cell, and stimulates [[dephosphorylation]] of [[myosin II|myosin]], which initiates relaxation of smooth muscle cells in blood vessels.

<!-- ONE POSSIBLE SOURCE:

{{cite journal |vauthors = Tfelt-Hansen PC, Tfelt-Hansen J |title = Nitroglycerin headache and nitroglycerin-induced primary headaches from 1846 and onwards: a historical overview and an update |journal = Headache |volume = 49 |issue = 3 |pages = 445–56 |date = March 2009 |pmid = 19267787 |doi = 10.1111/j.1526-4610.2009.01342.x }}

-->

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 [[headache]]s,<ref name= AS1847>{{cite journal |vauthors = Sobrero A |title=Sur plusieur composés détonants produits avec l'acide nitrique et le sucre, la dextrine, la lactine, la mannite et la glycérine|journal=Comptes Rendus|date=1847|volume=24|pages=247–248|url=https://babel.hathitrust.org/cgi/pt?id=mdp.39015035450777;view=1up;seq=259|trans-title=On several detonating compounds produced with nitric acid and sugar, dextrin, lactose, mannitol, and glycerine|language=fr}} 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.)</ref><ref name= AS1849>{{cite journal |vauthors = Sobrero A |title=Sopra alcuni nuovi composti fulminanti ottenuti col mezzo dell'azione dell'acido nitrico sulle sostante organiche vegetali|journal=Memorie della Reale Accademia delle Scienze di Torino|date=1849|volume=10|pages=195–201|url=https://babel.hathitrust.org/cgi/pt?id=iau.31858045931643;view=1up;seq=281|series=2nd series|trans-title=On some new explosive products obtained by the action of nitric acid on some vegetable organic substances|language=it}} 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.)</ref> which suggested a [[vasodilation]] effect (as suggested by Sobrero).<ref>(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.</ref> [[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]].<ref>{{cite journal |vauthors = Hering C |title=Glonoine, a new medicine for headache, &c. |journal=American Journal of Homoeopathy |date=1849 |volume=4 |issue=1 |pages=3–5 |url=https://babel.hathitrust.org/cgi/pt?id=mdp.39015009544423;view=1up;seq=171}} Note: Hering renamed nitroglycerine "glonoine".</ref><ref>{{cite journal |vauthors = Fye WB |title = Nitroglycerin: a homeopathic remedy |journal = Circulation |volume = 73 |issue = 1 |pages = 21–9 |date = January 1986 |pmid = 2866851 |doi = 10.1161/01.cir.73.1.21 |doi-access = free }} See pp. 22–23.</ref>

Following [[Thomas Brunton]]'s discovery that [[amyl nitrite]] could be used to treat chest pain, [[William Murrell (physician)|William Murrell]] experimented with the use of nitroglycerin to alleviate angina and reduce [[blood pressure]], and showed that the accompanying headaches occurred as a result of [[overdose]]. Murrell began treating patients with small doses of glyceryl trinitrate in 1878, and the substance was widely adopted after he published his results in ''[[The Lancet]]'' in 1879.<ref name = WM1879>{{cite journal |vauthors = Murrell W |title=Nitro-glycerine as a remedy for angina pectoris. |journal=The Lancet |volume=113 |issue=2894 |date= 1879 |pages=80–81, 113–115, 151–152, 225–227 |url = https://babel.hathitrust.org/cgi/pt?id=uc1.d0000772988;view=1up;seq=78 |doi=10.1016/s0140-6736(02)42404-x |hdl=2027/uc1.b5295238 |pmc=5901592}}</ref>

The medical establishment used the name "glyceryl trinitrate" or "trinitrin" to avoid alarming patients, because of a general awareness that nitroglycerin was explosive.<ref>{{cite book |vauthors = Sneader W |year = 2005 |title = Drug Discovery: A History |page = 433 |location = New York, NY |publisher = John Wiley & Sons |isbn = 978-0471899808 |url = https://books.google.com/books?id=mYQxRY9umjcC |url-status = live |archive-url = https://web.archive.org/web/20170908213943/https://books.google.com/books?id=mYQxRY9umjcC |archive-date = 8 September 2017 }}{{verification needed|date=March 2017}}</ref>{{verification needed|date=March 2017}}

Overdoses may generate [[methemoglobinemia]].<ref>{{cite journal |vauthors = Kaplan KJ, Taber M, Teagarden JR, Parker M, Davison R |title = Association of methemoglobinemia and intravenous nitroglycerin administration |journal = The American Journal of Cardiology |volume = 55 |issue = 1 |pages = 181–3 |date = January 1985 |pmid = 3917597 |doi = 10.1016/0002-9149(85)90324-8 }}</ref>

== Society and culture ==

=== Brand names ===

In the US, Nitrostat is marketed by [[Viatris]] after Upjohn was spun off from Pfizer.<ref>{{cite web | title=Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan | publisher=Pfizer | via=Business Wire | date=16 November 2020 | url=https://www.businesswire.com/news/home/20201116005378/en/ | access-date=17 June 2024}}</ref><ref>{{cite web | title=Nitrostat | website=Pfizer | url=https://www.pfizer.com/products/product-detail/nitrostat | access-date=17 June 2024}}</ref><ref>{{cite web | title=Brands | website=Viatris | date=16 November 2020 | url=https://www.viatris.com/en/products/brands | access-date=17 June 2024}}</ref>

== References ==

== Further reading ==

{{refbegin}}

* {{cite journal |vauthors = Ferreira JC, Mochly-Rosen D |title = Nitroglycerin use in myocardial infarction patients |journal = Circulation Journal |volume = 76 |issue = 1 |pages = 15–21 |date = 2012 |pmid = 22040938 |pmc = 3527093 |doi = 10.1253/circj.cj-11-1133 }}

* {{cite journal |vauthors = Lundberg JO, Weitzberg E, Gladwin MT |title = The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics |journal = Nature Reviews. Drug Discovery |volume = 7 |issue = 2 |pages = 156–67 |date = February 2008 |pmid = 18167491 |doi = 10.1038/nrd2466 |s2cid = 5141850 }}

* {{cite journal |vauthors = Marsh N, Marsh A |title = A short history of nitroglycerine and nitric oxide in pharmacology and physiology |journal = Clinical and Experimental Pharmacology & Physiology |volume = 27 |issue = 4 |pages = 313–9 |date = April 2000 |pmid = 10779131 |doi = 10.1046/j.1440-1681.2000.03240.x |s2cid = 12897126 }}

{{refend}}

{{Nitric oxide signaling}}

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