Nitroglycerin (drug)

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Nitrogylcerin (3D ball-and-stick model).png
Clinical data
Trade names Nitrol, others
AHFS/ Monograph
MedlinePlus a601086
  • US: C (Risk not ruled out)
Routes of
sublingual, transdermal, by mouth, intravenous
ATC code
Legal status
Legal status
  • AU: S3 (Pharmacist only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability <1%
Metabolism liver (rapid), red blood cells, vascular wall
Biological half-life 3 minutes
Excretion In urine, in bile
CAS Number
PubChem CID
Chemical and physical data
Formula C3H5N3O9
Molar mass 227.087 g/mol
3D model (Jmol)
 NYesY (what is this?)  (verify)

Nitroglycerin, also known as glyceryl trinitrate (GTN) is a medication used for heart failure, high blood pressure, and to treat and prevent chest pain from not enough blood flow to the heart or due to cocaine. This includes chest pain from a heart attack. It is taken by mouth, under the tongue, applied to the skin, or by injection into a vein.[1]

Common side effects include headache and low blood pressure. The low blood pressure can be severe. It is unclear if use in pregnancy is safe for the baby. It should not be used together with medications within the sildenafil (PDE5 inhibitor) family due to the risk of low blood pressure. Nitroglycerin is in the nitrate family of medications. While it is not entirely clear how it works, it is believed to function by dilating blood vessels.[1]

Nitroglycerin was written about as early as 1846 and came into medical use in 1878.[2][3] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[4] The wholesale cost in the developing world as of 2014, was US$0.06–0.22 per dose by mouth.[5] The drug nitroglycerin (GTN) is a formulation of the same chemical substance used as the explosive nitroglycerin.[3]

Medical uses[edit]

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 spasms.[1][6]


GTN 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.[7] 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 acute myocardial infarction (heart attack) and pulmonary edema, again working best if used quickly, within a few minutes of symptom onset, as a pulse dose. 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.[citation needed]

Other uses[edit]

Tentative evidence indicates efficacy of glyceryl trinitrate in the treatment of various tendinopathies, both in pain management and acceleration of soft tissue repair.[8][9][10][11][12]

GTN is also used in the treatment of anal fissures, though usually at a much lower concentration than that used for angina treatment.[13][better source needed]


After long-term use for chronic conditions, nitrate tolerance—tolerance to agents such as GTN— may develop in a patient, reducing its 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 effects,[citation needed] and was first described soon after the introduction of GTN in cardiovascular therapy. Studies have shown[weasel words] that nitrate tolerance is associated with vascular abnormalities which have the potential to worsen patients' prognosis.[14][full citation needed] These include endothelial and autonomic dysfunction.[15][full citation needed]

The mechanisms of nitrate tolerance have been investigated over the last 30 years, and several hypotheses to explain tolerance have been offered, including:

  1. plasma volume expansion;
  2. impaired transformation of GTN into NO or related species;
  3. counteraction of GTN vasodilation by neurohormonal activation;[16] and
  4. oxidative stress.[17][full citation needed]

Recent evidence suggests[weasel words] that deleterious GTN-induced production of oxygen free radicals might induce a number of abnormalities, include those described above, so that the oxidative stress hypothesis might represent a unifying principle.

Adverse events[edit]

Glyceryl trinitrate can cause severe hypotension, bradycardia, and severe headaches that necessitate analgesic intervention for pain relief, the painful nature of which can have a marked negative effect on patient compliance.

GTN 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.[18]

GTN transdermal patches should be removed before defibrillation due to the risk of explosion and/or burns,[19][verification needed][better source needed] but investigations have concluded that GTN patch explosions during defibrillation were due to voltage breakdown involving the metal mesh in some patches.[20]

Mechanism of action[edit]

GTN is a prodrug which must be denitrated, with the nitrite anion or a related species further 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 words] that organic nitrates produce NO by reacting with sulfhydryl groups, while others believe that enzymes such as glutathione S-transferases, cytochrome P450 (CYP), and xanthine oxidoreductase are the primary source of GTN bioactivation. In recent years,[when?] a great deal of evidence has been produced that supports the conclusion that GTN's clinically relevant denitration and reduction produce 1,2-glyceryl dinitrate (GDN) and NO, and that this reaction is catalysed by mitochondrial aldehyde dehydrogenase (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.[clarification needed] Thus, production of NO from exogenous sources such as GTN increases the level of cGMP within the cell, and stimultates dephosphorylation of myosin.


It was known almost from the time of the first synthesis of GTN by Ascanio Sobrero in 1846[citation needed] that handling and tasting of nitroglycerin could cause sudden intense headaches, which suggested a vasodilation effect (as suggested by Sobrero).[verification needed][citation needed] Constantine Hering developed a sublinguial form of nitroglycerin in 1847 and advocated for its dosing as a treatment of a number of diseases; however, it use as a specific treatment for blood pressure and chest pain was not among these.[citation needed]

Following Thomas Brunton's discovery that amyl nitrite could be used to treat chest pain, William Murrell experimented with the use of nitroglycerin to alleviate angina pectoris and reduce blood pressure, and showed that the accompanying headaches occurred as a result of overdose.

Murrell began treating patients with small doses of GTN in 1878, and the substance was widely adopted after he published his results in The Lancet in 1879.[21]

The medical establishment used the name "glyceryl trinitrate" or "trinitrin" to avoid alarming patients, because of a general awareness that nitroglycerin was explosive.[22][verification needed]


  1. ^ a b c "Nitroglycerin". The American Society of Health-System Pharmacists. Retrieved 8 December 2016. 
  2. ^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 454. ISBN 9783527607495. 
  3. ^ a b Ravina, Enrique (2011). The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs. John Wiley & Sons. p. 153. ISBN 9783527326693. 
  4. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016. 
  5. ^ IDPIG Staff (2014). "Glyceryl Trinitrate". International Medical Products Price Guide: International Drug Price Indicator Guide (IDPIG). Retrieved 8 December 2016 – via 
  6. ^ Yasue H, Nakagawa H, Itoh T, Harada E, Mizuno Y (February 2008). "Coronary artery spasm--clinical features, diagnosis, pathogenesis, and treatment". J Cardiol. 51 (1): 2–17. PMID 18522770. doi:10.1016/j.jjcc.2008.01.001. Retrieved 23 November 2016. 
  7. ^ "Nitro-Dur - FDA prescribing information, side effects and uses". Retrieved 31 March 2017. 
  8. ^ Goldin, M; Malanga, GA (September 2013). "Tendinopathy: a review of the pathophysiology and evidence for treatment.". The Physician and sportsmedicine. 41 (3): 36–49. PMID 24113701. doi:10.3810/psm.2013.09.2019. 
  9. ^ Andres, BM; Murrell, GA (2008). "Treatment of Tendinopathy: What Works, What Does Not, and What is on the Horizon". Clin. Orthop. Relat. Res. 466 (7): 1539–54. PMC 2505250Freely accessible. PMID 18446422. doi:10.1007/s11999-008-0260-1. 
  10. ^ Assem, Yusuf; Arora, Manit (1 January 2015). "Glyceryl trinitrate patches—An alternative treatment for shoulder impingement syndrome". Journal of Orthopaedic Translation. 3 (1): 12–20. doi:10.1016/ Retrieved 31 March 2017 – via ScienceDirect. 
  11. ^ Bokhari, Ali R.; Murrell, George A. C. (1 February 2012). "The role of nitric oxide in tendon healing". Journal of Shoulder and Elbow Surgery. 21 (2): 238–244. doi:10.1016/j.jse.2011.11.001. Retrieved 31 March 2017 – via ScienceDirect. 
  12. ^ Gambito, ED; Gonzalez-Suarez, CB; Oquiñena, TI; Agbayani, RB. "Evidence on the effectiveness of topical nitroglycerin in the treatment of tendinopathies: a systematic review and meta-analysis. syndrome". Arch Phys Med Rehabil. 91: 1291–305. PMID 20684913. doi:10.1016/j.apmr.2010.02.008. 
  13. ^ "Anal Fissure Symptoms, Treatment, Causes". Retrieved 31 March 2017. [better source needed]
  14. ^ Nakamura et al.[full citation needed]
  15. ^ Gori et al.[full citation needed]
  16. ^ Such activation is suggested to cause sympathetic activation, and release of vasoconstrictors such as endothelin and angiotensin II.
  17. ^ Hypothesis of Munzel et al. (1995).[full citation needed]
  18. ^ "Phosphodiesterase Inhibitors". CV Pharmacology. CV Pharmacology. Retrieved 3 April 2017. 
  19. ^ 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. Retrieved 30 March 2017. 
  20. ^ Liddle, R.; Richmond, W. (1998). "Investigation into voltage breakdown in glyceryl trinitrate patches". Resuscitation. 37 (3): 145–148. PMID 9715773. doi:10.1016/S0300-9572(98)00059-8. [non-primary source needed]
  21. ^ Murrell, William (February 1879). "Nitro-Glycerine as a Remedy for Angina Pectoris.". The Lancet. 113 (2894): 225–227. doi:10.1016/s0140-6736(02)42404-x. 
  22. ^ Sneader, Walter (2005). Drug Discovery: A History. New York, NY: John Wiley & Sons. p. 433. ISBN 0471899801. [verification needed]

Further reading[edit]