Glyceryl trinitrate (pharmacology)
Systematic (IUPAC) name
1,3-dinitrooxypropan-2-yl nitrate
Identifiers
CAS number	55-63-0
ATC code	C01DA02
PubChem	4510
DrugBank	APRD00153
Chemical data
Formula	C3H5N3O9
Mol. mass	227.087 g/mol
Pharmacokinetic data
Bioavailability	<1%
Metabolism	?
Half life	3 minutes
Excretion	?
Therapeutic considerations
Pregnancy cat.	C(US) Image File history File links Download high-resolution version (1100x1043, 48 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Nitroglycerin Glyceryl trinitrate (pharmacology) ... Image File history File links Download high-resolution version (1100x1049, 224 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Glyceryl trinitrate (pharmacology) ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Atomic mass 12. ... This article is about the chemistry of hydrogen. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless gas Atomic mass 14. ... General Name, Symbol, Number oxygen, O, 8 Chemical series Nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Atomic mass 15. ... The molecular mass (abbreviated MM) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... It has been suggested that Effective half-life be merged into this article or section. ... Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ... Motto: (Out Of Many, One) (traditional) In God We Trust (1956 to date) Anthem: The Star-Spangled Banner Capital Washington D.C. Largest city New York City None at federal level (English de facto) Government Federal constitutional republic  - President George Walker Bush (R)  - Vice President Dick Cheney (R) Independence from...
Legal status
Routes	Sublingual, Transdermal, Oral, Intravenous

Glyceryl trinitrate (GTN) has been used to treat angina and heart failure since at least 1880. Despite this, the mechanism of nitric oxide (NO) generation from GTN and the metabolic consequences of this bioactivation are still not entirely understood. In medical circles it is often referred to as "Nitro." The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... angina tonsillaris see tonsillitis. ... R-phrases , , , , S-phrases , , , Supplementary data page Structure and properties n, εr, etc. ...

Denitration of Glyceryl Trinitrate

GTN is a prodrug which must first be denitrated to produce the active metabolite NO. Nitrates which undergo denitration within the body to produce NO are called nitrovasodilators and their denitration occurs via a variety of mechanisms. The mechanism by which nitrates produce NO is widely disputed. Some believe that 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 a great deal of evidence has been produced which supports the belief that clinically relevant denitration of GTN to produce 1,2-glyceryl dinitrate (GDN) and NO is catalysed by mitochondrial aldehyde dehydrogenase (mtALDH). NO is a potent activator of guanylyl cyclase (GC) by heme-dependent mechanisms; this activation results in cGMP formation from guanosine triphosphate (GTP). Thus, NO increases the level of cGMP within the cell. A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. ... Nitrates are the salts of nitric acid. ... Nitrates are the salts of nitric acid. ... In organic chemistry, a sulfhydryl group or thiol group is a functional group composed of a sulfur and a hydrogen atom (-SH). ... The Glutathione S-transferase (GST) family of enzymes comprises a long list of cytosolic, mitochondrial, and microsomal proteins which are capable of multiple reactions with a multitude of substrates, both endogenous and xenobiotic. ... Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... Guanylate cyclase (EC 4. ... Structure of Heme b A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. ... Cyclic guanosine monophosphate (cGMP) is a second messenger derived from GTP. Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). ... Cyclic guanosine monophosphate (cGMP) is a second messenger derived from GTP. Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). ...

Uses

It is more useful in preventing angina attacks than reversing them once they have commenced. Patches of glyceryl trinitrate with a long activity duration are commercially available. It may also be given as a sublingual dose in the form of a tablet placed under the tongue or a spray into the mouth for the treatment of an angina attack. angina tonsillaris see tonsillitis. ...

Advantages

Long acting Nitrates can be more useful as they are generally more effective and stable in the short term.

Disadvantages

After long term use for treating chronic conditions, tolerance may develop in a patient reducing its effectiveness. Nitrate tolerance was first described soon after the introduction of GTN in cardiovascular therapy as the loss of symptomatic and hemodynamic effects of GTN and/or the need for higher dosages of the drug in order to achieve the same effects. The mechanisms of nitrate tolerance have been thoroughly investigated in the last 30 years and several hypotheses have been proposed. these include:

1. Impaired biotransformation of GTN to its active pinciple NO (or a NO-related species)
2. Neurohormonal activation, causing sympathetic activation and release of vasoconstrictors such as endothelin and angiotensin II which counteract the vasodilation induced by GTN
3. Plasma volume expansion
4. The oxidative stress hypothesis (proposed by Munzel et al in 1995).

Recent evidence suggests that the latter hypothesis might represent a unifying hypothesis, and a GTN-induced inappropriate production of oxygen free radicals might induce a number of abnormalities which include the ones described above. Furthermore, studies have shown that nitrate tolerance is associated with vascular abnormalities which have the potential to worsen patients prognosis (Nakamura et al): these include endothelial and autonomic dysfunction (Gori et al). In the short run, glyceryl trinitrate can cause severe headaches, necessitating analgesic (very rarely up to morphine) administration for relief of pain as well as severe hypotension, and, in certain cases, bradycardia. This makes some physicians nervous and should prompt caution when starting nitrate administration.

References

• Marsh N, Marsh A. (2000). "A short history of nitroglycerine and nitric oxide in pharmacology and physiology". Clin Exp Pharmacol Physiol 27 (4): 313-9. DOI:10.1046/j.1440-1681.2000.03240.x.