Definition
ChEBI: A nitroglycerol that is glycerol in which the hydrogen atoms of all three hydroxy groups are replaced by nitro groups. It acts as a prodrug, releasing nitric oxide to open blood vessels and so alleviate heart pain.
General Description
Colorless to pale-yellow, viscous liquid or solid (below 56°F). (Note: An explosive ingredient in dynamite (20-40%) with ethylene glycol dinitrate (80-60%).).
Reactivity Profile
Nitroalkanes, such as NITROGLYCERIN, range from slight to strong oxidizing agents. If mixed with reducing agents, including hydrides, sulfides and nitrides, they may begin a vigorous reaction that culminates in a detonation. Nitroalkanes are milder oxidizing agents, but still react violently with reducing agents at higher temperature and pressures. Nitroalkanes react with inorganic bases to form explosive salts. The presence of metal oxides increases the thermal sensitivity of nitroalkanes. Nitroalkanes with more than one nitro group are generally explosive. Nitroalkanes are insoluble in water. Flammable/combustible material. May be ignited by heat, sparks or flames. This compound is incompatible with the following: Heat, ozone, shock, acids. Note: An OSHA Class A Explosive (1910.109). .
Air & Water Reactions
Highly flammable.
Hazard
Severe explosion risk, highly sensitive to
shock and heat. Toxic by ingestion, inhalation, and
skin absorption. Toxic by skin absorption. Vasodilator.
Health Hazard
Inhalation or contact with material may irritate or burn skin and eyes. Fire may produce irritating, corrosive and/or toxic gases. Vapors may cause dizziness or suffocation. Runoff from fire control may cause pollution.
Potential Exposure
An explosive ingredient in dynamite
(20-40%) with ethylene glycol dinitrate (80-60%). It is also used in making other explosives, rocket propellants;
and medicine (vasodilator).
Fire Hazard
HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion hazard indoors, outdoors or in sewers. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water.
First aid
If this chemical gets into the eyes, remove any
contact lenses at once and irrigate immediately for at least
15 minutes, occasionally lifting upper and lower lids. Seek
medical attention immediately. If this chemical contacts the
skin, remove contaminated clothing and wash immediately
with soap and water. Seek medical attention immediately.
If this chemical has been inhaled, remove from exposure,
begin rescue breathing (using universal precautions, including
resuscitation mask) if breathing has stopped and CPR if
heart action has stopped. Transfer promptly to a medical
facility. When this chemical has been swallowed, get medical
attention. Give large quantities of water and induce
vomiting. Do not make an unconscious person vomit.
Shipping
UN1204 Nitroglycerin solution in alcohol with
not .1% nitroglycerin, Hazard Class: 3; Labels:
3-Flammable liquid. UN3064 Nitroglycerin, solution in
alcohol with .1% but not .5% nitroglycerin, Hazard
Class: 3; Labels: 3-Flammable liquid. UN0143
Nitroglycerin, desensitized with not ,40% nonvolatile,
water-insoluble phlegmatizer, by mass. It falls in Hazard
Class 1.1D (subsidiary hazard: 6.1).
Incompatibilities
Heat, ozone, shock, acids. An OSHA
Class A Explosive (1910.109). Heating may cause violent
combustion or explosion. May explosively decompose on
shock, friction, or concussion. Reacts with ozone causing
explosion hazard.
Description
Nitroglycerin is an oily, poisonous, clear to pale yellow, explosive liquid.Nitroglycerin is made by nitrating glycerol. Early industrial processes used a batch process
in which glycerol was added to a mixture with approximately equal volumes of nitric acid
and sulfuric acid.The sulfuric acid serves to ionize the nitric acid and removes water formed
in the nitration process.
Waste Disposal
Do not wash into sewer.
Consult with environmental regulatory agencies for guidance
on acceptable disposal practices. Generators of waste
containing this contaminant (≥100 kg/mo) must conform
with EPA regulations governing storage, transportation,
treatment, and waste disposal.
History
It was first prepared
in 1846 by the Italian chemist Ascanio Sobrero (1812–1888), who nitrated glycerol using a
mixture of nitric acid and sulfuric acid. Sobrero, who was injured in an explosion doing his
research, realized the compound’s danger and abandoned work on nitroglycerin. Twenty years
after Sobrero’s discovery, Alfred Nobel (1833–1896) developed its use commercially. Nobel
mixed nitroglycerin with other substances, searching for a safe way to transport it and make it less sensitive to heat and pressure.
nitroglycerin when it was first marketed,and Nobel continued to experiment with methods to
make nitroglycerin safer.One of these was mixing nitroglycerin with materials to make a solid
form of nitroglycerin. Nobel discovered that when nitroglycerin was mixed with a silica-based
diatomaceous earth material called kieselguhr,a relatively stable product resulted.The mixture
produced a paste that Nobel could pack into cardboard tubes;these could then be inserted
into holes drilled into rock structures and detonated.In 1867,Nobel patented his mixture and
called it dynamite,a name derived from the Greek word dunamis, meaning power.Nobel also
perfected a blasting cap made from mercury fulminate (Hg(ONC)2) and potassium chlorate
(KClO3) to detonate the nitroglycerin.
Indications
Nitroglycerin (also isosorbide nitrate) relaxes isolated
strips of human corpus cavernosum. Its mechanism
involves the stimulation of guanylate cyclase.
Clinically, nitroglycerin has been of limited use in the
treatment of ED.
Production Methods
Nitroglycerin is made by nitrating glycerol.Early industrial processes used a batch processin which glycerol was added to a mixture with approximately equal volumes of nitric acidand sulfuric acid.The sulfuric acid serves to ionize the nitric acid and removes water formedin the nitration process.Removing the water formed in nitration increases the yield of nitroglycerin.Acids and water must be removed from the desired nitroglycerin through a washingprocess. The production of nitroglycerin is highly exothermic,and it is important to keepthe temperature below room temperature to prevent an explosion. Early production methodsused cooling coils in the nitration vessels to regulate the temperature.During the latter halfof the 20th century, safer continuous production methods replaced batch processes.In thesemethods much smaller reactors are required,as glycerol is reacted with the acids.
Mechanism of action
Nitroglycerine reduces the load on the heart by dilating peripheral veins, reducing the
myocardial need for oxygen, and facilitating redistribution of coronary blood flow in the
region of the myocardium with reduced blood flow.
Clinical Use
Nitroglycerin is used extensively as an explosive in dynamite.A solution of the ester, if spilled or allowed to evaporate,will leave a residue of nitroglycerin. To prevent anexplosion of the residue, the ester must be decomposed byadding alkali. Even so, the material dispensed is so dilutethat the risk of explosions does not exist. It has a strong vasodilatingaction and, because it is absorbed through theskin, is prone to cause headaches among workers associatedwith its manufacture. This transdermal penetration is whynitroglycerin is useful in a patch formulation. In medicine, ithas the action typical of nitrites, but its action develops moreslowly and is of longer duration. Of all the known coronaryvasodilatory drugs, nitroglycerin is the only one capable ofstimulating the production of coronary collateral circulationand the only one able to prevent experimental myocardialinfarction by coronary occlusion.
Side effects
Vascular headache, postural hypotension, and reflex
tachycardia are common side effects of organic nitrate
therapy. Fortunately, tolerance to nitrate-induced headache
develops after a few days of therapy. Postural hypotension
and tachycardia can be minimized by proper
dosage adjustment and by instructing the patient to sit down when taking rapidly acting preparations. An effective
dose of nitrate usually produces a fall in upright
systolic blood pressure of 10 mm Hg and a reflex rise in
heart rate of 10 beats per minute. Larger changes than
these should be avoided, because a reduction in myocardial
perfusion and an increase in cardiac oxygen requirements
may actually exacerbate the angina.
Since nitrite ions oxidize the iron atoms of hemoglobin
and convert it to methemoglobin, there may be a
loss in oxygen delivery to tissues. While methemoglobinemia
does not follow therapeutic doses of organic nitrates,
it can be observed after overdosage or accidental
poisoning.
Synthesis
Nitroglycerine, 1,2,3-propantrioltrinitrate (19.1.1), is synthesized by nitrating
glycerol with nitric acid.
Drug interactions
Potentially hazardous interactions with other drugs
Anticoagulants: infusion of GTN reduces
anticoagulant effect of heparins.
Antidepressants: tricyclics may reduce effect of
sublingual tablets due to dry mouth.
Antimuscarinics: may reduce effect of sublingual
tablets due to dry mouth.
Avanafil, sildenafil, tadalafil, vardenafil: hypotensive
effect significantly enhanced - avoid concomitant
use.
Riociguat: avoid concomitant use due to risk of
hypotension.
Metabolism
Nitroglycerin is a lipid-soluble substance that is rapidly
absorbed across the sublingual or buccal mucosa. Its onset
of action occurs within 2 to 5 minutes, with maximal
effects observed at 3 to 10 minutes. Little residual activity
remains 20 to 30 minutes after sublingual administration.
The plasma half-life of nitroglycerin, given sublingually or by spray, is estimated to be 1 to 3 minutes.
Nitroglycerin and other organic nitrate esters undergo
first-pass metabolism and are rapidly metabolized
in the liver by the enzyme glutathione organic
nitrate reductase.
