Pentaerythritol tetranitrate

Toxicity

The toxicity of nitrate drugs are the result of nitrate conversion to nitrite in the body. Nitrite leads to the autocatalytic oxidation of oxyhemoglobin to both hydrogen peroxide and methemoglobin. This increase in methemoglobin levels is a condition known as methemoglobinemia and is manifested by tissue hypoxia, as methemoglobin is unable to bind oxygen .
Dizziness, redness of the skin (due to vasodilatation), skin irritation and headache are common adverse effects of this drug. Postural hypotension can also occur, especially if this drug is taken at higher doses or while standing .
PETN - Oral LD50 (mouse) = 25,000 mg/kg

Chemical properties

white crystalline powder

Chemical properties

Pentaerythrite tetranitrate (PETN) is a high explosive, especially when dry. PETN is a sand-like, white crystalline solid. Piratically odorless.

Originator

Pentanitrine, Promedica ,France,1948

The Uses of Pentaerythritol tetranitrate

Pentaerythritol tetranitrate (PETN) is a high explosive, often used as the booster in artillery ammunition. It is frequently used as a detonation fuse, which is a form of primacord in which PETN powder is wrapped in waterproof fabric.

The Uses of Pentaerythritol tetranitrate

Mainly in the manufacture of detonating fuse (Primacord), a waterproof textile filled with powdered PETN.

The Uses of Pentaerythritol tetranitrate

Pentaerythritol tetranitrate is used for chronic cardiac insufficiency. It prevents angina pectoris attacks and eases their course.

Background

Pentaerythritol tetranitrate is the nitrate ester of pentaerythritol that possesses explosive properties. When mixed with a plasticizer, this chemical forms a plastic explosive. It is recognized by the FDA to be a coronary vasodilator in the treatment of heart conditions such as angina .
It is a pentaerythritol nitrate in which all four hydroxy groups of pentaerythritol have been converted to the corresponding nitrate ester. It is a vasodilator with properties that are quite similar to those of glyceryl trinitrate, however, with a more prolonged duration of action. It is also one of the most powerful high explosives known and is a component of the plastic explosive known as Semtex .
PETN has the chemical formula C5H8N4O12. It is formed by reacting pentaerythritol (C5H12O4), an alcohol commonly used in paints and varnishes, with nitric acid (HNO2). The reacting solution is chilled to precipitate the PETN. It is then filtered out, washed, dried, and recrystallized to produce a colorless crystalline material that is stored and shipped as a mixture with water and alcohol .
Interestingly, this drug was studied for potential benefits in chronic ischemic heart failure patients. PETN targeting reactive oxygen species generation halted the changes of mitochondrial antioxidant enzymes and progressive fibrotic remodeling, leading to amelioration of cardiac functional performance in rats with ischemic heart failure .

Indications

Used for the treatment of angina pectoris .

Definition

ChEBI: A pentaerythritol nitrate in which all four hydroxy groups of pentaerythritol have been converted to the corresponding nitrate ester. It is a vasodilator with properties similar to those of glyceryl trinitrate, but with a more prolonged duration of action, and is used for treatment of angina pectoris. It is also one of the most powerful high explosives known and is a component of the plastic explosive known as Semtex.

Manufacturing Process

Cooling water was turned on and 420 parts nitric acid of 94% strength was introduced into the nitrator. The amount of acid was such that the ratio of nitric acid to pentaerythritol was 4.29. The agitator was started and the agitator speed adjusted to 120 rpm. 92 parts pentaerythritol, which had been screened previously through a 14-mesh screen was used in each charge. About 45 parts pentaerythritol was added to the nitrator at such a rate that the temperature in the nitrator gradually rose to 110°F. This required about 12 minutes. Time was allowed for the temperature rise to cease before each succeeding increment of material was added.
After reaching 110°F the charge was maintained at about said temperature from 12 to 14 minutes during which time approximately 30 parts pentaerythritol was added to the nitrator. During the following 14 minutes, approximately, the remainder of the 92 parts pentaerythritol was added in like manner to the charge and the temperature gradually reduced. The pentaerythritol was introduced into the acid in finely divided and welldispersed particles and not in large unitary quantities. The entire 92 parts of pentaerythritol tetranitrate was introduced in 35 to 40 minutes. The pentaerythritol thus obtained was separated from the spent acid by filtering or drowning in water. To recover the spent acid the charge was passed onto a nutsch and filtered. The crude product was washed with water, then with a weak water-soluble alkali solution, such as sodium carbonate for example, and subsequently with water in order to remove the acid.
After the removal of acid, the nitrate was dried by suction on the nutsch for about 15 minutes. The dried material was refined by means of acetone treatment or other suitable refining means. About 210 parts refined pentaerythritol tetranitrate per charge was obtained.

brand name

Pentritol Tempules (Rhone-Poulenc Rorer); Peritrate (Parke-Davis).

Therapeutic Function

Coronary vasodilator

Reactivity Profile

Pure PENTAERYTHRITE TETRANITRATE is an explosive. Severe explosion hazard when shocked or exposed to heat. Explodes when heated to 205-215°C. Highly dangerous when mixed with oxidizing agents. On decomposition Pentaerythritol tetranitrate emits highly toxic fumes of NOx (Sax and Lewis, 1987 pp. 699-700).

Health Hazard

Some are toxic and may be fatal if inhaled, swallowed or absorbed through skin. Contact may cause burns to skin and eyes. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may cause pollution.

Health Hazard

Skin contact can cause dermatitis. There is no report of any major adverse effects in humans. However, drawing a parallelism with other nitroorganics of similar structures, PETN is expected to cause poisoning with symptoms of headache, nausea, abdominal pain, and dyspnea.

Fire Hazard

PETN is a high explosive, as powerful as cyclonite. It is more sensitive than TNT to shock. It explodes on percussion or heating. The detonating temperature is 210°C (410°F). The detonation velocity is 7.9 km/s.

Pharmacokinetics

Organic nitrate which causes systemic vasodilation, decreasing cardiovascular preload .
Nitrate enters vascular smooth muscle and converted to nitric oxide (NO) which acts as a cellular messenger, leading to activation of cyclic GMP and, therefore, vasodilation .
The nitrovasodilator group of drugs relaxes most smooth muscles in the body, including those in the walls of arteries and veins, and selectively dilate large coronary vessels . Lower doses of nitrates increase coronary blood flow without significantly affecting systemic arterial pressure. Higher doses, especially if repeated frequently, decrease systolic and diastolic blood pressure as well as cardiac output, which can result in a headache, weakness, dizziness, and the activation of compensatory sympathetic reflexes, including tachycardia and peripheral arteriolar vasoconstriction .
Smooth muscles in the bronchi, biliary tract, gastrointestinal tract, ureters, and uterus also can be relaxed by nitrovasodilators. PETN seems to be unique among the long-acting nitrovasodilators in that patients do not demonstrate tolerance to treatment, which results in sustained vasodilation in humans with continuous PETN treatment .
Important to note is that this drug is devoid of induction of oxidative stress and related side-effects such as endothelial dysfunction or tolerance to nitrates. Some of these effects are related to special pharmacokinetics of PETN, but upon chronic administration, PETN also induces antioxidative pathways at the genomic level, resulting in increased expression of heme oxygenase-1 (HO-1) and ferritin, both possessing highly protective properties. There is good experimental evidence that at least part of the beneficial profile of long-term treatment with this drug is based on the activation of the heme oxygenase-1/ferritin system .

Safety Profile

Human systemic effects by ingestion: dermatitis. Effects are sirmlar to those of nitroglycerin, i.e., headache, weakness, and fall in blood pressure. Very low oral toxicity. Severe explosion hazard when shocked or exposed to heat. It explodes at 215’C. On decomposition it emits hghly toxic fumes of NO,; can react vigorously with oxidizing materials. Used in detonators and explosive specialities. See also NITRATES and EXPLOSIVES, HIGH.

Synthesis

Pentaerythritol tetranitrate, 2,2-bis(hydroxymethyl)-1,3- propandioltetranitrate (19.1.2), is also synthesized by a nitration reaction of pentaerythritol with nitric acid, but using 2,2-bis(hydroxymethyl)-1,3-propandiol instead of glycerol as the starting material.

Potential Exposure

First introduced following WWII, PETN shares the same chemical family as nitroglycerine. It is 70% more powerful than TNT. Used in the manufacture of fuses for detonation and explosive specialties, including the plastic explosive, Semtex, and in blasting caps. PETN is also used as a medical vasodilator to lower blood pressure by widening blood vessels to improve blood flow. PRTN has been used in terrorism attempts in 2001 by the so-called “shoe bomber,” in 2009 by the “underwear bomber,” and most recently in October 2010, hidden in printer cartridges being shipped internationally by passenger jet.

Metabolism

Extensively metabolized in the liver .
Metabolites: pentaerythritol trinitrate, pentaerythritol dinitrate, pentaerythritol mononitrate, & pentaerythritol (inactive)

Shipping

UN3344 Pentaerythrite tetranitrate mixture, desensitized, solid, n.o.s. with ＞10% but not ＞20% PETN, by mass, Hazard Class: 4.1; Labels: 4.1-Flammable solid. UN0150 Pentaerythrite tetranitrate, wetted or Pentaerythritol tetranitrate, wetted, or PETN, wetted or Pentaerythrite tetranitrate, or Pentaerythritol tetranitrate or PETN, desensitized, Hazard Class: 1D; Labels:1DExplosive (with a mass explosion hazard); D-Substances or articles which may mass detonate (with blast and/or fragment hazard) when exposed to fire.

Purification Methods

Crystallise pentaerythritol tetranitrate from acetone or acetone/EtOH. When crystallised from H2O at 0o, it may have m 26-28o (hydrate). It detonates more easily than TNT on percussion. The O-acetate, when crystallised from EtOH, has m 87-88o. Although it has been distilled at 60o/2mm, distillation should NOT be attempted as it is VERY EXPLOSIVE. Itis a vasodilator. [Marans et al. J Am Chem Soc 76 1304 1954, Camp et al. J Am Chem Soc 77 751 1955, Beilstein 1 IV 2816, 2 IV 264.]

Incompatibilities

Treat PETN as an unstable explosive. Rapid heating can cause detonation when heated to 210C. PETN is a dangerous high explosive and a strong oxidizer. PETN normally requires a blasting cap or other kind of detonator but may decompose explosively from concussion, shock, friction, static charges. Keep away from combustible materials; other oxidizers, for example, nitrates and permanganates. Contact with sulfur trioxide may cause detonation. Contact with reducing agents, e.g., zinc and alkaline metals may cause explosion. May explode in the presence of strong bases (i.e., sodium or potassium hydroxide). May react with heavy metals.

Waste Disposal

Seek expert help with this explosive material. Consult with environmental regulatory agencies for guidance on acceptable disposal practices. governing storage, transportation, treatment, and waste disposal.