Pralidoxime
Encyclopedia
Pralidoxime or 2-PAM, usually as the chloride or methiodide
salts, belongs to a family of compounds called oxime
s that bind to organophosphate
-inactivated acetylcholinesterase
. It is used to combat poisoning by organophosphates
or acetylcholinesterase inhibitors (nerve agents), in conjunction with atropine
and diazepam
. In India, it is marketed by Nucleus Inc. with the brand names LyoPAM and PurePAM.
Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor blood-brain barrier penetration, it has little effect on centrally-mediated respiratory depression. This is why atropine
which has excellent blood-brain barrier penetration, is concomitantly administered with pralidoxime during the treatment of organophosphate poisoning.
Intravenous infusions can lead to respiratory or cardiac arrest if given too quickly.
, mydriasis
, tachycardia
, dryness of the mouth and nose) may occur earlier than might be expected when atropine is used alone. This is especially true if the total dose of atropine has been large and the administration of pralidoxime has been delayed.
The following precautions should be kept in mind in the treatment of anticholinesterase poisoning, although they do not bear directly on the use of pralidoxime: since barbiturates are potentiated by the anticholinesterases, they should be used cautiously in the treatment of convulsions; morphine
, theophylline
, aminophylline
, succinylcholine, reserpine
, and phenothiazine
-type tranquilizer
s should be avoided in patients with organophosphate poisoning.
, giving pyridine-2-aldoxime, which is further reacted with methyl iodide, giving the desired pralidoxime.
Methiodide
In organic chemistry, a methiodide is a chemical derivative produced by the reaction of a compound with methyl iodide. Methiodides may be formed through the methylation of amines:...
salts, belongs to a family of compounds called oxime
Oxime
An oxime is a chemical compound belonging to the imines, with the general formula R1R2C=NOH, where R1 is an organic side chain and R2 may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted oximes form a closely related family of compounds...
s that bind to organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...
-inactivated acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...
. It is used to combat poisoning by organophosphates
Organophosphate poisoning
Organophosphate poisoning results from exposure to organophosphates , which cause the inhibition of acetylcholinesterase leading to the accumulation of acetylcholine in the body. Organophosphate poisoning most commonly results from exposure to insecticides or nerve agents...
or acetylcholinesterase inhibitors (nerve agents), in conjunction with atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
and diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
. In India, it is marketed by Nucleus Inc. with the brand names LyoPAM and PurePAM.
Mechanism of action
Pralidoxime, typically used in cases of organophosphate poisoning (causes ACHase inhibition), attaches to the site where a cholinesterase inhibitor has attached, then attaches to the inhibitor, removing the organophosphate from cholinesterase, allowing it to work normally again. This is known as "regenerating" or "reactivating" acetylcholinesterase allowing the breakdown of Ach at the synapse. After some time, though, some inhibitors can develop a permanent bond with cholinesterase, known as aging, where oximes such as pralidoxime can not reverse the bond. Pralidoxime is often used with atropine (a muscarinic antagonist) to help reduce the parasympathetic effects of organophosphate poisoning. Pralidoxime can also be used to treat neostigmine or pyridostigmine (both ACHase inhibitors) overdoses due to it's ACHase inhibitor regenerating capacities.Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor blood-brain barrier penetration, it has little effect on centrally-mediated respiratory depression. This is why atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
which has excellent blood-brain barrier penetration, is concomitantly administered with pralidoxime during the treatment of organophosphate poisoning.
Dosage
- Adults: 30 mg/kg (typically 1-2 g), administered by intravenous therapyIntravenous therapyIntravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
over 15–30 minutes or intramuscular injectionIntramuscular injectionIntramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...
or subcutaneous injectionSubcutaneous injectionA subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the...
, repeated 60 minutes later. It can also be given as a 500 mg/hr continuous IV infusion. - Children: 20–50 mg/kg followed by a maintenance infusion at 5–10 mg/kg/hr.
Intravenous infusions can lead to respiratory or cardiac arrest if given too quickly.
Interactions
When atropine and pralidoxime are used together, the signs of atropinization (flushingFlushing (physiology)
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...
, mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...
, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, dryness of the mouth and nose) may occur earlier than might be expected when atropine is used alone. This is especially true if the total dose of atropine has been large and the administration of pralidoxime has been delayed.
The following precautions should be kept in mind in the treatment of anticholinesterase poisoning, although they do not bear directly on the use of pralidoxime: since barbiturates are potentiated by the anticholinesterases, they should be used cautiously in the treatment of convulsions; morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, theophylline
Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
, aminophylline
Aminophylline
Aminophylline is a bronchodilator. It is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate-Properties:...
, succinylcholine, reserpine
Reserpine
Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...
, and phenothiazine
Phenothiazine
Phenothiazine is an organic compound that occurs in various antipsychotic and antihistaminic drugs. It has the formula S2NH. This yellow tricyclic compound is soluble in acetic acid, benzene, and ether. The compound is related to the thiazine-class of heterocyclic compounds...
-type tranquilizer
Tranquilizer
A tranquilizer, or tranquilliser , is a drug that induces tranquility in an individual.The term "tranquilizer" is imprecise, and is usually qualified, or replaced with more precise terms:...
s should be avoided in patients with organophosphate poisoning.
Contraindications
There are no known absolute contraindications for the use of pralidoxime. Relative contraindications include known hypersensitivity to the drug and other situations in which the risk of its use clearly outweighs possible benefit.Chemistry
Pralidoxime, 2-pyridinaldoxime methylchloride, is synthesized by reacting picolinaldehyde (2-formyl pyridine) with hydroxylamineHydroxylamine
Hydroxylamine is an inorganic compound with the formula NH2OH. The pure material is a white, unstable crystalline, hygroscopic compound. However, hydroxylamine is almost always provided and used as an aqueous solution. It is used to prepare oximes, an important functional group. It is also an...
, giving pyridine-2-aldoxime, which is further reacted with methyl iodide, giving the desired pralidoxime.
- D. Nachmansonn, S. Ginsburg, (1957).
- L.P. Black, (1964).
- D.E. Easterday, A.A. Kondritzer, (1964).
- W.B. McDowell, (1964).