Pralidoxime

Pralidoxime

Systematic (IUPAC) name
2-[(hydroxyimino)methyl]-1-methylpyridin-1-ium
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy cat.	C
Legal status	RX-only
Identifiers
CAS number	6735-59-7 Y
ATC code	V03AB04
PubChem	CID 6789253
DrugBank	APRD01193
ChemSpider	5193737 Y
UNII	P7MU9UTP52 N
KEGG	C07400 N
ChEBI	CHEBI:8354 N
ChEMBL	CHEMBL1420 Y
Synonyms	1-methylpyridine-6-carbaldehyde oxime
Chemical data
Formula	C7H9N2O+
Mol. mass	137.159 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C7H8N2O/c1-9-5-3-2-4-7(9)6-8-10/h2-6H,1H3/p+1 Y Key:JBKPUQTUERUYQE-UHFFFAOYSA-O Y
N(what is this?)  (verify)

Pralidoxime (2-pyridine aldoxime methyl chloride,) or 2-PAM, usually as the chloride or methiodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to combat poisoning by organophosphates^[1] 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.

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.^[2] 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 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 therapy over 15–30 minutes or intramuscular injection or subcutaneous injection, 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.^[3]

Interactions

When atropine and pralidoxime are used together, the signs of atropinization (flushing, 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 tranquilizers 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 hydroxylamine, giving pyridine-2-aldoxime, which is further reacted with methyl iodide, giving the desired pralidoxime.

• D. Nachmansonn, S. Ginsburg, U.S. Patent 2,816,113 (1957).
• L.P. Black, U.S. Patent 3,123,613 (1964).
• D.E. Easterday, A.A. Kondritzer, U.S. Patent 3,140,289 (1964).
• W.B. McDowell, U.S. Patent 3,155,674 (1964).

See also

• Mark I NAAK

References

1. ^ Jokanović M, Prostran M (2009). "Pyridinium oximes as cholinesterase reactivators. Structure-activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds". Curr. Med. Chem. 16 (17): 2177–88. doi:10.2174/092986709788612729. PMID 19519385. http://www.bentham-direct.org/pages/content.php?CMC/2009/00000016/00000017/0004C.SGM. 
2. ^ http://www.atsdr.cdc.gov/csem/cholinesterase/pam_medications.html
3. ^ Baxter Healthcare Corporation 2006, Protopam Prescribing Information

External links

• Chemical Bioweapons website
• Drugs.com