PRALIDOXIME
HAZARDTEXT ®
Information to help in the initial response for evaluating chemical incidents
-IDENTIFICATION
SYNONYMS
2-Formyl-1-methylpyridinium chloride oxime 2-PAM 2-PAM chloride 2-PAMCl Pralidoxime chloride Pralidoxima, cloruro de Pralidoxime, chlorure de Pralidoximi chloridum Pyridinium, 2-formyl-1-methyl-, chloride, oxime 2-Pyridine Aldoxime Methochloride CAS 51-15-0
IDENTIFIERS
USES/FORMS/SOURCES
Pralidoxime chloride is FDA-approved as an antidote to treat (1) poisoning due to those pesticides and chemicals of the organophosphate class which have anticholinesterase activity and (2) in the control of overdosage by anticholinesterase drugs used in the treatment of myasthenia gravis. The intramuscular auto-injector is used as an adjunct to atropine in the treatment of poisoning by nerve agents having anticholinesterase activity (Prod Info PROTOPAM(R) CHLORIDE injection, 2006). Pralidoxime cannot be used to treat poisoning due to phosphorus, inorganic phosphates or organophosphates that do not have anticholinesterase activity (Prod Info PRALIDOXIME, 2002).
Pralidoxime chloride is available as six 20 milliliters (mL) vials of 1 gram each of sterile pralidoxime chloride white to off-white porous cake, without diluent or syringe; 20 mL of Sterile Water for Injection, USP may be added to prepare the solution. These vials are administered by either intravenous injection or intravenous infusion after further dilution with physiologic saline. If intravenous injection is not possible, the vials may be administered by either intramuscular or subcutaneous routes (Prod Info PROTOPAM(R) CHLORIDE injection, 2006). Pralidoxime chloride is also available as prefilled auto-injectors which deliver 600 milligrams (mg) of pralidoxime chloride in 2 milliliters (mL) of a sterile solution containing 20 mg/mL of benzyl alcohol, and 11.26 mg/mL glycine in water for injection, USP (Prod Info PRALIDOXIME, 2002).
-CLINICAL EFFECTS
GENERAL CLINICAL EFFECTS
- USES: Pralidoxime chloride is used as an antidote to treat poisoning due to those pesticides and chemicals (eg, nerve agents) of the organophosphate class which have anticholinesterase activity and to control overdosage by anticholinesterase drugs used in the treatment of myasthenia gravis. Atropine and pralidoxime auto-injector is used by emergency medical services personnel to treat nerve agent or insecticide intoxication. Refer to "Anticholinergic poisoning", "Organophosphates", or "Military nerve agents" documents for more information regarding the use of pralidoxime in combination with atropine. Pralidoxime cannot be used to treat poisoning due to phosphorus, inorganic phosphates or organophosphates that do not have anticholinesterase activity.
- PHARMACOLOGY: Pralidoxime chloride reactivates cholinesterase (mainly outside CNS) which was inactivated by organophosphate pesticides through phosphorylation. By means of direct chemical reaction, it slows down the process of "aging" of phosphorylated cholinesterase to a permanently inactive form. Pralidoxime also detoxifies certain organophosphates.
- EPIDEMIOLOGY: Overdose is rare.
Data are limited. Overdose effects observed in healthy volunteers include dizziness, blurred vision, diplopia, headache, impaired accommodation, nausea, and slight tachycardia. In one case report, rapid infusion of pralidoxime resulted in blurred vision, difficulty opening eyes, lateral gaze palsy, hypertension, tachycardia, rigidity of the extremities, and respiratory arrest.
It is difficult to differentiate side effects of pralidoxime from effects of the poison or atropine. Blurred vision, diplopia and impaired accommodation, dizziness, headache, drowsiness, nausea, tachycardia, hypertension, hyperventilation, muscular weakness, and elevations in liver enzymes and creatine phosphokinase were observed in healthy volunteers.
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
-FIRST AID
FIRST AID AND PREHOSPITAL TREATMENT
- Gastrointestinal decontamination is not recommended; administered via the parenteral route.
-RANGE OF TOXICITY
MAXIMUM TOLERATED EXPOSURE
- Range of toxicity has not been established. It is difficult to differentiate side effects of pralidoxime from effects of the poison or atropine. A dose of 14 mg/kg IV was reported to cause CNS toxicity (Prod Info PROTOPAM(R) CHLORIDE injection, 2006).
- CHILDREN: One study reviewed information on pralidoxime use in children (aged 16 years and younger) using published reports (from 2001 to 2004) and retrospective detailed TESS data. Overall, 81 patients met inclusion criteria and received atropine and pralidoxime for suspected organophosphate exposure. Five cases were identified; 2 patients expired and 3 patients experienced mild adverse effects. It was determined that neither the adverse effects nor death was the direct result of pralidoxime administration (Quail & Shannon, 2007).
- ADULT: Following the accidental injection of a pralidoxime chloride autoinjector, an Air Force aviator recovered with no specific treatment (Yamane, 1999).
- RAPID INFUSION: A 41-year-old man presented to an ED 1.5 hours after ingesting about 250 mL of diethoxy organophosphate pesticide (34% diazinon emulsion). Although he did not have any cholinergic symptoms, he was started on pralidoxime (PAM; a loading dose of 2-g IV infusion of PAM diluted with 150 mL of 0.9% saline over 30 min and then 12 g of PAM diluted with 500 mL of 5% dextrose as a continuous infusion at a rate of 21 mL/hour using an infusion pump). While being prepared for discharge about 36 hours after presentation, he inadvertently received about 150 to 200 mL of PAM solution (about 4 to 5 g of pralidoxime) rapidly infused over 10 to 20 min. He rapidly developed blurred vision, difficulty opening his eyes, lateral gaze palsy, hypertension (BP 190/110 mmHg), tachycardia (116 beats/min), and rigidity of the extremities. His condition deteriorated and he developed respiratory arrest, necessitating intubation, mechanical ventilation, and sedation. His condition gradually improved and he was discharged on hospital day 5 (Jeong et al, 2015).
- Carcinogenicity Ratings for CAS6735-59-7 :
ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed EPA (U.S. Environmental Protection Agency, 2011): Not Listed IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed MAK (DFG, 2002): Not Listed NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed
TOXICITY AND RISK ASSESSMENT VALUES
- EPA Risk Assessment Values for CAS6735-59-7 (U.S. Environmental Protection Agency, 2011):
LD50- (INTRAMUSCULAR)GUINEA_PIG: LD50- (INTRAMUSCULAR)MOUSE: LD50- (INTRAPERITONEAL)MOUSE: LD50- (INTRAVENOUS)MOUSE: LD50- (ORAL)MOUSE: LD50- (INTRAVENOUS)RABBIT: LD50- (INTRAMUSCULAR)RAT: LD50- (INTRAVENOUS)RAT:
-STANDARDS AND LABELS
WORKPLACE STANDARDS
- ACGIH TLV Values for CAS6735-59-7 (American Conference of Governmental Industrial Hygienists, 2010):
- AIHA WEEL Values for CAS6735-59-7 (AIHA, 2006):
- NIOSH REL and IDLH Values for CAS6735-59-7 (National Institute for Occupational Safety and Health, 2007):
- OSHA PEL Values for CAS6735-59-7 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
- OSHA List of Highly Hazardous Chemicals, Toxics, and Reactives for CAS6735-59-7 (U.S. Occupational Safety and Health Administration, 2010):
ENVIRONMENTAL STANDARDS
- EPA CERCLA, Hazardous Substances and Reportable Quantities for CAS6735-59-7 (U.S. Environmental Protection Agency, 2010):
- EPA CERCLA, Hazardous Substances and Reportable Quantities, Radionuclides for CAS6735-59-7 (U.S. Environmental Protection Agency, 2010):
- EPA RCRA Hazardous Waste Number for CAS6735-59-7 (U.S. Environmental Protection Agency, 2010b):
- EPA SARA Title III, Extremely Hazardous Substance List for CAS6735-59-7 (U.S. Environmental Protection Agency, 2010):
- EPA SARA Title III, Community Right-to-Know for CAS6735-59-7 (40 CFR 372.65, 2006; 40 CFR 372.28, 2006):
- DOT List of Marine Pollutants for CAS6735-59-7 (49 CFR 172.101 - App. B, 2005):
- EPA TSCA Inventory for CAS6735-59-7 (EPA, 2005):
LABELS
- NFPA Hazard Ratings for CAS6735-59-7 (NFPA, 2002):
-PERSONAL PROTECTION
SUMMARY
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
PROTECTIVE CLOTHING
- CHEMICAL PROTECTIVE CLOTHING. Search results for CAS 6735-59-7.
-PHYSICAL HAZARDS
FIRE HAZARD
- FLAMMABILITY CLASSIFICATION
- NFPA Flammability Rating for CAS6735-59-7 (NFPA, 2002):
- FIRE CONTROL/EXTINGUISHING AGENTS
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
- NFPA Extinguishing Methods for CAS6735-59-7 (NFPA, 2002):
EVACUATION PROCEDURES
- Editor's Note: An ERG guide with information appropriate to this material does not exist.
- AIHA ERPG Values for CAS6735-59-7 (AIHA, 2006):
- DOE TEEL Values for CAS6735-59-7 (U.S. Department of Energy, Office of Emergency Management, 2010):
- AEGL Values for CAS6735-59-7 (National Research Council, 2010; National Research Council, 2009; National Research Council, 2008; National Research Council, 2007; NRC, 2001; NRC, 2002; NRC, 2003; NRC, 2004; NRC, 2004; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2005; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2007; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2006; 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National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2009; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances, 2008; 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62 FR 58840, 1997; 65 FR 14186, 2000; 65 FR 39264, 2000; 65 FR 77866, 2000; 66 FR 21940, 2001; 67 FR 7164, 2002; 68 FR 42710, 2003; 69 FR 54144, 2004):
- NIOSH IDLH Values for CAS6735-59-7 (National Institute for Occupational Safety and Health, 2007):
CONTAINMENT/WASTE TREATMENT OPTIONS
-PHYSICAL/CHEMICAL PROPERTIES
MOLECULAR WEIGHT
- 172.6 (Prod Info PROTOPAM(R) CHLORIDE injection, 2006)
DESCRIPTION/PHYSICAL STATE
- Pralidoxime is an odorless, white, nonhygroscopic, crystalline powder which is soluble in water (Prod Info PROTOPAM(R) CHLORIDE injection, 2006).
-REFERENCES
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