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Pralidoxime

Editor: Mayur Parmar Updated: 5/1/2023 5:47:53 PM

Indications

Of the agents in the class of chemical compounds called oximes, pralidoxime (2-PAM), used in the United States, and obidoxime, used in a few European nations, are the primary drugs that find clinical use. P2S and HI-6 are also used in some parts of the world. These drugs were collectively developed in the 1950s with a vision to develop an antidote that could reverse the inhibition of acetylcholinesterase enzyme brought about by the exposure to organophosphate compounds.

Developed in Germany in the pre-WWII era, the initial intent for organophosphate compounds was for use as insecticides. However, it did not take long for these compounds to be weaponized, given how harmful they were due to their property of irreversibly inactivating the acetylcholinesterase enzyme. This usage of organophosphate compounds as pesticides and as weapons of mass destruction continues to this day, forming a basis for the FDA approved indications of drugs like pralidoxime:

  • Pralidoxime has approval as an antidote for nerve agent poisoning. Reports indicate that chemical weapons like sarin, tabun, soman, and cyclosarin were used in the 1980 Iran-Iraq war, the 1995 Tokyo subway attack, the Gulf war, and the 2013 Syrian civil war.[1][2]
  • Pralidoxime also has approval as an antidote for organophosphate-based pesticides. Today organophosphate-based pesticides are widely used in agriculture all over the world. Poor yield, drought, debt, and extreme working hours often drive farmers into depression.[3][4] Thus, easy access and cheap cost make organophosphate pesticides a pathway for committing suicide; this is especially rampant in primarily agriculture-based economies like that of many developing countries today. Lack of adequate education and protection also leads to a high incidence of accidental poisonings in this cohort. Instances of over-the-counter availability of these compounds coupled with their well-known notoriety as potent poisons have led to a high incidence of suicides using organophosphate compounds in the general population as well.[5] Annually, there are about a million reported cases of accidental organophosphate poisoning globally. The number of suicidal poisonings is almost double that, and the combined death toll exceeds 200,000.[6]
  • Pralidoxime has also received approval to manage an overdose of acetylcholinesterase drugs prescribed for myasthenia gravis and Alzheimer dementia.

A non-FDA approved but under-evaluation use for pralidoxime is:

  • Pralidoxime shows promise when used as a universal electrochemical marker to detect the type of compound organophosphate causing the poisoning.[7]

At present, there is some ambiguity regarding whether all organophosphate toxicity cases should receive oximes. The recommendation is for oximes to be administered within 48 hours in these cases. This is covered in greater detail in the Mechanism of Action section.

Mechanism of Action

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Mechanism of Action

Acetylcholinesterase enzyme is responsible for the hydrolysis of the neurotransmitter acetylcholine at the various muscarinic and nicotinic sites in the body and hence does not let it accumulate. This enzyme has a serine site and an anionic site on its molecule. The serine site lies within the enzyme's active site and is attacked by the organophosphate molecule; this leads to the phosphorylation of the serine site and the formation of a strong covalent bond inactivating the active site of the enzyme in the process. Unlike poisoning with carbamates, this interaction is irreversible.  

Pralidoxime is an acetylcholinesterase enzyme re-activator. It works by attaching to the anionic site of the enzyme. At this site, the pralidoxime molecule is close to the OP molecule. The pralidoxime molecule has a higher affinity to become phosphorylated by the OP compound than the serine site of the enzyme, leading to the pralidoxime molecule sacrificing itself by getting phosphorylated instead of the enzyme. The OP molecule detaches from the enzyme to do this, leading to two things. First is the formation of an organophosphate-pralidoxime complex, which quickly hydrolyzes. The second is restoring the active site of the acetylcholinesterase enzyme, making it available for action once again.[8]

Pralidoxime's primary action is restoring acetylcholinesterases at nicotinic sites in the body, relieving symptoms like muscle weakness, fasciculations, and paralysis. Although it has some muscarinic action as well, it is not clinically significant as that is well taken care of by the co-administration of atropine.[9]

Pralidoxime (2-PAM) also should be given to affect the nicotinic receptors in organophosphate toxicity since atropine only works on muscarinic receptors. Pralidoxime reactivates the phosphorylated AChE by binding to the organophosphate. However, to work, it must be given within 48 hours of the poisoning. The agent does not cause respiratory depression and can be combined with atropine. Evidence regarding the use of oximes to treat organophosphate poisoning is equivocal, and interpretation is challenging. Until this pharmacology is better elucidated and/or other treatments become available, all organophosphate toxicity patients should be treated with an oxime.[10][11]

The pressor action of pralidoxime is less clearly understood. Earlier the thought was that the stimulation of alpha-adrenergic receptors mediated this vasopressor effect, based on a study by Stavinoha et al. that demonstrated that alpha-adrenergic blockers like phentolamine effectively blocked the increase in systemic arterial pressure brought about by pralidoxime.This concept, however, was disproved by Carrier et al. when they showed that in an isolated aortic strip preparation, there was no effect of phentolamine on the response of the aorta when exposed to pralidoxime. They suggested that the intracellular alteration of calcium ion storage drives the cardiovascular effects of pralidoxime.[12]

Administration

Time of Administration

Pralidoxime and atropine administration should take place as soon as the patient is decontaminated, stabilized, and there is a provisional diagnosis of organophosphate poisoning. Earlier it was believed that pralidoxime is more or less ineffective after 24 to 48 hours of exposure. The reason for this is the phenomenon of aging.[13] Aging refers to the dealkylation of the phosphorylated enzyme, leading to the electrons shuffling in a way that further strengthens the covalent bond between the OP and the acetylcholine enzyme to the point that even pralidoxime is unable to reactivate the enzyme. The extent and rate of aging depend on the characteristics of the given compound, but as a rule of thumb, weaponized organophosphates are expected to age very quickly and are therefore extremely dangerous. For example, the half-life of an acetylcholinesterase molecule exposed to nerve agent soman can be as low as 1.3 minutes.  

Recent studies, however, have shown that a delayed administration of pralidoxime may still be beneficial due to instances of prolonged absorption of the compound or high lipid solubility. OP compounds like fenthion and fenitrothion are notorious for the same. Sometimes it is a metabolite of the original OP compound that is toxic. All these factors form the rationale for the late administration of pralidoxime.[14]

Dose

Traditionally, the recommended dosage of pralidoxime has been 1 to 2 g in 100 mL saline as an intravenous infusion over 15 to 30 minutes. The same can be repeated after 1 hour if the nicotinic symptoms like muscle fasciculations persist. Additional doses require caution. Recent updates dictate that pralidoxime should be administered intravenously at 30 mg/kg initially over 30 min, followed by a constant infusion of 8 mg/kg/hr in dextrose 5% solution.[15] This sequence can continue either until all the nicotinic symptoms of OP poisoning resolve or until atropine is no longer needed.[5]

However, even the upper limits of these WHO-recommended dosage regimes have been questioned by several clinicians.[16][17] A study conducted by Pawar et al. demonstrated that a higher dosage regime than the one recommended by WHO is more beneficial. Also, this study sheds light on the advantage of continuous infusion of pralidoxime over repeated boluses.[18] The limitations of this study were that it did not include severely poisoned patients and took place in a relatively well-equipped hospital.

Route of Administration

Besides the intravenous route mentioned above, pralidoxime can also be administered via the intramuscular route. An autoinjector is now available that combines it with atropine and diazepam. Drug delivery using an autoinjector has shown to be better than using a needle and syringe—this autoinjector co-administers pralidoxime and atropine. The synergism of pralidoxime with atropine has been described later under drug interactions. Militaries worldwide now issue these autoinjectors to their soldiers for quick administration in the event of a nerve agent attack.[19]

The intraosseous route of administration of pralidoxime has been explored in recent years. Studies have shown that utilizing this route can reduce the time required to reach therapeutic plasma concentrations by more than eight times.[20]

A recent novel breakthrough utilizing an infusion micropump for delivery of pralidoxime has shown better results than the traditional routes.[21]

Administration in Pediatric, Pregnant/Nursing Females and Geriatric Age Group

Studies have shown minimal or no adverse effects when using the pralidoxime-atropine autoinjector in children as young as 15 months, but only atropine is recommended for children under one year of age.[22][23] The doses used for children are recommended to be comparable to that of adults and have been well-tolerated.[24]

Data regarding the use of oximes in pregnant and nursing females is scanty and inconclusive.[25]

Studies highlighting dosages in the geriatric age group are also sparse. The clinician must weigh the potential benefits and harms before deciding on the course of therapy. Co-morbidities like renal insufficiency merit consideration. 

Adverse Effects

  • Adverse effects of pralidoxime iodide in healthy volunteers included blurred vision, diplopia, dizziness, impaired accommodation, headache, and nausea.[26] Other rare side effects may be tachycardia, raised blood pressure, and hyperventilation. However, these adverse effects are difficult to discern in patients with OP poisoning as similar symptoms occur in patients not treated with pralidoxime. Atropine has a similar adverse event profile as well, and it is almost always co-administered in OP poisoning, making it even more challenging to pin down the actual cause.
  • If pralidoxime iodide is used instead of pralidoxime chloride, large doses require careful administration as excess iodine can lead to thyroid toxicity.[27]
  • The loading dose of oxime should be given slowly as a bolus because a rapid infusion can cause tachycardia, diastolic hypertension, vomiting, and aspiration.[8]
  • Administering pralidoxime in a patient with myasthenia gravis may precipitate a myasthenic crisis. Vigilance is necessary.

Contraindications

  • For a long time, pralidoxime has been strictly contraindicated in managing carbamate-induced toxicity. This limitation was primarily because the studies conducted with one particular carbamate, carbaryl, showed poor outcomes.[28][29] The results were then extrapolated to other carbamates as well. However, case reports and clinical trials with other carbamates like neostigmine, rivastigmine, methomyl, and aldicarb have shown favorable outcomes when treated with pralidoxime.[28][30][31][32] Thus, carbaryl remains the only contraindication among carbamates. 
  • In all other instances, pralidoxime should be contraindicated if there is a history of prior drug allergy upon exposure.

Monitoring

Pharmacokinetics

It has been well established that a minimum plasma concentration of 4mg/L of pralidoxime is necessary to protect the acetylcholinesterase enzyme against OP compounds.[33] With the traditional dosing technique of giving a 1 g  bolus of the drug over 15 to 30 minutes, computer simulations have shown that the plasma concentration will fall below therapeutic levels in as little as 1.5 hours. However, a randomized, cross-over design trial conducted on healthy volunteers proved that a loading dose followed by a continuous infusion of 9 to 19 mg/kg/hr is more effective in maintaining the required plasma levels.[34] Moreover, all the volunteers subjected to the short infusion regime showed adverse effects like blurred vision and dizziness.

Pralidoxime distributes evenly in the body's fluid compartments and has not been shown to bind to either hemoglobin or plasma proteins[8]. Pralidoxime is a quaternary ammonium oxime and is therefore not expected to cross the blood-brain barrier.

Absorption

When given via the intramuscular route, pralidoxime shows zero-order kinetics. However, co-administration with avizafone and atropine accelerates the absorption of the drug due to modified blood flow at the injection site to the point that the best mechanical model applicable for this process shifts to first-order kinetics.[19]

Elimination

Sidell et al. determined that the kidneys actively secrete pralidoxime in its original form without undergoing any significant metabolism. Most of the excretion is via urine and feces.[35] Thus, it is advisable to adjust the dose of pralidoxime in patients with a reduced renal function as its plasma clearance becomes markedly reduced.

Drug Interactions

Pralidoxime has no known deleterious drug interactions. There is positive evidence suggesting its synergism when co-administered with atropine. On the one hand, pralidoxime was detected in the plasma earlier and in higher concentrations when given along with atropine and avizafone. On the other hand, the signs of atropinization also occurred earlier than expected when given alone. This synergy is the rationale behind including these drugs together in the auto-injector.[19][36]

Toxicity

Pralidoxime is a relatively nontoxic drug, and instances of its toxicity are rare. In healthy volunteers, dizziness, diplopia, headache, tachycardia, and blurred vision may occur in the event of an overdose. These symptoms, however, are difficult to discern in a patient with organophosphate poisoning. Supportive therapy is sufficient to treat pralidoxime toxicity.  

Enhancing Healthcare Team Outcomes

Time is the golden resource in managing a case of organophosphate poisoning. It is, therefore, imperative to make a provisional diagnosis as early as possible by assessing the relevant clues from history like occupation, history of clinical depression and prior suicide attempts, and the typical smell of pesticides from clothes. Timely diagnosis and rapid initiation of treatment require flawless interprofessional teamwork and communication and coordination between an emergency department clinician, anesthesiologist, intensivist, nurse practitioner, poison control center, pharmacists and nursing staff, and other specialists depending on the particular organ system involved. Each area must be able to provide input on the case and contribute from their area of expertise.

This process can be streamlined by equipping the hospitals in high incidence areas with the necessary drugs and supportive equipment, including adequate protection for doctors themselves. Specialized training and drills for tackling hazards like a chemical attack are essential at regular intervals. In instances where significant time has elapsed since the exposure, aging should be assumed. The intensive care unit must be alerted without delay, but pralidoxime administration is still recommended due to the reasons mentioned above. Interprofessional care coordination and information sharing are crucial to success in OP poisoning and optimizing pralidoxime therapy, driving improved patient outcomes. [Level 5]

Meanwhile, efforts can be directed at reducing the incidence of organophosphate poisoning by educating farmers about the toxic nature of these compounds and the proper safety measures necessary while using these chemicals. Highly toxic pesticides, like chlorpyrifos, should be banned. The psychiatry team also holds an important place in the management as patients with a history of depression and prior suicide attempts must be counseled aggressively.

In recent years several randomized control trials and meta-analyses have questioned the advantage of the addition of pralidoxime over atropine alone in the management of OP poisoning.[37][38] [Level 1] But these trials have some limitations like lack of inclusion of factors such as the patient's age, comorbidities, intoxication severity, regional variability of the type of organophosphate compound available, and time since exposure. The dosage of pralidoxime used was also not fixed.

With hundreds of thousands of fatalities each year, the socioeconomic impact of organophosphate poisoning cannot be ignored. Until the shortcomings mentioned above are addressed in future studies, and until we have unequivocal evidence that pralidoxime is ineffective, we must continue to include it in the current therapeutic regimen.

References


[1]

Okumura T, Hisaoka T, Yamada A, Naito T, Isonuma H, Okumura S, Miura K, Sakurada M, Maekawa H, Ishimatsu S, Takasu N, Suzuki K. The Tokyo subway sarin attack--lessons learned. Toxicology and applied pharmacology. 2005 Sep 1:207(2 Suppl):471-6     [PubMed PMID: 15979676]


[2]

Pohanka M. [Cholinesterase activity assays and their use in the diagnosis of various pathological states including poisoning by neurotoxic agents]. Ceska a Slovenska farmacie : casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti. 2017 Summer:66(4):147-153     [PubMed PMID: 29351376]


[3]

Viswanathan DJ, Veerakumar AM, Kumarasamy H. Depression, Suicidal Ideation, and Resilience among Rural Farmers in a Drought-Affected Area of Trichy District, Tamil Nadu. Journal of neurosciences in rural practice. 2019 Apr-Jun:10(2):238-244. doi: 10.4103/jnrp.jnrp_257_18. Epub     [PubMed PMID: 31001011]


[4]

Hawes NJ, Wiggins AT, Reed DB, Hardin-Fanning F. Poor sleep quality is associated with obesity and depression in farmers. Public health nursing (Boston, Mass.). 2019 May:36(3):270-275. doi: 10.1111/phn.12587. Epub 2019 Feb 13     [PubMed PMID: 30761585]

Level 2 (mid-level) evidence

[5]

Syed S, Gurcoo SA, Farooqui AK, Nisa W, Sofi K, Wani TM. Is the World Health Organization-recommended dose of pralidoxime effective in the treatment of organophosphorus poisoning? A randomized, double-blinded and placebo-controlled trial. Saudi journal of anaesthesia. 2015 Jan:9(1):49-54. doi: 10.4103/1658-354X.146306. Epub     [PubMed PMID: 25558199]

Level 1 (high-level) evidence

[6]

Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet (London, England). 2008 Feb 16:371(9612):597-607     [PubMed PMID: 17706760]


[7]

Zheng Q, Chen Y, Fan K, Wu J, Ying Y. Exploring pralidoxime chloride as a universal electrochemical probe for organophosphorus pesticides detection. Analytica chimica acta. 2017 Aug 22:982():78-83. doi: 10.1016/j.aca.2017.06.006. Epub 2017 Jun 17     [PubMed PMID: 28734368]


[8]

Eyer P. The role of oximes in the management of organophosphorus pesticide poisoning. Toxicological reviews. 2003:22(3):165-90     [PubMed PMID: 15181665]

Level 3 (low-level) evidence

[9]

Tush GM, Anstead MI. Pralidoxime continuous infusion in the treatment of organophosphate poisoning. The Annals of pharmacotherapy. 1997 Apr:31(4):441-4     [PubMed PMID: 9101007]

Level 3 (low-level) evidence

[10]

Thiermann H, Worek F. Pro: Oximes should be used routinely in organophosphate poisoning. British journal of clinical pharmacology. 2022 Dec:88(12):5064-5069. doi: 10.1111/bcp.15215. Epub 2022 Feb 7     [PubMed PMID: 35023196]


[11]

Robb EL, Baker MB. Organophosphate Toxicity. StatPearls. 2023 Jan:():     [PubMed PMID: 29261901]


[12]

Jung YH, Ryu DH, Jeung KW, Na JY, Lee DH, Lee BK, Heo T, Min YI. Effect of pralidoxime on coronary perfusion pressure during cardiopulmonary resuscitation in a pig model. Clinical and experimental emergency medicine. 2019 Sep:6(3):204-211. doi: 10.15441/ceem.18.036. Epub 2019 May 7     [PubMed PMID: 31036784]


[13]

Marrs TC, Rice P, Vale JA. The role of oximes in the treatment of nerve agent poisoning in civilian casualties. Toxicological reviews. 2006:25(4):297-323     [PubMed PMID: 17288500]


[14]

Burillo-Putze G, Hoffman RS, Howland MA, Duenas-Laita A. Late administration of pralidoxime in organophosphate (fenitrothion) poisoning. The American journal of emergency medicine. 2004 Jul:22(4):327-8     [PubMed PMID: 15258887]

Level 3 (low-level) evidence

[15]

Buckley NA, Eddleston M, Li Y, Bevan M, Robertson J. Oximes for acute organophosphate pesticide poisoning. The Cochrane database of systematic reviews. 2011 Feb 16:(2):CD005085. doi: 10.1002/14651858.CD005085.pub2. Epub 2011 Feb 16     [PubMed PMID: 21328273]

Level 1 (high-level) evidence

[16]

de Silva HJ, Wijewickrema R, Senanayake N. Does pralidoxime affect outcome of management in acute organophosphorus poisoning? Lancet (London, England). 1992 May 9:339(8802):1136-8     [PubMed PMID: 1349368]

Level 1 (high-level) evidence

[17]

Peter JV, Cherian AM. Organic insecticides. Anaesthesia and intensive care. 2000 Feb:28(1):11-21     [PubMed PMID: 10701030]


[18]

Pawar KS, Bhoite RR, Pillay CP, Chavan SC, Malshikare DS, Garad SG. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet (London, England). 2006 Dec 16:368(9553):2136-41     [PubMed PMID: 17174705]

Level 1 (high-level) evidence

[19]

Abbara C, Rousseau JM, Lelièvre B, Turcant A, Lallement G, Ferec S, Bardot I, Diquet B. Pharmacokinetic analysis of pralidoxime after its intramuscular injection alone or in combination with atropine-avizafone in healthy volunteers. British journal of pharmacology. 2010 Dec:161(8):1857-67. doi: 10.1111/j.1476-5381.2010.01007.x. Epub     [PubMed PMID: 20804498]

Level 1 (high-level) evidence

[20]

Uwaydah NI, Hoskins SL, Bruttig SP, Farrar H, Copper NC, Deyo DJ, Dubick MA, Kramer GC. Intramuscular versus Intraosseous Delivery of Nerve Agent Antidote Pralidoxime Chloride in Swine. Prehospital emergency care. 2016 Jul-Aug:20(4):485-92. doi: 10.3109/10903127.2014.942479. Epub 2016 May 9     [PubMed PMID: 27158860]


[21]

Liu HX, Liu CF, Yang WH. Clinical study of continuous micropump infusion of atropine and pralidoxime chloride for treatment of severe acute organophosphorus insecticide poisoning. Journal of the Chinese Medical Association : JCMA. 2015 Dec:78(12):709-13. doi: 10.1016/j.jcma.2015.08.006. Epub 2015 Oct 3     [PubMed PMID: 26441220]


[22]

Baker MD. Antidotes for nerve agent poisoning: should we differentiate children from adults? Current opinion in pediatrics. 2007 Apr:19(2):211-5     [PubMed PMID: 17496768]

Level 3 (low-level) evidence

[23]

Quail MT, Shannon MW. Pralidoxime safety and toxicity in children. Prehospital emergency care. 2007 Jan-Mar:11(1):36-41     [PubMed PMID: 17169874]


[24]

Foltin G, Tunik M, Curran J, Marshall L, Bove J, van Amerongen R, Cherson A, Langsam Y, Kaufman B, Asaeda G, Gonzalez D, Cooper A. Pediatric nerve agent poisoning: medical and operational considerations for emergency medical services in a large American city. Pediatric emergency care. 2006 Apr:22(4):239-44     [PubMed PMID: 16651913]


[25]

Nurulain SM, Kornelia T, Naqvi SN, Sharma C, Ojha S, Adem A. Oxime-type acetylcholinesterase reactivators in pregnancy: an overview. Archives of toxicology. 2014 Mar:88(3):575-84. doi: 10.1007/s00204-013-1160-z. Epub 2013 Nov 21     [PubMed PMID: 24258240]

Level 3 (low-level) evidence

[26]

Jokanović M, Prostran M. Pyridinium oximes as cholinesterase reactivators. Structure-activity relationship and efficacy in the treatment of poisoning with organophosphorus compounds. Current medicinal chemistry. 2009:16(17):2177-88     [PubMed PMID: 19519385]

Level 3 (low-level) evidence

[27]

Eyer P, Buckley N. Pralidoxime for organophosphate poisoning. Lancet (London, England). 2006 Dec 16:368(9553):2110-1     [PubMed PMID: 17174692]


[28]

Natoff IL, Reiff B. Effect of oximes on the acute toxicity of anticholinesterase carbamates. Toxicology and applied pharmacology. 1973 Aug:25(4):569-75     [PubMed PMID: 4741778]

Level 3 (low-level) evidence

[29]

Kurtz PH. Pralidoxime in the treatment of carbamate intoxication. The American journal of emergency medicine. 1990 Jan:8(1):68-70     [PubMed PMID: 2403479]


[30]

Hoffman RS, Manini AF, Russell-Haders AL, Felberbaum M, Mercurio-Zappala M. Use of pralidoxime without atropine in rivastigmine (carbamate) toxicity. Human & experimental toxicology. 2009 Sep:28(9):599-602. doi: 10.1177/0960327109107044. Epub 2009 Sep 15     [PubMed PMID: 19755437]

Level 3 (low-level) evidence

[31]

Ekins BR, Geller RJ. Methomyl-induced carbamate poisoning treated with pralidoxime chloride. The Western journal of medicine. 1994 Jul:161(1):68-70     [PubMed PMID: 7941519]

Level 3 (low-level) evidence

[32]

Burgess JL, Bernstein JN, Hurlbut K. Aldicarb poisoning. A case report with prolonged cholinesterase inhibition and improvement after pralidoxime therapy. Archives of internal medicine. 1994 Jan 24:154(2):221-4     [PubMed PMID: 8285817]

Level 3 (low-level) evidence

[33]

HOLMES R, ROBINS EL. The reversal by oximes of neuromuscular block produced by anticholinesterases. British journal of pharmacology and chemotherapy. 1955 Dec:10(4):490-5     [PubMed PMID: 13276609]


[34]

Medicis JJ, Stork CM, Howland MA, Hoffman RS, Goldfrank LR. Pharmacokinetics following a loading plus a continuous infusion of pralidoxime compared with the traditional short infusion regimen in human volunteers. Journal of toxicology. Clinical toxicology. 1996:34(3):289-95     [PubMed PMID: 8667466]

Level 1 (high-level) evidence

[35]

Sidell FR, Groff WA, Ellin RI. Blood levels of oxime and symptoms in humans after single and multiple oral doses of 2-pyridine aldoxime methochloride. Journal of pharmaceutical sciences. 1969 Sep:58(9):1093-8     [PubMed PMID: 5346072]


[36]

Namba T, Nolte CT, Jackrel J, Grob D. Poisoning due to organophosphate insecticides. Acute and chronic manifestations. The American journal of medicine. 1971 Apr:50(4):475-92     [PubMed PMID: 4324629]


[37]

Kharel H, Pokhrel NB, Ghimire R, Kharel Z. The Efficacy of Pralidoxime in the Treatment of Organophosphate Poisoning in Humans: A Systematic Review and Meta-analysis of Randomized Trials. Cureus. 2020 Mar 4:12(3):e7174. doi: 10.7759/cureus.7174. Epub 2020 Mar 4     [PubMed PMID: 32257715]

Level 1 (high-level) evidence

[38]

Eddleston M, Eyer P, Worek F, Juszczak E, Alder N, Mohamed F, Senarathna L, Hittarage A, Azher S, Jeganathan K, Jayamanne S, von Meyer L, Dawson AH, Sheriff MH, Buckley NA. Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial. PLoS medicine. 2009 Jun 30:6(6):e1000104. doi: 10.1371/journal.pmed.1000104. Epub 2009 Jun 30     [PubMed PMID: 19564902]

Level 1 (high-level) evidence