Are Oximes Still Indicated for Acute Organophosphorus Insecticide Self-Poisoning?

Eddleston, Michael

doi:10.1007/s13181-018-0651-y

Cited by 9 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Systematic reviews of clinical trials of pralidoxime, including high-dose regimens (infusions of 0.5 g/h after a loading dose), compared with placebo support the idea that it does not prevent death or intubation (Tables 1 and 2) or shorten the duration of ventilation (87,88). Of note, several of these studies included high-dose infusions for up to 7 days without benefit (89), indicating that inadequate dosing (81,86) is not responsible for the lack of effect. The lack of efficacy may be due to the very large doses of OP insecticide ingested during self-harm.…”

Section: Oximesmentioning

confidence: 99%

Novel Clinical Toxicology and Pharmacology of Organophosphorus Insecticide Self-Poisoning

Eddleston

2019

Annu. Rev. Pharmacol. Toxicol.

Self Cite

104

View full text Add to dashboard Cite

Organophosphorus insecticide self-poisoning is a major global health problem, killing over 100,000 people annually. It is a complex multi-organ condition, involving the inhibition of cholinesterases, and perhaps other enzymes, and the effects of large doses of ingested solvents. Variability between organophosphorus insecticides-in lipophilicity, speed of activation, speed and potency of acetylcholinesterase inhibition, and in the chemical groups attached to the phosphorus-results in variable speed of poisoning onset, severity, clinical toxidrome, and case fatality. Current treatment is modestly effective, aiming only to reactivate acetylcholinesterase and counter the effects of excess acetylcholine at muscarinic receptors. Rapid titration of atropine during resuscitation is lifesaving and can be performed in the absence of oxygen. The role of oximes in therapy remains unclear. Novel antidotes have been tested in small trials, but the great variability in poisoning makes interpretation of such trials difficult. More effort is required to test treatments in adequately powered studies. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

show abstract

Section: Oximesmentioning

confidence: 99%

Novel Clinical Toxicology and Pharmacology of Organophosphorus Insecticide Self-Poisoning

Eddleston

2019

Annu. Rev. Pharmacol. Toxicol.

Self Cite

104

View full text Add to dashboard Cite

show abstract

“…The proper interpretation of the origin and significance of markers of tissue damage such as increased levels of C-reactive protein, fibrinogen, lactate, amylase [ 165 ] or serum troponin level and other markers of cardiac damage [ 166 ] in combination with hypoalbuminemia is of crucial importance in guiding treatment of the “secondary” effects of acute AOPP ( Figure 1 ) if we wish to improve survival in such patients [ 167 , 168 , 169 , 170 ] after decades of therapeutic stagnation [ 171 , 172 , 173 ].…”

Section: Acetylcholinesterase and Albumin Measurement: Importance For...mentioning

confidence: 99%

Organophosphorus Poisoning: Acute Respiratory Distress Syndrome (ARDS) and Cardiac Failure as Cause of Death in Hospitalized Patients

Ramadori

2023

IJMS

View full text Add to dashboard Cite

Industrial production of food for animals and humans needs increasing amounts of pesticides, especially of organophosphates, which are now easily available worldwide. More than 3 million cases of acute severe poisoning are estimated to occur worldwide every year, and even more cases remain unreported, while 200,000–350,000 incidentally or intentionally poisoned people die every year. Diagnostic and therapeutic procedures in organophosphate poisoning have, however, remained unchanged. In addition to several neurologic symptoms (miosis, fasciculations), hypersecretion of salivary, bronchial, and sweat glands, vomiting, diarrhea, and loss of urine rapidly induce dehydration, hypovolemia, loss of conscience and respiratory distress. Within hours, signs of acidosis due to systemic hypoxia can be observed at first laboratory investigation after hospitalization. While determination of serum-cholinesterase does not have any diagnostic value, it has been established that hypoalbuminemia alone or accompanied by an increase in creatinine, lactate, or C-reactive protein serum levels has negative prognostic value. Increased serum levels of C-reactive protein are a sign of systemic ischemia. Protective mechanical ventilation should be avoided, if possible. In fact, acute respiratory distress syndrome characterized by congestion and increased weight of the lung, accompanied by heart failure, may become the cause of death. As the excess of acetylcholine at the neuronal level can persist for weeks until enough newly, locally synthesized acetylcholinesterase becomes available (the value of oximes in reducing this time is still under debate), after atropine administration, intravenous albumin and fluid infusion should be the first therapeutic interventions to reestablish normal blood volume and normal tissue oxygenation, avoiding death by cardiac arrest.

show abstract

“…The most important application of oximes is their ability to treat OP poisoning by the reactivation of acetylcholinesterase, which is inactivated by the OPs that form the dimethyl-or diethylphosphoryl-acetylcholinesterase complex [24,46]. The current known organophosphates that are used as nerve poisons include sarin, cyclosarin, tabun, VX, Russian VX, Chinese VX, soman and novichok (Figure 5) [47][48][49][50].…”

Section: Oximes As Organophosphate (Op) Poisoning Antidotesmentioning

confidence: 99%

“…The 7-ACA intermediate (34) is obtained by the esterification of intermediate (44) in an aqueous solution of methyl acetate. The resulting intermediate (34) is coupled with the tetrazole intermediate (46), in the presence of boron trifluoride to obtain the intermediate 47, which is subsequently treated with intermediate 43 in the final step to afford the desired compound cefmenoxime. Scheme 6.…”

Section: Cefmenoximementioning

confidence: 99%

FDA-Approved Oximes and Their Significance in Medicinal Chemistry

2022

View full text Add to dashboard Cite

Despite the scientific advancements, organophosphate (OP) poisoning continues to be a major threat to humans, accounting for nearly one million poisoning cases every year leading to at least 20,000 deaths worldwide. Oximes represent the most important class in medicinal chemistry, renowned for their widespread applications as OP antidotes, drugs and intermediates for the synthesis of several pharmacological derivatives. Common oxime based reactivators or nerve antidotes include pralidoxime, obidoxime, HI-6, trimedoxime and methoxime, among which pralidoxime is the only FDA-approved drug. Cephalosporins are β-lactam based antibiotics and serve as widely acclaimed tools in fighting bacterial infections. Oxime based cephalosporins have emerged as an important class of drugs with improved efficacy and a broad spectrum of anti-microbial activity against Gram-positive and Gram-negative pathogens. Among the several oxime based derivatives, cefuroxime, ceftizoxime, cefpodoxime and cefmenoxime are the FDA approved oxime-based antibiotics. Given the pharmacological significance of oximes, in the present paper, we put together all the FDA-approved oximes and discuss their mechanism of action, pharmacokinetics and synthesis.

show abstract

Are Oximes Still Indicated for Acute Organophosphorus Insecticide Self-Poisoning?

Cited by 9 publications

References 24 publications

Novel Clinical Toxicology and Pharmacology of Organophosphorus Insecticide Self-Poisoning

Novel Clinical Toxicology and Pharmacology of Organophosphorus Insecticide Self-Poisoning

Organophosphorus Poisoning: Acute Respiratory Distress Syndrome (ARDS) and Cardiac Failure as Cause of Death in Hospitalized Patients

FDA-Approved Oximes and Their Significance in Medicinal Chemistry

Contact Info

Product

Resources

About