-
Toxins Nov 2023In a few regions of the globe, deliberate botanical intoxication may induce significant rates of toxicity and fatality. The objective of this report was to describe... (Review)
Review
INTRODUCTION
In a few regions of the globe, deliberate botanical intoxication may induce significant rates of toxicity and fatality. The objective of this report was to describe plant self-intoxication using the experiences of the southeastern France poison control center (PCC) between 2002 and 2021.
RESULTS
During those 20 years, 262 deliberate plants poisonings were reported involving 35 various plants. In most of the cases, poisoning was caused by (n = 186, 71%), followed by the genus (4.2%), (3.8%), (1.9%), (1.2%), (1.9%), (1.5%), and (1.2%). Through the 262 plants poisonings, 19 patients among the 186 poisonings received Digifab as an antidote and 1 patient received physostigmine among the 11 Datura poisonings. Only four deaths were reported for this review, each involving .
DISCUSSION
The first involved species was (71% of all plants poisonings), then sp and . It is explained by this native local species' important repartition. Most patients must be admitted to an emergency department for adapted medical care; however, only 41 of them described severe poisonings symptoms. Even fewer needed an antidote, only 20 patients. There is no protocol for the use of a specific treatment, and it might be interesting to develop one for this purpose.
MATERIAL AND METHODS
This retrospective review was realized with files managed by the southeastern France PCC based in Marseille from 2002 to 2021. Our department covers the complete French Mediterranean coast, Corsica, and tropical islands (Reunion Island, Mayotte). For every patient, toxicity was evaluated using the Poison Severity Score (PSS).
Topics: Humans; Antidotes; France; Plant Poisoning; Poisons; Suicide, Attempted
PubMed: 38133175
DOI: 10.3390/toxins15120671 -
British Journal of Pharmacology Jun 2016In cases of organophosphate poisoning, patients are treated with a combination of antidotes. In addition to these poison-directed antidotes, patients may require extra... (Review)
Review
In cases of organophosphate poisoning, patients are treated with a combination of antidotes. In addition to these poison-directed antidotes, patients may require extra oxygen and artificial ventilation; other modalities may also be needed due to the wide range of toxic effects. Anisodamine is a belladonna alkaloid, and like other drugs from this family is non subtype-selective muscarinic, and a nicotinic cholinoceptor antagonist, which has been employed in traditional Chinese medicine. As a muscarinic antagonist, it displays similar pharmacological effects to atropine and scopolamine. However, anisodamine is not only less potent than atropine and scopolamine but also less toxic. Current in vitro and animal model studies have demonstrated that anisodamine has protective effects in a variety of diseases. Organophosphate poisoning involves not only the central and peripheral nervous systems, but also the cardiac and respiratory systems, as well as activation of inflammatory processes and oxidative stress. Therefore, the anticholinergic and additional activities of anisodamine appear to be relevant and justify its consideration as an addition to the existing remedies. However, more research is needed, as at present data on the role of anisodamine in the management of organophosphate poisoning are limited. Here, we review the beneficial effects of anisodamine on processes relevant to organophosphate poisoning.
Topics: Animals; Antidotes; Humans; Organophosphate Poisoning; Solanaceous Alkaloids
PubMed: 27010563
DOI: 10.1111/bph.13486 -
Spotlight on idarucizumab and its potential for the reversal of anticoagulant effects of dabigatran.Drug Design, Development and Therapy 2016Idarucizumab is the first targeted antidote of dabigatran, a direct oral anticoagulant used for prevention and treatment of venous thromboembolism and prevention of... (Review)
Review
Idarucizumab is the first targeted antidote of dabigatran, a direct oral anticoagulant used for prevention and treatment of venous thromboembolism and prevention of stroke in atrial fibrillation. Idarucizumab is a humanized fragment of a monoclonal antibody, which binds dabigatran reversibly with high affinity and, when administered intravenously, immediately neutralizes its anticoagulant effect. It is rapidly cleared by the kidney with captured dabigatran. In Phase I and II trials, no significant adverse events have been reported. Specifically, idarucizumab has no anticoagulant or procoagulant effect by itself. Idarucizumab is currently being evaluated in an ongoing Phase III trial, in patients treated with dabigatran presenting with severe active bleeding or requiring emergency surgery or an invasive procedure and are at high risk of bleeding. The results of the interim analysis confirm the ability of idarucizumab to neutralize dabigatran instantaneously, without rebound effect, except in rare patients with very high baseline levels of anticoagulant. Although not definitely proving clinical efficacy, due to the noncontrolled design of the trial and the heterogeneity of patient conditions, these promising results on an intermediate criterion with strong rationale have led to the approval of idarucizumab for these indications. However, several questions are unresolved. First, activity measurement of dabigatran in blood, useless in current practice, could be useful to guide the treatment and avoid over- or underutilization of the antidote; but so far, it has not been largely available in real time. Second, the translation of anticoagulant neutralization to an effect on mortality and better outcome is highly dependent on the global management of these patients, especially rapid diagnosis, supportive care, and easy access to antidote administration. Although idarucizumab represents a remarkable achievement in drug design and development, whether it will be an important step toward improved safety of patients treated with dabigatran in the real world will have to be demonstrated in the postmarketing phase.
Topics: Administration, Intravenous; Administration, Oral; Animals; Antibodies, Monoclonal, Humanized; Antidotes; Antithrombins; Blood Coagulation; Blood Coagulation Tests; Blood Loss, Surgical; Dabigatran; Drug Monitoring; Hemorrhage; Humans; Postoperative Hemorrhage; Risk Factors; Treatment Outcome
PubMed: 27274201
DOI: 10.2147/DDDT.S94167 -
Internal and Emergency Medicine Oct 2022Colchicine is a tricyclic, lipid-soluble alkaloid which has long been used to treat gout and many immunological diseases. Due to its narrow therapeutic window and long... (Review)
Review
Colchicine is a tricyclic, lipid-soluble alkaloid which has long been used to treat gout and many immunological diseases. Due to its narrow therapeutic window and long half-life of elimination, colchicine overdose occurs occasionally. Unfortunately, some patients lost their lives because of colchicine overdose or suicide. Acute colchicine poisoning can lead to original gastrointestinal disorders, shock, progressive multiple organ failure, and myelosuppression. Although many researchers in the world performed lots of research, there are currently no specific antidotes for colchicine poisoning. Meanwhile, there are no management guidelines to treat patients with acute colchicine poisoning until now. Herein, we systematically elaborate on the clinical features and progress in the management of acute colchicine poisoning in adults according to the previous literature. This paper will provide some valuable and available information for clinicians.
Topics: Adult; Antidotes; Colchicine; Humans; Lipids; Multiple Organ Failure; Poisoning; Suicide
PubMed: 36028733
DOI: 10.1007/s11739-022-03079-6 -
British Journal of Clinical Pharmacology Mar 2016Sometimes mistakenly characterized as a 'universal antidote,' activated charcoal (AC) is the most frequently employed method of gastrointestinal decontamination in the... (Review)
Review
Sometimes mistakenly characterized as a 'universal antidote,' activated charcoal (AC) is the most frequently employed method of gastrointestinal decontamination in the developed world. Typically administered as a single dose (SDAC), its tremendous surface area permits the binding of many drugs and toxins in the gastrointestinal lumen, reducing their systemic absorption. Like other decontamination procedures, the utility of SDAC attenuates with time, and, although generally safe, it is not free of risk. A large body of evidence demonstrates that SDAC can reduce the absorption of drugs and xenobiotics but most such studies involve volunteers and have little generalizability to clinical practice. Few rigorous clinical trials of SDAC have been conducted, and none validate or refute its utility in those patients who are intuitively most likely to benefit. Over the past decade, a growing body of observational data have demonstrated that SDAC can elicit substantial reductions in drug absorption in acutely poisoned patients. The challenge for clinicians rests in differentiating those patients most likely to benefit from SDAC from those in whom meaningful improvement is doubtful. This is often a difficult determination not well suited to an algorithmic approach. The present narrative review summarizes the data supporting the benefits and harms of SDAC, and offers pragmatic suggestions for clinical practice.
Topics: Animals; Antidotes; Charcoal; Drug Overdose; Humans; Time Factors
PubMed: 26409027
DOI: 10.1111/bcp.12793 -
Annual Review of Pharmacology and... Jan 2019Organophosphorus insecticide self-poisoning is a major global health problem, killing over 100,000 people annually. It is a complex multi-organ condition, involving the... (Review)
Review
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.
Topics: Animals; Antidotes; Humans; Insecticides; Organophosphate Poisoning; Organophosphorus Compounds
PubMed: 30230960
DOI: 10.1146/annurev-pharmtox-010818-021842 -
Clinical and Applied... Mar 2015Anticoagulants have been used in clinical practice for more than 50 years. Their indications expand, as more people are diagnosed each year with atrial fibrillation and... (Review)
Review
Anticoagulants have been used in clinical practice for more than 50 years. Their indications expand, as more people are diagnosed each year with atrial fibrillation and venous thromboembolism. Vitamin K antagonists have been the most popular choice due to their effectiveness and their ability to reverse bleeding using a known antidote; oral and intravenous vitamin K have long been known to reverse the effects of warfarin. With new classes of anticoagulants making their way onto the market, such as factor Xa inhibitors (rivaroxaban, apixaban) and direct thrombin inhibitors (dabigatran), the need for new reversal agents is paramount. Patients tend to be more receptive to these medications because they do not require routine blood monitoring, can be used at fixed doses, and do not have major drug or food interactions. Antidotes for these medications have shown promise in animal models and are currently in clinical trials.
Topics: Administration, Oral; Antidotes; Factor Xa Inhibitors; Hemorrhage; Humans
PubMed: 25115762
DOI: 10.1177/1076029614545211 -
Nature Communications Dec 2023Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in...
Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in eukaryotes, the molecular mechanisms behind their selfish behavior are poorly understood. In several fission yeast species, single-gene KMDs belonging to the wtf gene family exert selfish killing by expressing a toxin and an antidote through alternative transcription initiation. Here we investigate how the toxin and antidote products of a wtf-family KMD gene can act antagonistically. Both the toxin and the antidote are multi-transmembrane proteins, differing only in their N-terminal cytosolic tails. We find that the antidote employs PY motifs (Leu/Pro-Pro-X-Tyr) in its N-terminal cytosolic tail to bind Rsp5/NEDD4 family ubiquitin ligases, which ubiquitinate the antidote. Mutating PY motifs or attaching a deubiquitinating enzyme transforms the antidote into a toxic protein. Ubiquitination promotes the transport of the antidote from the trans-Golgi network to the endosome, thereby preventing it from causing toxicity. A physical interaction between the antidote and the toxin enables the ubiquitinated antidote to translocate the toxin to the endosome and neutralize its toxicity. We propose that post-translational modification-mediated protein localization and/or activity changes may be a common mechanism governing the antagonistic duality of single-gene KMDs.
Topics: Schizosaccharomyces; Antidotes; Ubiquitination; Golgi Apparatus; Ubiquitin; Endosomal Sorting Complexes Required for Transport; Ubiquitin-Protein Ligases
PubMed: 38097609
DOI: 10.1038/s41467-023-44151-9 -
Basic & Clinical Pharmacology &... Jun 2023Antidote stocking has been described in several studies from many countries to be problematic and constantly insufficient. During our institution's previous experience... (Review)
Review
Antidote stocking has been described in several studies from many countries to be problematic and constantly insufficient. During our institution's previous experience with a medication event that resulted from lack of antidote stocking, we initiated a review of all our antidotes and realized the lack of data on utilization in the literature that would help us in planning for our stocks. Therefore, we conducted this retrospective review of antidotes utilized at a large tertiary care hospital over a period of 6 years. The paper describes the types of antidotes and toxins involved, together with important patient characteristics and antidote utilization data that can be useful to other healthcare institutions in planning for their antidote stocks.
Topics: Humans; Antidotes; Retrospective Studies; Saudi Arabia; Tertiary Care Centers; Pharmacy Service, Hospital; Poisoning
PubMed: 36894519
DOI: 10.1111/bcpt.13856 -
Thrombosis Research May 2024Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or... (Review)
Review
Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes.
Topics: Humans; Antidotes; Anticoagulants; Administration, Oral; Factor Xa Inhibitors; Drug Monitoring; Recombinant Proteins; Factor Xa; Antibodies, Monoclonal, Humanized
PubMed: 38626592
DOI: 10.1016/j.thromres.2024.04.005