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PloS One 2022Antidote stocking represents a major challenge to hospitals all over the world, including Kuwait. In order to assist hospitals to reduce costs and improve patient care,...
Antidote stocking represents a major challenge to hospitals all over the world, including Kuwait. In order to assist hospitals to reduce costs and improve patient care, an essential antidote list can be used as an initial foundation for securing sufficient antidote availability at healthcare institutions. The aim of our study is to generate a nationally relevant essential antidote list for emergency care hospitals in Kuwait using the e-Delphi method by establishing consensus through a multidisciplinary expert group of healthcare providers. An electronic survey with 47 essential antidotes was developed. The e-Delphi method was used, with three rounds of voting, to determine expert consensus on an essential antidote list for hospitals in Kuwait. A purposive sample of healthcare professionals from governmental and private hospitals were selected for this study (n = 30). Consensus was gained if ≥75% of the expert panel agreed on the inclusion of the antidote, without any strong disagreements. Round 1 of the e-Delphi resulted in 41 antidotes reaching consensus and seven new antidotes suggested by the expert panel. Round 2 had two antidotes (out of seven newly suggested ones) reaching consensus. Round 3 was a confirmatory round, where the expert group agreed on their previous rounds' opinions. This resulted in the development of an essential antidote list with 43 antidotes. The optimal approach for ensuring adequate availability of antidotes is continuous monitoring of local poisoning incidence and antidote requirements through collaborations between academic researchers and emergency care clinicians. The development of an essential antidote list, with expert consensus, is one of the initial steps in securing a foundation for appropriate provision of antidotes at all healthcare institutions. This is the first study that the authors are aware of that demonstrates that the e-Delphi technique can consolidate recommendations of experts in emergency medicine to provide a list of essential antidotes.
Topics: Antidotes; Consensus; Delphi Technique; Emergency Medical Services; Humans; Pharmacy Service, Hospital
PubMed: 35709136
DOI: 10.1371/journal.pone.0269456 -
Critical Care (London, England) Jun 2019In light of an aging population with increased cardiovascular comorbidity, the use of oral anticoagulation (OAC) is steadily expanding. A variety of pharmacological... (Review)
Review
In light of an aging population with increased cardiovascular comorbidity, the use of oral anticoagulation (OAC) is steadily expanding. A variety of pharmacological alternatives to vitamin K antagonists (VKA) have emerged over recent years (direct oral anticoagulants, DOAC, i.e., dabigatran, rivaroxaban, apixaban, and edoxaban) which show a reduced risk for the occurrence of intracerebral hemorrhage (ICH). Yet, in the event of ICH under OAC (OAC-ICH), hematoma characteristics are similarly severe and clinical outcomes likewise substantially limited in both patients with VKA- and DOAC-ICH, which is why optimal acute hemostatic treatment in all OAC-ICH needs to be guaranteed. Currently, International Guidelines for the hemostatic management of patients with OAC-ICH are updated as several relevant large-sized observational studies and recent trials have established treatment approaches for both VKA- and DOAC-ICH. While the management of VKA-ICH is mainly based on the immediate reversal of elevated levels of international normalized ratio using prothrombin complex concentrates, hemostatic management of DOAC-associated ICH is challenging requiring specific antidotes, notably idarucizumab and andexanet alfa. This review will provide an overview of the latest studies and trials on hemostatic reversal agents and timing and summarizes the effects on hemorrhage progression and clinical outcomes in patients with OAC-ICH.
Topics: Administration, Oral; Anticoagulants; Antidotes; Antithrombins; Blood Coagulation; Cerebral Hemorrhage; Factor Xa; Factor Xa Inhibitors; Humans; Recombinant Proteins; Tranexamic Acid
PubMed: 31171018
DOI: 10.1186/s13054-019-2492-8 -
Tidsskrift For Den Norske Laegeforening... May 2024A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a...
BACKGROUND
A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a history of COPD, hypertension and polymyalgia rheumatica. A medication error involving methotrexate, used for autoimmune diseases, was discovered during her medical history review.
CASE PRESENTATION
The patient arrived with stable vital signs, including 94 % oxygen saturation and a respiratory rate of 20 breaths/min. She had been taking 2.5 mg of methotrexate daily for the past three weeks instead of the prescribed weekly dose of 15 mg. Other examinations revealed no alarming findings, except for a slightly elevated D-dimer level.
INTERPRETATION
Considering her medical history and exclusion of other differential diagnoses, methotrexate toxicity was suspected. The patient was admitted to the hospital and intravenous folinic acid was initiated as an antidote treatment. Five days later, the patient was discharged with an improvement in the shortness of breath. This case underscores the importance of effective communication in health care, particularly in complex cases like this, where understanding dosages and administration is crucial. Medical history, clinical examinations and medication reviews, often involving clinical pharmacists, are vital in the A&E to reveal medication errors.
Topics: Humans; Medication Errors; Female; Methotrexate; Aged; Dyspnea; Leucovorin; Antidotes; Antirheumatic Agents
PubMed: 38747669
DOI: 10.4045/tidsskr.23.0657 -
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 -
Neurobiology of Disease Jan 2020
Topics: Animals; Antidotes; Humans; Medical Countermeasures; Nerve Agents; Neurotoxicity Syndromes
PubMed: 31374245
DOI: 10.1016/j.nbd.2019.104557 -
British Journal of Clinical Pharmacology Mar 2016The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are... (Review)
Review
The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be effective in these poisonings, there are substantial practical problems with its use and so fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically-toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive, or the physician may prefer ethanol due to experience.
Topics: Acidosis; Antidotes; Ethanol; Ethylene Glycol; Ethylene Glycols; Fomepizole; Humans; Methanol; Pyrazoles
PubMed: 26551875
DOI: 10.1111/bcp.12824 -
American Family Physician Aug 2009N-acetylcysteine is the acetylated variant of the amino acid L-cysteine and is widely used as the specific antidote for acetaminophen overdose. Other applications for... (Review)
Review
N-acetylcysteine is the acetylated variant of the amino acid L-cysteine and is widely used as the specific antidote for acetaminophen overdose. Other applications for N-acetylcysteine supplementation supported by scientific evidence include prevention of chronic obstructive pulmonary disease exacerbation, prevention of contrast-induced kidney damage during imaging procedures, attenuation of illness from the influenza virus when started before infection, treatment of pulmonary fibrosis, and treatment of infertility in patients with clomiphene-resistant polycystic ovary syndrome. Preliminary studies suggest that N-acetylcysteine may also have a role as a cancer chemopreventive, an adjunct in the eradication of Helicobacter pylori, and prophylaxis of gentamicin-induced hearing loss in patients on renal dialysis.
Topics: Acetaminophen; Acetylcysteine; Antidotes; Expectorants; Female; Free Radical Scavengers; Hearing Loss; Humans; Influenza, Human; Neoplasms; Polycystic Ovary Syndrome; Respiratory Tract Diseases
PubMed: 19621836
DOI: No ID Found -
Current Opinion in Biotechnology Dec 2008Receptor-ligand interactions are fundamental to the regulation of cell physiology, enabling the communication between cells and their environment via signal... (Review)
Review
Receptor-ligand interactions are fundamental to the regulation of cell physiology, enabling the communication between cells and their environment via signal transduction. Receptors are also exploited by toxins and infectious agents to mediate pathogenesis. Over the past 20 years, however, this bi-partite paradigm for cellular regulation, that is, receptors and their ligands, has been revised to include an unforeseen participant namely, soluble receptors or molecular decoys. Decoys function as nature's modifiers of potent responses such as inflammation, stimulation of cell proliferation and triggering apoptosis. Decoys not only provide the means to fine tune the regulation of these phenomena; they also serve as potential leads for the development of recombinant anti-toxins, anti-viral agents and novel therapeutics for combating cancer and inflammatory disease.
Topics: Animals; Antidotes; Immunologic Factors; Molecular Mimicry
PubMed: 18977299
DOI: 10.1016/j.copbio.2008.10.001 -
Molecules (Basel, Switzerland) Mar 2020Poisoning is the greatest source of avoidable death in the world and can result from industrial exhausts, incessant bush burning, drug overdose, accidental toxication or... (Meta-Analysis)
Meta-Analysis Review
Poisoning is the greatest source of avoidable death in the world and can result from industrial exhausts, incessant bush burning, drug overdose, accidental toxication or snake envenomation. Since the advent of Albert Calmette's cobra venom antidote, efforts have been geared towards antidotes development for various poisons to date. While there are resources and facilities to tackle poisoning in urban areas, rural areas and developing countries are challenged with poisoning management due to either the absence of or inadequate facilities and this has paved the way for phyto-antidotes, some of which have been scientifically validated. This review presents the scope of antidotes' effectiveness in different experimental models and biotechnological advancements in antidote research for future applications. While pockets of evidence of the effectiveness of antidotes exist and with ample biotechnological developments, the utilization of analytic assays on existing and newly developed antidotes that have surpassed the proof of concept stage, as well as the inclusion of antidote's short and long-term risk assessment report, will help in providing the required scientific evidence(s) prior to regulatory authorities' approval.
Topics: Animals; Antidotes; Biotechnology; Disease Models, Animal; Drug Development; Drug Evaluation, Preclinical; Humans; Phytochemicals; Poisoning; Treatment Outcome
PubMed: 32225103
DOI: 10.3390/molecules25071516 -
Molecules (Basel, Switzerland) Jul 2022Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs,... (Review)
Review
Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs, antipsychotic, and immunosuppressant drugs are known to induce cardiotoxic and neurotoxic effects. Recent studies have demonstrated that the impairment of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is a primary event in the pathophysiology of drug-induced cardiotoxicity and neurotoxicity. The Nrf2 pathway regulates the expression of different genes whose products are involved in antioxidant and inflammatory responses and the detoxification of toxic species. Cardiotoxic drugs, such as the anthracycline doxorubicin, or neurotoxic drugs, such as paclitaxel, suppress or impair the Nrf2 pathway, whereas the rescue of this pathway counteracts both the oxidative stress and inflammation that are related to drug-induced cardiotoxicity and neurotoxicity. Therefore Nrf2 represents a novel pharmacological target to develop new antidotes in the field of clinical toxicology. Interestingly, carnosine (β-alanyl-l-histidine), an endogenous dipeptide that is characterized by strong antioxidant, anti-inflammatory, and neuroprotective properties is able to rescue/activate the Nrf2 pathway, as demonstrated by different preclinical studies and preliminary clinical evidence. Starting from these new data, in the present review, we examined the evidence on the therapeutic potential of carnosine as an endogenous antidote that is able to rescue the Nrf2 pathway and then counteract drug-induced cardiotoxicity and neurotoxicity.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Antidotes; Antioxidants; Cardiotoxicity; Carnosine; Humans; NF-E2-Related Factor 2; Neurotoxicity Syndromes; Oxidative Stress
PubMed: 35889325
DOI: 10.3390/molecules27144452