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Current Drug Safety 2015The advent of new oral anticoagulants (NOAC) has increased the armamentarium against thromboembolic diseases but has given rise to a conundrum on their reversal. NOAC's... (Review)
Review
The advent of new oral anticoagulants (NOAC) has increased the armamentarium against thromboembolic diseases but has given rise to a conundrum on their reversal. NOAC's have comparable efficacy to traditional vitamin K antagonists with similar rates of major bleeding. However there is no standardized method for reversal of these agents and no specific antidote. This is of concern not only in acute bleeding episodes but also in clinical scenarios where emergency surgery is required. Recent studies have investigated reversal of dabigatran, rivaroxaban, and apixaban using prothrombin complex concentrates (PCC), recombinant factor VIIa, and in the case of dabigatran, a monoclonal antibody. These studies have been encouraging in showing improvement of bleeding times and blood loss in most models, especially with the use of PCCs and the dabigatran antibody. Of note the majority of common currently used coagulation assays may not correlate with clinical reversal. The management of overt bleeding with NOACs is difficult due to the lack of clinical trials. Current animal trials, case reports and hemostatic testing on human blood have shown some promise; provide guidance but warrant further investigation.
Topics: Administration, Oral; Animals; Anticoagulants; Antidotes; Blood Coagulation; Blood Coagulation Tests; Blood Loss, Surgical; Elective Surgical Procedures; Emergencies; Hemorrhage; Humans; Perioperative Care; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 25877809
DOI: 10.2174/1574886310666150416123530 -
Pediatric Emergency Care Sep 2021Methylene blue has been in medicinal use for centuries and is best known as an antidotal treatment for acquired methemoglobinemia (MetHB). More recently, methylene blue... (Review)
Review
Methylene blue has been in medicinal use for centuries and is best known as an antidotal treatment for acquired methemoglobinemia (MetHB). More recently, methylene blue has gained recognition for its efficacious use in the treatment of ifosfamide neurotoxicity and refractory vasoplegic shock in both the pediatric and adult critical care literature, extending its use beyond MetHB. Methylene blue's mechanism of action is somewhat complex and based partly on its oxidizing capabilities, ironically the same mechanism that causes MetHB. This review will examine methylene blue's use in the treatment of acquired MetHB and ifosfamide neurotoxicity and review the current literature regarding its role in critically ill pediatric and adult patients with refractory vasoplegic shock. Methylene blue's pharmacologic actions, dosing, and adverse effects will also be discussed.
Topics: Adult; Antidotes; Child; Humans; Methemoglobinemia; Methylene Blue
PubMed: 34463662
DOI: 10.1097/PEC.0000000000002526 -
Diabetologia Oct 2023
Topics: Antidotes; Incretins; Venoms
PubMed: 37594570
DOI: 10.1007/s00125-023-05987-4 -
Advanced Drug Delivery Reviews Aug 2015Toxins delivered by envenomation, secreted by microorganisms, or unintentionally ingested can pose an immediate threat to life. Rapid intervention coupled with the... (Review)
Review
Toxins delivered by envenomation, secreted by microorganisms, or unintentionally ingested can pose an immediate threat to life. Rapid intervention coupled with the appropriate antidote is required to mitigate the threat. Many antidotes are biological products and their cost, methods of production, potential for eliciting immunogenic responses, the time needed to generate them, and stability issues contribute to their limited availability and effectiveness. These factors exacerbate a world-wide challenge for providing treatment. In this review we evaluate a number of polymer constructs that may serve as alternative antidotes. The range of toxins investigated includes those from sources such as plants, animals and bacteria. The development of polymeric heavy metal sequestrants for use as antidotes to heavy metal poisoning faces similar challenges, thus recent findings in this area have also been included. Two general strategies have emerged for the development of polymeric antidotes. In one, the polymer acts as a scaffold for the presentation of ligands with a known affinity for the toxin. A second strategy is to generate polymers with an intrinsic affinity, and in some cases selectivity, to a range of toxins. Importantly, in vivo efficacy has been demonstrated for each of these strategies, which suggests that these approaches hold promise as an alternative to biological or small molecule based treatments.
Topics: Animals; Antidotes; Heavy Metal Poisoning; Humans; Poisoning; Polymers; Toxins, Biological
PubMed: 26026975
DOI: 10.1016/j.addr.2015.05.011 -
British Journal of Clinical Pharmacology Mar 2016Paracetamol overdose prior to the introduction of acetylcysteine was associated with significant morbidity. Acetylcysteine is now the mainstay of treatment for... (Review)
Review
Paracetamol overdose prior to the introduction of acetylcysteine was associated with significant morbidity. Acetylcysteine is now the mainstay of treatment for paracetamol poisoning and has effectively reduced rates of hepatotoxicity and death. The current three-bag intravenous regimen with an initial high loading dose was empirically derived four decades ago and has not changed since. This regimen is associated with a high rate of adverse effects due mainly to the high initial peak acetylcysteine concentration. Furthermore, there are concerns that the acetylcysteine concentration is not adequate for 'massive' overdoses and that the dose and duration may need to be altered. Various novel regimens have been proposed, looking to address these issues. Many of these modified regimens aim to decrease the rate of adverse reactions by slowing the loading dose and thereby decrease the peak concentration. We used a published population pharmacokinetic model of acetylcysteine to simulate these modified regimens. We determined mean peak and 20 h acetylcysteine concentrations and area under the under the plasma concentration-time curve to compare these regimens. Those regimens that resulted in a lower peak acetylcysteine concentration have been shown in studies to have a lower rate of adverse events. However, these studies were too small to show whether they are as effective as the traditional regimen. Further research is still needed to determine the optimum dose and duration of acetylcysteine that results in the fewest side-effects and treatment failures. Indeed, a more patient-tailored approach might be required, whereby the dose and duration are altered depending on the paracetamol dose ingested or paracetamol concentrations.
Topics: Acetaminophen; Acetylcysteine; Antidotes; Drug Administration Schedule; Drug Overdose; Humans
PubMed: 26387650
DOI: 10.1111/bcp.12789 -
JAAPA : Official Journal of the... Nov 2022
Topics: Humans; Antidotes; Shame
PubMed: 36282582
DOI: 10.1097/01.JAA.0000885132.75809.45 -
The Veterinary Clinics of North... Nov 2018Use of intravenous lipid emulsion (ILE) as an antidote for severe cardiotoxicity and neurotoxicity has expanded in the veterinary world in the past decade. Despite... (Review)
Review
Use of intravenous lipid emulsion (ILE) as an antidote for severe cardiotoxicity and neurotoxicity has expanded in the veterinary world in the past decade. Despite advances in understanding of potential mechanisms of action of antidotal ILE, knowledge gaps remain in efficacy, appropriate dosing rates for various toxicants, and potential adverse reactions. Use of ILE in management of toxicoses of veterinary patients should be considered investigational, and should not be first-line treatment of most toxicoses, especially where established treatment protocols have good likelihood of positive outcomes. Use of ILE in veterinary toxicology cases requires judicious assessment of individual cases and proper informed consent of clients.
Topics: Animals; Antidotes; Fat Emulsions, Intravenous; Poisoning; Toxicology; Veterinary Medicine
PubMed: 30115370
DOI: 10.1016/j.cvsm.2018.07.006 -
Journal of Trace Elements in Medicine... 2015The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The... (Review)
Review
The present review provides an update of the general principles for the investigation and use of chelating agents in the treatment of intoxications by metals. The clinical use of the old chelators EDTA (ethylenediamine tetraacetate) and BAL (2,3-dimercaptopropanol) is now limited due to the inconvenience of parenteral administration, their own toxicity and tendency to increase the neurotoxicity of several metals. The hydrophilic dithiol chelators DMSA (meso-2,3-dimercaptosuccinic acid) and DMPS (2,3-dimercapto-propanesulphonate) are less toxic and more efficient than BAL in the clinical treatment of heavy metal poisoning, and available as capsules for oral use. In copper overload, DMSA appears to be a potent antidote, although d-penicillamine is still widely used. In the chelation of iron, the thiols are inefficient, since iron has higher affinity for ligands with nitrogen and oxygen, but the new oral iron antidotes deferiprone and desferasirox have entered into the clinical arena. Comparisons of these agents and deferoxamine infusions are in progress. General principles for research and development of new chelators are briefly outlined in this review.
Topics: Administration, Oral; Antidotes; Benzoates; Chelating Agents; Deferasirox; Deferiprone; Deferoxamine; Heavy Metal Poisoning; Humans; Penicillamine; Poisoning; Pyridones; Succimer; Triazoles; Trientine; Unithiol
PubMed: 25457281
DOI: 10.1016/j.jtemb.2014.10.001 -
The American Journal of Geriatric... Feb 2022
Topics: Antidotes; Health Status; Humans; Loneliness; Social Isolation
PubMed: 34210595
DOI: 10.1016/j.jagp.2021.05.019 -
Journal of Applied Toxicology : JAT Jan 2021Accidental intoxications from environmental pollutants, as well as intentional self- and chemical warfare-related poisonings affect millions of people worldwide each... (Review)
Review
Accidental intoxications from environmental pollutants, as well as intentional self- and chemical warfare-related poisonings affect millions of people worldwide each year. While many toxic agents can readily enter the central nervous system (CNS), the blood-brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. Consequently, poisoning antidotes usually cannot reach their site of action in the CNS in therapeutically relevant concentrations, and thus only provide effective protection to the peripheral nervous system. This limitation can be overcome by encapsulating the antidotes in nanoparticles (NP), which can enhance their CNS accumulation without damaging the integrity of the BBB. Among nanocarriers, polymer-based drug delivery systems exhibit remarkable benefits, such as bioavailability, cell uptake and tissue retention. Furthermore, due to their capacity to mask unfavorable physicochemical properties of cargo drugs, polymeric NPs were able to improve BBB transport of various pharmaceuticals. However, while polymer NP-mediated treatment of various pathological brain conditions, such as glioma and Alzheimer's disease were exhaustively studied, the application of polymeric nanocarriers for brain-targeted delivery of antidote molecules has not been adequately examined. To display its therapeutic potential, we review the state of the art of polymer NP-assisted CNS delivery of antidotes for various poisonings, including heavy metal and organophosphorus intoxications.
Topics: Antidotes; Biological Transport; Blood-Brain Barrier; Central Nervous System Diseases; Metals, Heavy; Nanoparticle Drug Delivery System; Polymers
PubMed: 32666582
DOI: 10.1002/jat.4029