-
Journal of Thrombosis and Thrombolysis Feb 2016Non-vitamin K oral anticoagulants (NOACs) have been a major addition to our therapeutic armamentarium. They are at least as effective as warfarin in the... (Review)
Review
Non-vitamin K oral anticoagulants (NOACs) have been a major addition to our therapeutic armamentarium. They are at least as effective as warfarin in the thromboprophylaxis of non-valvular atrial fibrillation and management of thromboembolic disease, with a more favorable safety profile. Their predictable pharmacokinetics and pharmacodynamics allow for a fixed oral dosing without the need for anticoagulation monitoring. A major concern regarding NOACs is the lack of a readily available antidote to reverse their anticoagulation effect in case of life-threatening bleeding or need for emergent surgery. In this review, we summarize preclinical and clinical data on (a) hemostatic agents used to reverse NOACs, and (b) novel, target-specific NOACs reversal agents under development. The prothrombin complex concentrates, activated prothrombin complex concentrates and recombinant activated factor VII are hemostatic agents that have been assessed in reversing NOACs. Preclinical studies with hemostatic agents report variable results and there is only limited clinical data available to date. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly. Aripazine is a universal anticoagulation reversal agent. Preclinical studies show promising results and these agents are already in different stages of clinical development. Phase I and II clinical trials demonstrate efficacy in reversing NOACs without major side effects. Until these agents become commercially available, management of patients receiving NOACs who present with major bleeding or require emergent surgery should focus on (a) immediate discontinuation of NOACs, (b) supportive measures or postponing surgery for 12-24 h after the last NOAC dose, and/or
Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Factor Xa; Humans; Recombinant Proteins; Vitamin K
PubMed: 26627486
DOI: 10.1007/s11239-015-1297-0 -
Neurobiology of Disease Jan 2020
Topics: Animals; Antidotes; Humans; Medical Countermeasures; Nerve Agents; Neurotoxicity Syndromes
PubMed: 31374245
DOI: 10.1016/j.nbd.2019.104557 -
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 -
Archives de Pediatrie : Organe Officiel... Jul 2016Acute pesticide poisoning in children is rare but potentially serious. Some clinical patterns (toxidromes) are suggestive of the drug class: cholinergic crisis for... (Review)
Review
Acute pesticide poisoning in children is rare but potentially serious. Some clinical patterns (toxidromes) are suggestive of the drug class: cholinergic crisis for organophosphate or carbamate insecticides; neurological syndrome for rodenticides; digestive and respiratory syndrome for herbicides. Treatment is symptomatic and only a few patients are treated with an antidote: atropine and pralidoxime for organophosphate insecticides, vitamin K for anticoagulant rodenticides.
Topics: Antidotes; Child; Humans; Pesticides; Poisoning
PubMed: 27266642
DOI: 10.1016/j.arcped.2016.04.021 -
RNA (New York, N.Y.) Apr 2023In this short Perspective, we discuss the history of, and recent progress toward, the development of aptamers that can serve as rapid onset anticoagulants during...
In this short Perspective, we discuss the history of, and recent progress toward, the development of aptamers that can serve as rapid onset anticoagulants during cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and catheter-based diagnostic and interventional procedures, several million of which are performed each year worldwide. Aptamer anticoagulants provide potent and antidote-controllable anticoagulation and have low immunogenicity. New methods of aptamer isolation and engineering have not only improved the quality of aptamers, but also accelerated their development. Unfortunately, no aptamer identified to date can produce an anticoagulant effect as potent as that produced by unfractionated heparin (UFH), the standard anticoagulant for CPB. We have suggested several possible strategies to amplify the anticoagulant potency of existing aptamer anticoagulants.
Topics: Heparin; Aptamers, Nucleotide; Blood Coagulation; Anticoagulants; Antidotes
PubMed: 36697262
DOI: 10.1261/rna.079503.122 -
ACS Applied Materials & Interfaces Sep 2022Organophosphorus compounds (OPs) pose great military and civilian hazards. However, therapeutic and prophylactic antidotes against OP poisoning remain challenging. In...
Organophosphorus compounds (OPs) pose great military and civilian hazards. However, therapeutic and prophylactic antidotes against OP poisoning remain challenging. In this study, we first developed a novel nanoscavenger (rOPH/ZIF-8@E-Lipo) against methyl paraoxon (MP) poisoning using enzyme immobilization and erythrocyte-liposome hybrid membrane camouflage techniques. Then, we evaluated the physicochemical characterization, stability, and biocompatibility of the nanoscavengers. Afterward, we examined acetylcholinesterase (AChE) activity, cell viability, and intracellular reactive oxygen species (ROS) to indicate the protective effects of the nanoscavengers . Following the pharmacokinetic and biodistribution studies, we further evaluated the therapeutic and prophylactic detoxification efficacy of the nanoscavengers against MP in various poisoning settings. Finally, we explored the penetration capacity of the nanoscavengers across the blood-brain barrier (BBB). The present study validated the successful construction of a novel nanoscavenger with excellent stability and biocompatibility. , the resulting nanoscavenger exhibited a significant protection against MP-induced AChE inactivation, oxidative stress, and cytotoxicity. , apart from the positive therapeutic effects, the nanoscavengers also exerted significant prophylactic detoxification efficacy against single lethal MP exposure, repeated lethal MP challenges, and sublethal MP poisoning. These excellent detoxification effects of the nanoscavengers against OPs may originate from a dual-mode mechanism of inner recombinant organophosphorus hydrolase (rOPH) and outer erythrocyte membrane-anchored AChE. Finally, and studies jointly demonstrated that monosialoganglioside (GM1)-modified rOPH/ZIF-8@E-Lipo could penetrate the BBB with high efficiency. In conclusion, a stable and safe dual-modal nanoscavenger was developed with BBB penetration capability, providing a promising strategy for the treatment and prevention of OP poisoning.
Topics: Acetylcholinesterase; Antidotes; Aryldialkylphosphatase; Cholinesterase Inhibitors; G(M1) Ganglioside; Liposomes; Organophosphorus Compounds; Paraoxon; Reactive Oxygen Species; Tissue Distribution
PubMed: 36089739
DOI: 10.1021/acsami.2c11737 -
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 -
Supportive Care in Cancer : Official... Sep 2022Oncologists are exposed to suffering, loss, and death, and as a result may experience guilt. The study examined two competing hypotheses regarding the relation between...
PURPOSE
Oncologists are exposed to suffering, loss, and death, and as a result may experience guilt. The study examined two competing hypotheses regarding the relation between locus of control (LOC) and guilt among oncologists and the mediating role of helplessness.
METHOD
Eighty-three oncologists answered a demographic questionnaire; the Levenson's "Internal, Powerful Others, and Chance" scale; the Guilt Inventory; and the Learned Helplessness Scale.
RESULTS
Oncologists reported moderate levels of guilt, high levels of internal LOC, and low levels of external LOC and helplessness. The results indicate a significant negative relationship between internal LOC and guilt and a significant positive relationship between external LOC (powerful others) and guilt, both mediated by helplessness. It seems that oncologists with external LOC feel helplessness and this metamorphoses into guilt, due to its potentially protective role against feelings of helplessness.
CONCLUSIONS
Oncologists are at risk for guilt. Whereas an internal LOC plays an important role as a resilience factor in terms of helplessness, an external LOC is a risk factor for helplessness and guilt. A paradoxical association between guilt and helplessness was found. The implication of which is that guilt may be produced to avoid helplessness; in other words, guilt, however painful, might be preferable to feeling helpless. Interventions focusing on oncologists' coping with uncontrolled situations in their daily work, decreasing their sense of helplessness and guilt, should be implanted.
Topics: Antidotes; Guilt; Helplessness, Learned; Humans; Internal-External Control; Oncologists
PubMed: 35674794
DOI: 10.1007/s00520-022-07196-y -
Critical Reviews in Toxicology Oct 2020Organophosphorus agents (OP) are widely used as pesticides due to their cost effectiveness, yet they present a significant public health risk owing to their high... (Review)
Review
Organophosphorus agents (OP) are widely used as pesticides due to their cost effectiveness, yet they present a significant public health risk owing to their high toxicity, especially in cases of occupational exposure in agriculture, during suicide attempts using pesticides, and as nerve agents in warfare. Their vigorous permeability through inhalation, ingestion, and dermal exposure results in a high number of reported OP poisoning cases and alarming mortality rates. Initial first-aid management involves decontamination, ventilation, and hemodialysis. Additionally, current treatment guidelines recommend prompt administration of atropine as a first-line antidote, oximes as a follow-up, benzodiazepines for seizure control, and pyridostigmine for prophylaxis. Nevertheless, current treatment options are associated with several challenges. Thus, recent research has focused on investigating novel approaches for their potential in improving current management strategies. This article intends to review recent advances in OP poisoning treatment, including agents investigated for their use as an alternative or adjunctive therapy, novel formulations such as nasal drops or sublingual tablets for emergency administration of atropine, as well as innovative strategies for enhanced oximes delivery and overall efficacy. However, two major barriers may limit these innovations, ethical issues associated with their clinical assessment in emergencies, and limited profitability in countries where most cases occur.
Topics: Animals; Antidotes; Atropine; Chemical Warfare Agents; Cholinesterase Inhibitors; Humans; Organophosphate Poisoning; Organophosphates; Organophosphorus Compounds; Oximes; Pesticides; Seizures
PubMed: 33185501
DOI: 10.1080/10408444.2020.1837069 -
Expert Review of Clinical Pharmacology Jul 2019: Intravenous lipid emulsion (ILE) administration is capable of reversing the acute cardiac and neurological toxicity caused by local anesthetic agents. In recent years,... (Review)
Review
: Intravenous lipid emulsion (ILE) administration is capable of reversing the acute cardiac and neurological toxicity caused by local anesthetic agents. In recent years, ILE has also been explored as a potential antidote for cardiotoxicity caused by non-anesthetic agents too. : The potential mechanisms, safety, and efficacy of this approach are considered. Data were sought from published reports listed in PubMed and EMBASE, and abstracts of meetings of the North American Congress of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists. There were reports involving 298 patients where ILE has been administered for severe drug toxicity. Clinical improvement was observed in 57 of 59 patients with local anesthetic toxicity (96.6%); there were 239 patients where toxicity was due to non-anesthetic agents, and ILE apparently improved clinical outcome in 215 (72.1%). : Response rates were similar between ILE treated toxicity caused by lipid soluble and non-lipid soluble drugs. Potential adverse effects of ILE include interference with laboratory assays, acute pancreatitis, and adult respiratory distress syndrome, although the rate of occurrence is difficult to ascertain.
Topics: Anesthetics, Local; Animals; Antidotes; Cardiotoxicity; Drug-Related Side Effects and Adverse Reactions; Fat Emulsions, Intravenous; Humans
PubMed: 31106655
DOI: 10.1080/17512433.2019.1621163