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Drug Metabolism Letters 2021Due to its easy availability, rapid and severe toxicity, and no specific antidote, aluminum phosphide has emerged as a lethal toxin, commonly used for suicidal intent in... (Review)
Review
Due to its easy availability, rapid and severe toxicity, and no specific antidote, aluminum phosphide has emerged as a lethal toxin, commonly used for suicidal intent in agricultural communities. Despite various advances in medicine, this compound's toxicity is poorly understood, and it still has a very high case fatality rate with no definitive treatment options available. This review aims to understand the mechanism of toxicity, clinical toxidrome of acute aluminum phosphide poisoning, and the available therapeutic options, including recent advances. A literature review was performed searching PubMed, EMBASE Ovid, and Cochrane Library, using the following search items: ("aluminum phosphide poisoning" OR "aluminum phosphide poisoning toxicity" OR "aluminum phosphide ingestion") AND ("management" OR "therapy" OR "treatment"). Selected articles were discussed amongst all the authors to shape this review. High case fatality rate and lack of any specific antidote are persisting challenges. Therapeutic measures need to be implemented from all fronts - reducing easy access to the poison, developing less toxic alternatives for use as a pesticide, and more studies directed at developing an effective reversal agent for phosphine. The advent of promising agents like glucose-insulin-potassium infusion and lipid emulsion is a new ray of hope in the complete recovery in this fatal poisoning. The need of the hour is to find an agent that rapidly and effectively reverses aluminum phosphide's toxic effects. Large multicenter controlled trials are required to establish the role of glucose-insulin-potassium and lipid emulsion.
Topics: Aluminum Compounds; Antidotes; Glucose; Humans; Multicenter Studies as Topic; Pesticides; Phosphines
PubMed: 34818996
DOI: 10.2174/1872312814666210813115625 -
Current Drug Targets 2018Evidence-based review of the existing literature ultimately recommends stocking of Methylene Blue (MB) as an emergency antidote in the United States. The same is... (Review)
Review
Evidence-based review of the existing literature ultimately recommends stocking of Methylene Blue (MB) as an emergency antidote in the United States. The same is reported around the world in Japan, Greece, Italy and Canada. The observation that MB is always present as the main antidote required in emergency and critical care units calls for a revisit on its effects on the NO/cGMP system to reemphasize its multisystem actions. Therefore, the present review aimed to display the role of MB in emergency units, concerning: 1) Polytrauma and circulatory shock; 2) Neuroprotection, 3) Anaphylaxis and, 4) Overdose and poisoning.
Topics: Anaphylaxis; Antidotes; Clinical Trials as Topic; Critical Care; Drug Overdose; Emergency Service, Hospital; Evidence-Based Medicine; Humans; Methylene Blue; Multiple Trauma; Nervous System Diseases; Poisoning
PubMed: 29611486
DOI: 10.2174/1389450119666180403100410 -
British Journal of Clinical Pharmacology Mar 2016An understanding of mechanisms, potential benefits and risks of antidotes is essential for clinicians who manage poisoned patients. Of the dozens of antidotes currently... (Review)
Review
An understanding of mechanisms, potential benefits and risks of antidotes is essential for clinicians who manage poisoned patients. Of the dozens of antidotes currently available, only a few are regularly used. These include activated charcoal, acetylcysteine, naloxone, sodium bicarbonate, atropine, flumazenil, therapeutic antibodies and various vitamins. Even then, most are used in a minority of poisonings. There is little randomized trial evidence to support the use of most antidotes. Consequently, decisions about when to use them are often based on a mechanistic understanding of the poisoning and the expected influence of the antidote on the patient's clinical course. For some antidotes, such as atropine and insulin, the doses employed can be orders of magnitude higher than standard dosing. Importantly, most poisoned patients who reach hospital can recover with supportive care alone. In low risk patients, the routine use of even low risk antidotes such as activated charcoal is unwarranted. In more serious poisonings, decisions regarding antidote use are generally guided by a risk/benefit assessment based on low quality evidence.
Topics: Antidotes; Humans; Patient Selection; Poisoning; Risk Assessment
PubMed: 26816206
DOI: 10.1111/bcp.12894 -
Trends in Genetics : TIG Mar 2019Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic... (Review)
Review
Wolbachia bacteria inhabit the cells of about half of all arthropod species, an unparalleled success stemming in large part from selfish invasive strategies. Cytoplasmic incompatibility (CI), whereby the symbiont makes itself essential to embryo viability, is the most common of these and constitutes a promising weapon against vector-borne diseases. After decades of theoretical and experimental struggle, major recent advances have been made toward a molecular understanding of this phenomenon. As pieces of the puzzle come together, from yeast and Drosophila fly transgenesis to CI diversity patterns in natural mosquito populations, it becomes clearer than ever that the CI induction and rescue stem from a toxin-antidote (TA) system. Further, the tight association of the CI genes with prophages provides clues to the possible evolutionary origin of this phenomenon and the levels of selection at play.
Topics: Animals; Antidotes; Arthropods; Bacterial Toxins; Culicidae; Cytoplasm; Drosophila; Gene Transfer Techniques; Symbiosis; Vector Borne Diseases; Wolbachia
PubMed: 30685209
DOI: 10.1016/j.tig.2018.12.004 -
Vnitrni Lekarstvi 2016Methanol mass poisoning occurs across the world quite frequently, but the complete clinical and laboratory data of the patients are only rarely available. Approximately... (Review)
Review
UNLABELLED
Methanol mass poisoning occurs across the world quite frequently, but the complete clinical and laboratory data of the patients are only rarely available. Approximately 138 cases of poisoning were documented in the Czech Republic, 107 patients were hospitalized. Another 31 persons died out of hospital. About 60 % of the hospitalized patients survived intoxication without consequences, one half of the remaining 40 % died and the other half survived with the CNS and/or sight impaired. The Czech study successfully used modern diagnostic methods. A positive effect of the prehospital first aid with an oral antidote has been proven and a comparable effect of ethanol and fomepizole has been reached during hospital therapy. Higher efficiency of intermittent therapy has been determined as compared to continual hemodialysis. No connection was found between cerebral hemorrhage and systemic anticoagulation during hemodialysis. Magnetic resonance imaging revealed brain lesions in more than 50 % of the examined persons. During the follow-up visits over months and years improvement regarding the damage to the optic nerve was found in patients with a lesion of mild to medium degree. Isolated cases of poisoning still occur.
KEY WORDS
antidote - long-term follow-up - hemodialysis - methanol - methanol intoxication - CNS damage - vision impairment.
Topics: Antidotes; Czech Republic; Ethanol; Fomepizole; Humans; Methanol; Pyrazoles; Renal Dialysis
PubMed: 27627087
DOI: No ID Found -
Environmental Science and Pollution... Jun 2019The global burden of heavy metal especially mercury, arsenic, lead, and cadmium toxicities remains a significant public health challenge. Developing nations are... (Review)
Review
The global burden of heavy metal especially mercury, arsenic, lead, and cadmium toxicities remains a significant public health challenge. Developing nations are particularly at high risk and carry the highest burden of this hazard. Chelation therapy has been the mainstay for treatment of heavy metal poisoning where the chelating agent binds metal ions to form complex ring-like structures called "chelates" to enhance their elimination from the body. Metal chelators have some drawbacks such as redistribution of some heavy metals from other tissues to the brain thereby increasing its neurotoxicity, causing loss of essential metals such as copper and zinc as well as some serious adverse effects, e.g., hepatotoxicity. The use of natural antidotes, which are easily available, affordable, and with little or no side effects compared to the classic metal chelators, is the focus of this review and suggested as cheaper options for developing nations in the treatment of heavy metal poisoning.
Topics: Antidotes; Biological Products; Chelating Agents; Chelation Therapy; Heavy Metal Poisoning; Humans; Inactivation, Metabolic; Metals, Heavy
PubMed: 31079302
DOI: 10.1007/s11356-019-05104-2 -
Clinical Toxicology (Philadelphia, Pa.) Mar 2022Hydrogen cyanide and methanethiol are two toxic gases that inhibit mitochondrial cytochrome oxidase. Cyanide is generated in structural fires and methanethiol is...
CONTEXT
Hydrogen cyanide and methanethiol are two toxic gases that inhibit mitochondrial cytochrome oxidase. Cyanide is generated in structural fires and methanethiol is released by decaying organic matter. Current treatments for cyanide exposure do not lend themselves to treatment in the field and no treatment exists for methanethiol poisoning. Sodium tetrathionate (tetrathionate), a product of thiosulfate oxidation, could potentially serve as a cyanide antidote, and, based on its chemical structure, we hypothesized it could react with methanethiol.
RESULTS
We show that tetrathionate, unlike thiosulfate, reacts directly with cyanide under physiological conditions, and based on rabbit studies where we monitor cyanide poisoning in real-time, tetrathionate likely reacts directly with cyanide . We found that tetrathionate administered by intramuscular injection rescues >80% of juvenile, young adult, and old adult mice from exposure to inhaled hydrogen cyanide gas that is >80% lethal. Tetrathionate also rescued young adult rabbits from intravenously administered sodium cyanide. Tetrathionate was reasonably well-tolerated by mice and rats, yielding a therapeutic index of ∼5 in juvenile and young adult mice, and ∼3.3 in old adult mice; it was non-mutagenic in Chinese Hamster ovary cells and by the Ames bacterial test. We found by gas chromatography-mass spectrometry that both tetrathionate and thiosulfate react with methanethiol to generate dimethyldisulfide, but that tetrathionate was much more effective than thiosulfate at recovering intracellular ATP in COS-7 cells and rescuing mice from a lethal exposure to methanethiol gas.
CONCLUSION
We conclude that tetrathionate has the potential to be an effective antidote against cyanide and methanethiol poisoning.
Topics: Animals; Antidotes; CHO Cells; Cricetinae; Cricetulus; Cyanides; Humans; Mice; Rabbits; Rats; Sulfhydryl Compounds; Tetrathionic Acid; Thiosulfates
PubMed: 34328378
DOI: 10.1080/15563650.2021.1953517 -
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 -
Toxicology Mar 2019
Topics: Animals; Antidotes; Humans; Nervous System; Neuroprotective Agents; Organophosphate Poisoning; Prognosis; Risk Factors
PubMed: 30769051
DOI: 10.1016/j.tox.2019.02.007