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1.
Georgian Med News ; (320): 111-115, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34897055

RESUMO

Aluminum phosphide (AlP) has been known for more than 80 years as an effective pesticide for grain protection, but also as a suicidal agent used for human self-poisoning. Phosphine gas released in contact with stomach acid after oral ingestion of AlP is responsible for its toxicity. The poison affects all systems, so the mortality rate is quite high, especially after deliberate ingestions. We report the first case of severe AlP poisoning seen in our institution with a fatal outcome and furthermore, we present literature review on existing and newer treatment options. A 35-year-old woman with a history of epilepsy was admitted to the University Clinic for Toxicology in Skopje two hours after deliberate ingestion of one tablet of phostoxin (AlP). The first signs of poisoning were vomiting and abdominal pain, leukocytosis, prolonged PT, as well as inverted T waves in D3, AVF and left precordial leads on ECG. After developing respiratory failure and hypotension she was transferred to the intensive care unit (ICU). Her blood pressure was 80/40 mmHg, pulse rate 120/min. Laboratory findings showed signs of hepatic lesion, rhabdomyolysis and renal failure (AST 2267.42 U/L, ALT 2102.26 U/L, CPK 1334.81U/L, blood urea nitrogen 23.03 mmol/L, creatinine 211.9 µmol/L). Arterial blood gas analyses showed metabolic acidosis (pO2 9.6 kPa, pCO2 4.14 kPa, pH 7.15, bicarbonate 11 mmol/L, BE -15). The patient was placed on mechanical ventilation. Despite fluid supplementation, intensive therapy and inotropic support, hemodynamic instability worsened and cardiopulmonary resuscitation was performed three times. Unfortunately, the patient had a fatal outcome on the fourth day of intoxication. Solid formulations of AlP are very toxic. One tablet of phostoxin containing 3 grams of AlP is sufficient for the progression of life-threatening symptoms and fatal outcome. In the absence of antidote and elucidated mechanisms of toxicity, the key to treatment is rapid decontamination and initiation of resuscitation measures.


Assuntos
Acidose , Praguicidas , Adulto , Antídotos , Gasometria , Protocolos Clínicos , Feminino , Humanos , Literatura de Revisão como Assunto
3.
Acta Medica (Hradec Kralove) ; 64(3): 145-152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34779379

RESUMO

AIM: The comparison of neuroprotective and central reactivating effects of the oxime K870 in combination with atropine with the efficacy of standard antidotal treatment in tabun-poisoned rats. METHODS: The neuroprotective effects of antidotal treatment were determined in rats poisoned with tabun at a sublethal dose using a functional observational battery 2 h and 24 h after tabun administration, the tabun-induced brain damage was investigated by the histopathological evaluation and central reactivating effects of oximes was evaluated by the determination of acetylcholinesterase activity in the brain using a standard spectrophotometric method. RESULTS: The central reactivating efficacy of a newly developed oxime K870 roughly corresponds to the central reactivating efficacy of pralidoxime while the ability of the oxime HI-6 to reactivate tabun-inhibited acetylcholinesterase in the brain was negligible. The ability of the oxime K870 to decrease tabun-induced acute neurotoxicity was slightly higher than that of pralidoxime and similar to the oxime HI-6. These results roughly correspond to the histopathological evaluation of tabun-induced brain damage. CONCLUSION: The newly synthesized oxime K870 is not a suitable replacement for commonly used oximes in the antidotal treatment of acute tabun poisonings because its neuroprotective efficacy is only slightly higher or similar compared to studied currently used oximes.


Assuntos
Substâncias para a Guerra Química , Reativadores da Colinesterase , Organofosfatos , Oximas , Venenos , Compostos de Piridínio , Acetilcolinesterase , Animais , Antídotos/farmacologia , Substâncias para a Guerra Química/toxicidade , Inibidores da Colinesterase/farmacologia , Reativadores da Colinesterase/farmacologia , Oximas/farmacologia , Compostos de Pralidoxima , Compostos de Piridínio/farmacologia , Ratos , Ratos Wistar
4.
Environ Pollut ; 291: 118137, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536650

RESUMO

Paraquat (PQ) is a toxic, organic herbicide for which there is no specific antidote. Although banned in some countries, it is still used as an irreplaceable weed killer in others. The lack of understanding of the precise mechanism of its toxicity has hindered the development of treatments for PQ exposure. While toxicity is thought to be related to PQ-induced oxidative stress, antioxidants are limited in their ability to ameliorate the untoward biological responses to this agent. Summarized in this review are data on the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of PQ, focusing on the essential roles of individual transporters and enzymes in these processes. Based on these findings, strategies are proposed to design and test specific and effective antidotes for the clinical management of PQ poisoning.


Assuntos
Herbicidas , Paraquat , Antídotos , Antioxidantes , Herbicidas/toxicidade , Estresse Oxidativo , Paraquat/toxicidade
5.
Cells ; 10(7)2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34359914

RESUMO

Chronic kidney disease is characterized by markedly increased risk for cardiovascular mortality, vascular calcification, and ventricular hypertrophy, and is associated with increased systemic oxidative stress. Hyperphosphatemia, reflecting diminished glomerular phosphate (Pi) clearance, coupled with a compensatory increase in fibroblast growth factor 23 (FGF23) secretion are thought to be key mediators of this risk. Elevated serum and dietary Pi and elevated plasma FGF23 are associated with increased cardiovascular and total mortality in people with normal baseline renal function. FGF23 may mediate some of this risk by promoting cardiac hypertrophy via activation of fibroblast growth factor receptor 4 on cardiomyocytes. Elevated serum Pi can also cause a profound increase in systemic oxidative stress, and this may reflect the ability of Pi to act directly on mitochondria to boost membrane potential and thereby increase respiratory chain superoxide production. Moreover, elevated FGF23 likewise induces oxidative stress in vascular endothelium via activation of NADPH oxidase complexes. In vitro exposure of vascular smooth muscle cells to elevated Pi provokes an osteoblastic phenotypic transition that is mediated by increased mitochondrial oxidant production; this is offset dose-dependently by increased exposure to magnesium (Mg). In vivo, dietary Mg is protective in rodent models of vascular calcification. It is proposed that increased intracellular Mg opposes Pi's ability to increase mitochondrial membrane potential; this model could explain its utility for prevention of vascular calcification and predicts that Mg may have a more global protective impact with regard to the direct pathogenic effects of hyperphosphatemia.


Assuntos
Antídotos/farmacologia , Magnésio/farmacologia , Potencial da Membrana Mitocondrial , Estresse Oxidativo , Fosfatos/efeitos adversos , Calcificação Vascular/etiologia , Animais , Disponibilidade Biológica , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
6.
Pediatr Emerg Care ; 37(9): 474-477, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34463662

RESUMO

ABSTRACT: 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.


Assuntos
Metemoglobinemia , Azul de Metileno , Adulto , Antídotos/uso terapêutico , Criança , Humanos , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/tratamento farmacológico , Azul de Metileno/uso terapêutico
8.
Med Klin Intensivmed Notfmed ; 116(6): 491-498, 2021 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-34463792

RESUMO

BACKGROUND: Severe bleeding under antithrombotic therapy is common and challenging in intensive care medicine; on the one hand, rapid bleeding control must be achieved and, on the other hand, thromboembolic complications must be avoided. AIMS: The paper will provide a brief overview of direct oral anticoagulants, therapeutic options and precise instructions for dealing with severe bleeding. RESULTS: In addition to general measures in direct oral anticoagulant (DOAC)-associated major bleeding, prothrombin complex concentrate (PCC), idarucizumab and andexanet alfa are available as specific antidote therapy. In case of bleeding under heparin therapy, protamine sulfate is available as a possible antidote. CONCLUSIONS: In particular, the importance of andexanet alfa in the treatment of factor Xa inhibitor-associated bleeding requires further investigation.


Assuntos
Fibrinolíticos , Hemorragia , Administração Oral , Anticoagulantes/efeitos adversos , Antídotos/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Fibrinolíticos/efeitos adversos , Hemorragia/tratamento farmacológico , Hemorragia/terapia , Humanos , Proteínas Recombinantes/uso terapêutico
9.
Forensic Sci Rev ; 33(2): 117-143, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34247144

RESUMO

Methanol has a very simple chemical structure (CH3OH) considering its potential health hazard, including the many poisoning deaths after ingestion. In countries where authentic alcoholic beverages are expensive, restricted, or banned for religious or other reasons, some people resort to purchasing alcoholic drinks made illegally. These clandestine sources of "booze" often contain high concentrations of methanol, added by the perpetrators to enhance potency and increase profits. Although an effective medical treatment for methanol poisoning exists, because most such incidents occur in socially deprived parts of the world, the hospital emergency facilities are scarce and/or inadequate. Trace amounts of methanol (median ~1.0 mg/L) are produced endogenously via certain enzymatic processes, such as one-carbon metabolism. Methanol and methyl esters are also contained in fresh fruits and vegetables as well as in alcoholic beverages. During a period of heavy drinking the blood-methanol concentration (BMC) increases and might surpass 10 mg/L, which is considered a biomarker for alcohol abuse and alcoholism. Methanol itself has a low intrinsic toxicity, but is converted in the body into two highly toxic metabolites, formaldehyde and formic acid. This metabolism is delayed by co-ingestion of ethanol, which creates a latent period of 12-24 h before toxic symptoms develop. Accordingly, when patients are admitted to hospital for diagnosis and treatment, a life-threatening metabolic acidosis has already developed and is irreversible. Symptoms of methanol poisoning include blurred vision, breathlessness, nausea, gastric pains, and acid-base disturbances and deficiency of oxygen in arterial blood. The visual disturbances might even develop into permanent blindness, owing to an interaction of toxic metabolites with the optic nerve. The minimum lethal dose of ethanol in humans is not easy to specify, because most poisonings involve co-ingestion of ethanol, which to some extent protects the patient from toxic sequelae. Effective antidotes for treatment of methanol poisoning are administration of ethanol or the therapeutic drug fomepizole (Antizol®), which is 4-methyl pyrazole (4-MP). Both treatments work by blocking the metabolism of methanol by liver alcohol dehydrogenase (ADH). The metabolic acidosis caused by the accumulation of formic acid in the body is treated with sodium bicarbonate, which helps to normalize pH in the bloodstream. Thereafter, methanol and its metabolites in the blood are removed by hemodialysis. However, the long-term prognosis for survivors of methanol poisoning is not good, because many are elderly males who are in poor health and often suffer from an alcohol-use disorder.


Assuntos
Antídotos , Metanol , Idoso , Etanol , Fomepizol , Toxicologia Forense , Humanos , Masculino
10.
J Control Release ; 337: 59-70, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34273418

RESUMO

Cyanide induces acute lethal poisoning resulting from inhibition of cytochrome c oxidase located in the complex IV (Complex IV) of mitochondria. However, current therapies for cyanide poisoning using hydroxocobalamin and nitrous acid compounds remain a clinical issue. Here, we show that liposome-encapsulated methemoglobin (metHb@Lipo), nanosized biomimetic red blood cells, replicate the antidotal mechanism of nitrous acid compounds against cyanide poisoning, achieving superior efficacy and fast action with no adverse effects. The structure of metHb@Lipo, which consists of concentrated methemoglobin in its aqueous core and a lipid membrane resembling the red blood cell membrane, provides favorable characteristics as a cyanide antidote, such as binding properties and membrane permeability. Upon cyanide exposure, metHb@Lipo maintained the mitochondrial function in PC12 cells, resulting in a cell viability comparable to treatment with nitrous acid compounds. In a mouse model of cyanide poisoning, metHb@Lipo treatment dramatically improved mortality with a rapid recovery from the symptoms of cyanide poisoning compared to treatment with nitrous acid compounds. Furthermore, metHb@Lipo also possesses satisfactory pharmacokinetic properties without long-term bioaccumulation and toxicity. Our findings showed a novel concept to develop drugs for cyanide poisoning and provide a promising possibility for biomimetic red blood cell preparations for pharmaceutical applications.


Assuntos
Antídotos , Metemoglobina , Animais , Antídotos/uso terapêutico , Cianetos , Eritrócitos , Lipossomos , Camundongos , Ratos
11.
ACS Chem Neurosci ; 12(15): 2865-2877, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34284583

RESUMO

Organophosphorus (OP) cholinesterase inhibitors, which include insecticides and chemical warfare nerve agents, are very potent neurotoxicants. Given that the actual treatment has several limitations, the present study provides a general method, called the zebrafish-OP-antidote test (ZOAT), and basic scientific data, to identify new antidotes that are more effective than the reference pyridinium oximes after acute OP poisoning. The reactivation capacity of a chemical compound can be measured using in vivo and ex vivo acetylcholinesterase (AChE) assays. We demonstrated that it is possible to differentiate between chemical compound protective efficacies in the central and peripheral nervous system via the visual motor response and electric field pulse motor response tests, respectively. Moreover, the ability to cross the brain-blood barrier can be estimated in a physiological context by combining an AChE assay on the head and trunk-tail fractions and the cellular and tissue localization of AChE activity in the whole-mount animal. ZOAT is an innovative method suitable for the screening and rapid identification of chemicals and mixtures used as antidote for OP poisoning. The method will make it easier to identify more effective medical countermeasures for chemical threat agents, including combinatorial therapies.


Assuntos
Reativadores da Colinesterase , Intoxicação por Organofosfatos , Acetilcolinesterase , Animais , Antídotos/farmacologia , Inibidores da Colinesterase/farmacologia , Reativadores da Colinesterase/farmacologia , Larva , Intoxicação por Organofosfatos/tratamento farmacológico , Oximas , Peixe-Zebra
12.
Sci Rep ; 11(1): 14710, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282204

RESUMO

The population of bumble bees and other pollinators has considerably declined worldwide, probably, due to the toxic effect of pesticides used in agriculture. Inexpensive and available antidotes can be one of the solutions for the problem of pesticide toxicity for pollinators. We studied the properties of the thiazine dye Methylene blue (MB) as an antidote against the toxic action of pesticides in the bumble bee mitochondria and found that MB stimulated mitochondrial respiration mediated by Complex I of the electron transport chain (ETC) and increased respiration of the mitochondria treated with mitochondria-targeted (chlorfenapyr, hydramethylnon, pyridaben, tolfenpyrad, and fenazaquin) and non-mitochondrial (deltamethrin, metribuzin, and penconazole) pesticides. MB also restored the mitochondrial membrane potential dissipated by the pesticides affecting the ETC. The mechanism of MB action is most probably related to its ability to shunt electron flow in the mitochondrial ETC.


Assuntos
Abelhas , Azul de Metileno/farmacologia , Mitocôndrias/efeitos dos fármacos , Praguicidas/envenenamento , Agricultura , Animais , Antídotos/farmacologia , Abelhas/efeitos dos fármacos , Abelhas/metabolismo , Citoproteção/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Polinização/efeitos dos fármacos , Polinização/fisiologia , Piretrinas/envenenamento
13.
Toxicol Sci ; 183(2): 393-403, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34270781

RESUMO

Exposure to hydrogen sulfide (H2S) can cause neurotoxicity and cardiopulmonary arrest. Resuscitating victims of sulfide intoxication is extremely difficult, and survivors often exhibit persistent neurological deficits. However, no specific antidote is available for sulfide intoxication. The objective of this study was to examine whether administration of a sulfonyl azide-based sulfide-specific scavenger, SS20, would rescue mice in models of H2S intoxication: ongoing exposure and post-cardiopulmonary arrest. In the ongoing exposure model, SS20 (1250 µmol/kg) or vehicle was administered to awake CD-1 mice intraperitoneally at 10 min after breathing 790 ppm of H2S followed by another 30 min of H2S inhalation. Effects of SS20 on survival were assessed. In the post-cardiopulmonary arrest model, cardiopulmonary arrest was induced by an intraperitoneal administration of sodium sulfide nonahydrate (125 mg/kg) in anesthetized mice. After 1 min of cardiopulmonary arrest, mice were resuscitated with intravenous administration of SS20 (250 µmol/kg) or vehicle. Effects of SS20 on survival, neurological outcomes, and plasma H2S levels were evaluated. Administration of SS20 during ongoing H2S inhalation improved 24-h survival (6/6 [100%] in SS20 vs 1/6 [17%] in vehicle; p = .0043). Post-arrest administration of SS20 improved 7-day survival (4/10 [40%] in SS20 vs 0/10 [0%] in vehicle; p = .0038) and neurological outcomes after resuscitation. SS20 decreased plasma H2S levels to pre-arrest baseline immediately after reperfusion and shortened the time to return of spontaneous circulation and respiration. These results suggest that SS20 is an effective antidote against lethal H2S intoxication, even when administered after cardiopulmonary arrest.


Assuntos
Parada Cardíaca , Sulfeto de Hidrogênio , Animais , Antídotos/farmacologia , Azidas , Parada Cardíaca/induzido quimicamente , Parada Cardíaca/tratamento farmacológico , Camundongos , Sulfetos/toxicidade
14.
Farm Hosp ; 45(4): 180-183, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-34218763

RESUMO

OBJECTIVE: To describe the development of the Antidotos_bot chatbot tool, which is used to facilitate the search for information in the Antidote Administration Guide and to perform useful calculations in the use of antidotes. METHOD: In January 2019, we proposed developing a freely accessible chatbot on Telegram® using Xenioo®. Software development  defined the way it interacts with users and incorporated calculation  functionalities. Internal validation was conducted and it was presented as  Antidotos_bot in June 2019. RESULTS: Antidotos_bot included information in Spanish on 49 antidotes and 57 poisonings. Three types of calculations were provided  and two treatment algorithms could be consulted. Consultation was  possible through 332 questions. Internal validation needed five sets of  training over 2 months. By July 2020, it had 415 users. The most  frequently consulted antidotes were glucagon, penicillin G, protamine, n- acetylcysteine and flumazenyl. Regarding monthly activity, there was an  average of 29 calculations and an average of three new users and three  queries per user. CONCLUSIONS: Antidotos_bot is a poisoning management decisionmaking tool that provides up-to-date information in a user-friendly manner. It could contribute to improving the quality and safety of care in  emergency situations.


Assuntos
Antídotos , Envenenamento , Antídotos/uso terapêutico , Humanos , Envenenamento/tratamento farmacológico , Encaminhamento e Consulta , Software
15.
Clin Toxicol (Phila) ; 59(8): 683-697, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34128439

RESUMO

CONTEXT: Sodium azide is a highly toxic chemical. Its production has increased dramatically over the last 30 years due to its widespread use in vehicular airbags, and it is available for purchase online. Thus, accidental exposure to azide or use as a homicidal or suicidal agent could be on the rise, and secondary exposure to medical personnel can occur. No antidote exists for azide poisoning. We conducted a systematic review of azide poisoning to assess recent poisoning reports, exposure scenarios, clinical presentations, and treatment strategies. METHODS: We searched both medical and newspaper databases to review the literature between 01/01/2000 and 12/31/2020, pairing the controlled vocabulary and keyword terms "sodium azide" or "hydrazoic acid" with terms relating to exposures and outcomes, such as "ingestion," "inhalation," "exposure," "poisoning," and "death." We included all peer-reviewed papers and news articles describing human azide poisoning cases from English and non-English publications that could be identified using English keywords. Data abstracted included the number, age, and gender of cases, mode of exposure, exposure setting, azide dose and route of exposure, symptoms, outcome, and treatment modalities. RESULTS: We identified 663 peer-reviewed papers and 303 newspaper articles. After removing duplicated and non-qualifying sources, 54 publications were reviewed describing 156 cases, yielding an average of 7.8 reported azide poisoning cases per year. This rate is three times higher than in a previous review covering the period of 1927 to 1999. Poisoning occurred most commonly in laboratory workers, during secondary exposure of medical personnel, or from a ripped airbag. Hypotension occurred commonly, in some cases requiring vasopressors and one patient received an intra-aortic ballon pump. Gastric lavage and/or activated charcoal were used for oral azide ingestion, and sodium nitrite, sodium thiosulfate, and/or hydroxocobalamin were used in severely poisoned patients. CONCLUSIONS: Recent increases in azide poisoning reports may stem from greater commercial use and availability. Treatment of systemic poisoning may require aggressive hemodynamic support due to profound hypotension. Based on mechanistic considerations, hydroxocobalamin is a rational choice for treating azide poisoning.


Assuntos
Envenenamento/etiologia , Envenenamento/terapia , Azida Sódica/envenenamento , Adulto , Idoso , Antídotos/uso terapêutico , Feminino , Humanos , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Nitrito de Sódio/uso terapêutico , Tentativa de Suicídio , Tiossulfatos/uso terapêutico
16.
Expert Rev Clin Pharmacol ; 14(10): 1267-1278, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34187297

RESUMO

INTRODUCTION: Acetylcysteine is the standard treatment for preventing hepatotoxicity caused by acetaminophen overdose. Several novel approaches to the management of acetaminophen overdose have been suggested to improve patient safety by reducing adverse drug reactions and dosing errors. This article reviews these alternative treatment regimens and intends to offer a detailed assessment of the available options to assist providers in managing cases of acetaminophen overdose. AREAS COVERED: This review article covers observational and experimental studies that assessed the efficacy and safety of alternative intravenous acetylcysteine regimens for acetaminophen overdose. A literature search was conducted using PubMed, ProQuest, and Scopus to identify the studies, which included results through April 2021. The assessment of alternative regimens consists of a discussion on the limitations and benefits, barriers to implementation, and important considerations for each regimen. EXPERT OPINION: Several alternative regimens have been studied and implemented in various institutions. Many of these dosing regimens have supporting safety data but most lack robust data. A reduction in infusion-related side effects is an important outcome, but established efficacy, local poison center familiarity with the regimen, institutional resources, and patient-specific factors should be equally considered when deciding on implementing and using an alternative dosing strategy.


Assuntos
Acetaminofen/envenenamento , Acetilcisteína/administração & dosagem , Antídotos/administração & dosagem , Acetilcisteína/efeitos adversos , Administração Intravenosa , Analgésicos não Narcóticos/envenenamento , Antídotos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Overdose de Drogas/tratamento farmacológico , Humanos
17.
Chemistry ; 27(53): 13280-13305, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34185362

RESUMO

Nerve agents are tetrahedral organophosphorus compounds (OPs) that were developed in the last century to irreversibly inhibit acetylcholinesterase (AChE) and therefore impede neurological signaling in living organisms. Exposure to OPs leads to a rapid development of symptoms from excessive salivation, nasal congestion and chest pain to convulsion and asphyxiation which if left untreated may lead to death. These potent toxins are prepared on a large scale from inexpensive staring materials, making it feasible for terrorist groups or states to use them against military and civilians. The existing antidotes provide limited protection and are difficult to apply to a large number of affected individuals. While new prophylactics are currently being developed, there is still need for therapeutics capable of both preventing and reversing the effects of OP poisoning. In this review, we describe how the science of molecular recognition can expand the pallet of tools for rapid and safe sequestration of nerve agents.


Assuntos
Agentes Neurotóxicos , Acetilcolinesterase , Antídotos , Inibidores da Colinesterase/toxicidade , Humanos , Agentes Neurotóxicos/toxicidade , Compostos Organofosforados
18.
Sci Rep ; 11(1): 11615, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34079035

RESUMO

This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between 2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (P < 0.001), shock (P < 0.001) and kidney injury (P = 0.001) than survivors did. Kaplan-Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test, P < 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045-166.667, P = 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Antídotos/uso terapêutico , Inseticidas/toxicidade , Intoxicação por Organofosfatos/tratamento farmacológico , Pneumonia Aspirativa/tratamento farmacológico , Insuficiência Respiratória/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/fisiopatologia , Afeto/efeitos dos fármacos , Idoso , Atropina/uso terapêutico , Clorpirifos/antagonistas & inibidores , Clorpirifos/toxicidade , Feminino , Humanos , Inseticidas/antagonistas & inibidores , Masculino , Mevinfós/antagonistas & inibidores , Mevinfós/toxicidade , Pessoa de Meia-Idade , Intoxicação por Organofosfatos/etiologia , Intoxicação por Organofosfatos/mortalidade , Intoxicação por Organofosfatos/fisiopatologia , Compostos Organotiofosforados/antagonistas & inibidores , Compostos Organotiofosforados/toxicidade , Pneumonia Aspirativa/induzido quimicamente , Pneumonia Aspirativa/mortalidade , Pneumonia Aspirativa/fisiopatologia , Compostos de Pralidoxima/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/mortalidade , Transtornos Psicóticos/fisiopatologia , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/fisiopatologia , Estudos Retrospectivos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/mortalidade , Convulsões/fisiopatologia , Choque/induzido quimicamente , Choque/tratamento farmacológico , Choque/mortalidade , Choque/fisiopatologia , Análise de Sobrevida , Resultado do Tratamento
19.
Vet Clin North Am Equine Pract ; 37(2): 327-337, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34116921

RESUMO

Equine toxicologic emergencies are relatively uncommon but can cause significant morbidity and mortality in a group of comanaged horses. The field veterinarian's role is to triage the situation, as well as the individual animal. Individual patient stabilization should focus on support of essential organ functions, providing time for treatments to have an effect or for elimination of the toxicant. Decontamination procedures can follow patient stabilization, if appropriate. Antidotes are often not available or feasible for equine intoxications. The field veterinarian should emphasize triage and stabilization before referral and on-site identification and collection of diagnostic samples to support the diagnosis.


Assuntos
Doenças dos Cavalos/terapia , Envenenamento/terapia , Animais , Antídotos/uso terapêutico , Carvão Vegetal/uso terapêutico , Descontaminação , Emergências/veterinária , Doenças dos Cavalos/diagnóstico , Cavalos , Envenenamento/diagnóstico , Triagem , Médicos Veterinários
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