Antidotes in Poisoning

Chacko, Binila; Peter, John Victor

doi:10.5005/jp-journals-10071-23310

Cited by 10 publications

(8 citation statements)

References 43 publications

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“…Flumazenil is used as an antidote in the case of an overdose of benzodiazepines, drugs with a sedative, hypnotic, anticonvulsant, and muscle-relaxant effect [ 98 , 99 ]. The mechanism of action of flumazenil is based on interaction with GABA receptors.…”

Section: Flumazenilmentioning

confidence: 99%

“…The total dose of flumazenil should not exceed 2 mg in one treatment. In the case of recurrent somnolence, it is possible to use intravenous infusions [ 98 , 99 ]. It should not be used in patients with seizure disorders, prolonged QRS interval, or tolerance to benzodiazepines, including dependence on benzodiazepines and their derivatives [ 98 ].…”

Section: Flumazenilmentioning

confidence: 99%

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Antidotes in Clinical Toxicology—Critical Review

Kobylarz,

Noga,

Frydrych

et al. 2023

Toxics

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Poisoning and overdose are very important aspects in medicine and toxicology. Chemical weapons pose a threat to civilians, and emergency medicine principles must be followed when dealing with patients who have been poisoned or overdosed. Antidotes have been used for centuries and modern research has led to the development of new antidotes that can accelerate the elimination of toxins from the body. Although some antidotes have become less relevant due to modern intensive care techniques, they can still save lives or reduce the severity of toxicity. The availability of antidotes is crucial, especially in developing countries where intensive care facilities may be limited. This article aims to provide information on specific antidotes, their recommended uses, and potential risks and new uses. In the case of poisoning, supportive therapies are most often used; however, in many cases, the administration of an appropriate antidote saves the patient’s life. In this review, we reviewed the literature on selected antidotes used in the treatment of poisonings. We also characterised the antidotes (bio)chemically. We described the cases in which they are used together with the dosage recommendations. We also analysed the mechanisms of action. In addition, we described alternative methods of using a given substance as a drug, an example of which is N-acetylcysteine, which can be used in the treatment of COVID-19. This article was written as part of the implementation of the project of the Polish Ministry of Education and Science, “Toxicovigilance, poisoning prevention, and first aid in poisoning with xenobiotics of current clinical importance in Poland”, grant number SKN/SP/570184/2023.

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Section: Flumazenilmentioning

confidence: 99%

Section: Flumazenilmentioning

confidence: 99%

Antidotes in Clinical Toxicology—Critical Review

Kobylarz,

Noga,

Frydrych

et al. 2023

Toxics

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“…Mitochondria are the organelle that most efficiently controls energy availability in cells, and certainly energy production and life are strictly connected. Indeed, impairment of energy production is difficult to reverse and results in rapid death [18]. Conversely, it has been shown that by Parkin-mediated mitochondrial autophagy (mitophagy) [19], the generation of viable, but mitochondria-depleted fibroblasts have amelioration of multiple features of senescence [20], as well as those induced by ionizing radiation, such as the production of ROS and the senescence-associated secretory phenotype, the complex of factors including matrix metalloproteinases, growth factors, and proinflammatory cytokines (SASP) [21].…”

Section: Mitochondria Energy Availability and Autophagy Or Apoptosismentioning

confidence: 99%

Protein Syntheses and Autophagy: In Contrast or in Synchrony?

Dioguardi¹,

Scarabelli²,

Pasini³

et al. 2021

Preprint

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Background. Sarcopenia, defined as the loss of skeletal muscle mass and function, is a major clinical problem in many chronic illnesses, in cancer and in the elderly. Exercise and adequate nutrition, peculiarly dependents on availability of essential amino acids, considered the primary strategies for prevention and treatment of protein synthetic deficits, affect both the efficient scavenging of aged and overused protein molecules and the renewal, by maintaining muscular protein synthesis. Many questions still remain about the regulation of protein syntheses and degradation. Degradation of inefficient proteins or organelles is performed by the sum of micro and macro-autophagy plus ubiquitin-proteasome system, activities known as proteostasis, necessary to preserve and promote protein masses and consequently, the body’s reserves. However, how protein synthesis is regulated, and how activation of the mTOR complex may modulate and transduce the flow of information provided by exercise and nutrition to balance proteostasis and syntheses, is far from being fully understood. We suggest that energy production and availability, thus also mitochondria, may have a pivotal role in synchronizing activity and functional outcomes of protein syntheses, and that those syntheses, since higly energy demanding, are main effectors of AMPK dependent autophagy activation by consuming ATP and producing AMP. Conclusion. While in normal conditions protein syntheses drive autophagy activation by decreasing ATP to AMP ratio, conversely autophagy may be inefficiently activated when chronic both low production and consumption of ATP would result in lowest concentrations of AMP, and therefore both blunted rates of protein syntheses and autophagy would be observed. We suggest that this functional hypothesis may explain sarcopenia in many pathological conditions , as in cancer or in aging muscles.

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“…Toxicological emergencies are often encountered in intensive care unit practice. They can be the result of a drug overdose, or due to drug toxicity that is linked to the use of inappropriate dosages and/or unexpected drug interactions [ 1 ]. Cardiotoxicity represents one of the most common adverse drug effects [ 2 ], but different drugs have also been shown to induce clinically relevant neurotoxic effects [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…According to this scenario, an antidote should act as “an agent able to increase the mean toxic/lethal dose of a toxin” [ 6 ]. Different mechanisms can underlie the clinical efficacy of currently available antidotes [ 4 ], such as: (i) preventing the absorption of the toxin; (ii) directly counteracting the toxin by competitive enzyme inhibition (e.g., fomepizole) or competitive receptor blocking (e.g., naloxone); (iii) inhibiting the conversion of the toxin to more toxic metabolites (e.g., N -acetyl-cysteine), finally antagonizing its end organ effects and promoting the elimination of the xenobiotics [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Potential of Carnosine as an Antidote against Drug-Induced Cardiotoxicity and Neurotoxicity: Focus on Nrf2 Pathway

et al. 2022

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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.

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Antidotes in Poisoning

Cited by 10 publications

References 43 publications

Antidotes in Clinical Toxicology—Critical Review

Antidotes in Clinical Toxicology—Critical Review

Protein Syntheses and Autophagy: In Contrast or in Synchrony?

The Therapeutic Potential of Carnosine as an Antidote against Drug-Induced Cardiotoxicity and Neurotoxicity: Focus on Nrf2 Pathway

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