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La Revue de Medecine Interne May 2024Methemoglobinemia (MetHb) refers to the state of oxidation of the iron ion "ferrous" (Fe to iron "ferric" (Fe) within the heme molecule that makes up hemoglobin (Hb).... (Review)
Review
Methemoglobinemia (MetHb) refers to the state of oxidation of the iron ion "ferrous" (Fe to iron "ferric" (Fe) within the heme molecule that makes up hemoglobin (Hb). This state is physiological if its level remains controlled. The ferrous state of the heme molecule occurs in the event of significant oxidative stress. The pathophysiology of MetHb involves NADH, NADPH and glucose cycle enzymes such as cytochrome-b5-reductase. MetHb can be acquired or more rarely, congenital. Acquired causes include drug-induced effects such as topical anesthetics, or toxic effects such as nitrites. Primary causes are linked to enzyme deficiencies or constitutional Hb abnormalities. Excessively high MetHb causes symptoms of varying intensity, depending on the level of MetHb and associated comorbidities. Clinical signs are dominated by cyanosis, indicative of tissue hypoxia, which can be complicated by severe metabolic disorders leading to death. Diagnosis can be complex, as the resulting biological abnormalities may go undetected. Treatment is mainly based on identifying the etiology and restoring the heme molecule to its physiological state. Methylene blue is the main antidote in cases of elevated MetHb, but precautions must be taken in its use, and its physico-chemical effects must be understood. We provide an update on methemoglobinemia, summarizing its pathophysiology and clinical presentations, complementary tests and therapeutic principles.
PubMed: 38777656
DOI: 10.1016/j.revmed.2024.05.001 -
Drugs May 2024Dimdazenil (Junoenil) is a small-molecule, oral, partial positive allosteric modulator of the gamma-aminobutyric acid (GABA) receptor that is being developed by Zhejiang... (Review)
Review
Dimdazenil (Junoenil) is a small-molecule, oral, partial positive allosteric modulator of the gamma-aminobutyric acid (GABA) receptor that is being developed by Zhejiang Jingxin Pharmaceutical in collaboration with Evotec for the treatment of insomnia. Dimdazenil is designed to overcome issues associated with full GABA receptor agonists, such as tolerance, withdrawal symptoms and associated adverse effects. On 29 November 2023, dimdazenil oral capsules received approval in China for the short-term treatment of insomnia. This article summarizes the milestones in the development of dimdazenil leading to this first approval for insomnia.
Topics: Humans; Drug Approval; Sleep Initiation and Maintenance Disorders; China; GABA Modulators; Receptors, GABA-A; Administration, Oral; Flumazenil
PubMed: 38546956
DOI: 10.1007/s40265-024-02020-9 -
Current Opinion in Clinical Nutrition... Mar 2024Unintentional intoxication comprises a major chunk of all intoxications. Most patients are in the pediatric age group with another set of patients being the elderly.... (Review)
Review
PURPOSE OF REVIEW
Unintentional intoxication comprises a major chunk of all intoxications. Most patients are in the pediatric age group with another set of patients being the elderly. Substances found to cause accidental intoxication vary from country to country and even within different regions of a country. Frequent reviews of current literature are needed to be abreast of trends.
RECENT FINDINGS
Prescription drugs and household chemicals are major culprits when it comes to accidental intoxication. Acetaminophen, digoxin and metformin are some of the prominent prescription drugs frequently associated with unintentional intoxications. Increasingly alcohol based hand sanitizers are becoming an important etiology of these events, following their increased usage during the COVID-19 pandemic. Pattern recognition to identify class of intoxicant and supportive care including prevention of further absorption and increased excretion are cornerstones of therapy. Antidote when available should be used promptly.
SUMMARY
Knowledge about current epidemiology of accidental intoxications, toxidrome pattern recognition and appropriate antidote usage beside adequate and timely supportive care help in successful management of the unfortunate victim of accidental intoxication.
Topics: Humans; Child; Aged; Antidotes; Pandemics; Ethanol; Metformin
PubMed: 38260945
DOI: 10.1097/MCO.0000000000001013 -
Toxics Aug 2023Poisoning and overdose are very important aspects in medicine and toxicology. Chemical weapons pose a threat to civilians, and emergency medicine principles must be... (Review)
Review
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 -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.
PubMed: 37755734
DOI: 10.3390/toxics11090723 -
British Journal of Clinical Pharmacology Jan 2024Paracetamol (acetaminophen) was marketed in the 1950s as a nonprescription analgesic/antipyretic without any preclinical toxicity studies. It became used increasingly... (Review)
Review
Paracetamol (acetaminophen) was marketed in the 1950s as a nonprescription analgesic/antipyretic without any preclinical toxicity studies. It became used increasingly for self-poisoning, particularly in the UK and was belatedly found to cause acute liver damage, which could be fatal. Management of poisoned patients was difficult as maximum abnormalities of liver function were delayed for 3 days or more after an overdose. There was no treatment and the mechanism of hepatotoxicity was not known. The paracetamol half-life was prolonged with liver damage occurring when it exceeded 4 h and the Rumack-Matthew nomogram was an important advance that allowed stratification of patients into separate zones of risk. It is used to guide prognosis and treatment and its predictive value could be increased by combining it with the paracetamol half-life. The problems of a sheep farmer in Australia in the early 1970s led to the discovery of the mechanism of paracetamol hepatotoxicity, and the first effective treatment of overdosage with intravenous (IV) cysteamine. This had unpleasant side effects and administration was difficult. N-acetylcysteine soon became the treatment of choice for paracetamol overdose and given early it was very effective when administered either IV or orally. N-acetylcysteine could cause anaphylactoid reactions, particularly early during IV administration when the concentrations were highest. Simpler and shorter regimes with slower initial rates of infusion have now been introduced with a reduced incidence of these adverse effects. In addition, there has been a move to use larger doses of N-acetylcysteine given over longer periods for patients who are more severely poisoned and those with risk factors. There has been much interest recently in the search for novel biomarkers such as microRNAs, procalcitonin and cyclophilin that promise to have greater specificity and sensitivity than transaminases. Paracetamol-protein adducts predict hepatotoxicity and are specific biomarkers of toxic paracetamol metabolite exposure. Another approach would be measurement of the plasma levels of cysteine and inorganic sulfate. It is 50 years since the first effective treatment for paracetamol poisoning and, apart from liver transplantation, there is still no effective treatment for patients who present late.
Topics: Humans; Animals; Sheep; Acetaminophen; Acetylcysteine; Chemical and Drug Induced Liver Injury; Analgesics, Non-Narcotic; Drug Overdose; Liver Diseases; Biomarkers; Antidotes
PubMed: 37683599
DOI: 10.1111/bcp.15903 -
Journal of Medical Toxicology :... Oct 2023Since 2010, medical toxicology physicians from the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) have provided reports on...
Since 2010, medical toxicology physicians from the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) have provided reports on their in-hospital and clinic patient consultations to a national case registry, known as the ToxIC Core Registry. De-identified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This thirteenth annual report provides data from 7206 patients entered into the Core Registry in 2022 by 35 participating sites comprising 52 distinct healthcare facilities, bringing the total case count to 94,939. Opioid analgesics were the most commonly reported exposure agent class (15.9%), followed by ethanol (14.9%), non-opioid analgesic (12.8%), and antidepressants (8.0%). Opioids were the leading agent of exposure for the first time in 2022 since the Core Registry started. There were 118 fatalities (case fatality rate of 1.6%). Additional descriptive analyses in this annual report were conducted to describe the location of the patient during hospitalization, telemedicine consultations, and addiction medicine treatments.
Topics: Humans; United States; Drug Overdose; Antidotes; Registries; Analgesics, Non-Narcotic; Ethanol; Analgesics, Opioid; Poisoning; Toxicology
PubMed: 37644342
DOI: 10.1007/s13181-023-00962-2 -
JAAPA : Official Journal of the... May 2024Acute liver failure, commonly caused by acetaminophen overdose, is associated with numerous systemic complications including cerebral edema, hypotension, acute kidney...
Acute liver failure, commonly caused by acetaminophen overdose, is associated with numerous systemic complications including cerebral edema, hypotension, acute kidney injury, and infection. Management is primarily supportive, with an emphasis on excellent neurocritical care. Although some antidotes and targeted treatments exist, the only definitive treatment remains orthotopic liver transplant.
Topics: Humans; Acetaminophen; Acute Kidney Injury; Analgesics, Non-Narcotic; Antidotes; Brain Edema; Drug Overdose; Liver Failure, Acute; Liver Transplantation
PubMed: 38595172
DOI: 10.1097/01.JAA.0000000000000001