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Toxics May 2024From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to... (Review)
Review
From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to antihistamines alone. The most common antihistamine found in all these reported deaths is diphenhydramine, a ubiquitous, over-the-counter and clinically important medication. Currently, there is no antidote for diphenhydramine overdose. This review summarizes the adverse health effects and current emergency medicine treatments for diphenhydramine. Several emergency medicine case reports are reviewed, and the efficacy and outcomes of a variety of treatments are compared. The treatments reviewed include the more traditional antihistamine overdose therapeutics physostigmine and sodium bicarbonate, as well as newer ones such as donepezil, dexmedetomidine, and lipid emulsion therapy. We conclude that more study is needed to determine the ideal therapeutic approach to treating antihistamine overdoses.
PubMed: 38922056
DOI: 10.3390/toxics12060376 -
Journal of Medical Toxicology :... May 2024
PubMed: 38806888
DOI: 10.1007/s13181-024-01007-y -
Cureus Apr 2024Myasthenia gravis (MG) is an autoimmune disorder in which, most commonly, there is a production of autoantibodies against the nicotinic acetylcholinergic receptors at...
Myasthenia gravis (MG) is an autoimmune disorder in which, most commonly, there is a production of autoantibodies against the nicotinic acetylcholinergic receptors at the neuromuscular junction, resulting in skeletal muscle weakness. For pediatric patients, literature addressing the psychiatric implications of MG and suitable treatment options for individuals with concurrent psychiatric illnesses is scarce. In this case report, an adolescent with MG and comorbid depression was treated following a suicide attempt via self-poisoning. The patient experienced an improvement of depressive symptoms upon initiating fluoxetine, despite concerns raised by previous studies suggesting that fluoxetine might block acetylcholine receptors at the neuromuscular junction with varying degrees of affinity, potentially worsening MG symptoms. In this case, our patient exhibited sustained control of her MG symptoms without exacerbation once she was started on fluoxetine. This case highlights the value of further investigation into the safety and efficacy of selective serotonin reuptake inhibitors (SSRIs) in the management of depression among pediatric patients with MG.
PubMed: 38756305
DOI: 10.7759/cureus.58408 -
The Journal of Emergency Medicine May 2024Anticholinergic toxicity is commonly encountered in the emergency department. However, the availability of physostigmine, a central acetylcholinesterase inhibitor used...
BACKGROUND
Anticholinergic toxicity is commonly encountered in the emergency department. However, the availability of physostigmine, a central acetylcholinesterase inhibitor used to reverse anticholinergic delirium, has been significantly limited due to national drug shortages in the United States. Several articles have explored the viability of rivastigmine as an alternative treatment in these patients.
CASE REPORT
A 33-year-old man presented to the emergency department after a suspected suicide attempt. The patient was found with an empty bottle of diphenhydramine at the scene. On arrival, he was tachycardic and delirious, with dilated and nonreactive pupils and dry skin. As the clinical picture was highly suggestive of anticholinergic toxicity, the patient was treated with oral rivastigmine at a starting dose of 4.5 mg to reverse his anticholinergic delirium. Although a repeat dose was required, his delirium resolved without recurrence. Why Should an Emergency Physician Be Aware of This? Oral rivastigmine has been applied successfully here and in other case reports to reverse anticholinergic delirium with the benefit of prolonged agitation control. Emergency physicians may consider this medication in consultation with a specialist, with initial doses starting at 4.5-6 mg, if encountering anticholinergic delirium when physostigmine is not available.
Topics: Humans; Rivastigmine; Male; Delirium; Adult; Cholinesterase Inhibitors; Cholinergic Antagonists; Administration, Oral; Suicide, Attempted; Emergency Service, Hospital
PubMed: 38658202
DOI: 10.1016/j.jemermed.2024.03.017 -
European Journal of Case Reports in... 2024Sudden onset of reduced consciousness, psychomotor agitation and mydriasis are all indicative of an anticholinergic toxidrome. It is important to note that numerous...
INTRODUCTION
Sudden onset of reduced consciousness, psychomotor agitation and mydriasis are all indicative of an anticholinergic toxidrome. It is important to note that numerous drugs, as well as certain herbs and plants, possess anticholinergic properties.
CASE DESCRIPTION
An 84-year-old female patient had sudden nocturnal onset of uncoordinated hand movements and altered mental status. Shortly after, the patient's 83-year-old husband developed symptoms of dysarthria, gait ataxia, vertigo, and delirium.
CONCLUSION
Anticholinergic syndrome consists of a combination of central and peripheral anticholinergic symptoms. Physostigmine given intravenously resulted in rapid reversal of symptoms. Thorn apple seeds had been accidentally ingested and were identified as the cause.
LEARNING POINTS
The clinical presentation of an anticholinergic toxidrome includes both central and peripheral symptoms such as altered consciousness, mydriasis, dry mucous membranes and skin, and tachycardia.Prompt recognition of anticholinergic toxidrome and the administration of physostigmine can lead to rapid reversal of symptoms and improved patient outcomes.Treatment with physostigmine is indicated when a patient with an agitated delirium does not respond adequately to titrated benzodiazepines.
PubMed: 38584905
DOI: 10.12890/2024_004381 -
Clinical Toxicology (Philadelphia, Pa.) Feb 2024Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural...
INTRODUCTION
Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural disturbance. Physostigmine is an effective treatment for anticholinergic delirium, but its availability is limited. As rivastigmine is readily available, it has been used to manage anticholinergic delirium; however, there is limited research investigating its use.
METHOD
This was a retrospective review of patients with anticholinergic delirium treated in two toxicology units with rivastigmine (oral capsule or transdermal patch) from January 2019 to June 2023. The primary outcome was the use of further parenteral treatment (sedation or physostigmine) for delirium post rivastigmine administration.
RESULTS
Fifty patients were administered rivastigmine for the management of anticholinergic delirium. The median age was 36 years (interquartile range: 25-49 years) and 27 (54 per cent) were females. Features consistent with anticholinergic toxicity included tachycardia in 44 (88 per cent) and urinary retention requiring catheterisation in 40 (80 per cent). Forty-three patients (86 per cent) were treated with physostigmine before rivastigmine administration. Twenty-two were managed with transdermal rivastigmine (most commonly 9.5 mg/24 hour patch), and 28 with oral rivastigmine 6 mg. Further parenteral sedation and/or physostigmine treatment were required more often in patients given transdermal than oral rivastigmine [16/22 (73 per cent) versus 9/28 (32 per cent), = 0.010)]. No patients had bradycardia or gastrointestinal symptoms following rivastigmine administration. One patient with a history of epilepsy had a seizure, 1.5 hours post physostigmine administration and 7 hours post transdermal rivastigmine.
DISCUSSION
Rivastigmine has been increasingly used for the management of patients with anticholinergic delirium, due to the lack of availability of physostigmine. In this case series, rivastigmine transdermal patch appeared to be less effective than oral rivastigmine capsules, likely due to its slow onset of action and/or insufficient dose.
CONCLUSION
Rivastigmine can be used to treat anticholinergic delirium. In our case series oral rivastigmine appeared more effective than transdermal rivastigmine.
Topics: Female; Humans; Adult; Male; Rivastigmine; Physostigmine; Cholinergic Antagonists; Cholinesterase Inhibitors; Delirium
PubMed: 38465631
DOI: 10.1080/15563650.2024.2319854 -
Journal of Pharmacological and... 2024An adverse effect of drug candidates, seizure is a serious issue in drug development. Improving evaluation systems for seizure liability is crucial for selecting good...
Improved seizure liability detection by combining rat hippocampal brain slice electrophysiology with in vivo behavior observation following intracerebroventricular drug administration.
An adverse effect of drug candidates, seizure is a serious issue in drug development. Improving evaluation systems for seizure liability is crucial for selecting good candidates. Firstly, in vitro electrophysiological measurement by a multielectrode array system in rat hippocampal brain slices was employed to confirm an increase in electrically evoked population spike (PS) area, the occurrence of multiple population spikes (MPSs), and thereby the seizure liability of five positive control chemicals: picrotoxin, 4-aminopyridine, pentylenetetrazole, penicillin G, and chlorpromazine. Aspirin, a negative control, did not affect PS area or generate MPSs. Furthermore, baclofen, an anticonvulsant drug, decreased PS area and inhibited the increase in PS area or occurrence of MPSs induced by picrotoxin. A comparative study of seizure liability among carbapenem antibiotics revealed that tienam > carbenin > omegacin and finibax. Despite leading to a strong decrease in PS area, physostigmine, cisplatin, and paroxetine still produced MPSs. Therefore, the increase in PS area or the occurrence of the MPS are considered significant evaluation parameters for seizure liability. In contrast, the in vitro electrophysiological measurement could not detect the seizure liability of diphenhydramine or fluvoxamine. A follow-up study of in vivo mouse behavioral change induced by intracerebroventricular administration of these drugs clearly detected convulsions. The in vitro electrophysiological study using hippocampal brain slices combined with in vivo behavior observation study of drug candidates administered by intracerebroventricular injection can implement to assess the seizure liability of even small amounts, especially in the early stages of drug development.
Topics: Rats; Mice; Animals; Picrotoxin; Behavior Observation Techniques; Follow-Up Studies; Seizures; Electrophysiology; Hippocampus; Brain
PubMed: 38432527
DOI: 10.1016/j.vascn.2024.107496 -
Journal of Medical Toxicology :... Jan 2024Physostigmine fell out of widespread use in the 1980s due to safety concerns; however, more recent research has demonstrated that its safety profile is better than...
INTRODUCTION
Physostigmine fell out of widespread use in the 1980s due to safety concerns; however, more recent research has demonstrated that its safety profile is better than previously thought. These studies have mainly included adults. We theorized that improved safety data may lead to more acceptance. Our objectives, therefore, were to characterize current frequency of use of physostigmine in pediatric patients as well as to study adverse effect rates in a national pediatric patient population.
METHODS
The National Poison Data System was queried for cases of patients aged 0-18 years that involved single-substance exposures to antimuscarinic xenobiotics that were reported to a poison center between January 1, 2000, and December 31, 2020. Cases were stratified into groups by therapy received: benzodiazepines alone, benzodiazepines and physostigmine, physostigmine alone, or no physostigmine or benzodiazepines. Patient demographics, clinical effects, and medical outcomes were analyzed.
RESULTS
A total of 694,132 cases were reviewed, and 150,075 were included for analysis. Nearly 5% (7562/150,075) of patients received specific pharmacological therapy with benzodiazepines, physostigmine, or both. A benzodiazepine as a single agent was the most frequently used pharmacologic therapy (92% of 7562). Among patients receiving any pharmacological therapy, only 8.3% (n = 627) of patients received physostigmine. Frequency of serious outcomes significantly increased across the study period among patients receiving benzodiazepines alone or with physostigmine. There was no increase in serious outcomes among patients receiving only physostigmine.
CONCLUSIONS
Physostigmine frequency of use was low overall, but when used, was associated with less severe outcomes when compared to benzodiazepines.
PubMed: 38265619
DOI: 10.1007/s13181-024-00988-0 -
Naunyn-Schmiedeberg's Archives of... Jul 2024Cognitive disorders are associated with valproate and drugs used to treat neuropsychological diseases. Cannabidiol (CBD) has beneficial effects on cognitive function....
Role of hippocampal and prefrontal cortical cholinergic transmission in combination therapy valproate and cannabidiol in memory consolidation in rats: involvement of CREB- BDNF signaling pathways.
PURPOSE
Cognitive disorders are associated with valproate and drugs used to treat neuropsychological diseases. Cannabidiol (CBD) has beneficial effects on cognitive function. This study examined the effects of co-administration of CBD and valproate on memory consolidation, cholinergic transmission, and cyclic AMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway in the prefrontal cortex (PFC) and hippocampus (HPC).
METHODS
One-trial, step-through inhibitory test was used to evaluate memory consolidation in rats. The intra-CA1 injection of physostigmine and atropine was performed to assess the role of cholinergic transmission in this co-administration. Phosphorylated CREB (p-CREB)/CREB ratio and BDNF levels in the PFC and HPC were evaluated.
RESULTS
Post-training intraperitoneal (i.p.) valproate injection reduced memory consolidation; however, post-training co-administration of CBD with valproate ameliorated memory impairment induced by valproate. Post-training intra-CA1 injection of physostigmine at the ineffective doses in memory consolidation (0.5 and 1 µg/rat), plus injection of 10 mg/kg of CBD as an ineffective dose, improved memory loss induced by valproate, which was associated with BDNF and p-CREB level enhancement in the PFC and HPC. Conversely, post-training intra-CA1 injection of ineffective doses of atropine (1 and 2 µg/rat) reduced the positive effects of injection of CBD at a dose of 20 mg/kg on valproate-induced memory loss associated with BDNF and p-CREB level reduction in the PFC and HPC.
CONCLUSION
The results indicated a beneficial interplay between valproate and CBD in the process of memory consolidation, which probably creates this interaction through the BDNF-CREB signaling pathways in the cholinergic transmission of the PFC and HPC regions.
Topics: Animals; Valproic Acid; Brain-Derived Neurotrophic Factor; Male; Prefrontal Cortex; Signal Transduction; Cannabidiol; Cyclic AMP Response Element-Binding Protein; Hippocampus; Rats, Wistar; Memory Consolidation; Rats; Drug Therapy, Combination; Synaptic Transmission
PubMed: 38189934
DOI: 10.1007/s00210-023-02941-4 -
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