-
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 -
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 -
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 -
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 -
The Journal of Pediatric Pharmacology... 2023Included on the World Health Organization Model Lists of Essential Medicines, atropine remains a cornerstone medication that is used for a myriad of clinical...
Included on the World Health Organization Model Lists of Essential Medicines, atropine remains a cornerstone medication that is used for a myriad of clinical indications. Systemically, atropine carries indications for the treatment of asymptomatic and symptomatic bradycardia, reduction of salivation and bronchial secretions prior to surgery, and as an antidote for a variety of poisoning agents (i.e., carbamate or organophosphate insecticides, nerve agents, muscarine-containing mushrooms). Topically, atropine is administered via the ophthalmic route for the treatment of cycloplegia, mydriasis, and amblyopia or may be administered sublingually to treat chronic sialorrhea. As an anticholinergic, supratherapeutic concentrations of atropine result in a toxidrome typical of other anticholinergic medication overdoses. However, it is easy to overlook atropine as the causative agent when being administered topically, potentially resulting in an unnecessarily extensive and complicated workup. This case report describes the systemic absorption of atropine administered through the ophthalmic route at normal doses, resulting in stroke-like symptoms in an adolescent male. Upon identifying that the patient was being treated with atropine ophthalmic drops prior to hospital arrival, a dose of intravenous physostigmine was administered, resulting in complete reversal of all toxidrome symptoms.
PubMed: 38130339
DOI: 10.5863/1551-6776-28.6.565 -
Frontiers in Aging Neuroscience 2023Loss of neuropeptide Y (NPY)-expressing interneurons in the hippocampus and decaying cholinergic neuromodulation are thought to contribute to impaired cognitive function...
Loss of neuropeptide Y (NPY)-expressing interneurons in the hippocampus and decaying cholinergic neuromodulation are thought to contribute to impaired cognitive function during aging. However, the interaction of these two neuromodulatory systems in maintaining hippocampal synaptic plasticity during healthy aging has not been explored so far. Here we report profound sex differences in the Neuropeptide-Y (NPY) levels in the dorsal dentate gyrus (DG) with higher NPY concentrations in the male mice compared to their female counterparts and a reduction of NPY levels during aging specifically in males. This change in aged males is accompanied by a deficit in theta burst-induced long-term potentiation (LTP) in the medial perforant path-to-dorsal DG (MPP-DG) synapse, which can be rescued by enhancing cholinergic activation with the acetylcholine esterase blocker, physostigmine. Importantly, NPYergic transmission is required for this rescue of LTP. Moreover, exogenous NPY application alone is sufficient to recover LTP induction in aged male mice, even in the absence of the cholinergic stimulator. Together, our results suggest that in male mice NPYergic neurotransmission is a critical factor for maintaining dorsal DG LTP during aging.
PubMed: 38020778
DOI: 10.3389/fnagi.2023.1283581 -
BMC Complementary Medicine and Therapies Nov 2023Myrtus communis L. (MC) has been used in Mesopotamian medicine. Here, the cholinesterase (ChE) inhibitory potential of its methyl alcohol extracts has been investigated...
BACKGROUND
Myrtus communis L. (MC) has been used in Mesopotamian medicine. Here, the cholinesterase (ChE) inhibitory potential of its methyl alcohol extracts has been investigated and computationally dissected.
METHOD
The ChE inhibition has been measured based on usual Ellman's colorimetric method compared to a canonical ChE inhibitor, eserine. Through a deep text mining, the structures of phytocompounds (= ligands) of MC were curated from ChemSpider, PubChem, and ZINC databases and docked into protein targets, AChE (PDB 1EVE) and BChE (PDB 1P0I) after initial in silico preparedness and binding affinity (BA; kcal/mol) reported as an endpoint. The calculation of ADMET (absorption, distribution, metabolism, excretion, and toxicity) features of phytocompounds were retrieved from SwissADME ( http://www.swissadme.ch/ ) and admetSAR software to predict the drug-likeness or lead-likeness fitness. The Toxtree v2.5.1, software platforms ( http://toxtree.sourceforge.net/ ) have been used to predict the class of toxicity of phytocompounds. The STITCH platform ( http://stitch.embl.de ) has been employed to predict ChE-chemicals interactions.
RESULTS
The possible inhibitory activities of AChE of extracts of leaves and berries were 37.33 and 70.00%, respectively as compared to that of eserine while inhibitory BChE activities of extracts of leaves and berries of MC were 19.00 and 50.67%, respectively as compared to that of eserine. Phytochemicals of MC had BA towards AChE ranging from -7.1 (carvacrol) to -9.9 (ellagic acid) kcal/mol. In this regard, alpha-bulnesene, (Z)-gamma-Bisabolene, and beta-bourbonene were top-listed low toxic binders of AChE, and (Z)-gamma-bisabolene was a more specific AChE binder. Alpha-cadinol, estragole, humulene epoxide II, (a)esculin, ellagic acid, patuletin, juniper camphor, linalyl anthranilate, and spathulenol were high class (Class III) toxic substances which among others, patuletin and alpha-cadinol were more specific AChE binders. Among intermediate class (Class II) toxic substances, beta-chamigrene was a more specific AChE binder while semimyrtucommulone and myrtucommulone A were more specific BChE binders.
CONCLUSION
In sum, the AChE binders derived from MC were categorized mostly as antiinsectants (e.g., patuletin and alpha-cardinal) due to their predicted toxic classes. It seems that structural amendment and stereoselective synthesis like adding sulphonate or sulphamate groups to these phytocompounds may make them more suitable candidates for considering in preclinical investigations of Alzheimer's disease.
Topics: Cholinesterase Inhibitors; Myrtus; Physostigmine; Myrtaceae; Fruit; Ellagic Acid; Cholinesterases
PubMed: 37990185
DOI: 10.1186/s12906-023-04241-z -
Oxford Medical Case Reports Sep 2023Antimuscarinic drug toxicity is a common pediatric emergency, which produces central and peripheral symptoms. Treatment of agitation and hyperactive antimuscarinic...
Antimuscarinic drug toxicity is a common pediatric emergency, which produces central and peripheral symptoms. Treatment of agitation and hyperactive antimuscarinic delirium, with first-line agents like cholinesterase inhibitors or benzodiazepines, is imperative to prevent severe toxicity. Intravenous physostigmine salicylate is a cholinesterase inhibitor that is commonly used to treat central antimuscarinic delirium. Its chemical structure facilitates crossing of the blood-brain barrier. Overlapping nationwide physostigmine and benzodiazepine shortages have prompted consideration of therapeutic alternatives. Rivastigmine is a long-acting cholinesterase inhibitor with a similar chemical structure to physostigmine. It represents a potential therapeutic option for antimuscarinic delirium. Rivastigmine offers potential benefits over physostigmine including a longer duration of action, slower rate of central nervous system penetration, more favorable side effect profile, and availability in multiple formulations. A paucity of literature exists describing the use of rivastigmine for central antimuscarinic delirium. We describe the effective use of oral rivastigmine in a child with central antimuscarinic delirium.
PubMed: 37771682
DOI: 10.1093/omcr/omad096 -
Journal of Research in Medical Sciences... 2023Diphenhydramine (DPH) is an antihistamine medication that in overdose can result in anticholinergic symptoms and serious complications, including arrhythmia and coma. We...
BACKGROUND
Diphenhydramine (DPH) is an antihistamine medication that in overdose can result in anticholinergic symptoms and serious complications, including arrhythmia and coma. We aimed to compare the value of various machine learning (ML) models, including light gradient boosting machine (LGBM), logistic regression (LR), and random forest (RF), in the outcome prediction of DPH poisoning.
MATERIALS AND METHODS
We used the National Poison Data System database and included all of the human exposures of DPH from January 01, 2017 to December 31, 2017, and excluded those cases with missing information, duplicated cases, and those who reported co-ingestion. Data were split into training and test datasets, and three ML models were compared. We developed confusion matrices for each, and standard performance metrics were calculated.
RESULTS
Our study population included 53,761 patients with DPH exposure. The most common reasons for exposure, outcome, chronicity of exposure, and formulation were captured. Our results showed that the average precision-recall area under the curve (AUC) of 0.84. LGBM and RF had the highest performance (average AUC of 0.91), followed by LR (average AUC of 0.90). The specificity of the models was 87.0% in the testing groups. The precision of models was 75.0%. Recall (sensitivity) of models ranged between 73% and 75% with an F1 score of 75.0%. The overall accuracy of LGBM, LR, and RF models in the test dataset was 74.8%, 74.0%, and 75.1%, respectively. In total, just 1.1% of patients (mostly those with major outcomes) received physostigmine.
CONCLUSION
Our study demonstrates the application of ML in the prediction of DPH poisoning.
PubMed: 37496638
DOI: 10.4103/jrms.jrms_602_22 -
Wiener Klinisches Magazin : Beilage Zur... 2023Impaired consciousness is a frequent phenomenon after general anesthesia. In addition to the classical causes (e.g., overhang of sedatives), an impairment of... (Review)
Review
Impaired consciousness is a frequent phenomenon after general anesthesia. In addition to the classical causes (e.g., overhang of sedatives), an impairment of consciousness can also be an adverse side effect of drugs. Many drugs used in anesthesia can trigger these symptoms. Alkaloids, such as atropine can trigger a central anticholinergic syndrome, opioids can promote the occurrence of serotonin syndrome and the administration of a neuroleptic can lead to neuroleptic malignant syndrome. These three syndromes are difficult to diagnose due to the individually very heterogeneous symptoms. Mutual symptoms, such as impaired consciousness, tachycardia, hypertension and fever further complicate the differentiation between the syndromes; however, more individual symptoms, such as sweating, muscle tension or bowl sounds can be helpful in distinguishing these syndromes. The time from the trigger event can also help to differentiate the syndromes. The central anticholinergic syndrome is the fastest to appear, usually taking just a few of hours from trigger to clinical signs, serotonin syndrome takes several hours up to 1 day to show and neuroleptic malignant syndrome usually takes days. The clinical symptoms can range from mild to life-threatening. Generally, mild cases are treated with discontinuation of the trigger and extended observation. More severe cases can require specific antidotes. The specific treatment recommended for central anticholinergic syndrome is physostigmine with an initial dose of 2 mg (0.04 mg/kg body weight, BW) administered over 5 min. For serotonin syndrome an initial dose of 12 mg cyproheptadine followed by 2 mg every 2 h is recommended (maximum 32 mg/day or 0.5 mg/kgBW day) but this medication is only available in Germany as an oral formulation. For neuroleptic malignant syndrome 25-120 mg dantrolene (1-2.5 mg/kgBW maximum 10 mg/kgBW day) is the recommended treatment.
PubMed: 37251531
DOI: 10.1007/s00740-023-00492-1