anticholinergic poisoning

Organophosphorus compounds (OP) are a constant problem, both in the military and in the civilian field, not only in the form of acute poisoning but also for their long-lasting consequences. No antidote has been found that satisfactorily protects against the toxic effects of organophosphates. Likewise, there is no universal cure to avert damage after poisoning. The key mechanism of organophosphate toxicity is the inhibition of acetylcholinesterase. The overstimulation of nicotinic or muscarinic receptors by accumulated acetylcholine on a synaptic cleft leads to activation of the glutamatergic system and the development of seizures...

Organophosphates (OPs) are inhibitors of acetylcholinesterase and have deleterious effects on the central nervous system. Clinical manifestations of OP poisoning include convulsions, which represent an underlying toxic neuro-pathological process, leading to permanent neuronal damage. This neurotoxicity is mediated through the cholinergic, GABAergic and glutamatergic (NMDA) systems. Pharmacological interventions in OP poisoning are designed to mitigate these specific neuro-pathological pathways, using anticholinergic drugs and GABAergic agents...

ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a prominent health challenge characterized by complex aetiology and limited therapeutic breakthroughs. Datura metel (DM) is a medicinal plant containing active phytoconstituents with neuropharmacological potentials. In traditional medicine, it exerts anticholinergic, anti-inflammatory and antioxidant effects, and protection from organophosphate poisoning inclusively involved in the pharmacotherapy of PD. Its other PD-related medicinal potency include treatment of motor sickness and bradycardia...

Nerve agent poisoning is still a threat to civilization. Nerve agents function by binding with the enzyme acetylcholinesterase irreversibly. Accumulation of acetylcholine in the synapse causes over-stimulation of muscarinic and nicotinic acetylcholinergic receptors. Thus miosis, glandular hyper secretion, bronchoconstriction, vomiting, diarrhea and bradycardia occurs (by M1-M5 receptors stimulation); whereas convulsion and seizures occur due to the nicotinic receptors. Atropine is a non-selective muscarinic antagonists but no nicotinic antagonists are known...

Tropane alkaloids (TAs) are among the most valued chemical compounds known since pre-historic times. Poisonous plants from Solanaceae family (Hyoscyamus niger, Datura, Atropa belladonna, Scopolia lurida, Mandragora officinarum, Duboisia) and Erythroxylaceae (Erythroxylum coca) are rich sources of tropane alkaloids. These compounds possess the anticholinergic properties as they could block the neurotransmitter acetylcholine action in the central and peripheral nervous system by binding at either muscarinic and/or nicotinic receptors...

Atropine (ATR) is extracted from a belladonna plant that belongs to a class of anticholinergic drugs and is therefore involved in the treatment of the overdose of cholinergic drugs or mushroom poisoning. It is a well-known blocker of muscarinic acetylcholine receptors (mAChRs) that are expressed in various tumor cells, including breast tumors from animal and human origin, but it has yet to be recommended as an anticancer drug. Our in silico docking analysis indicates that atropine has a roust virtual binding, with a stable binding energy, to two major signaling molecules involved in EMT regulation: E-cad and ZEB-2...

Datura spp. is a potentially poisonous plant that is widely spread and is simply accessible, which can yield poisoning with a central and peripheral anticholinergic effect. We reported cases of family poisoning caused by the herbal tea with refreshing effects that were identified as Datura spp.

Datura stramonium (also called thorn apple or Jimson weed) is a plant that contains atropine, scopolamine, and hyoscyamine, giving it anticholinergic effects when consumed. We report the case of a 32-year-old male in Qatar who intentionally ingested seeds from Jimson weed mixed with milk. The patient became severely confused and delirious, eventually requiring admission to the intensive care unit (ICU) for two days for management. The patient was discharged safely with no complications afterward. The case is unique in that Jimson weed is not common in Qatar, and due to the adverse effects of this plant, this case serves to highlight to both the general population and healthcare professionals the effects of ingestion and the appropriate management plan for toxicity caused by Jimson weed...

Overdoses with the sedating antihistamines alimemazine, hydroxyzine, promethazine and propiomazine have received attention in recent years in Sweden. The Poisons Information Center has noted an increase in calls regarding intoxications, and the National Board of Forensic Medicine has concluded that these substances have directly contributed to a large number of poisoning deaths. When prescribing alimemazine, hydroxyzine, promethazine and propiomazine, their pharmacological properties, such as antihistaminergic and anticholinergic effects, and their anti-arrhythmic potential must be considered...

Most research on medical countermeasures for nerve agent exposure assumes a military scenario, in which (autoinjector) treatment is envisaged to be available immediately. In a civilian setting however, treatment is delayed until arrival of first-aid responders. This may significantly affect treatment efficacy and the requirements for secondary intensive care. The aim of the current study was to develop a guinea pig model to evaluate the efficacy of delayed treatment following nerve agent exposure. We identified a trigger-to-treat based on a progressive stage of the toxidrome following VX exposure, which was associated with the subsiding of clonic movements...

BACKGROUND: Harmine is a β-carboline alkaloid that displays antidepressant, antitumor and other pharmacological effects. However, the strong toxic effects limit its clinical application, and should be first considered. PURPOSE: To evaluate the in vivo toxicity of harmine and explore intervention strategies against its toxicity. METHODS: The in vivo toxicity of harmine was assessed from the symptoms, biochemical indices, and cardiovascular effects in mice...

OBJECTIVE: Drug-induced delirium has been attributed to opioid, benzodiazepine, antipsychotic, antihistaminic and anticholinergic drug groups at therapeutic doses. Delirium also occurs in hospital-treated self-poisoning (at supra-therapeutic doses), although the causative drug classes are not well established and co-ingestion is common. We tested the magnitude and direction of association of five major drug groups with incident cases of delirium. METHODS: A retrospective longitudinal cohort ( n  = 5131) study was undertaken of deliberate and recreational/chronic misuse poisoning cases from a regional sentinel toxicology unit...

Background: Cuscuta reflexa (dodder) belonging to the family Convolvulaceae has many ethno-medicinal uses such as antidiarrheal and antiemetic. This plant has been employed to treat diarrhea, where the antidiarrheal use of this plant is well established in different communities around the world without scientific bases. In addition, the antibacterial, anthelmintic, anticholinergic, and antihistaminic effects of this parasitic vine are partly responsible for the folkloric antidiarrheal use of this plant...

Anticholinergic plants of the family Solanaceae have a long history of use as medicines, poisons, and recreational drugs. Though they were the intoxicating substances of choice throughout Europe for centuries, their use for these purposes has declined with the globalisation of other recreational drugs. The present study sought to examine the level of knowledge surrounding these plants among individuals who had used other hallucinogenic plants or mushrooms in Slovenia. Participants were questioned in regards to the anticholinergic Solanaceae that are known to grow wild in Slovenia: Atropa belladonna L...

BACKGROUND Clozapine is a well-proven atypical antipsychotic drug used for therapy of treatment-resistant schizophrenia. Over the last decades only a few cases of clozapine poisoning have been reported. Hence, guidelines for in-hospital management are currently not available. Most of the reported cases underwent detoxication measures as charcoal therapy and/or gastric lavage. However, there is no evidence for primary detoxication to improve clinical outcome. In contrast, use of therapy with intravenous physostigmine in the case of anticholinergic syndrome is restricted due to concerns about safety and dosing...

AIM: To synthesize and evaluate the fused heterocyclic imidazopyridine oxime as a reactivator against paraoxon inhibited acetylcholinesterase. BACKGROUND: Organophosphorus compounds (OPs) include parathion, malathion, chlorpyrifos, monocrotophos, and diazinon which are commonly used in agriculture for enhancing agricultural productivity via killing crop-damaging pests. However, people may get exposed to OPs pesticides unintentionally/intentionally via ingestion, inhalation or dermal...

Tropane alkaloids (TAs) are secondary plant metabolites derived mainly from Solanaceae plant families, with the most virulent invasive species being Datura stramonium. Datura stramonium commonly grows in cereal fields and produce TAs (e.g., hyoscyamine and scopolamine) which may accidentally contaminate cereals (and cereal-based foods) at occasionally high levels. Dietary exposure to TAs can be toxic and depending on the dose ingested can cause outcomes ranging from anticholinergic effects to acute poisoning and death...

Phosphylation of the pivotal enzyme acetylcholinesterase (AChE) by nerve agents (NAs) leads to irreversible inhibition of the enzyme and accumulation of neurotransmitter acetylcholine, which induces cholinergic crisis, that is, overstimulation of muscarinic and nicotinic membrane receptors in the central and peripheral nervous system. In severe cases, subsequent desensitisation of the receptors results in hypoxia, vasodepression, and respiratory arrest, followed by death. Prompt action is therefore critical to improve the chances of victim's survival and recovery...

Physostigmine is a cholinesterase inhibitor used therapeutically in patients with anticholinergic delirium that is so severe that intubation may be required for airway protection. Given that a wide variety of medications have anticholinergic properties, and the current standard of care is typically a central nervous system depressant, hospitalizations are often lengthy and normally require a critical-care level of attention. Despite this, physostigmine is often underutilized and poorly understood in the clinical setting...

Acetylcholinesterase (AChE) is an important drug target in neurological disorders like Alzheimer's disease, Lewy body dementia, and Parkinson's disease dementia as well as for other conditions like myasthenia gravis and anticholinergic poisoning. In this study, we have used a combination of high-throughput screening, machine learning, and docking to identify new inhibitors of this enzyme. Bayesian machine learning models were generated with literature data from ChEMBL for eel and human AChE inhibitors as well as butyrylcholinesterase inhibitors (BuChE) and compared with other machine learning methods...