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Introduction: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning.
Methods: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry.
Results: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l.
Conclusion: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.
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http://dx.doi.org/10.1186/cc4937 | DOI Listing |
Neuroscience
March 2025
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, México. Electronic address:
Synaptic activity is thought to be the primary input of the frequency bands conveyed in the electroencephalogram (EEG) and local field potentials (LFPs) recorded on the cortex. Here we ask whether synaptic activity observed in parvalbumin expressing (PV + ) neurons recorded in isolated cortical tissue bear these frequency bands. The muscarinic agonist carbachol (CCh) was used to increase cortical excitability.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
March 2025
Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Straße 4, Halle, Saale, D-06112, Germany.
The calcitonin gene-related peptide (CGRP) is an endogenous peptide that is known to be involved in the development of a migraine. CGRP is also present in the human heart, acts via CGRP receptors, and has been shown to increase the force of contraction (FOC) in isolated, electrically driven human atrial preparations (HAP) from adult patients obtained during open-heart surgery. Here, the hypothesis was tested that the positive inotropic effect (PIE) of CGRP could be attenuated by three anti-migraine drugs, namely ubrogepant, erenumab (both CGRP receptor antagonists), and eptinezumab (a CGRP antagonist).
View Article and Find Full Text PDFFront Pharmacol
February 2025
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität, Berlin, Germany.
Objective: Intestinal current measurement (ICM) provides a sensitive bioassay for assessment of cystic fibrosis transmembrane conductance regulator (CFTR) function in rectal biopsies and is used as a diagnostic tool for cystic fibrosis (CF). Furthermore, ICM was shown to be sensitive to detect pharmacological rescue of CFTR function by CFTR modulators in people with CF carrying responsive mutations. Results from clinical trials of CFTR modulators across age groups indicate that CFTR function in the sweat duct may be age-dependent with children reaching higher levels than adults.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
March 2025
Department of Pharmaceutical Toxicology, Acıbadem Mehmet Ali Aydınlar University Faculty of Pharmacy, İstanbul, Turkiye.
Cylophosphamide (CP)-induced acute cystitis is a debilitating bladder dysfunction commonly observed in cancer patients, primarily resulting from oxidative damage and inflammation in the bladder tissue. Dimethyl fumarate (DMF) is a fumaric acid ester approved for the treatment of multiple sclerosis due to its antioxidant and anti-inflammatory properties. Thus, we aimed to investigate the multiple effects of DMF, involving both its potential synergistic effect with CP on the SH-SY5Y cells and its uroprotective effect on CP-induced acute cystitis.
View Article and Find Full Text PDFFront Physiol
February 2025
Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia.
Introduction: Antimuscarinics are the first-line pharmaceutical treatment for overactive bladder (OAB). However, some literature suggests that responses to these antimuscarinics can influence a variety of non-muscarinic receptors. This study aimed to identify any non-muscarinic influences on contraction from commonly prescribed clinical antimuscarinics using porcine detrusor or urothelium with lamina propria (U&LP) tissues.
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