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Anesthesiology May 2024
PubMed: 38810018
DOI: 10.1097/ALN.0000000000005009 -
Cureus Apr 2024Central and autonomic nervous system signs of organophosphate poisoning (OP), such as altered consciousness, noticeable lacrimation, and salivation, can be influenced by...
Central and autonomic nervous system signs of organophosphate poisoning (OP), such as altered consciousness, noticeable lacrimation, and salivation, can be influenced by medications used in intensive care settings, such as atropine and pralidoxime methyl (PAM). Because of this, there are no established methods for assessing the duration of OP while receiving antidotal treatment. In the present case, we used the Neurological Pupil Index (NPi) to evaluate the duration of OP in an 82-year-old woman who attempted suicide by ingesting up to 100 mL of fenitrothion. Until hospitalization day (HD) 20, discontinuation of atropine led to the recurrence of altered consciousness, while its reinstatement resulted in improvement; this made it difficult to assess the prolongation of OP based on signs and symptoms. Until HD 20, the NPi remained at 0/0, and subsequently, it increased. Additionally, even after discontinuing atropine, consciousness, tearing, and salivation did not worsen, indicating recovery from OP. On HD 26, serum acetylcholinesterase (AChE) levels were elevated above the measurable level for the first time, following an increase in the NPi. In this case, assessing the persistence of OP based on signs was challenging because these signs improved with atropine and PAM treatment. The improvement in NPi levels coincided with an improvement in poisoning, suggesting that NPi is useful for evaluating the duration of OP. NPi is noninvasive and sensitive compared to AChE, which is used to gauge the persistence of OP and could be used to allow earlier cessation of medication and guide appropriate treatment durations.
PubMed: 38800312
DOI: 10.7759/cureus.58872 -
JFMS Open Reports 2024A 1-year-old male neutered domestic shorthair cat presented on an emergency basis with clinical signs suspected to be secondary to organophosphate (OP) toxicity. The...
CASE SUMMARY
A 1-year-old male neutered domestic shorthair cat presented on an emergency basis with clinical signs suspected to be secondary to organophosphate (OP) toxicity. The control of clinical abnormalities (bradycardia, obtundation, tachypnea, anorexia) was achieved using high-dose continuous rate intravenous infusion (CRI) of atropine sulfate (maximum rate 0.1 mg/kg/h). After 5 days of hospitalization, the patient made a full clinical recovery without the development of atropine toxicity, intermediate syndrome or delayed polyneuropathy at 4 weeks after discharge.
RELEVANCE AND NOVEL INFORMATION
Treatment of OP toxicity in cats is sparsely reported in veterinary literature. Current standards of treatment and published protocols recommend the use of atropine sulfate as intermittent boluses for the treatment of muscarinic signs of toxicity; however, there is a paucity of information regarding the safety and efficacy of atropine sulfate as a CRI for severe toxicosis as described in humans. This report includes the first published case using such a treatment protocol in a cat.
PubMed: 38799116
DOI: 10.1177/20551169241249637 -
Pharmaceuticals (Basel, Switzerland) May 2024Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative...
Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12-39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.
PubMed: 38794204
DOI: 10.3390/ph17050633 -
Life (Basel, Switzerland) May 2024Scopolamine and atropine are two medicinal alkaloids derived from L. with anticholinergic properties. This study explored how methyl jasmonate (MJ), a plant growth...
Modulation of Tropane Alkaloids' Biosynthesis and Gene Expression by Methyl Jasmonate in L.: A Comparative Analysis of Scopolamine, Atropine, and Hyoscyamine Accumulation.
Scopolamine and atropine are two medicinal alkaloids derived from L. with anticholinergic properties. This study explored how methyl jasmonate (MJ), a plant growth regulator, affects the biosynthesis and accumulation of these alkaloids in different plant tissues. The expression levels of putrescine N-methyltransferase (), tropinone reductase I (), and hyoscyamine 6β-hydroxylase (), three critical enzymes in the biosynthetic pathway, were also analyzed. The results indicated that MJ at 150 µM increased the production of scopolamine and atropine in both leaves and roots, while MJ at 300 µM had an adverse effect. Furthermore, MJ enhanced the expression of , and genes in the roots, the primary site of alkaloid synthesis, but not in the leaves, the primary site of alkaloid storage. These results imply that MJ can be applied to regulate the biosynthesis and accumulation of scopolamine and atropine in , thereby improving their production efficiency.
PubMed: 38792639
DOI: 10.3390/life14050618 -
Frontiers in Pharmacology 2024Glycopyrrolate is commonly researched as a preoperative medication or in conjunction with cholinesterase inhibitors to counteract the lingering muscarinic effects of...
Effects of glycopyrrolate and atropine for oral secretions and perioperative hemodynamics in children undergoing tonsillectomy and adenoidectomy: a prospective, single-center, randomized, double-blind, controlled trial.
INTRODUCTION
Glycopyrrolate is commonly researched as a preoperative medication or in conjunction with cholinesterase inhibitors to counteract the lingering muscarinic effects of non-depolarizing muscarinic agents. However, studies have yielded inconsistent results regarding the superiority of glycopyrrolate over other anti-cholinergic drugs, such as atropine, particularly its effect on heart rate, blood pressure (BP), and glandular secretions. This study aimed to evaluate the differences in perioperative oral secretions, hemodynamics, and recovery quality with glycopyrrolate versus those with atropine before anesthesia induction in children undergoing tonsillectomy and adenoidectomy.
METHODS
In this prospective, single-center, randomized, double-blind, controlled trial, a total of 103 children were randomly assigned to group A (n = 51, glycopyrrolate 0.005 mg/kg) or B (n = 52, atropine 0.01 mg/kg). The follow-up anesthetic induction and maintenance protocols were the same in both groups. Vital signs, duration of surgery, extubation time, degree of wetness around the vocal cords during tracheal intubation, weight of oral secretions, and perioperative complications were recorded.
RESULTS
No significant differences were observed in the degree of wetness around the vocal cords during tracheal intubation, as well as in the weight of oral secretions, duration of surgery, or extubation time, between the two groups. The intraoperative and postoperative heart rates were lower in group A than in group B (110.18 ± 10.58 vs. 114.94 ± 11.14, = 0.028; 96.96 ± 10.81 vs. 103.38 ± 10.09, = 0.002). The differences observed in the intraoperative and preoperative heart rates were lower in group A than in group B (23.84 ± 9.62 vs. 29.65 ± 8.75, = 0.002). The differences observed in the postoperative and preoperative heart rates were lower in group A than in group B (10.63 ± 9.97 vs. 18.09 ± 9.39, = 0.000).
CONCLUSION
Glycopyrrolate showed a smoother change in heart rate than atropine during and after tonsillectomy and adenoidectomy, with no effect on BP or recovery quality, and did not increase oral secretions. The findings indicate that glycopyrrolate can serve as an alternative to atropine to prevent secretions in anesthesia induction for tonsillectomy and adenoidectomy in children. This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2200063578; Date of Registration: 12/09/2022).
PubMed: 38783938
DOI: 10.3389/fphar.2024.1344786 -
Frontiers in Toxicology 2024Acute intoxication with high levels of organophosphate (OP) cholinesterase inhibitors can cause cholinergic crisis, which is associated with acute, life-threatening...
Acute intoxication with high levels of organophosphate (OP) cholinesterase inhibitors can cause cholinergic crisis, which is associated with acute, life-threatening parasympathomimetic symptoms, respiratory depression and seizures that can rapidly progress to status epilepticus (SE). Clinical and experimental data demonstrate that individuals who survive these acute neurotoxic effects often develop significant chronic morbidity, including behavioral deficits. The pathogenic mechanism(s) that link acute OP intoxication to chronic neurological deficits remain speculative. Cellular senescence has been linked to behavioral deficits associated with aging and neurodegenerative disease, but whether acute OP intoxication triggers cellular senescence in the brain has not been investigated. Here, we test this hypothesis in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague-Dawley rats were administered DFP (4 mg/kg, s.c.). Control animals were administered an equal volume (300 µL) of sterile phosphate-buffered saline (s.c.). Both groups were subsequently injected with atropine sulfate (2 mg/kg, i.m.) and 2-pralidoxime (25 mg/kg, i.m.). DFP triggered seizure activity within minutes that rapidly progressed to SE, as determined using behavioral seizure criteria. Brains were collected from animals at 1, 3, and 6 months post-exposure for immunohistochemical analyses of p16, a biomarker of cellular senescence. While there was no immunohistochemical evidence of cellular senescence at 1-month post-exposure, at 3- and 6-months post-exposure, p16 immunoreactivity was significantly increased in the CA3 and dentate gyrus of the hippocampus, amygdala, piriform cortex and thalamus, but not the CA1 region of the hippocampus or the somatosensory cortex. Co-localization of p16 immunoreactivity with cell-specific biomarkers, specifically, NeuN, GFAP, S100β, IBA1 and CD31, revealed that p16 expression in the brain of DFP animals is neuron-specific. The spatial distribution of p16-immunopositive cells overlapped with expression of senescence associated β-galactosidase and with degenerating neurons identified by FluoroJade-C (FJC) staining. The co-occurrence of p16 and FJC was positively correlated. This study implicates cellular senescence as a novel pathogenic mechanism underlying the chronic neurological deficits observed in individuals who survive OP-induced cholinergic crisis.
PubMed: 38745692
DOI: 10.3389/ftox.2024.1360359 -
Radiology Case Reports Aug 2024Choroidal detachment (CD) is a rare and potentially vision-threatening complication of glaucoma surgery. Inflammation and prolonged ocular hypotony can promote fluid...
Choroidal detachment (CD) is a rare and potentially vision-threatening complication of glaucoma surgery. Inflammation and prolonged ocular hypotony can promote fluid accumulation between the choroid and sclera. Risk factors include trauma, advanced age, use of anticoagulant medications, systemic hypertension, atherosclerosis, and diabetes. CD ultrasound findings will show 2 layers, detaching as far anteriorly as the ciliary bodies, that protrude convexly into the vitreous without extending to the optic disc, often described as the appositional or In contrast, retinal detachments will show a distinct "V" shape due to the retina's fixation to the optic nerve head posteriorly. In the case of hemorrhagic CD, therapy should be targeted at reducing intraocular pressure. In this case, the patient was started on atropine and prednisolone drops and discontinued on all glaucoma medications in the left eye. While serous choroidal detachments are usually benign, persistent choroidal effusions may cause significant morbidity with hemorrhagic CD having a worse prognosis. Point of care ultrasound can help emergency physicians quickly distinguish between choroidal and retinal detachments and thus guide management in a safe and timely manner.
PubMed: 38737180
DOI: 10.1016/j.radcr.2024.04.017 -
Molecules (Basel, Switzerland) May 2024The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has...
The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has been provided for the human enzyme so far. In the present work, a steady-state kinetic analysis performed by spectrophotometry showed that highly purified human plasma BChE tetramer slowly hydrolyzes atropine at pH 7.0 and 25 °C. The affinity of atropine for the enzyme is weak, and the observed kinetic rates versus the atropine concentration was of the first order: the maximum atropine concentration in essays was much less than . Thus, the bimolecular rate constant was found to be / = 7.7 × 10 M min. Rough estimates of catalytic parameters provided slow < 40 min and high = 0.3-3.3 mM. Then, using a specific organophosphoryl agent, echothiophate, the time-dependent irreversible inhibition profiles of BChE for hydrolysis of atropine and the standard substrate butyrylthiocholine (BTC) were investigated. This established that both substrates are hydrolyzed at the same site, i.e., S198, as for all substrates of this enzyme. Lastly, molecular docking provided evidence that both atropine isomers bind to the active center of BChE. However, free energy perturbations yielded by the Bennett Acceptance Ratio method suggest that the L-atropine isomer is the most reactive enantiomer. In conclusion, the results provided evidence that plasma BChE slowly hydrolyzes atropine but should have no significant role in its metabolism under current conditions of medical use and even under administration of the highest possible doses of this antimuscarinic drug.
Topics: Butyrylcholinesterase; Atropine; Humans; Kinetics; Hydrolysis; Molecular Docking Simulation; Models, Molecular
PubMed: 38731631
DOI: 10.3390/molecules29092140 -
The Journal of Pharmacology and... May 2024Substantial clinical and preclinical evidence indicates that transient receptor potential vanilloid 1 (TRPV1) receptors are expressed on terminals of colorectal...
Substantial clinical and preclinical evidence indicates that transient receptor potential vanilloid 1 (TRPV1) receptors are expressed on terminals of colorectal chemoreceptors and mechanoreceptors and are involved in various rectal hypersensitivity disorders with common features of colorectal overactivity. These stimulatory properties of TRPV1 receptors on colorectal function suggested that brief stimulation of TRPV1 might provide a means of pharmacologically activating the colorectum to induce defecation in patients with an "unresponsive" colorectum. The current studies explored the basic features of TRPV1 receptor-induced contractions of the colorectum in anesthetized rats with and without acute spinal cord injury (aSCI). Cumulative concentration-response curves to intrarectal (IR) capsaicin (CAP) solutions (0.003% to 3.0%) were performed in anesthetized aSCI and spinal intact rats. CAP produced an "inverted U", cumulative concentration-response curve with a threshold for inducing colorectal contractions at 0.01% and a peak response at 0.1% and slight decreases in responses up to 3%. Decreases in responses with concentrations > 0.1% are due to a rapid desensitization (i.e. 30 min) of TRPV1 receptors to each successive dose. Desensitization appeared fully recovered within 24 hours in spinal intact rats. Colorectal contractions were completely blocked by atropine, indicating a reflexogenic activation of parasympathetic neurons, and responses were completely unaffected by a neurokinin 2 receptor antagonist, indicating that release of neurokinin A (NKA) from afferent terminals and subsequent direct contractions of the smooth muscle was not involved. IR administration of 3 other TRPV1 receptor agonists produced similar results as CAP. Individuals with spinal cord injury often lose control of defecation. Time consuming and inconvenient bowel programs using digital stimulation of the rectum and manual extraction of stool are used to empty the bowel. We show that intrarectal administration of the TRPV1 receptor agonist, capsaicin, can induce rapid onset, short duration colorectal contractions capable of inducing defecation in spinal cord injured and intact rats. Therefore, TRPV1 agonists show promise as a potential therapeutics to induce defecation in individuals with neurogenic bowel.
PubMed: 38719479
DOI: 10.1124/jpet.123.001989