Atropine and hyoscine

Shutt, L.E.; Bowes, John E.

doi:10.1111/j.1365-2044.1979.tb06327.x

Cited by 65 publications

(24 citation statements)

References 150 publications

(2 reference statements)

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“…Based on the particular OP, route, duration, and level of exposure, the onset of clinical symptoms can be quite rapid, requiring a quick-acting, efficacious therapeutic regimen to mitigate the pharmacologic effects (Eddleston et al, 2008;Newmark, 2007). In the United States, the primary components of the FDA-approved and currently fielded medical countermeasures to counter OP poisoning are a competitive muscarinic receptor antagonist (atropine) to mitigate the excitotoxic effect at post-synaptic targets (Shutt and Bowes, 1979), and an AChE oxime reactivator, pralidoxime chloride (2-PAM Cl), to augment OP dissociation from and reactivation of inhibited AChE (US FDA, 2006). The combination of these two therapeutic strategies aims to reduce the hyperstimulation of parasympathetic nerves that results from the over-accumulation of ACh (Harris and Stitcher, 1983;Eyer, 2003).…”

Section: Introductionmentioning

confidence: 99%

Toxicity and median effective doses of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig

et al. 2016

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-Anticholinesterases, such as organophosphorus pesticides and warfare nerve agents, present a significant health threat. Onset of symptoms after exposure can be rapid, requiring quick-acting, efficacious therapy to mitigate the effects. The goal of the current study was to identify the safest antidote with the highest therapeutic index (TI = oxime 24-hr LD 50 /oxime ED 50 ) from a panel of four oximes deemed most efficacious in a previous study. The oximes tested were pralidoxime chloride (2-PAM Cl), MMB4 DMS, HLö-7 DMS, and obidoxime Cl 2 . The 24-hr median lethal dose (LD 50 ) for the four by intramuscular (IM) injection and the median effective dose (ED 50 ) were determined. In the ED 50 study, male guinea pigs clipped of hair received 2x LD 50 topical challenges of undiluted Russian VX (VR), VX, or phorate oxon (PHO) and, at the onset of cholinergic signs, IM therapy of atropine (0.4 mg/kg) and varying levels of oxime. Survival was assessed at 3 hr after onset clinical signs. The 3-hr 90th percentile dose (ED 90 ) for each oxime was compared to the guinea pig pre-hospital human-equivalent dose of 2-PAM Cl, 149 μmol/kg. The TI was calculated for each OP/oxime combination. Against VR, MMB4 DMS had a higher TI than HLö-7 DMS, whereas 2-PAM Cl and obidoxime Cl 2 were ineffective. Against VX, MMB4 DMS > HLö-7 DMS > 2-PAM Cl > obidoxime Cl 2 . Against PHO, all performed better than 2-PAM Cl. MMB4 DMS was the most effective oxime as it was the only oxime with ED 90 < 149 μmol/kg against all three topical OPs tested.

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Section: Introductionmentioning

confidence: 99%

Toxicity and median effective doses of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig

et al. 2016

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“…Atropine is a naturally occurring alkaloid found in many plants 1. The pharmacological action of atropine on the heart is due to antagonism of the binding of acetylcholine secreted by efferent Vagus nerves on the post-synaptic membrane in the sinoatrial node.…”

Section: Introductionmentioning

confidence: 99%

“…Historically, atropine was used during chloroform anaesthesia to prevent the potentially fatal bradyarrhythmias 1. Subsequently, atropine was ‘rediscovered’ twice in the twentieth century; first as an adjuvant to ether anaesthesia to prevent excessive salivation and later to antagonise the ‘vago-mimetic’ bradycardic effects of suxamethonium 1.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, atropine was ‘rediscovered’ twice in the twentieth century; first as an adjuvant to ether anaesthesia to prevent excessive salivation and later to antagonise the ‘vago-mimetic’ bradycardic effects of suxamethonium 1. The introduction of safer anaesthetic agents led to the discontinuation of routine atropine use during anaesthetic induction.…”

Section: Introductionmentioning

confidence: 99%

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The therapeutic value of atropine for critical care intubation

Jones

2015

Arch Dis Child

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Recent studies of atropine during critical care intubation (CCI) have revealed that neonates frequently experience bradycardia, are infrequently affected by ventricular arrhythmias and conduction disturbances and deaths have not been reported in a series of studies. The indiscriminate use of atropine is unlikely to alter the outcome during neonatal CCI other than reducing the frequency of sinus tachycardia. In contrast, older children experience a similar frequency of bradycardia to neonates and are more frequently affected by ventricular arrhythmias and conduction disturbances. Mortality during CCI is in the order of 0.5%. Atropine has a beneficial effect on arrhythmias and conduction disturbances and may reduce paediatric intensive care unit mortality. The use of atropine for children >1 month of age may positively influence outcomes beyond a reduction in the frequency of sinus bradycardia. There is indirect evidence that atropine should be used for intubation during sepsis. Atropine should be considered when using suxamethonium. The reliance on heart rate as the sole measure of haemodynamic function during CCI is no longer justifiable. Randomised trials of atropine for mortality during CCI in general intensive care unit populations are unlikely to happen. As such, future research should be focused on establishing of a gold standard for haemodynamic decompensation for CCI. Cardiac output or blood pressure are the most likely candidates. The 'lost beat score' requires development but has the potential to be developed to provide an estimation of risk of haemodynamic decompensation from ECG data in real time during CCI.

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“…64 This study involved electrophysiological studies of cultured murine gastric ICC. Another study showed that atropine (a muscarinic antagonist used to increase cardiac output and dry bodily secretions during anesthesia) 72 showed a decrease in slow wave frequency as well as dysrhythmia of slow waves in the stomach, but showed no effect in the small intestine. 65 The methodology in this study involved implanting electrodes in canine stomach and small intestine to observe slow waves in vivo.…”

Section: Effect Of Anticholinergic Drugs On Slow Wave Motilitymentioning

confidence: 99%

Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs

et al. 2017

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ABSTRACT. Anticholinergic drugs are well-known to cause adverse effects, such as constipation, but their effects on baseline contractile activity in the gut driven by slow waves is not well established. In a video-based gastrointestinal motility monitoring (GIMM) system, a mouse's small intestine was placed in Krebs solution and recorded using a high definition camera. Untreated controls were recorded for each specimen, then treated with a therapeutic concentration of the drug, and finally, treated with a supratherapeutic dose of the drug. Next, the video clips showing gastrointestinal motility were processed, giving us the segmentation motions of the intestine, which were then converted via Fast Fourier Transform (FFT) into their respective frequency spectrums. These contraction quantifications were analyzed from the video recordings under standardised conditions to evaluate the effect of drugs. Six experimental trials were included with benztropine and promethazine treatments. Only the supratherapeutic dose of benztropine was shown to significantly decrease the amplitude of contractions; at therapeutic doses of both drugs, neither frequency nor amplitude was significantly affected. We have demonstrated that intestinal slow waves can be analyzed based on the colonic frequency or amplitude at a supratherapeutic dose of the anticholinergic medications. More research is required on the effects of anticholinergic drugs on these slow waves to ascertain the true role of ICC in neurologic control of gastrointestinal motility.

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Atropine and hyoscine

Cited by 65 publications

References 150 publications

Toxicity and median effective doses of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig

Toxicity and median effective doses of oxime therapies against percutaneous organophosphorus pesticide and nerve agent challenges in the Hartley guinea pig

The therapeutic value of atropine for critical care intubation

Analysis of spatiotemporal pattern and quantification of gastrointestinal slow waves caused by anticholinergic drugs

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