Possible mechanisms of anti-cholinergic drug-induced bradycardia

Meyer, E. C.; Sommers, K. De

doi:10.1007/bf00558245

Cited by 29 publications

(8 citation statements)

References 7 publications

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“…Pitschner et ctt. (1989) have also excluded the block ade of the M1 receptors located on peripheralsympathetic ganglia as a possible explanation for the cardiodeceleratory effects of these agents, as had been suggested earlier (Meyer and Sommers 1988). In the present study, scopolamine increased the HR variability, but also resulted in dry mouth.…”

Section: Discussionsupporting

confidence: 79%

Effects of scopolamine on immediate postural changes in heart rate and R—R variance in humans

Yeragani

Pohl

Balon

et al. 1992

Human Psychopharmacology

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To examine the anticholinergic effects of scopolamine, postural tests were performed in nine healthy male volunteers after they received intravenous infusions of 0.2 mg of scopolamine, 0.4 mg of glycopyrrolate, or placebo on separate days under double-blind randomized conditions. Compared to the placebo and glycopyrrolate conditions, scopolamine produced a significantly exaggerated HR response to standing from supine posture. Scopolamine also produced a significant increase in R-R variance during supine deep breathing and standing conditions as compared to glycopyrrolate and placebo conditions. At the same time, scopolamine also produced a significant dry mouth. These findings suggest that the effects of scopolamine in low doses on the above cardiac variables are vagomimetic.

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Section: Discussionsupporting

confidence: 79%

Effects of scopolamine on immediate postural changes in heart rate and R—R variance in humans

Yeragani

Pohl

Balon

et al. 1992

Human Psychopharmacology

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“…Hence, when muscarinic antagonists such as atropine are applied, they may not simply affect muscarinic receptors at the atrial myocardium but also in the cardiac neurons. This may provide another explanation for seemingly paradoxical phenomena such as atropine-induce bradycardia (44,45), as prior studies on the RAGP using atropine to mitigate cholinergic inputs to the myocardium may have inadvertently impacted RAGP neurophysiology (33,46). Genetic association studies that implicate muscarinic receptors in HR recovery in exercise or ion channels with sudden unexplained death in epilepsy are agnostic to tissue type (47,48).…”

Section: Discussionmentioning

confidence: 95%

Innervation and Neuronal Control of the Mammalian Sinoatrial Node: A Comprehensive Atlas

Hanna

Dacey

Brennan

et al. 2020

Preprint

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Cardiac function is under exquisite intrinsic cardiac neural control. Neuroablative techniques to modulate control of cardiac function are currently being studied in patients, albeit with variable and sometimes deleterious results. Recognizing the major gaps in our understanding of cardiac neural control, we sought to evaluate neural regulation of impulse initiation in the sinoatrial node as an initial discovery step. Here, we report an in-depth, multi-scale structural and functional characterization of the innervation of the sinoatrial node (SAN) by the right atrial ganglionated plexus (RAGP) in porcine and human hearts. Combining intersectional strategies including tissue clearing, immunohistochemical and ultrastructural techniques, we have delineated a comprehensive neuroanatomic atlas of the RAGP-SAN complex. The RAGP shows significant phenotypic diversity of neurons while maintaining predominant cholinergic innervation. Cellular and tissue-level electrophysiologic mapping and ablation studies demonstrate interconnected ganglia with synaptic convergence within the RAGP to modulate SAN automaticity, atrioventricular (AV) conduction and left ventricular (LV) contractility. For the first time, we demonstrate that intrinsic cardiac neurons influence the pacemaking site in the heart. This provides an experimental demonstration of a discrete neuronal population controlling a specific geographic region of the heart (SAN) that can serve as a framework for further exploration of other parts of the intrinsic cardiac nervous system (ICNS) in mammalian hearts and for developing targeted therapies.

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“…Glycopyrrolate, in contrast, is almost lacking cholinomimetic effects at low doses (22); at higher doses, when equi-effective doses of atropine and glycopyrrolate are used, there are only minor differences between the two agents in their effects on heart rate (23). Recently it has been suggested that atropine-induced bradycardia results from the M,-blockade of sympathetic ganglia, and low concentrations of anticholinergics may cause an increase in acetylcholine, perhaps due to a presynaptic effect on nerve endings (16,24). All these drugs give rise to a profound inhibition of salivation and secretions of the gastrointestinal tract.…”

Section: Effects Of Anticholinergic Drugsmentioning

confidence: 99%

Pharmacokinetics and related pharmacodynamics of anticholinergic drugs

Ali‐Melkkilä

Kanto

Iisalo

1993

Acta Anaesthesiol Scand

156

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The pharmacokinetics and some pharmacodynamic properties of atropine, glycopyrrolate and scopolamine are reviewed. With the development of new analytical methods for drug determination, it is now possible to measure relatively low concentrations of these drugs in biological fluids and, consequently, some new kinetic data have been collected. Following intravenous administration, a fast disappearance from the circulation is observed and due to a high total clearance value their elimination phase half-lives vary from 1 to 4 h. All these agents are nonselective muscarinic receptor antagonists, but their actions on various organ systems with cholinergic innervation show considerable diversity. The cardiovascular effects are of short duration; other peripheral muscarinic effects and CNS effects can last up to 8 h or even longer. Differing from atropine and scopolamine, glycopyrrolate as a quaternary amine penetrates the biological membranes (blood-CNS, placental barriers) slowly and incompletely, making it the drug of choice for elderly patients with coexisting diseases and for obstetric use. Similarly, its oral absorption is slow and erratic, and hence it cannot be used as an oral premedicant. Atropine, scopolamine and glycopyrrolate have a definitely faster absorption rate, when injected into the deltoid muscle compared with administration into the gluteal or vastus lateralis muscles. There appear to be significant differences in the metabolism and renal excretion of these agents. Scopolamine is apparently excreted into the urine mainly as inactive metabolites, nearly half of the atropine dose administered is recovered in the urine as the parent drug or as active metabolites and about 80% of glycopyrrolate is excreted as unchanged drug or active metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

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Possible mechanisms of anti-cholinergic drug-induced bradycardia

Cited by 29 publications

References 7 publications

Effects of scopolamine on immediate postural changes in heart rate and R—R variance in humans

Effects of scopolamine on immediate postural changes in heart rate and R—R variance in humans

Innervation and Neuronal Control of the Mammalian Sinoatrial Node: A Comprehensive Atlas

Pharmacokinetics and related pharmacodynamics of anticholinergic drugs

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