Contribution of vagal blockade to the tachycardia induced by the antimuscarinic agents atropine and pirenzepine

Chassaing, Chantal; Boucher, Michel; Breysse, C.; Duchêne-Marullaz, P

doi:10.1111/j.1474-8673.1992.tb00384.x

Cited by 9 publications

(5 citation statements)

References 18 publications

(18 reference statements)

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“…It is well established that ‘classical’ (nonsubtype receptor selective) antimuscarinics may increase heart rate through blockade of vagal inhibitory input [168,169]. Although cardiac arrhythmia and tachycardia are among the precautions listed in the full prescribing information for oxybutynin IR, a study of 21 elderly patients with OAB who had been treated with oxybutynin IR for ≥4 weeks had no significant change from baseline for heart rate, PR interval, or QTc parameters [170].…”

Section: Tolerability and Safetymentioning

confidence: 99%

Muscarinic receptor antagonists for overactive bladder

2007

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From time to time we publish a full review of drugs that are available for the treatment of common conditions. In this issue, the review is written by two of the leading authorities in the world, Paul Abrams and Karl‐Erik Andersson, on the topic of overactive bladder and antimuscarinic agents. This in‐depth review covers the entire range of questions that might be asked about this common area of interest. Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urgency urinary incontinence, usually with frequency and nocturia. OAB symptoms are often associated with detrusor overactivity (DO). Like OAB symptoms, the prevalence of DO increases with age and can have a neurogenic and/or myogenic aetiology. Bladder outlet obstruction can be a contributing factor in DO, possibly through cholinergic denervation of the detrusor and supersensitivity of muscarinic receptors to acetylcholine, although the prevalence of OAB is similar in men and women across age groups. Acetylcholine is the primary contractile neurotransmitter in the human detrusor, and antimuscarinics exert their effects on OAB/DO by inhibiting the binding of acetylcholine at muscarinic receptors M2 and M3 on detrusor smooth muscle cells and other structures within the bladder wall. Worldwide, there are six antimuscarinic drugs currently marketed for the treatment of OAB: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin. Each has demonstrated efficacy for the treatment of OAB symptoms, but their pharmacokinetic and adverse event profiles differ somewhat due to structural differences (tertiary vs quaternary amines), muscarinic receptor subtype selectivities, and organ selectivities. Antimuscarinics are generally well tolerated, even in special populations (e.g. men with bladder outlet obstruction, elderly patients, children). The most frequently reported adverse events in clinical studies of antimuscarinics are dry mouth, constipation, headache, and blurred vision; few patients withdraw from clinical trials because of adverse events. Development of an antimuscarinic with functional selectivity for the bladder would reduce the occurrence of antimuscarinic adverse events. The therapeutic potential of several other agents, such as α3‐adrenoceptor agonists, purinergic receptor antagonists, phosphodiesterase inhibitors, neurokinin‐1 receptor antagonists, opioids, and Rho‐kinase inhibitors, is also under investigation for the treatment of OAB.

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Section: Tolerability and Safetymentioning

confidence: 99%

Muscarinic receptor antagonists for overactive bladder

2007

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“…Sinus tachycardia occurring in response to methoctramine and atropine administration in this study was similar to that occurring after atropine administration in other studies of conscious dogs. In two previous studies, administration of intravenous atropine, 200 mg/kg, to trained conscious dogs resulted in heart rates greater than 225 bpm (Donald et al, 1967;Chassaing et al, 1992). The duration of tachycardia after atropine administration was not noted in one of the previous studies and exceeded the 30-min duration of recording in the other study.…”

Section: Discussionmentioning

confidence: 77%

Effects of a selective and a nonselective muscarinic cholinergic antagonist on heart rate and intestinal motility in dogs

Hendrix

Robinson

1997

Vet Pharm & Therapeutics

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The effects of methoctramine, a cardioselective muscarinic cholinergic antagonist, on heart rate and small intestinal motor activity were compared to those of the nonselective competitive muscarinic antagonist, atropine. Methoctramine or atropine, 6, 10, 30, 60 micrograms/kg, or sterile isotonic saline, was administered intravenously to six conscious dogs in cross-over studies. Methoctramine administration caused dose-dependent tachycardia without affecting intestinal motility, while atropine administration caused dose-dependent tachycardia accompanied by significant reductions in small intestinal motility. Additionally, methoctramine did not inhibit intestinal smooth muscle contractile activity initiated by the muscarinic agonist bethanechol, while atropine inhibited bethanechol-induced contractile activity in a dose-dependent manner. Calculated, dosages of methoctramine and atropine required to produce a 50% increase in heart rate over baseline were 35.1 +/- 5.3 and 39.5 +/- 6.2 micrograms/kg, respectively. This dosage of atropine caused a 93 +/- 13.9% reduction in intestinal motility. These findings suggest that selective muscarinic antagonists may be useful drugs for those veterinary patients in which nonselective muscarinic antagonists have the potential to produce untoward effects on intestinal motility.

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“…Several vagolytic compounds, including GLY, have been shown to increase heart rate beyond that which occurs in vagotomized dogs (Rigel et al ., ), indicating that the tachycardia induced by antimuscarinic agents is not solely due to vagal blockade. This ‘excess tachycardia’ may be a result of ganglionic blockade, yet its mechanisms are not fully understood (Schuil et al ., ; Chassaing et al ., ; Rigel & Katona, )…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of glycopyrrolate following a continuous‐rate infusion in the horse

Rumpler

Kandala

Vickroy

et al. 2013

Vet Pharm & Therapeutics

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Glycopyrrolate (GLY) is an antimuscarinic agent that is used in humans and domestic animals primarily to reduce respiratory tract secretions during anesthesia and to reverse intra-operative bradycardia. Although GLY is used routinely in veterinary patients, there is limited information regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties in domestic animals, and an improved understanding of the plasma concentration-effect relationship in racehorses is warranted. To accomplish this, we characterize the pharmacokinetic-pharmacodynamic (PK-PD) actions of GLY during and after a 2-h constant-rate intravenous infusion (4 μg/kg/h) and evaluate potential PK-PD models for cardiac stimulation in adult horses. Measurements of plasma GLY concentrations, heart and respiration rates, and frequency of bowel movements were performed in six Thoroughbred horses. The time course for GLY disposition in plasma followed a tri-exponential equation characterized by rapid disappearance of GLY from blood followed by a prolonged terminal phase. Physiological monitoring revealed significant (P < 0.01) increases in heart (>70 bpm) and respiratory rates accompanied by a marked and sustained delay in the frequency of bowel movements (1.1 ± 0.2 h [saline group] vs. 6.0 ± 2.0 h [GLY group]). Two of six horses showed signs of colic during the 8-h observation period after the end of the GLY infusion, but were treated and recovered without further complications. The relationship between plasma GLY concentration and heart rate exhibited counterclockwise hysteresis that was adequately described using an effect compartment.

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Contribution of vagal blockade to the tachycardia induced by the antimuscarinic agents atropine and pirenzepine

Cited by 9 publications

References 18 publications

Muscarinic receptor antagonists for overactive bladder

Muscarinic receptor antagonists for overactive bladder

Effects of a selective and a nonselective muscarinic cholinergic antagonist on heart rate and intestinal motility in dogs

Pharmacokinetics and pharmacodynamics of glycopyrrolate following a continuous‐rate infusion in the horse

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