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Atropine and glycopyrronium show similar binding patterns to M2 (cardiac) and M3 (submandibular gland) muscarinic receptor subtypes in the rat.

Atropine and glycopyrronium are frequently used for premedication to reduce oral and respiratory secretions and prevent bradycardia. Glycopyrronium is said to have similar antisialagogue effects, but is less likely to cause significant tachycardia than atropine. Different antimuscarinic receptor selectivity patterns could explain the differences. The aim of this investigation was to determine the possible selectivity of glycopyrronium for M2 and M3 muscarinic receptor subtypes. Muscarinic receptor subtypes in Wistar rat ventricle and submandibular gland homogenates were characterized with [3H]-N-methylscopolamine ([3H]-NMS) by ligand binding studies. Inhibition of [3H]-NMS binding by non-labelled compounds showed the following order: in rat ventricle: glycopyrronium > atropine >> otenzepad > hexahydrosiladiphenidol (HHSiD) > pirenzepine; in rat submandibular gland: glycopyrronium > atropine >> HHSiD >> pirenzepine > otenzepad. These were similar to the expected order of frequency of M2 and M3 subtypes, respectively. Glycopyrronium showed similarly high affinities for both M2 (Ki = 1.889 (SEM 0.049) nmol litre-1) and M3 (Ki = 1.686 (0.184) nmol litre-1) subtypes. Glycopyrronium bound to a homogeneous population of binding sites in both tissues and showed no selectivity for M2 or M3 muscarinic receptor subtypes.

Animals↗

The effect of physostigmine on diazepam-induced ventilatory depression: a double-blind study.

The authors conducted a double-blind crossover study to determine the effects of physostigmine salicylate on hyperoxic ventilatory response to carbon dioxide (VE RCO2) and on awareness in healthy subjects previously sedated with diazepam. Diazepam 0.4 mg/kg iv decreased the slope of VE RCO2 from 2.41 +/- 0.19 to 1.30 +/- 0.15 1 . min-1 . mmHg-1 (mean +/- SEM, P less than 0.001). Subsequent injection of physostigmine 2.0 mg iv was associated with a 0.20 +/- 0.28 1 . min-1 . mmHg-1 decrease in slope; this was significantly different from the 0.56 +/- 0.22 1 . min-1 . mmHg-1 increase in slope associated with saline placebo (P less than 0.05). Level of consciousness, on the other hand, increased more after physostigmine than after saline (P less than 0.01). The authors conclude that despite an apparent increase in awareness resulting from physostigmine administration, the accompanying decrease in ventilatory drive may contraindicate its use in patients who previously have received diazepam.

Adult↗

Volume and pH of gastric contents following anticholinergic premedication.

The effects of anticholinergic premedication with 1.0 mg atropine, 0.5 mg hyoscine and 0.2 mg glycopyrronium on volume and pH of gastric contents were studied and compared with a group receiving no anticholinergic premedication. The antisialogogue effects were also compared. Though the groups receiving atropine and glycopyrronium had the lowest mean aspirated volume and the highest mean pH respectively there was no essential difference between the various groups receiving anticholinergic premedication. However, the pH values were above 2.5 in the majority of these patients in comparison with the control group. The antisialogogue effects of the three anticholinergic drugs were similar.

Adult↗

Comparison of atropine and glycopyrronium in patients with pre-existing cardiac disease.

The effects of atropine and glycopyrronium, when given intravenously with neostigmine during the reversal of neuromuscular blockade in patients with cardiovascular disease, were compared in a double blind trial. Atropine was associated with a significantly greater elevation of heart rate and rate-pressure product than glycopyrronium. This elevation was also more sustained with atropine. The entire atropine population also showed a significantly greater incidence of ST-segment depression on the electrocardiogram than that observed in those who had received glycopyrronium. Furthermore, patients with ischaemic heart disease and previous myocardial infarction who received atropine showed a significantly greater incidence of dysrhythmias than those given glycopyrronium. It is suggested that at the time of reversal of neuromuscular blockade in patients with cardiovascular disease, glycopyrronium is a more suitable agent than atropine.

Aged↗

Prevention of neostigmine-induced colonic activity. A comparison of atropine and glycopyrronium.

Colonic intraluminal pressure was recorded in eight patients receiving either atropine 1.2 mg (n = 4) or glycopyrronium 0.6 mg (n = 4) intravenously in a randomised, double-blind fashion and followed after 5 minutes by neostigmine 2.5 mg. Estimations of total colonic activity were made from the area under the recording of intraluminal pressure. There were no significant differences in mean intraluminal pressures or total colonic activity between the two groups. It is concluded that glycopyrronium offers no advantage over atropine with respect to protection of the bowel against the effects of neostigmine.

Adult↗

Ventilation and the oculocardiac reflex. Prevention of oculocardiac reflex during surgery for squints: role of controlled ventilation and anticholinergic drugs.

A randomised prospective study was carried out in children undergoing surgery for squint correction, to determine the value of controlled ventilation as a prophylaxis against the occurrence of the oculocardiac reflex. One hundred patients anaesthetised with nitrous oxide/oxygen and halothane were randomly assigned to either ventilated or spontaneously breathing groups of 50 each. Half the patients in each group received glycopyrronium 7.5 micrograms/kg intravenously at the time of induction of anaesthesia. Heart rate, rhythm, blood pressure and end tidal CO2 concentration were monitored throughout. A positive oculocardiac reflex, defined as a fall in heart rate of 20% or more and/or the occurrence of dysrhythmias, was observed in 72% of spontaneously breathing patients and in 100% of ventilated patients not receiving prophylactic intravenous glycopyrronium. The incidence of a positive reflex in patients receiving glycopyrronium was 10% (4 and 16% respectively in spontaneously breathing and ventilated patients). It is concluded that controlled ventilation is of no value as a preventive measure against the occurrence of the oculocardiac reflex in patients undergoing squint surgery and that prophylaxis is safely achieved with the use of intravenous glycopyrronium.

Adolescent↗

Bradycardia associated with the use of vecuronium. A comparative study with pancuronium with and without glycopyrronium.

One hundred and twenty patients undergoing anaesthesia for elective surgery received either pancuronium or vecuronium for muscle relaxation. Within each of these two groups, half were given glycopyrronium and the remainder an inert placebo. The incidence of bradycardia or bradydysrhythmias was higher in the group having vecuronium compared with those given pancuronium. Glycopyrronium afforded protection against undesirable vagal activity.

Adolescent↗

Bradycardia during intra-abdominal surgery. Modification by pre-operative anticholinergic agents.

The aim of the present study was to examine, in a double-blind, randomised manner, the effects of glycopyrronium 0.005 mg/kg, atropine 0.01 mg/kg or a placebo (normal saline) on the frequency of bradycardia in 92 patients scheduled for major abdominal or gynaecological surgery. All patients received fentanyl, halothane and vecuronium. The frequency of bradycardia in the group that received saline was 18%. No cases occurred in either anticholinergic group. Mean heart rates intra-operatively were not significantly different between the atropine and glycopyrronium groups. It is suggested that the routine use of pre-operative anticholinergic agents should be considered when a similar anaesthetic technique is employed.

Abdomen↗

Hypoxaemia after premedication in cardiac patients. Glycopyrronium compared with hyoscine.

Arterial blood gases were analysed before and approximately one hour after premedication in two groups of 10 patients awaiting cardiac surgery. One group received intramuscular papaveretum and hyoscine, the other papaveretum and glycopyrronium. Similar, small but statistically significant reductions in mean arterial oxygen tension and oxygen saturation, and increases of arterial carbon dioxide tension occurred in both groups. Hypoxaemia in individual patients was unpredictable and in some was clinically relevant.

Drug Combinations↗