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The effects of glycopyrrolate in doses of 5, 10 and 15 microgram/kg and atropine 10, 20 and 30 microgram/kg on heat rate and rhythm was studied in anesthetised patients. Both drugs produced a dose-related increase in heart rate. Glycopyrrolate was approximately twice as potent as atropine in increasing heart rate. The average time taken to achieve peak effect was 2-6 and 3-7 minutes for atropine and glycopyrrolate respectively, and this was significantly different. The smallest doses of both drugs were generally associated with supraventricular dysrhythmias, whereas these were mainly ventricular following the highest dose of both drugs.

Twenty-four patients receiving ECT were systematically studied to compare the effects of two dosages of atropine and two dosages of glycopyrrolate as preanesthetic agents. Glycopyrrolate resulted in more cardiac arrhythmias, nausea and vomiting, and episodes of bradycardia than atropine (p = .4). More patients receiving atropine showed post-ECT confusion, but the clinical impact of this was minimal. Atropine appears to be preferable to glycopyrrolate for use in ECT preanesthesia.

Atropine 0.015 mg kg-1 and glycopyrrolate 0.0075 mg kg-1 were compared as antimuscarinic agents during reversal of pancuronium block with neostigmine 0.03 mg kg-1 in 30 patients anaesthetized with thiopental - N2O- fentanyl and undergoing minor surgery. The decrease of heart rate was more pronounced in patients who received atropine-neostigmine. The mean of the lowest heart rate was 44.3 beats min-1 in the atropine group compared with 54.3 beats min-1 in the glycopyrrolate group. Five patients with atropine-neostigmine developed a transient nodal rhythm as compared with two of those receiving glycopyrrole-neostigmine (non-significant difference). Recovery from anaesthesia, as assessed by the awakening after the discontinuation of N2O administration, was more rapid in patients given glycopyrrolate. In conclusion, glycopyrrolate seems to have advantages over atropine when used during reversal of pancuronium block with neostigmine.

This is a case report of a 39-year-old patient who developed supraventricular tachycardia secondary to a ritodrine-glycopyrrolate interaction. The cardiovascular effects of ritodrine as well as the possible mechanism for this interaction are discussed. Suggested treatment for ritodrine-induced tachycardia in the parturient are presented.

Glycopyrrolate, 0.2 mg, or atropine, 0.6 mg, was administered intravenously together with methohexitone for the induction of anaesthesia in unpremedicated patients. The use of atropine, compared with glycopyrrolate, was associated with a greater rise in heart rate, a greater number of patients whose heart rates doubled, and a higher incidence of dysrhythmias. Glycopyrrolate is recommended for use as an intravenous anticholinergic agent, particularly in patients with cardiovascular impairment.

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.

In a double-blind study, the effects of atropine and glycopyrrolate (dosage ratio 2:1) following i.m. and i.v. administration were compared with respect to salivation, heart rate, and blood pressure before, during and after i.v. infusion anaesthesia with ketamine and diazepam for alloplastic hip or knee surgery in 30 patients above the age of 50 years. Given with the premedicant, the two drugs were equally effective in reducing salivation. A slight increase in heart rate was seen after atropine only (P less than 0.005). Increases in heart rate and blood pressure during induction of anaesthesia were similar in the two groups. A second dose of the test drug was given with neostigmine for reversal of neuromuscular blockade. Again, there were no statistically significant differences with respect to salivation, blood pressure, heart rate, nausea and/or vomiting, unpleasant dreams and arousal time.

This is a case report of a one year old infant weighing 6.7 kilograms with a preoperative diagnosis of partial anomalous pulmonary venous drainage whose anaesthetic was complicated by cardiovascular collapse following addition of nitrous oxide to oxygen administered to the patient using a T-piece breathing circuit. The cardiovascular pathopharmacology of all the drugs administered to the patient before the event as well as that of nitrous oxide is discussed in detail. The drugs discussed are atropine 0.1 mg (0.01 mg . kg-1), glycopyrrolate 0.07 mg (0.01 mg . kg-1), morphine 0.9 mg (0.14 mg . kg-1) methylprednisone sodium succinate 165 mg (23.5 mg . kg-1) sodium thiopentone 40 mg (5.7 mg . kg-1), metocurine 3.4 mg (0.4 mg . kg-1).

Eight controlled 1- or 2-wk experiments involving 225 healthy male subjects and one study of 18 patients with hypertension, nine of whom were long-term users of a wax-matrix potassium chloride preparation, were conducted to evaluate the upper gastrointestinal safety of oral KCl supplements. All subjects in the short-term studies had normal upper gastrointestinal tracts. Subjects were examined again after at least 7 days of treatment with one of three commonly prescribed wax-matrix KCl tablets, KCl liquid, microencapsulated KCl, a potassium- sparer , or placebo. Some received an anticholinergic drug with treatment to induce delayed gastric motility. Diet and compliance to treatment regimens were controlled. Results indicate that upper mucosal injury, particularly erosions (43%) and ulcerations (11%), were more frequent after wax-matrix tablets. These changes occurred much less frequently after liquid KCl (0%), microencapsulated KCl (10.5% erosions, 1.2% ulcers), and the potassium-sparing drug (0%). More serious and more frequent lesions were associated with slowed motility. No occult bleeding was noted. Symptomatic complaints did not correlate with endoscopic findings. In the long-term study, patients with hypertension were examined endoscopically after 19 to 23 mo on KCl and again after 1 wk. Six of nine of the patients with hypertension treated for nearly 2 yr with a wax-matrix KCl supplement had significant lesions. One had developed ulceration after 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

In a carefully controlled multicenter investigation of the effects of oral potassium chloride (KCl) supplements on the gastrointestinal mucosa, 120 healthy men with no endoscopically apparent gastrointestinal lesions were confined to a research ward for 18 days. By random assignment, they were given 60 mEq/day (20 mEq TID) of KCl as either a microencapsulated gelatin capsule, a wax/polymer matrix tablet, or a powder-in-liquid formulation or a placebo capsule for two weeks. All subjects were given glycopyrrolate concomitantly to delay gastric emptying. After treatment was completed, endoscopic examinations of the esophagus, stomach, and duodenum were performed and evaluated by specialists blinded to the particular treatment given. Mild to moderate gastrointestinal irritation, characterized by erythema and edema, was found with similar frequency in all four treatment groups. Two of 30 subjects given the microencapsulated KCl had a single erosion each. Single or multiple erosions were also observed in 14/30 men given the wax/polymer matrix tablet, in 7/30 given the powder, and in 1/30 given placebo. One subject given the wax/polymer matrix tablet had a gastric ulcer. The incidence of gastrointestinal injury with the microencapsulated form was significantly less (P less than 0.01) than that with the wax/polymer matrix tablet and was not significantly different from that seen with either the powder or placebo.

The effects on the upper gastrointestinal tract of five different preparations of KCl were compared in 90 healthy subjects treated with glycopyrrolate. The KCl preparations studied were wax-matrix KCl, microencapsulated KCl, liquid KCl, experimental extended-release capsules, experimental extended-release tablets,and placebo. The subjects were endoscoped prior to and after seven days of dosing. Upper gastrointestinal mucosal pathology was seen with all of the potassium preparations as well as with placebo. No statistically significant differences between the various KCl groups or between KCl groups and placebo were seen. All of the lesions were superficial, except for one ulcer seen with the microencapsulated KCl. None of the subjects developed occult gastrointestinal bleeding. There were no differences in the incidence of abdominal symptoms.

Anticholinergic aerosols provide effective bronchodilation in some patients with obstructive lung disease. Glycopyrrolate is a quaternary ammonium anticholinergic compound that is poorly absorbed from mucus membranes, thus reducing anticholinergic side effects. In 20 adult patients with asthma, we evaluated bronchodilation to a single administration of metered-dose glycopyrrolate aerosol (GA) to ascertain its onset and duration of action along with evaluation of safety. In this randomized, double-blind, placebo-controlled, single-dose, crossover trial, bronchodilation was evaluated on five separate occasions to either placebo or a GA dose of 80, 240, 480, or 960 micrograms. Baseline spirometry for each patient on each visit was similar (mean FEV1 +/- SD of 62.2 +/- 13.6% predicted). After aerosol dosing, spirometry was measured at 30 minutes and then at hourly intervals up to 12 hours. Compared to placebo, metered-dose aerosols of 240, 480 and 960 micrograms elicited significantly greater bronchodilation at each test time. Furthermore, significant bronchodilation was noted within 30 minutes of dosing and was sustained for at least 12 hours. Bronchodilation with the 480 and 960 micrograms dose was equal, and both were greater than 240 micrograms. A subset of four asthma patients with baseline FEV1 values less than 50% predicted did not have a bronchodilating response with GA. No notable side effects occurred. Thus, a single aerosol dose of GA provides clinically significant, safe 12-hour bronchodilation in patients with asthma without severe airway obstruction (i.e., FEV1 greater than 50% predicted).

Memory changes are known to be associated with electroconvulsive therapy (ECT). The anticholinergic drugs used prior to the procedure have also been suspected of causing cognitive deficits. The present study was designed to assess memory and concentration in depressed patients receiving 0.6 mg atropine, 0.2 mg glycopyrrolate or placebo before anaesthesia and ECT. Glycopyrrolate is an anticholinergic agent lacking central nervous system effects. Anaesthesia and bilateral ECT resulted in significant short-term memory deficit, but this was seen equally in each of the groups of patients irrespective of which premedication was given. As no regimen was superior, as far as effect on memory is concerned, premedication for ECT should be chosen according to other criteria.

The effects on the lower oesophageal sphincter (LOS) of the simultaneous administration of glycopyrrolate 0.5 mg and neostigmine 2.5 mg, when given to antagonize neuromuscular blockade, were studied in 10 healthy patients undergoing gynaecological surgery. LOS pressure and gastric pressure (GP) were measured for 20 min after the administration of the drug combination and barrier pressure (BrP) was calculated (LOS-GP). There was a significant reduction in BrP which lasted, in some patients, for the duration of the study. These results contrast with those of a similar study looking at the effects of atropine and neostigmine in which the decrease in BrP, although significant, was transient, and in which control values were regained after 5 min.

The symptom complex of localized facial gustatory sweating and flushing during mastication (The Frey syndrome) is a common sequela of parotidectomy with facial nerve dissection. A thorough review of the literature concerning the Frey syndrome is reported. The procedure of tympanic neurectomy has received special emphasis with a review of 73 cases of tympanic neurectomy. The treatment modalities available, if tympanic neurectomy fails, are discussed. Important guidelines for the safe use of topical therapy to control gustatory sweating are presented as an alternative to surgical therapy. The author studied 129 post parotidectomy patients in whom 60% noted symptomatic gustatory sweating, and approximately one-fourth fo these symptomatic patients requested topical anticholinergic therapy, with one patient electing tympanic neurectomy. The only form of medical treatment presently available utilizes the topical application of scopolamine, a drug having potentially significant central nervous system side effects if systemically absorbed. In an effort to find an effective drug for topical application with a more favorable therapeutic index than scopolamine, glycopyrrolate was investigated. Glycopyrrolate was compared in varying concentrations to topical scopolamine in a personally conducted double blind clinical trial involving 16 patients. Initial results of this investigation suggest that topical glycopyrrolate in concentrations 0f 0.5% and 1.0% provide complete effective control of gustatory sweating for at least several days duration after a single application. There have been no significant side effects with the use of topical glycopyrrolate to date. Commercial topical antiperspirants were also investigated and found to be of limited benefit.

A controlled single-blind trial has been carried out to determine the value of long-term anticholinergic therapy in duodenal ulcer. Of 106 male patients with symptomatic and radiologically proven duodenal ulcer admitted to the trial, 91 completed the study. Patients were divided randomly into three groups. They received either glycopyrronium, or 1-hyoscyamine in a sustained-release form, or inert tablets for one year. Progress was judged on the basis of frequency and severity of symptoms, monthly assessments by patients, antacid consumption, and radiology. By all criteria, glycopyrronium and 1-hyoscyamine were not significantly superior to placebo. Symptomatic improvement, both subjective and objective, occurred in approximately 80% of all patients during the year of observation; there was no significant difference between the groups.