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PubMed1982

Premedication with atropine or glycopyrrolate in children. Effects on heart rate and rhythm during induction and maintenance of anesthesia.

Atropine 15 micrograms/kg and glycopyrrolate 5 or 10 microgram/kg were studied as anticholinergic premedicants in groups of 20 children each. A control group of 20 children did not receive anticholinergic premedication. Both atropine and the higher dose of glycopyrrolate produced significant increases in heart rate prior to induction of anaesthesia. The subsequent increase during the process of induction was less than in those who had not received an anticholinergic drug or glycopyrrolate 5 micrograms/kg. Dysrhythmias during induction of anaesthesia occurred slightly less frequently in the patients given atropine or the higher dose of glycopyrrolate. Although the incidence was similar in these two groups, ventricular ectopic beats occurred less frequently following the use of glycopyrrolate. The control of secretions was also superior with this anticholinergic premedicant.

Adolescent↗

PubMed1982

Advantages of glycopyrrolate over atropine during reversal of pancuronium block.

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.

Adult↗

PubMedDate not supplied

Hemodynamic effects of atropine and glycopyrrolate in isoflurane-xylazine-anesthetized dogs.

Alterations in parasympathetic tone are partially responsible for xylazine's hemodynamic effects. The purpose of this study was to evaluate and compare the hemodynamic changes caused by the administration of intravenous (IV) atropine or glycopyrrolate after IV xylazine in isoflurane-anesthetized dogs. Six healthy beagles (8.2 to 10.7 kg) were used in two trials separated by 7 days. Anesthesia was induced and maintained with isoflurane in 100% oxygen with controlled ventilation. Once constant end-tidal isoflurane (1.8%) and arterial partial pressure of carbon dioxide (35 to 45 mm Hg) values were reached, baseline data were recorded and xylazine (0.5 mg/kg, i.v.) was given. In trial 1 atropine (0.1 mg/kg, i.v.) was given 5 minutes after xylazine, and in trial 2 glycopyrrolate (0.025, mg/kg, i.v.), was given 5 minutes after xylazine. Hemodynamic variables were recorded 3 minutes after xylazine and 3 minutes after anticholinergic administration. In trial 2, bilateral vagotomies were performed 10 minutes after glycopyrrolate, and hemodynamic variables were recorded 3 minutes later. Heart rate, cardiac index, and stroke index decreased; arterial pressure and systemic vascular resistance increased after xylazine. Heart rate, cardiac index, and rate pressure product increased after anticholinergic administration. Significant differences between atropine and glycopyrrolate were not observed in any of the hemodynamic parameters. Similarly, significant differences between glycopyrrolate and bilateral vagotomy were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

PubMed1990

Radioreceptor assay for pharmacokinetic studies of glycopyrrolate.

A sensitive radioreceptor assay for the determination of glycopyrrolate concentrations in human plasma, urine and cerebrospinal fluid (CSF) is described. The applicability of the assay for kinetic studies in human was studied by determining the plasma concentrations and the renal excretion in three gynaecological surgical patients, who received 8 micrograms/kg of glycopyrrolate as a premedication intramuscularly. Tritiated N-methyl scopolamine was used to label the muscarinic cholinergic receptors in the membrane preparation obtained from the rat brain. The limit of detection of the assay was 70 ng/l in plasma, 2 micrograms/l in urine and 140 ng/l in CSF. There was no evidence of cross-reactivity of glycopyrrolate derivatives in clinical concentrations. A very rapid absorption was found with a mean maximum plasma concentration (Cmax) of 14.26 (range 12.02-16.97) micrograms/l and mean Tmax (time to Cmax) of 13.3 (range 10-15) min. and almost 50% of the dose administered was excreted into the urine within 3 hr. The CSF levels of glycopyrrolate were under detection limit. It is concluded that the sensitivity of the method is sufficient for pharmacokinetic studies of glycopyrrolate after therapeutic dosing.

Aged↗

PubMed1987

Prolonged effect of inhaled glycopyrrolate in asthma.

Glycopyrrolate, a quaternary ammonium anticholinergic compound is a potentially useful bronchodilator. To determine the efficacy, optimal dose, and duration of action of inhaled glycopyrrolate, we gave the drug to 11 asthmatic patients. Each subject received placebo or glycopyrrolate (100, 200, 600, or 1,200 micrograms) by inhalation in a double-blind, randomized, crossover design. Measurements included FEV1, FVC, heart rate, and blood pressure before administration of the drug and periodically for 12 hours. For eight hours following all doses of glycopyrrolate, both FEV1 and FVC (both as percent of predicted) were significantly greater for drug than for placebo. Glycopyrrolate may be a useful long-acting drug for the treatment of asthma.

Adolescent↗

PubMedDate not supplied

Effects of neostigmine and glycopyrrolate on pulmonary resistance in spinal cord injury.

Preliminary findings in subjects with spinal cord injury (SCI) suggest that neostigmine administered intravenously increases colonic tone, increases colonic contractions, and facilitates bowel evacuation. Of concern are potential pulmonary side effects, including an increase in airway secretions and bronchospasm. The objectives of the study were to determine the effects of intravenously administered neostigmine or neostigmine combined with glycopyrrolate on forced oscillation indices in persons with SCI. Pulmonary resistances at 5 Hz (R5) and 20 Hz (R20) were measured with the use of an impulse oscillation system (IOS) in 11 subjects with SCI. Values were obtained before and after the intravenous administration of 2 mg of neostigmine alone and, on a separate day, before and after the administration of 2 mg of neostigmine combined with 0.4 mg of glycopyrrolate. Baseline R5 and R20 values before neostigmine correlated significantly with baseline values before neostigmine combined with glycopyrrolate. Following neostigmine, mean R5 values increased 25% and mean R20 values increased 18%. Following neostigmine combined with glycopyrrolate, mean R5 values fell 9% and mean R20 values fell 7%. In summary, baseline IOS values obtained on 2 different days were highly reproducible in this population. Neostigmine alone induced significant bronchoconstriction, whereas neostigmine combined with glycopyrrolate caused bronchodilation.

Adult↗

PubMed2003

Treatment of compensatory gustatory hyperhidrosis with topical glycopyrrolate.

Gustatory hyperhidrosis is facial sweating usually associated with the eating of hot spicy food or even smelling this food. Current options of treatment include oral anticholinergic drugs, the topical application of anticholinergics or aluminum chloride, and the injection of botulinum toxin. Thirteen patients have been treated to date with 1.5% or 2% topical glycopyrrolate. All patients had gustatory hyperhidrosis, which interfered with their social activities, after transthroacic endoscopic sympathectomy, and which was associated with compensatory focal hyperhidrosis. After applying topical glycopyrrolate, the subjective effect was excellent (no sweating after eating hot spicy food) in 10 patients (77%), and fair (clearly reduced sweating) in 3 patients (23%). All had reported incidents of being very embarrassed whilst eating hot spicy foods. Adverse effects included a mildly dry mouth and a sore throat in 2 patients (2% glycopyrrolate), a light headache in 1 patient (1.5% glycopyrrolate). The topical application of a glycopyrrolate pad appeared to be safe, efficacious, well tolerated, and a convenient method of treatment for moderate to severe symptoms of gustatory hyperhidrosis in post transthoracic endoscopic sympathectomy or sympathicotomy patients, with few side effects.

Administration, Topical↗

PubMed2001

[Glycopyrrolate treatment for drooling in an adult with cerebral palsy].

BACKGROUND: The aim of the study was to assess the effect of glycopyrrolate on drooling in an adult male patient with cerebral palsy. MATERIAL AND METHODS: After a thorough medical examination and consent in writing from his guardian, a baseline sum score for frequency and seriousness of drooling was established over a two-week period in addition to data on shifts of bibs, urination, defecation and observation of behaviour. Glycopyrrolate (1 mg) tablets were then administered, starting with one tablet daily the third week and increasing the daily dose by one tablet per week until a maximum of four tablets during week 6 and four days of week 7, when the daily dose was reduced to two tablets for three days. In the four weeks 8-11, three tablets were given daily. In week 12 the dose was reduced to two tablets and for the weeks 13-15 no glycopyrrolate was given. RESULTS: As long as the patient received three to four tablets of glycopyrrolate daily, drooling was markedly reduced, and bibs were not necessary on some days. After withdrawal, drooling increased to approximately the same level as before treatment. INTERPRETATION: For shorter periods, glycopyrrolate can be given in controlled doses provided that an adequate medical assessment has been undertaken.

Administration, Oral↗

PubMed1990

beta-Glucuronide and sulfate conjugation of scopolamine and glycopyrrolate.

The metabolism of scopolamine and glycopyrrolate was studied in 11 healthy parturients undergoing cesarean section. After a single intramuscular injection of scopolamine (5 micrograms/kg, n = 7) or glycopyrrolate (6 micrograms/kg, n = 4), the concentrations of the drugs in the urine were determined up to 8-12 h using a radioreceptor assay. This assay measures scopolamine and glycopyrrolate with their possible active metabolites. The effect of beta-glucuronidase and sulfatase incubation on the drug concentrations was also studied. The concentrations of scopolamine and/or its active metabolites were on the average 7 times higher after incubation indicating that beta-glucuronide or sulfate conjugation is an important metabolic pathway for scopolamine. On the contrary, the glycopyrrolate concentrations increased only slightly between 1 and 3 hours after the drug injection. Thus, beta-glucuronide or sulfate conjugation plays only a minor part in the metabolism of glycopyrrolate.

Female↗

PubMed1988

Comparative potency of atropine sulphate and glycopyrrolate on heart rate in man.

Disagreement as to the effect of glycopyrrolate and atropine sulphate at various dosages on heart rate has been reported in the literature. Of particular interest is the question of whether small doses of glycopyrrolate cause bradycardia. Three groups of subjects were studied. The QRS complexes of the electrocardiogram were continuously recorded on a microcomputer. Group 1 consisted of 10 healthy volunteers who were given two doses of atropine sulphate 1.25 micrograms kg-1 and glycopyrrolate 0.75 micrograms kg-1, in random order at two different times, i.v. Monitoring continued until heart rate returned to baseline. Group 2 consisted of 24 women, ASA class I or II, scheduled for gynaecological operations. Each patient received fractionated i.v. doses of either atropine sulphate 2.5, 2.5 and 5 micrograms kg-1 or glycopyrrolate 1.5, 1.5 and 3.0 micrograms kg-1 at 3-min intervals. Heart rate was measured continuously for 1 h before drug injection and for 10 min after the last dose. Group 3 consisted of six volunteers given both drugs in the same dose and time schedule as Group 2, but heart rate was monitored for 180 min after the last dose. In Group 1, the incidence of bradycardia and increases in heart rate after the first dose were statistically significant for both atropine sulphate and glycopyrrolate when compared with baseline values. In Group 2, both drugs significantly increased the heart rate and had similar times to peak effect. In Group 3, bradycardia occurred only with atropine sulphate. Increases in heart rate, peak heart rate and duration of action were similar with both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Cardiac performance in cats after administration of xylazine or xylazine and glycopyrrolate: echocardiographic evaluations.

Cardiac performance was evaluated in 9 healthy cats sedated with xylazine. Each cat was evaluated echocardiographically before and after the administration of xylazine or xylazine and glycopyrrolate. Each cat was echocardiographically evaluated during manual restraint only (control value), after IM administration of 0.55 mg of xylazine/kg of body weight, after IM administration of 2.2 mg of xylazine/kg, and after IM administration of 0.011 mg of glycopyrrolate/kg followed 10 minutes later by IM administration of 2.2 mg of xylazine/kg. Echocardiographic indices of cardiac performance (fractional shortening, left ventricular wall amplitude, aortic amplitude, mitral valve E point septal separation) indicated a significant decrease (P less than 0.05) in the left ventricular function and heart rate after the small (0.55 mg/kg) and large (2.2 mg/kg) dosages of xylazine. With the administration of glycopyrrolate, the bradycardia was minimized, but cardiac performance was not improved. After administration of glycopyrrolate, cardiac performance decreased, but the decrease was not significant when compared with the ventricular performance of the cats after administration of the large dosage of xylazine. Compared with control values, the reduction in left ventricular function values associated with administration of xylazine or xylazine and glycopyrrolate was independent of the heart rate. Therefore, the alpha-2 adrenergic agonist xylazine has a marked depressive effect on cardiac performance in the cat, and premedication with glycopyrrolate may not completely alleviate the undesirable bradycardia, but may actually be detrimental to the cardiovascular system.

Animals↗

PubMed1981

Reversal of neuromuscular blockade: dose determination studies with atropine and glycopyrrolate given before or in a mixture with neostigmine.

Glycopyrrolate and atropine were studied in doses of 5, 10, or 15 microgram/kg and 10, 20, or 30 microgram/kg, respectively, given intravenously either before or in a mixture with neostigmine, 50 microgram/kg, at the time of reversal of neuromuscular block. When given first, both anticholinergic drugs produced a dose-related increase in heart rate; following the administration of neostigmine the heart rates decreased. When administered in a mixture with neostigmine, the 20- and 30-microgram/kg doses, but not the 10-microgram/kg dose of atropine were associated with an initial increase in heart rate. This was, however, absent with all the doses of glycopyrrolate. The 5-microgram/kg dose of glycopyrrolate and 10-microgram/kg dose of atropine given either before or in a mixture with neostigmine were associated with unacceptable decreases in heart rate and needed further anticholinergic drug administration. The 10-microgram/kg dose of glycopyrrolate, when administered in a mixture with neostigmine, was associated with the most stable heart rates. Increasing the dose to 15 microgram/kg was not associated with undue tachycardia and is not hazardous. Atropine, 20 microgram/kg, necessitated a further administration of atropine in nearly a third of patients in this group due to bradycardia (heart rate of 50 beats/min or less) and would be considered inadequate. Increasing the dose to 30 microgram/kg prevented bradycardia but was accompanied by significant initial tachycardia and a higher incidence of dysrhythmias when administered before neostigmine. The frequency of dysrhythmias was otherwise similar. It is recommended that anticholinergic drugs be administered in a mixture with neostigmine. Glycopyrrolate, administered in this way in a dose of 10 microgram/kg, is associated with stable heart rates.

Atropine↗

PubMed1999

Effects of intravenously administered glycopyrrolate in anesthetized horses.

The purpose of this study was to determine the heart rate (HR) and blood pressure (BP) effect of glycopyrrolate in anesthetized horses with low HR (< or = 30 beats/min). The horses were randomly treated with glycopyrrolate (2.5 micrograms/kg body weight (BW)) or saline, intravenously (i.v.) (n = 17). If HR failed to increase (by > 5 beats/min within 10 min), glycopyrrolate (same dose) was administered. Heart rate increased by > 5 beats/min in 3 out of 9 horses following the initial glycopyrrolate treatment. Overall changes in HR and mean BP were not significantly different, while systolic and diastolic BP increased significantly (P < 0.025 using a Bonferroni corrected paired t-test). On the 2nd treatment, 3 out of 7 horses given 2.5 micrograms/kg BW glycopyrrolate, and 4 out of 5 horses given 5.0 micrograms/kg BW (total dose) showed an increase in heart rate of > 5 beats/min, which was significant. A significant increase in BP was produced following treatment with 2.5 micrograms/kg BW, but not following 5.0 micrograms/kg BW. A final increase in HR, of > 5 beats/min, was associated with a significant rise in BP (P < 0.05 using an unpaired t-test). In conclusion, an increase in HR can occur with 2.5 to 5.0 micrograms of glycopyrrolate/kg BW, i.v., and results in improvement in BP in anesthetized horses.

Adjuvants, Anesthesia↗

PubMed1999

Diabetic gustatory sweating successfully treated with topical glycopyrrolate: report of a case and review of the literature.

BACKGROUND: Gustatory sweating is a more common manifestation of diabetes mellitus than is appreciated. It is a distressing problem that has been difficult to treat safely. METHODS: Daily topical application of glycopyrrolate roll-on lotion was offered as an alternative to oral anticholinergic agents to an 87-year-old woman with long-standing type 2 diabetes mellitus who complained of profuse sweating after eating. RESULTS: Gustatory sweating was relieved by application of glycopyrrolate and reappeared when the glycopyrrolate was briefly withdrawn to confirm its therapeutic effect. CONCLUSION: For moderate to severe symptoms of diabetic gustatory sweating, topical application of glycopyrrolate is safe, effective, well tolerated, and convenient.

Administration, Cutaneous↗

PubMed2000

Treatment of sialorrhea with glycopyrrolate: A double-blind, dose-ranging study.

OBJECTIVE: To determine the safety and efficacy of glycopyrrolate in the treatment of developmentally disabled children with sialorrhea. DESIGN: Placebo-controlled, double-blind, crossover dose-ranging study. SETTING: Outpatient facilities in 2 pediatric hospitals. PATIENTS: Thirty-nine children with both developmental disabilities and excessive and bothersome sialorrhea. MAIN OUTCOME MEASURES: Parent and investigator evaluation of change in sialorrhea and adverse effects. RESULTS: Glycopyrrolate in doses of 0.10 mg/kg per dose is effective at controlling sialorrhea. Even at low doses, 20% of children may exhibit adverse effects severe enough to require discontinuation. CONCLUSIONS: Glycopyrrolate is effective in the control of excessive sialorrhea in children with developmental disabilities. Approximately 20% of children given glycopyrrolate may experience substantial adverse effects, enough to require discontinuation of medication. Arch Pediatr Adolesc Med. 2000;154:1214-1218.

Adolescent↗

PubMed1995

The effects of scopolamine, lorazepam, and glycopyrrolate on classical conditioning of the human eyeblink response.

Human eyeblink conditioning, a relatively simple form of learning and memory, has previously been shown to be impaired by the central and peripheral anticholinergic scopolamine. The present study compared the behavioral effects of scopolamine with the benzodiazepine lorazepam and a peripherally active anticholinergic, glycopyrrolate. Thirty-six healthy normal volunteers (mean age: 23.7 years) were studied with 12 assigned double-blind to each of three drug conditions (0.5 mg scopolamine IV, 2 mg lorazepam PO, or 0.2 mg glycopyrrolate IV). Subjects underwent classical conditioning of the eyeblink response in which the conditioned stimulus was an 80 dB binaural tone, and the unconditioned stimulus was a 2 psi airpuff to the right eye. Ten trials of unpaired stimulus presentations were followed by 60 paired trials and finally by an extinction period of five tone-alone presentations. An eyeblink response that occurred during the tone but before the airpuff was scored as a conditioned response (CR). Subjects treated with lorazepam (43% mean CRs) and scopolamine (51% mean CRs) exhibited a significantly lower asymptotic level of conditioning than those treated with glycopyrrolate (85% mean CRs; P < 0.01). However, during extinction, lorazepam-treated subjects (35% CRs) showed a lower overall level of responding to the tone than either scopolamine (60% CRs) or glycopyrrolate (62% CRs) treated subjects (P < 0.05). It seems unlikely that these differences could be accounted for by drug-induced alterations in motor responses because there were no significant differences between the three drug conditions in the frequency, latency, or amplitude of unconditioned responses to the airpuff. Overall, our data indicate that scopolamine and lorazepam impair eyeblink conditioning and suggest that some of the effects of benzodiazepines and anticholinergics on learning and memory can be differentiated using this paradigm.

Adult↗

PubMed1981

Anatomical dead space and airway resistance after glycopyrrolate or atropine premedication.

The effects of atropine and glycopyrrolate on anatomical dead space, one and three second forced expiratory volume, maximal expiratory flow rate, and total forced expiratory volume were determined in ten healthy volunteers. Using Fowler's single breath nitrogen analyzing technique, atropine was found to increase dead space by 19.2 per cent at one hour, declining to 11.02 per cent at four hours. Glycopyrrolate increased dead space by 21.57 per cent at one hour, 29.28 per cent at two hours, and 26.65 per cent at four hours. When compared to the effects of saline control injection, the dead space increases are significant. The difference between glycopyrrolate and atropine is significant only at four hours. Increases in maximal expiratory flow rate induced by atropine and glycopyrrolate were significant at one-half hour, while atropine alone induced a significant increase in one second forced expiratory volume. Three second forced expiratory volume and total forced expiratory volume were not significantly altered.

Adult↗

PubMed1997

A randomised controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweating.

The treatment of gustatory sweating in diabetes mellitus is usually with oral anti-cholinergic drugs, but these frequently lead to unacceptable side effects. Glycopyrrolate is an anti-muscarinic agent that can be applied topically and is efficacious in gustatory sweating occurring in other conditions. In a double-blind placebo-controlled crossover study, we assessed the value of glycopyrrolate in 13 diabetic patients with gustatory sweating. Sweating was measured by a sweat challenge, and diaries recorded by the patients throughout the 2 weeks of each treatment period. Compared to placebo, glycopyrrolate reduced the sweat response to a challenge by 82% (p < 0.01). The frequency of episodes of gustatory sweating during the treatment period was also reduced by 51% (p < 0.01), with a nearly 100% reduction in the frequency of episodes of severe sweating (p < 0.01). In conclusion, topically applied glycopyrrolate is a very effective treatment in reducing both the severity and frequency of diabetic gustatory sweating.

Administration, Topical↗