Analytical lifecycle management oriented development and validation of a new stability-indicating ultra-fast liquid chromatographic method: case study of Glycopyrrolate

A new stability-indicating liquid chromatographic method was developed and validated for the estimation of glycopyrrolate in pharmaceutical formulations. A contemporary approach to analytical life-cycle management was followed to develop a robust and reliable chromatographic method. Scouted method variables such as % methanol, the strength of tetra butyl ammonium hydrogen sulfate and mobile phase flow rate were optimized using the design of experiment approach and their effect on critical quality attributes was studied. The critical quality attributes viz. retention time, theoretical plate count and symmetry factor were highly influenced by the three critical method variables. Optimum chromatography was attained on a C-18 column with a mobile phase methanol: 10 mM tetra butyl ammonium hydrogen sulfate (80:20, v/v) flowing at 1.0 mL.min-1. Chromatographic method specificity was ensured by degrading the drug forcefully. Validation studies postulated method acceptability and suitability for estimating glycopyrrolate in both bulk as well as injection formulation. Results for parameters viz. linearity (5-250 µg.mL-1), accuracy (>99%) and precision (<2%) advocated method reliability. Overall the method was reliable and of optimum quality and, possess the potential of application in routine and bio-analytical purposes

Effects of glycopyrrolate premedication on preventing postoperative catheter-related bladder discomfort in patients receiving ureteroscopic removal of ureter stone / 대한마취과학회지

BACKGROUND: Glycopyrrolate given as reversing agents of muscle relaxants has been reported to be effective in reducing postoperative catheter-related bladder discomfort (CRBD). However, it remains unclear whether glycopyrrolate as premedication is also effective. This study aims to investigate the effectiveness of glycopyrrolate as premedication on preventing CRBD in the post-anesthesia care unit (PACU). METHODS: Eighty-three patients who received elective ureteroscopic removal of ureteral stone were randomly assigned to the control (n = 43) or the glycopyrrolate group (n = 40). The glycopyrrolate group was treated with glycopyrrolate 0.3 mg as premedication while the control group received 0.9% saline 1.5 ml. The incidence and severity of CRBD and pain score using numerical rating scale (NRS) were measured in the PACU. RESULTS: The incidence of CRBD (26 of 40 patients vs. 41 of 43 patients, relative risk [RR] = 0.68, 95% Confidence interval [CI] = 0.53–0.86, P = 0.001) and the moderate to severe CRBD incidence (6 of 40 patients vs. 20 of 43 patients, RR = 0.32, 95% CI = 0.14–0.72, P = 0.002) were lower in the glycopyrrolate group than in the control group. Also, postoperative pain NRS score was found to be lower in the glycopyrrolate group (median = 1 [Q1 = 0, Q3 = 2]) compared to the control group (3 [1, 5], median difference = 1.00, 95% CI = 0.00–2.00, P = 0.002). CONCLUSIONS: The use of glycopyrrolate 0.3 mg as premedication in patients receiving ureteroscopic removal of ureteral stone reduced the incidence and severity of CRBD, and decreased postoperative pain in the PACU.

Effectiveness of Oral Glycopyrrolate Use in Compensatory Hyperhidrosis Patients

Compensatory hyperhidrosis or reflex hyperhidrosis is the increase in sweating in the postoperative stage of thoracic sympathectomy or lumbar sympathectomy. It shares several features with anxiety disorders and has a negative impact on a patient's quality of life. Oralglycopyrrolate is one of the treatment options available. This study reviewed case notes in a series of 19 patients with compensatory hyperhidrosis. We made a comparison between the Milanez de Campos score of a pre-glycopyrrolate medication group and the Milanez de Campos score of a post-glycopyrrolate medication group. The Beck Depression Inventory (BDI) score, Beck Anxiety Inventory (BAI) score, and autonomic nervous system (ANS) scale score were also compared between the pre-medication and post-medication groups. In the post-glycopyrrolate medication group, there was decrease in the Milanez de Campos score, BAI score, and BDI score (P 0.05). Glycopyrrolate is an effective medication in the treatment of compensatory hyperhidrosis that, can alleviate anxiety and improve patients' quality of life.

Comparison of hemodynamic changes between phenylephrine and combined phenylephrine and glycopyrrolate groups after spinal anesthesia for cesarean delivery / 대한마취과학회지

BACKGROUND: Hypotension remains a common clinical problem of spinal anesthesia for cesarean delivery and phenylephrine is used as a vasopressor to address this. However, phenylephrine reduces maternal cardiac output (CO) due to reflex bradycardia. Glycopyrrolate is safe for the fetus, and increases heart rate (HR). Using a noninvasive measure of CO, we compared maternal hemodynamic changes between the phenylephrine only group (group P) and the phenylephrine plus glycopyrrolate group (group PG). METHODS: In this randomized study, 60 women scheduled for elective cesarean delivery were allocated to group P (n = 30) or group PG (n = 30). In both groups, phenylephrine was infused at 50 microg/min. This infusions stopped if systolic blood pressure (SBP) was higher than the baseline value, and phenylephrine 100 microg was injected if SBP was lower than 80% of the baseline value from spinal anesthesia to delivery. In group PG, glycopyrrolate 0.2 mg was injected intravenously after spinal anesthesia. Hemodynamic parameters, such as SBP, heart rate (HR), stroke volume index (SVI), cardiac index (CI) were measured before and until 15 min after spinal anesthesia. RESULTS: There were no significant differences in SBP and SVI compared to the baseline value in each group and between the two groups. HR and CI reduced significantly from 8 min to 15 min in group P compared to the baseline value as well as group PG for each time-point. However, HR and CI were maintained in group PG. CONCLUSIONS: The use of glycopyrrolate added to phenylephrine infusion to prevent hypotension by spinal anesthesia for cesarean delivery was effective in maintaining HR and CI.

Efficacy of Glycopyrrolate in Primary Hyperhidrosis Patients

BACKGROUND: Primary hyperhidrosis is a disorder of excessive sweating, which shares several features with anxiety disorders and has a negative impact on a patient's quality of life. Oral glycopyrrolate is one of the treatments available. There are a few published studies on the use of glycopyrrolate given orally in the treatment of hyperhidrosis. METHODS: Thies is study was a review of case notes in a series of 36 patients with primary hyperhidrosis. We made a comparison between the Keller's scale score of a pre-glycopyrrolate medication group and the Keller's scale score f a post-glycopyrrolate medication group. The Milanez de Campos score, Short Form_36 (SF-36) score, Beck Depression Inventory (BDI) score, Beck Anxiety Inventory (BAI) score, and autonomic nervous system (ANS) scale score were also compared between the two groups. RESULTS: In the post-glycopyrrolate medication group, there were declines in Keller's scale, and Milanez de Campos scale score and BAI score (P < 0.001). In addition, there were increases in SF_36 score in the post-glycopyrrolate medication group (P = 0.03) However, no changes were seen in, BDI score and ANS score in the post-glycopyrrolate medication group (P < 0.001). CONCLUSIONS: Glycopyrrolate is an effective initial method of treating primary hyperhidrosis that, reduces anxiety and improve patients' quality of life.

Anesthetic management in pediatric patient with Angelman syndrome: A case report / 대한마취과학회지

The Angelman syndrome is characterized by an abnormality of chromosome 15, where a subunit of the gamma amino-butyric acid receptor is coded. The clinical features are developmental delay, microcephaly, wide mouth, prognathia which usually do not have problem with intubation. But, muscular atrophy may induce delayed recovery from neuromuscular blockade. Moreover, there are case reports that vagal hypertonia such as severe bardycardia or asystole occurred during anesthesia. We present a 5-year-9-month-old male Angelman syndrome patient who underwent a left and right rectus ophthalmicus muscle recession. We gave him prophylactic glycopyrrolate before anesthetic induction and induced and maintained anesthesia with sevoflurane and oxygen. After that we monitored train-of-four ratio for evaluation of neuromuscular blockade. There is no complication during operation and recovery from anesthesia.

Combined atropine and glycopyrrolate in organophosphate poisoning: The right solution for an old problem.

Unintentional and intentional organophosphate (OP) poisonings continue to be a significant cause of morbidity and mortality in India. Conventional treatment with atropine may lead to CNS toxicity, although control of secretions may still be inadequate. The aim of this study was to assess the effectiveness of atropine along with glycopyrrolate in organophosphate poisonings. A prospective randomized double-blinded, placebo-con-trolled trial was done in an emergency department of a university hospital. Patients who consumed OP compounds were included. Pregnant women, hypothermic adults, mixed poisonings, and concomitant alcoholic intoxications were excluded. The subjects received either atropine and glycopyrrolate, or atropine and a matching placebo as a bolus through a peripheral IV line. All other aspects of treatment were carried out as per standard procedure. Seventy six victims were involved during a six month period, 38 belonging to the study group, and the remaining to the control group. There were no significant differences in demographic data, time of arrival, or time of starting treatment. Results revealed that the duration on ventilator was reduced in 60% of the study group as compared to the control group, reduction in the duration of ICU stay occurred in 20% of control group, while it was 72% of the study group. CNS toxicity occurred in 40% of control group, and 2% of study group. Intermediate syndrome developed in 8 of 38 subjects in the control group, and 1 of 38 in the study group. Development of respiratory tract infection was seen in 12% of the control group, while it occurred in only 5% of the study group. Addition of glycopyrrolate appears to be a promising new intervention in the management of OP poisoning.

Anticholinergic Relieves Bronchospasm Occurring during Spinal Anesthesia in a Asthmatic Patient: A case report / 대한마취과학회지

Placement of the endotracheal tube is a potent airway irritant that may trigger bronchospasm in asthmatic patients. But bronchospasm has been reported in association with regional anesthesia, but no clear understanding of the mechanism involved. This case describes acute bronchospasm during spinal anesthesia in lower limb surgery. In this case, bronchospasm was relieved by intravenous injection of glycopyrrolate, not by beta-agonist inhaler. We experienced repeated bronchospasm which was also very effectively treated by intravenous injection of glycopyrrolate.

Effects of Glycopyrrolate or Atropine on Hemodynamic Responses during Anesthetic Induction with Remifentanil and Sevoflurane in Elderly Patients / 대한마취과학회지

BACKGROUND: This study was conducted to determine the effect of glycopyrrolate or atropine on attenuating hemodynamic responses such as bradycardia and hypotension during anesthetic induction with remifentanil and sevoflurane in elderly patients, in a randomized placebo-controlled double blinded manner. METHODS: 60 patients over 65 years with ASA physical status 1 or 2 were allocated to one of three groups of 20 each. Each group received saline placebo (group C) or glycopyrrolate 4microgram/kg (group G) or atropine 0.5 mg (group A) immediately after induction of anesthesia, and then remifentanil 1microgram/kg bolus was given over 30s. Mean arterial pressure (MAP) and heart rate (HR) were measured before anesthetic induction, before intubation, and during 5 minutes after intubation at 1 minute interval. RESULTS: MAP remained stable and HR increased significantly 1 min after intubation in all groups. MAP decreased significantly during 2-5 minute after intubation in all groups. HR decreased in the group C, remained stable in the group G, and increased in the group A significantly during 3-5 minute after intubation. Hypotension (systolic blood pressure < 90 mmHg checked twice) occurred in 8 patients in the group C, 1 patient in the group G, and none in the group A. CONCLUSIONS: Glycopyrrolate and atropine attenuated the hemodynamic responses to laryngoscropy and intubation during anesthetic induction with remifentanil 1microgram/kg bolus dose and sevoflurane.

A Treatment Experience of Focal Hyperhidrosis in Sacrococcygeal Region: A report of two cases / 대한통증학회지

Essential hyperhidrosis is a socially disabling and emotionally embarrassing condition. Localized excessive sweating in the sacrococcygeal region is a rare form of focal hyperhidrosis. Although numerous treatment options exist, including botulinum toxin and sympathetic neurolysis, there has been no generally accepted form of treatment. The following cases describe the successful reduction of excessive sweating in the sacrococcygeal region, without side effects, after local applications of topical glycopyrrolate and the use of fast drying clothes.

Effect of Oral Glycopyrrolate in Essential Hyperhidrosis / 대한마취과학회지

BACKGROUND: Essential hyperhidrosis is a pathologic condition caused by excessive secretion of the eccrine sweat glands. This is an embarrassing condition, which severely reduces the quality of life and may result in psychological disturbance. Our purpose was to determine the therapeutic efficacy of oral glycopyrrolate in term of its strength, safety, and side effects. METHODS: Oral glycopyrrolate was given to 104 patients, 53 men and 51 women with a mean age of 24 years. Patients controlled the dosage of glycopyrrolate for a week. Attention was focused on patient satisfaction, onset time, duration, degree of reducing perspiration and side effects. RESULTS: Ninety eight of 104 patients (94%) were satisfied with their improved condition. The most common maximum dose/day was 2 mg. The overall mean onset time was 2.3 hours and the duration of the effect was 7.4 hours. Dry mouth occurred in 40 patients. Sixty eight of patients (65%) experienced reduced excessive sweating caused by oral glycopyrrolate. CONCLUSIONS: The administration of oral glycopyrrolate is a safe and effective method of treating essential hyperhidrosis, and appears to be an acceptable therapeutic option in any form of hyperhidrosis.

Core Temperature Changes according to Premedication / 대한마취과학회지

BACKGROUND: It is well known that body core temperature reduces during general anesthesia. Midazolam premedication for relieving anxiety might also reduce body core temperature by inhibiting tonic thermoregulatory vasoconstriction in elderly patients. Therefore, an effort to maintain temperature must be started before anesthesia. This study was designed to evaluate the effect on body core temperature of midazolam, atropine and glycopyrrolate, which are commonly used for premedication. METHODS: Six hundred and eleven patients of ASA physical status 1 or 2, aged 18 to 65, were involved in this study. They were randomly assigned to premedication with: 1) saline control (n = 92); 2) midazolam 0.04 mg/kg (n = 96); 3) midazolam 0.04 mg/kg with glycopyrrolate 0.004 mg/kg (n = 117); 4) midazolam 0.04 mg/kg with atropine 0.01 mg/kg (n = 93); 5) glycopyrrolate 0.004 mg/kg (n = 116); and 6) atropine 0.01 mg/kg (n = 97). All premedication was given intramuscularly about 30 min before operation. Temperatures were measured at the tympanic membrane at the time of premedication and 30 min after premedication. RESULTS: Temperatures increased slightly after injection in the control (0.14 +/- 0.36oC; mean +/- SD) and this increase was less in the midazolam group (0.07 +/- 0.39oC). The changes of temperature in the midazolam with glycopyrrolate (0.16 +/- 0.39oC), midazolam with atropine (0.19 +/- 0.40oC), and in the glycopyrrolate group were no different from that of the control group. However, there was a statistically significant increase in temperature after injection in the atropine group (0.26 +/- 0.42oC) versus the control group. Compared with the midazolam group, a statistically significant increase in temperature was observed in the midazolam with atropine, the glycopyrrolate, and in the atropine group. CONCLUSIONS: From these results, low dose midazolam (0.04 mg/kg), midazolam with glycopyrrolate, and midazolam with atropine for premedication have little affect on temperature. Midazolam with glycopyrrolate premedication is recommended for preserving body core temperature.

Anesthetic Management of the Patient with Persistent Penile Erection Developed after Spinal Anesthesia: A case report / 대한마취과학회지

A 50-year-old man with bladder cancer had spinal anesthesia for transurethral resection of bladder. After he had spinal block at the T8 level, he developed a persistent penile erection, making it impossible to introduce the 24 French cystoscope. To treat a persistent penile erection, intravenous glycopyrrolate was incrementally given for a total of 0.4 mg. A persistent penile erection was markedly subsided 5 minutes after last 0.2 mg glycopyrrolate was given. Then corpus cavernosum blood was aspirated. The cystoscope was easily introduced, and transurethral resection of bladder proceeded without further complication.

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 embrasssed 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.

Dose Thoracoscopic Sympathectomy for Hyperhidrosis Increase Airway Pressure? / 대한마취과학회지

BACKGROUND: Bilateral interruption of the upper thoracic sympathetic chain at T2 level represents a selective cure for essential hyperhidrosis. Following the surgical sympathectomy, significant changes in pulmonary function has been observed. Our hypothesis was that thoracic sympathectomy may increase airway resistance during mechanical ventilation and which may be attenuated by the anticholinergics. METHODS: 21 patients with essential hyperhidrosis in ASA physical status class 1 under going thoracoscopic sympathectomy, they were randomizely divided into two groups: glycopyrrolate premedication group (n=13) and non-premedication, control group (n=9). Glycopyrrolate 0.2 mg was administered 30 minutes before the induction of anesthesia. Blood pressure, heart rate, peak airway pressure, plateau pressure were measured at before and immediate after sympathectomy. Respiratory compliance and resistance were calculated. RESULTS: After thoracoscopic sympathectomy, there was significant increase in mean peak airway pressure (15 +/- 3 vs 18 +/- 3 cmH2O, P<0.05) and decrease in respiratory compliance (52 +/- 12 vs 45 +/- 10 ml/cmH2O, P<0.05) compared to baseline. However there was no significant difference between glycopyrolate premedication group and non-premedication group. Conclusion: Thoracoscopic upper dorsal sympathectomy in patients with essential hyperhidrosis causes increase peak airway pressure and decrease the compliance of respiratory system during mechanical ventilation.

THE STUDY OF ANESTHETIC EFFECT USING KETAMINE, MIDAZOLAM, GIYCOPYRROLATE IN THE OPERATION OF PEDIATRIC PATIENTS

Ketamine hydrochloride is a unique dissociative anesthetic agent that has been used in children for more than 20 years. Ketamine is devoid of sedation and hypnotic properties but has profound analgesic and amnesic characteristics even in low doses. It is recommended to use with benzodiazepines for the alleviation of ketamine-induced emergence reaction and with anticholinergic agent for the antisialogogue affect. We used the intramuscular ketamine, midazolam, and glycopyrrolate in thirty pediatric patients who were uncontrolled by conventional behaviour management in the OPD of Chungbuk National University Hospital Oral & Maxillofacial Surgery and Emergency Room. The results were as follows: 1. 20 males and 10 females were involved and the average age was 3 years(range, 19 months to 6 years). 2. The anesthetic technique was used for the following reasons: 10 for the I & D of submandibular abscess, 2 for the post operative wound care of cleft lip, and 4 for the other causes. 3. Average onset time of anesthesia was 5.1 minutes(range, 2 to 10 minutes) and average working time was 26 minutes(range, 12 to 50 minutes). 4. 24(80%) of 30 children were rated as 'Cooperative of sleeping' within an average 4.8, and the other children(20%) were rated as 'Intermittent crying or fighting'. 5. Emesis occurred during the recovery period in 2 children, but there was no airway compromise or aspiration. Other side effects were a transient rash(10%), and random movement(7%). 6. The recovery room behavior was quite and uneventful in 23(77%) children and mild agitation in 7(23%) ones.

The Effects of Atropine and Glycopyrrolate on the Recovery from Mivacurium: Induced Neuromuscular Blockade in the Rabbit / 대한마취과학회지

BACKGROUND: Antimuscarinic agents are used to block undesirable muscarinic effects of `anticholinesterase given to reverse the residual neuromuscular blockade produced by muscle relaxants. However, besides antimuscarinic effects, atropine was known to have some positive effects on the recovery from neuromuscular blockade by acting at the presynaptic muscarinic receptor of the neuromuscular junction. But there have been few reports about the neuromuscular effects of glycopyrrolate. So we observed the neuromuscular effects of atropine and glycopyrrolate, and compared two. METHODS: Mivacurium(0.064 mg/kg) was administered intravenously and the experimental groups were divided into 5 groups: the control group (no antimuscarinic agent administered), Al group (0.02 mg/kg atropine administered), A2 group (0.04 m atropine administered), Gl group (0.01 mg/kg glycopyrrolate administered) and G2 group (0.02 mg/kg glycopyrrolate administered). The left cammon peroneal nerve was stimulated by the 0.1 Hz single twitch and 100 Hz tetanic stimuli. We manitored the mechanical activity of the anterior tibialis muscle and observed recovery index, tetanic fade, and post-tetanic potentiation. RESULTS: There were no significant differences in recovery indices and post-tetanic potentiations among the 5 groups. Significant differences were found in tetanic fades between the experimental groups(A1, A2, Gl, G2) and the control group(P<0.05). However no significant differences in tetanic fades were found among the experimental groups. CONCLUSIONS: Atropine and glycopyrrolate hastened the recovery from mivacurium induced neuromuscular blockade. The neuromuscular recovery effects of glycopyrmlate were found to be similar to atropine at equipotent dose.

The Effect of Oral Clonidine Premedication and Adequate Dose of Intravenous Glycopyrrolate for Correction of Bradycardia in Children / 대한마취과학회지

BACKGROUND: Clonidine is one of the effective premedicant but may cause biadycardia and hypotension. This study was designed to investigate the efficacy of two doses of oral clonidine as a premedicant and to evaluate the interaction between clonidine and intravenous glycopyrrolate, according to dose. METHODS: Sixty children(3-8 years old) were randomly selected and assigned to one of thtee groups: control(no premedication, n=20), clonidine 2(2 ug/kg, n=20), clonidine 4(4 ug/kg, n=20). Patients received clonidine orally 90 min before the estimated time of arrival at the operating room. Vital signs and percutaneous oxygen saturation were evaluated before premedication, 60 min, 90 min after premedication and then sedation score was evaluated on arrival at the operating room. After record the baseline heart rate, all patients received glycopyrrolate 4 ug/kg intravenously and changes of heart rate were evaluated. Incremental doses of glycopyrrolate (2 ug/kg every 3 min) were administered until heart rate increase by 20 beats/min. RESULTS: The sedation score was significantly higher in the clonidine 4 group(Ridit score=4.8, p=0.03). In the clonidine 4 group, the heart rate was decreased significantly compared to other groups. In each group, there were no differences in blood pressure, respiratory rate, percutaneous oxygen saturation. Doses required to increase heart rate by 20 beats/min were 5.8+/-1.2 ug/kg in the control group, 7.2+/-1.6 ug/kg in the Clonidine 2 group, 8.1+/-1.8 ug/kg in the clonidine 4 group and there were no significant differences between 3 groups. CONCLUSIONS: Oral clonidine 4 ug/kg produced satisfactory sedation and decreased heart rate but no patient required to treatment for bradycardia. Oral clonindine premedication did not blunt the response of heart rate to intravenous glycopyrrolate.

The Effect of Pretreated Pyridostigmine on the Change of Blood Pressure and Heart Rate Following Intrathecally Injected Clonidine in Cats / 대한마취과학회지

Intrathecal clonidine injection induces analgesia without significant respiratory depression, but decreases blood pressure and causes sedation. Injection of spinal cholinesterase inhibitor alone increases blood pressure in animals, and enhances clonidine induced analgesia. To evaluate the effect of pretreated pyridostigmine on the change of blood pressure and heart rate, clonidine was injected intrathecally in cats. We divided fifteen cats into three groups and administered saline(0.5 cc) to group 1, pyridostigmine(0.5 cc, 2.5 mg) to group 2, pyridostigmine(0.5 cc, 2.5 mg) and glycopyrrolate(0.5 cc, 0.1 mg) to group 3 before 20 minute of clonidine injection and measured mean arterial pressure, heart rate, P CO2 and central venous pressure. The results were as follows: 1)After clonidine injection, all mean arterial pressure values were significantly reduced in group 1, but in group 3, 20, 30 and 40 minutes values were significantly reduced, and 10, 40 minutes values after clonidine injection were not reduced significantly in group 2 compared to group 1. 2)After clonidine injection, heart rates were significantly reduced in all groups, but there was no significant difference between group 1, group 2 and group 3. 3)There was no significant difference of central venous pressure in any groups. 4)There was no significant difference for reversal of pyridostigmines effect by glycopyrrolate. Based on these results, these data suggest that pyridostigmine pretreatment counteracts clonidine induced hypotension, but further study of spinal az adrenergic-cholinergic combination for pain therapy is needed before clinical application.

Dose - response for Glycopyrrloate and Heart Rate in Children Anesthetized with Halothane and Nitrous Oxide / 대한마취과학회지

The dose-response for glycopyrrolate and heart rate in anesthetized children has not heen defined. We determined the dose-response for glyeopyrrolate and heart rate in 50 children, ASA physical status l and 2, anesthetized with halothane and nitrous oxide. Anesthesia was induced with 60-70% nitrous oxide in oxygen and halothane(1.5-2.0 vo1%). After induction of aneethesia, glycopyrrolate in a dose of 4, 6, 8, 12 or 16ug Xkg(-1) was administered by rapid infusion to each subject. The effects of glycopyrrolate on heart rate, heart rhythm and systolic blood pressure were compared among dosage groups, and dose-response curve for peak heart rate was constructed, Glycopyrrolate increased the heart rate in a dose-related manner upto 12 ug X kg(-1) except 16 ugX kg(-1). Fifty percent maximal response corresponded to 6.1 ug X kg(-1), and 95% maximal response corresponded to 11.1 ug X kg(-1) . None of the patients had nonsinus rhythm after glycopyrrolate injection. Except for glycopyrrolate given at 4 ug x kg(-1), the systolic blood pressure increased significantly after all other doses. Glycopyrrolate in doses greater than or equal to 6 ug X kg(-1) increased the heart rate and systolic blood pressure in children anesthetized with halothane and nitrous oxide.