Glycopyrrolate

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Continuing Education Activity

Glycopyrrolate, also known as glycopyrronium, is an anticholinergic drug. Glycopyrrolate has been widely used as a preoperative medication to inhibit salivary gland and respiratory secretions. The most frequent reasons for administering anticholinergics include producing an antisialagogue effect, creating a sedative and amnesic effect, and preventing reflex bradycardia. Glycopyrrolate is among the more common anticholinergic medications. It is used perioperatively as a muscarinic receptor antagonist. This activity outlines the indications, mechanism of action, dosing, important adverse effects, contraindications, monitoring, the toxicity of glycopyrrolate. It increases practitioners' knowledge regarding how to approach and use this medication and monitor it effectively to drive better patient outcomes.

Objectives:

  • Explain the mechanism of action of glycopyrrolate.
  • Identify the indications for using glycopyrrolate on a patient.
  • Review the necessary monitoring that must take place when utilizing glycopyrrolate.
  • Outline interprofessional team strategies for improving care coordination and communication to advance improved outcomes using glycopyrrolate when indicated.

Indications

Glycopyrrolate, also known as glycopyrronium, is an anticholinergic drug. It is a synthetically created quaternary amine with pyridine and a cyclopentane moiety within the compound's structure. Glycopyrrolate has been widely used as a preoperative medication to inhibit salivary gland and respiratory secretions. The most frequent reasons for administering anticholinergics include producing an antisialagogue effect, creating a sedative and amnesic effect, and preventing reflex bradycardia. Anticholinergics are not predictably effective in increasing gastric fluid pH or decreasing gastric fluid volume. Glycopyrrolate is among the most commonly used anticholinergic medications.

  • It is used perioperatively as a muscarinic receptor antagonist.[1][2]
  • The topical formulation of glycopyrrolate is indicated to treat primary axillary hyperhidrosis in nine years of age and older patients.[3] 
  • It is also helpful to reduce severe or chronic drooling in pediatric patients with neurologic conditions, such as cerebral palsy. The intravenous formulation of glycopyrrolate classically works to reverse vagal reflexes and bradycardia intraoperatively and reverse the muscarinic effects of cholinergic agents such as neostigmine or pyridostigmine.[4]
  • Glycopyrrolate may be administered to reverse the neuromuscular blockade due to nondepolarizing muscle relaxants postoperatively and is frequently used in conjunction with neostigmine, a cholinesterase inhibitor.[5]
  • Various oral inhalation formulations of glycopyrrolate are indicated for the long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).[6][7][8]

Other commonly used anticholinergics include atropine and scopolamine. Most frequently, clinicians use glycopyrrolate to reduce pharyngeal, tracheal, bronchial, and sialagogue effects preoperatively; decreased secretions are the desired effect during anesthesia when a tracheal tube is in place. A blockade of reflexive vagal cardiac inhibition reflexes during both intubation and anesthetic induction may also occur.

Mechanism of Action

Glycopyrrolate's primary mechanism of action is the blockage of acetylcholine's effects at the parasympathetic sites in various tissues. This blockage primarily occurs in the central nervous system, smooth muscle, and secretory glands. It also reduces the rate of salivation by preventing the stimulation of the acetylcholine receptors themselves. Glycopyrrolate does not cross the blood-brain barrier nor the placenta. It has a slower diffusion rate relative to other anticholinergic drugs such as atropine and scopolamine.[9][10]

Administration

Glycopyrrolate administration can be intravenous, intramuscular, oral, or topical. Glycopyrrolate exhibits onset of action within 1 minute when given intravenously and an elimination half-life of approximately 50 minutes. Glycopyrrolate undergoes urinary excretion and elimination. It differs from atropine in being a quaternary amine and has both cyclopentane and pyridine moieties in the compound.[11] 

Storage of the drug should be in a cool, dry area protected from light before administration. Promptly discard unused solution as it is unstable at a pH greater than 6. The typical dose of glycopyrrolate is one-half that of atropine. For instance, the premedication dose is 0.005 to 0.01 mg/kg up to 0.2 to 0.3 mg in adults. 

  • Glycopyrrolate for injection comes packaged as a solution of 0.2 mg/mL. Before intravenous administration, inspect the syringe to ensure there is no particulate matter. Intramuscular or intravenous administration requires no dilution and should be at a rate of 0.2 mg over 1 to 2 minutes. Additionally, it may be administered via the tubing of a running intravenous infusion of a compatible solution.[12]
  • Glycopyrrolate has a 2 to 4-hour duration of action after intravenous administration, while atropine has 30 minutes.
  • The topical formulation is available as a single-use cloth pre-moistened with a 2.4% glycopyrronium solution.[13] It is used no more than once every 24 hours on both underarms.
  • Inhalation formulation available as the dry powder inhaler 15.6 mcg capsule twice daily and as the nebulization solution of one 25 mcg vial inhaled twice daily.[8]
  • Oral tablets are available in 1mg, 1.5mg, and 2mg strength and oral solution is available in 1mg/5mL strength. The starting dose is 1 to 2 mg twice a day and titrated upward gradually based on patient response to the treatment.[14]

Special Population

Renal impairment: According to product labeling, dose adjustment might be necessary. Glycopyrolate's elimination can be severely impaired in patients with impaired kidney function.

Hepatic Impairment: According to product labeling, dose adjustment might be necessary.

Adverse Effects

  • Adverse reactions after glycopyrrolate administration may include anticholinergic symptoms such as mydriasis, hyperthermia, tachycardia, and cardiac arrhythmia. They may also include blurred vision, constipation, cycloplegia, dry mouth, dry skin, flushing, photophobia, urinary retention, and xerophthalmia.[15][2]
  • Glycopyrrolate may affect the patient's ability to perform tasks requiring mental alertness. In addition, the medication may induce drowsiness or blurred vision, which is exacerbated by the consumption of alcohol. Usage also requires close monitoring in patients with hepatic impairment. For example, patients may not be able to operate heavy machinery safely.
  • Use with discretion in patients with autonomic neuropathy or hyperthyroidism. Heat prostration can occur in the presence of fever, high ambient temperature, or physical exercise. Take caution to avoid this effect by limiting or discontinuing usage with exercise or in situations with elevated ambient temperatures.
  • Usage should generally be avoided in neonates. Patients under the age of 12 with pediatric spastic paralysis are more likely to exhibit an increased anticholinergic response, which elevates the risk for unwanted effects. A hyperexcitability reaction can potentially occur with higher than recommended dosages; use with caution.[16]

Contraindications

Glycopyrrolate is contraindicated in patients with hypersensitivity to glycopyrronium, excipients, or other ingredients in the anticholinergic class. The following is a list of medical conditions that would preclude the use of anticholinergic therapy, categorized by the system:

  • Ophthalmic: angle-closure glaucoma[17]
  • Cardiovascular: mitral stenosis and cardiovascular instability in acute hemorrhage[18]
  • Gastrointestinal: a hiatal hernia, gastrointestinal obstruction, paralytic ileus, reflux esophagitis, severe ulcerative colitis, toxic megacolon, intestinal atony in elderly or debilitated patients[19][20]
  • Neuromuscular: myasthenia gravis[21]
  • Urologic: obstructive uropathy[22]
  • The use of solid oral formulations of potassium chloride needs close monitoring if considering coadministration with glycopyrrolate.[23]

Monitoring

  • Glycopyrronium reduces the body's ability to sweat. Therefore, it may cause hyperthermia and heat stroke in hot environments. Other observed adverse effects include dry mouth, difficulty urinating, headaches, diarrhea, and constipation.
  • A dose adjustment may be necessary if urinary retention occurs. Existing renal impairment may be further complicated. In the general population, usage may increase the risk of confusion, hallucinations, and anticholinergic effects.[24]
  • Use glycopyrrolate with caution in patients with a hiatal hernia and reflux esophagitis. It can worsen prostatic hyperplasia symptoms and/or bladder neck destruction as it may increase urinary retention. In ulcerative colitis cases, a high dose may inhibit intestinal motility and worsen toxic megacolon or ileus symptoms. Glycopyrrolate administration is contraindicated in patients with ulcerative colitis. Since gastrointestinal motility may decline, constipation or intestinal pseudo-obstruction may occur. If the latter condition arises, it may result in pain from abdominal distention, nausea, or vomiting. If intestinal obstruction of any type is suspected, it is imperative to discontinue use and simultaneously reevaluate. Symptoms presenting as diarrhea, particularly in patients who have undergone bowel resections of the ileum or colon, warrant a lower threshold for clinical suspicion. When an obstruction is suspected, or if the patient has diarrhea, promptly discontinue treatment.[12]
  • Because of its quaternary structure, glycopyrrolate cannot cross the blood-brain barrier and is almost devoid of the central nervous system and ophthalmic activity. Potent inhibition of salivary gland and respiratory tract secretions is the primary rationale for using glycopyrrolate as a premedication. Heart rate usually increases after intravenous administration, but not intramuscular.[2] 
  • Monitor heart rate and maintain adequate hydration to avoid adverse events.

Toxicity

Acute toxicity with glycopyrrolate is secondary to an extension of the pharmacologic effects on the muscarinic cholinergic receptors. Muscarinic receptor sites reside in the brain's cerebral cortex, thalamus, hippocampus, and reticular activating system. They are also present in the postganglionic parasympathetic nervous system and other selected sites such as sweat glands. Anticholinergic agents block the effects of acetylcholine by competitively binding and blocking muscarinic receptors.

Central Nervous System Toxicity

Also called a central anticholinergic syndrome, central nervous system toxicity can be an undesirable side effect of any anticholinergic medication. It manifests as delirium or prolonged somnolence after anesthesia. While this is more likely to occur with scopolamine than atropine, the incidence should be low with the administration of proper dosages. However, elderly patients may be uniquely susceptible. Glycopyrrolate is less likely to cause this condition than other anticholinergic medications because it does not cross the blood-brain barrier.[25]

Tachycardia

The most likely response after intramuscular administration of atropine, glycopyrrolate, or scopolamine for premedication is an increase in heart rate, which may indicate a weak cholinergic antagonist effect of these drugs.

Enhancing Healthcare Team Outcomes

Glycopyrrolate is a frequently prescribed agent by the nurse practitioner, primary care provider, anesthesiologist, and internist. However, all healthcare workers who prescribe this agent should be aware of its potential adverse effects. Glycopyrronium may cause hyperthermia and heat stroke in hot environments as it reduces the body's ability to sweat. Clinicians should monitor liver function tests in patients with hepatic impairment. Nursing staff should monitor and inform the prescriber if urinary retention occurs and existing renal impairment is worsening. The use of glycopyrrolate in the general population may increase the risk of confusion, hallucinations, and other anticholinergic effects.[24] Nurses should counsel patients before administering glycopyrrolate therapy for common adverse effects like dry mouth, difficulty urinating, headaches, diarrhea, and constipation. Pharmacists should verify the dose and possible drug-disease interactions. Pharmacists should warn the patient that the medication may induce drowsiness or blurred vision, which is exacerbated by alcohol consumption. As health care team members, all MDs, DOs, PAs, NPs, nursing staff, and pharmacists should work in close collaboration to improve care coordination and communicate to advance better outcomes using glycopyrrolate when indicated.


Article Details

Article Author

Ariel Gallanosa

Article Author

Joshua Stevens

Article Editor:

Judy Quick

Updated:

10/11/2021 7:46:22 AM

PubMed Link:

Glycopyrrolate

References

[1]

Reisner C,Pearle J,Kerwin EM,Rose ES,Darken P, Efficacy and safety of four doses of glycopyrrolate/formoterol fumarate delivered via a metered dose inhaler compared with the monocomponents in patients with moderate-to-severe COPD. International journal of chronic obstructive pulmonary disease. 2018     [PubMed PMID: 29950826]

[2]

Chabicovsky M,Winkler S,Soeberdt M,Kilic A,Masur C,Abels C, Pharmacology, toxicology and clinical safety of glycopyrrolate. Toxicology and applied pharmacology. 2019 May 1;     [PubMed PMID: 30905688]

[3]

Albornoz López R,Arias Rico R,Torres Degayón V,Gago Sánchez A, [Formulation of topical glycopyrrolate for hyperhidrosis]. Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria. 2008 Nov-Dec;     [PubMed PMID: 19232224]

[4]

Fuchs-Buder T,Hofmockel R,Geldner G,Diefenbach C,Ulm K,Blobner M, [The use of neuromuscular monitoring in Germany]. Der Anaesthesist. 2003 Jun     [PubMed PMID: 12835874]

[5]

Nicolardot J,Engelman E,Coeckelenbergh S,Jungels C,Baurain M, Neostigmine accelerates recovery from moderate mivacurium neuromuscular block independently of train-of-four count at injection: a randomised controlled trial. British journal of anaesthesia. 2018 Aug     [PubMed PMID: 30032892]

[6]

Nebulized glycopyrrolate (Lonhala Magnair) for COPD. The Medical letter on drugs and therapeutics. 2018 Apr 23;     [PubMed PMID: 29667949]

[7]

Martinez FJ,Rabe KF,Ferguson GT,Fabbri LM,Rennard S,Feldman GJ,Sethi S,Spangenthal S,Gottschlich GM,Rodriguez-Roisin R,Arora S,Siler TM,Siddiqui S,Darken P,Fischer T,Maes A,Golden M,Orevillo C,Reisner C, Efficacy and Safety of Glycopyrrolate/Formoterol Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Patients With COPD. Chest. 2017 Feb;     [PubMed PMID: 27916620]

[8]

Tashkin DP,Gross NJ, Inhaled glycopyrrolate for the treatment of chronic obstructive pulmonary disease. International journal of chronic obstructive pulmonary disease. 2018;     [PubMed PMID: 29928118]

[9]

Both EB,Moreno-González D,García-Reyes JF,Dernovics M, Monitoring the degradation of atropine and scopolamine in soil after spiking with naturally contaminated organic millet. The Science of the total environment. 2018 Jun 1     [PubMed PMID: 29996405]

[10]

Gruber RP,Stone GC,Reed DR, Scopalamine-induced anterograde amnesia. International journal of neuropharmacology. 1967 May     [PubMed PMID: 6068339]

[11]

Glycopyrrolate null. 2006     [PubMed PMID: 30000540]

[12]

Sridharan K,Sivaramakrishnan G, Pharmacological interventions for treating sialorrhea associated with neurological disorders: A mixed treatment network meta-analysis of randomized controlled trials. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2018 May     [PubMed PMID: 29475576]

[13]

Olamiju B,Panse G,McFerren M, Therapeutic treatment of multiple eccrine hidrocystomas with topical glycopyrronium tosylate 2.4% solution. JAAD case reports. 2020 Apr;     [PubMed PMID: 32258325]

[14]

Walling HW, Systemic therapy for primary hyperhidrosis: a retrospective study of 59 patients treated with glycopyrrolate or clonidine. Journal of the American Academy of Dermatology. 2012 Mar     [PubMed PMID: 21820204]

[15]

Varssano D,Rothman S,Haas K,Lazar M, The mydriatic effect of topical glycopyrrolate. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 1996 Mar;     [PubMed PMID: 8720721]

[16]

Williams AM,Shave RE,Coulson JM,White H,Rosser-Stanford B,Eves ND, The influence of vagal control on sex-related differences in left ventricular mechanics and hemodynamics. American journal of physiology. Heart and circulatory physiology. 2018 Jun 1     [PubMed PMID: 29856652]

[17]

Jaroudi M,Fadi M,Farah F,El Mollayess GM, Glycopyrrolate induced bilateral angle closure glaucoma after cervical spine surgery. Middle East African journal of ophthalmology. 2013 Apr-Jun;     [PubMed PMID: 23741140]

[18]

Bali IM,Mirakhur RK, Comparison of Glycopyrrolate, atropine and hyoscine in mixture with neostigmine for reversal of neuromuscular block following closed mitral valvotomy. Acta anaesthesiologica Scandinavica. 1980 Aug;     [PubMed PMID: 7468122]

[19]

Glycopyrrolate LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012;     [PubMed PMID: 31643554]

[20]

Hunt ME,Yates JR,Vega H,Heidel RE,Buehler JM, Effects on Postoperative Gastrointestinal Motility After Neuromuscular Blockade Reversal With Sugammadex Versus Neostigmine/Glycopyrrolate in Colorectal Surgery Patients. The Annals of pharmacotherapy. 2020 Dec;     [PubMed PMID: 32468846]

[21]

Hindmarsh J,Everett P,Hindmarsh S,Lee M,Pickard J, Glycopyrrolate and the Management of     [PubMed PMID: 31976808]

[22]

Low J,Escobar M,Baquero S,Goldman HS,Rosen G, Glycopyrrolate and Post-Operative Urinary Retention: A Narrative Review. Cureus. 2020 Nov 8;     [PubMed PMID: 33312781]

[23]

Alsop WR,Moore JG,Rollins DE,Tolman KG, The effects of five potassium chloride preparations on the upper gastrointestinal mucosa in healthy subjects receiving glycopyrrolate. Journal of clinical pharmacology. 1984 May-Jun;     [PubMed PMID: 6747020]

[24]

Scott AJ,Mason SE,Langdon AJ,Patel B,Mayer E,Moorthy K,Purkayastha S, Prospective Risk Factor Analysis for the Development of Post-operative Urinary Retention Following Ambulatory General Surgery. World journal of surgery. 2018 Jun 14     [PubMed PMID: 29947990]

[25]

Misal US,Joshi SA,Shaikh MM, Delayed recovery from anesthesia: A postgraduate educational review. Anesthesia, essays and researches. 2016 May-Aug     [PubMed PMID: 27212741]