Glycopyrrolate, also known as glycopyrronium, is an anticholinergic drug. It is a synthetically created quaternary amine with both a 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 more common anticholinergic medications. It used perioperatively as a muscarinic receptor antagonist. Other commonly used anticholinergics include atropine and scopolamine. Most frequently, glycopyrrolate is used 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. 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. It is also used to reduce severe or chronic drooling in pediatric patients with neurologic conditions, such as cerebral palsy. The intravenous formulation of glycopyrrolate is classically used to reverse vagal reflexes and bradycardia intraoperatively, as well as to reverse the muscarinic effects of cholinergic agents such as neostigmine or pyridostigmine.
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.
Glycopyrrolate can be administered intravenously, intramuscularly or orally. Before intravenous administration, the syringe should be inspected to ensure there is no particulate matter. It may be administered without dilution when given intramuscularly or intravenously and should be given at a rate of 0.2 mg over 1 to 2 minutes. Additionally, it may be administered via tubing of a running intravenous infusion of a compatible solution. It should be stored in a cool, dry area protected from light before administration. Promptly discard unused solution as it is unstable at a pH greater than 6. 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 is severely impaired in patients with renal failure. Physically, glycopyrrolate differs from atropine in being a quaternary amine and has both cyclopentane and pyridine moieties in the compound. 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 is packaged as a solution of 0.2 mg/mL.
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.
Glycopyrrolate is contraindicated in patients with hypersensitivity to glycopyrronium or other ingredients in its class. The following is a list of medical conditions that would preclude the use of anticholinergic therapy, categorized by the system:
Additionally, the use of solid oral formulations of potassium chloride needs close monitoring if considering coadministration with glycopyrrolate.
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. The medication may induce drowsiness or blurred vision, which is exacerbated by the consumption of alcohol. Usage should also be closely monitored in patients with hepatic impairment. 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 for confusion, hallucinations, and anticholinergic effects.
Use glycopyrrolate with caution in patients with a hiatal hernia and reflux esophagitis. It can worsen symptoms of prostatic hyperplasia and/or bladder neck destruction as it may increase urinary retention. In cases of ulcerative colitis, a high dosage may result in the inhibition of intestinal motility and worsen symptoms of toxic megacolon or ileus. 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 any type of obstruction is suspected, or if the patient has diarrhea, promptly discontinue treatment.
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.
Glycopyrrolate may affect the patient's ability to perform tasks requiring mental alertness. For example, patients may not be able to operate heavy machinery safely.
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.
Because of its quaternary structure, glycopyrrolate cannot cross the blood-brain barrier and is almost devoid of 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. Glycopyrrolate has a 2- to 4-hour duration of action after intravenous administration; atropine's is 30 minutes.
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 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.
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.