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 also requires close monitoring 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 of confusion, hallucinations, and anticholinergic effects.[8]

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 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 an obstruction is suspected, or if the patient has diarrhea, promptly discontinue treatment.[6]

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.[9]

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. 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.

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.

Glycopyrrolate is a frequently prescribed agent by the nurse practitioner, primary care provider, anesthesiologist, and the internist. However, all healthcare workers who prescribe this agent should be aware of its potential adverse effects. 

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 pharmacist should warn the patient that the medication may induce drowsiness or blurred vision, which is exacerbated by alcohol consumption. Usage also requires close monitoring 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 of confusion, hallucinations, and anticholinergic effects.[8]