What is the effect of Glycopyrrolate (Glycopyrolate)?

From the Guidelines

Glycopyrrolate is recommended for reducing excessive secretions associated with dyspnea, particularly in patients with advanced cancer, at a dose of 0.2-0.4 mg IV or subcut q 4 hr prn, due to its minimal central nervous system effects and low risk of delirium compared to other anticholinergic agents 1.

Key Points

• Glycopyrrolate is an anticholinergic medication that reduces secretions and blocks certain autonomic nervous system effects.
• It is commonly used to decrease saliva and respiratory secretions before surgery, or to manage chronic conditions like chronic obstructive pulmonary disease (COPD).
• The medication works by blocking muscarinic acetylcholine receptors, reducing smooth muscle contractions in the airways, decreasing glandular secretions, and inhibiting vagal reflexes.
• Common side effects include dry mouth, constipation, urinary retention, and blurred vision.
• Glycopyrrolate should be used cautiously in patients with glaucoma, prostatic hypertrophy, or certain cardiac conditions.

Clinical Use

• In patients with advanced cancer, glycopyrrolate can be used to reduce excessive secretions associated with dyspnea, at a dose of 0.2-0.4 mg IV or subcut q 4 hr prn 1.
• The medication can also be used in combination with other agents, such as opioids and benzodiazepines, to manage dyspnea and other symptoms in patients with advanced cancer.
• In patients undergoing electroconvulsive therapy (ECT), glycopyrrolate can be used as an anticholinergic medication to prevent bradycardia, arrhythmia, or cardiac asystole, at a dose of 0.2-0.4 mg IV immediately before ECT 1.

Safety and Efficacy

• Glycopyrrolate has minimal central nervous system effects compared to other anticholinergic agents, making it a preferable choice in situations where cognitive side effects are concerning 1.
• The medication has been shown to be effective in reducing excessive secretions and improving symptoms in patients with advanced cancer and other conditions.
• However, glycopyrrolate can cause anticholinergic side effects, such as dry mouth, constipation, and urinary retention, and should be used cautiously in patients with certain medical conditions.

From the FDA Drug Label

CLINICAL PHARMACOLOGY: Glycopyrrolate, like other anticholinergic (antimuscarinic) agents, inhibits the action of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine but lack cholinergic innervation The highly polar quaternary ammonium group of glycopyrrolate limits its passage across lipid membranes, such as the blood-brain barrier, in contrast to atropine sulfate and scopolamine hydrobromide, which are highly non-polar tertiary amines which penetrate lipid barriers easily.

Glycopyrolate is an anticholinergic agent that inhibits the action of acetylcholine on various structures.

• It has a quaternary ammonium group that limits its passage across lipid membranes, such as the blood-brain barrier.
• The onset of action is generally evident within one minute after intravenous injection, and within 15 to 30 minutes after intramuscular administration.
• The vagal blocking effects persist for 2 to 3 hours, and the antisialagogue effects persist up to 7 hours 2.
• Adverse reactions may include xerostomia, urinary hesitancy and retention, blurred vision, and tachycardia 2.

From the Research

Overview of Glycopyrrolate

• Glycopyrrolate is an anticholinergic agent used for various medical applications, including reversal of neuromuscular blockade (NMB) and treatment of chronic drooling in children 3, 4.
• It has been compared to atropine in NMB reversal, with studies indicating superior efficacy and adverse effect profile for glycopyrrolate 3.

Dosage and Administration

• The recommended dosage ratio for NMB reversal is 0.2 mg glycopyrrolate to 1.0 mg neostigmine 3.
• Glycopyrrolate can be administered through various routes, including oral, intramuscular (i.m.), and intravenous (i.v.) 5, 6.
• Intravenous administration is more effective at reducing oral and gastric secretions compared to other routes 5.

Clinical Applications

• Glycopyrrolate is used for reversal of NMB drugs, particularly in conjunction with neostigmine 3.
• It is also used to treat chronic drooling in children with neurodevelopmental disabilities, with an oral solution approved by the US Food and Drug Administration in 2010 4.
• Glycopyrrolate has been evaluated for use in transesophageal echocardiography (TEE), but its use is not recommended due to lack of benefit and increased side effects 7.

Pharmacokinetics and Pharmacodynamics

• Glycopyrrolate has a short distribution phase half-life and elimination phase half-life, with a low distribution volume and high total plasma clearance value 6.
• The oral bioavailability of glycopyrrolate varies widely, with a median of 3.3% 4.
• The correlation between plasma concentration and drug effects is variable, and adverse effects such as dry mouth, constipation, and behavioral changes can occur, particularly at higher doses 4, 6.