GLYCOPYRRONIUM BROMIDE

Indications

• Chronic obstructive pulmonary disease (COPD)
• Asthma (as an adjunct therapy)
• Pre-operative medication to reduce secretions
• Management of excessive salivation

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations in pediatric patients.

Adults: Refer to the BNF for specific dosing information based on the indication and patient characteristics.

Mechanism of action

Glycopyrronium has the highest affinity for M1 muscarinic receptors, followed by M3, M2/M4, and M5. By antagonizing these receptors, particularly M3 which is responsible for bronchoconstriction and secretions, glycopyrronium decreases airway resistance and reduces the secretion of mucus in the airways, thereby facilitating easier breathing. It also decreases salivary and gastric secretions, contributing to its therapeutic effects in various conditions.

Pharmacodynamics

As a quaternary ammonium compound, glycopyrronium is one of the most commonly prescribed LAMAs with a long duration of action due to its slow dissociation from muscarinic receptors. It has a wider therapeutic index compared to other anticholinergic medications. Patients may experience side effects such as urinary retention, risk of overheating, and transient blurred vision as a result of its anticholinergic properties.

Pharmacokinetics

Glycopyrronium is well-absorbed following inhalation, with peak plasma concentrations occurring within a few hours. The drug undergoes hepatic metabolism, primarily via cytochrome P450 enzymes, and is excreted through both urine and feces. Its elimination half-life supports once-daily dosing in a clinical setting.

Adverse effects

• dry mouth
• blurred vision
• constipation
• urinary retention
• tachycardia
• confusion
• delirium

Interactions

• clozapine+glycopyrronium: Unknown (additive effect)
• antipsychotics, second generation+glycopyrronium: Unknown (additive effect)

Precautions

• use with caution in patients with urinary retention
• monitor for signs of overheating
• use with caution in elderly patients due to risk of confusion and delirium

Pregnancy

Glycopyrronium should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known if glycopyrronium is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.

Formulations

• oral solution
• inhalation solution
• tablet

Indications

• Hyperhidrosis (excessive sweating)
• Premedication in anesthetic procedures

Dosage

Children: Refer to the BNF for Children for specific dosing guidance.

Adults: Apply once daily to the affected area for hyperhidrosis, using the liquid formulation at body temperature.

Mechanism of action

Glycopyrronium bromide acts as a competitive antagonist of muscarinic acetylcholine receptors. By blocking these receptors, it inhibits glandular secretion and reduces the activity of smooth muscle, leading to a decrease in sweating and other secretory functions.

Pharmacodynamics

The pharmacodynamic effects of glycopyrronium bromide include a reduction in salivary, bronchial, and sweating secretions. The onset of action is generally rapid, with effects typically noted within 30 minutes after administration. These actions are particularly beneficial in managing conditions characterized by excessive secretion, such as hyperhidrosis.

Pharmacokinetics

Glycopyrronium bromide is poorly absorbed when applied topically, which minimizes systemic effects. When used systemically, it is well absorbed, with peak plasma concentrations achieved within 1-2 hours. The drug undergoes hepatic metabolism and has a half-life of approximately 1-2 hours. Renal excretion is a significant pathway for elimination, and thus caution is advised in patients with renal impairment.

Contra-indications

• Infections affecting the treatment site

Adverse effects

• Skin reactions
• Pain
• Paraesthesia

Precautions

• Avoid contact with eyes
• Avoid contact with mucous membranes
• Avoid use on broken or irritated skin
• Do not shave axillae or use depilatories within 12 hours of application

Pregnancy

Manufacturer advises caution, as specific studies on use during pregnancy are limited.

Breast-feeding

Manufacturer advises avoiding application to the breast area; no information available on presence in milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• 0.05% solution for topical use
• Powder for dry skin application

Mechanism of action

Glycopyrronium is a muscarinic antagonist with the highest affinity for M1 receptors, followed by M3, M2/M4, and M5. Muscarinic receptors M1 to M4 are found in the lung, although M3 is predominantly responsible for bronchoconstriction and airway secretions. Secretions from salivary and sweat glands, as well as gastric acid secretions, are also predominantly mediated by the M3 receptor. Salivary and gastric acid secretions are also partially mediated by the M1 receptor. Antagonism of these receptors decreases the volume of their respective secretions, and in the case of the gastrointestinal system, reduces the acidity of the stomach. In the cardiovascular system, muscarinic receptors M1 to M5 are all present, however the function of M5 has not been described in literature. Under normal circumstances, stimulation of the vagal nerve lowers the heart rate, potentially leading to intraoperative bradycardia. Studies in mice suggest that this stimulation is predominantly mediated by the M3 receptor, and mutant knockout mice are not susceptible to these effects.

Pharmacodynamics

Glycopyrronium is a quaternary ammonium compound that is one of the most commonly prescribed long acting muscarinic antagonists. Glycopyrronium slowly dissociated from muscarinic receptors, leading to a long duration of action. It has a wider therapeutic index than other anticholinergic medications, such as [tiotropium]. Patients should be counselled regarding the risk of worsening urinary retention, risk of overheating, and transient blurred vision.