Respiratory - Antimuscarinics, Bronchodilators: ipatropium, tiotropium, glycopyrronium

Question 1

Antimuscarinics, bronchodilators

Ipratropium, tiotropium, glycopyrronium

Common Indications

Answer 1

• In chronic obstructive pulmonary disease (COPD), short-acting antimuscarinics are used to relieve breathlessness, e.g. brought on by exercise or during exacerbations. Long-acting antimuscarinics (LAMAs) are used to prevent breathlessness and exacerbations.
• In asthma, short-acting antimuscarinics are used as adjuvant treatment for relief of breathlessness during acute exacerbations (added to a short-acting β2 agonist, e.g. salbutamol). Long-acting antimuscarinics are added to high-dose inhaled corticosteroids and long-acting β2 agonists at ‘step 4’ in the treatment of chronic asthma

Question 2

Antimuscarinics, bronchodilators: ipratropium, tiotropium, glycopyrronium

Mechanism of action

Answer 2

• Antimuscarinic drugs bind to the muscarinic receptor, they act as competitive inhibitor of acetylcholine.
• Stimulation of the muscarinic receptor brings about a wide range of parasympathetic ‘rest and digest’ effects.
• In blocking the receptor, antimuscarinics have the opposite effects: they increase heart rate and conduction; reduce smooth muscle tone, including in the respiratory tract; and reduce secretions from glands in the respiratory and gastrointestinal tracts.
• In the eye they cause relaxation of the pupillary constrictor and ciliary muscles, causing pupillary dilatation and preventing accommodation, respectively.

Question 3

Antimuscarinics, bronchodilators: ipratropium, tiotropium, glycopyrronium

Important adverse affects/warnings/interactions

Answer 3

• When antimuscarinic bronchodilators are taken by inhalation, there is relatively little systemic absorption.
• Adverse effects, apart from dry mouth, are uncommon
• Antimuscarinics should be used with caution in patients susceptible to angle-closure glaucoma, in whom they can precipitate a dangerous rise in intraocular pressure.
• They should be used with caution in patients with or at risk of arrhythmias.
• However, in practice, most patients can take these drugs by inhalation without major problems.
• Interactions are not generally a problem due to low systemic absorption

Question 4

Antimuscarinics, bronchodilators: ipratropium, tiotropium, glycopyrronium

Practical Prescribing

Answer 4

• Short-acting antimuscarinics such as ipratropium are prescribed four times daily or PRN when the patient feels breathless.
• They are prescribed at a standard dose (40 micrograms) by inhalation for stable patients, but at a much higher dose (250–500 micrograms 6-hrly) by nebulisation during an acute attack.
• Long-acting antimuscarinics (e.g. tiotropium, glycopyrronium) are prescribed for regular administration, generally once daily.