Anticholinergics

Question 1

What are the common indications?

Answer 1

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 are used to prevent breathlessness and exacerbations.
2. 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

How do anticholinergics work?

Answer 2

Bind to the muscarinic receptor, where they act as a 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.

Question 3

What are the main side effects?

Answer 3

Dry mouth is the most common side-effect of; also gastro-intestinal motility disorder (including constipation and diarrhoea), cough, and headache

Less commonly nausea, gastro-oesophageal reflux disease, dysphagia, tachycardia, palpitation, atrial fibrillation, throat irritation, pharyngitis, dysphonia, bronchospasm, including paradoxical bronchospasm, dizziness, urinary retention, mydriasis, angle-closure glaucoma, blurred vision, sinusitis, nasopharyngitis, and rash can occur.

Question 4

Give examples of anticholinergics used in respiratory medicine.

Answer 4

Aclidinium
Glycopyrronium
Tiotropium
Umeclidinium

Question 5

What warnings should be taken into account when prescribing anticholinergics?

Answer 5

Antimuscarinic bronchodilators should be used with caution in patients with prostatic hyperplasia, bladder outflow obstruction, and those susceptible to angle-closure glaucoma (see below); they may also be associated with paradoxical bronchospasm.

Acute angle-closure glaucoma has been reported with nebulised ipratropium, particularly when given with nebulised salbutamol (and possibly other beta2 agonists); care needed to protect patient’s eyes from nebulised drug or from drug powder.

Question 6

What are the important interactions cholinergics?

Answer 6

Interactions are not generally a problem due to low systemic absorption.

Question 7

When should short-acting antimuscarinics be used?

Answer 7

e.g. ipratropium to be taken four times daily or as needed 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.

Question 8

When should long-acting antimuscarinics be used?

Answer 8

e.g. tiotropium, glycopyrronium are prescribed for regular administration, generally once daily.

Question 9

How are anticholinergics eliminated?

Answer 9

Primarily eliminated renally via active secretion.

Question 10

Patient information?

Answer 10

Explain that you are offering a treatment to make their airways relax, which should therefore improve their breathing. They should understand that this treats the symptoms, not the disease. Ensure they are clear on how and when to take the inhaler (e.g. for acute symptoms, pre-emptively before exercise or regularly for long-acting medication). Discuss possible side effects, such as dry mouth, and advise them to chew gum or suck sweets (which should be sugar-free; see Antimuscarinics, genitourinary uses), or keep a bottle of water with them to relieve these.