Antimuscarinic Bronchodilators

Synonym: Anticholinergics

Antimuscarinic bronchodilators block the effects of acetylcholine on bronchiolar smooth muscle and reduce the normal vagal tone in bronchioles. They are useful in asthma¹ and especially effective in chronic obstructive pulmonary disease (COPD). Ipratropium is a short-acting bronchodilator, and tiotropium is a long-acting bronchodilator.²

Ipratropium

Asthma - The British Thoracic Society Guidelines on Asthma recommend short-acting antimuscarinic bronchodilators as an alternative to short-acting beta₂ agonists at Step 1 for the treatment of mild intermittent asthma. Short-acting beta₂ agonists tend to work quicker than antimuscarinics.³
The aerosol inhalation of ipratropium has a maximum effect after 30-60 minutes, and a duration of action 3 to 6 hours.⁴ Bronchodilation can usually be maintained with treatment 3 times a day.

Ipratropium by nebulisation may be added to other standard treatment where life-threatening asthma fails to improve with nebulised beta₂ agonist, oxygen standard therapy and steroids. Frequent doses up to every 20-30 minutes (250 mcg/dose mixed with the beta₂ agonist solution in the same nebuliser) should be used early. Evidence supports this treatment for the first two hours of a severe attack, and it should be started early. The dose frequency should be reduced as clinical improvement occurs.³

COPD - NICE Guidance on chronic obstructive pulmonary disease (COPD) recommends the use of short-acting antimuscarinic bronchodilators as an alternative to short-acting beta₂ agonists in the initial management of COPD.⁵

Most randomised controlled trials support the use of antimuscarinics and demonstrate short-term improvement in most (but not all) COPD patients compared to placebo.⁶
Note that only two interventions - smoking cessation and long-term oxygen - have been shown to have any effect on the long-term outcome of COPD.⁶

Tiotropium

NICE guidance recommends the use of a long-acting antimuscarinic bronchodilator in patients with moderate to severe COPD who fail to respond go short-acting beta₂ agonists and ipratropium.⁵ This is supported by systematic reviews and randomised trials which found that tiotropium caused significant improvement in forced expiratory volume in 1 second (FEV₁), health related quality of life, and reduced hospitalisations and exacerbations, compared to ipratropium or placebo.⁷
If further symptomatic relief is required, a four week trial of tiotropium combined with inhaled corticosteroid can be tried.⁵ Trial evidence suggests that combining tiotropium with a long-acting beta₂ agonist and an inhaled corticosteroid improves lung function and reduces hospitalisation, but makes no difference to exacerbation rates compared with tiotropium alone.⁸
Tiotropium was initially marketed as a dry powder with a Handihaler® device.⁹ It is also now available as a solution, delivered as a fine mist via a Respimat® device.¹⁰

• Dry mouth
• Nausea
• Constipation
• Headache
• Tachycardia

Inhaled antimuscarinics should be used with caution in glaucoma, prostatic hyperplasia and bladder outflow obstruction.

Randomised controlled trials suggest that, in children with mild to moderate exacerbations of asthma, adding ipratropium to an inhaled beta2 agonist significantly improved FEV₁ at one hour and at two hours, but made no difference to hospital admission.^12,13

A systematic review of adult patients with acute asthma showed that the addition of ipratropium to a beta₂ agonist administered in high doses through metered dose inhaler (MDI) plus spacer, significantly improved FEV₁, particularly in patients with FEV₁ less than 30%. Hospital admissions were significantly reduced.¹⁴

A combination of a long-acting beta2 agonist and a short-acting antimuscarinic can be tried in COPD if the patient continues to be symptomatic and has poor exercise tolerance.⁵ Randomised trials demonstrate a small but significant improvement with this combination.⁶

Duovent®¹⁵

This is a nebuliser solution containing fenoterol hydrobromide 1.25 mg plus ipratropium bromide 500 mcg per 4 ml vial. It is indicated in acute exacerbation of chronic asthma 3-4 times per day. It is not recommended for children under 14 years.

N.B. Acute glaucoma has been reported with nebulised ipratropium, particularly when given with nebulised salbutamol, so protect patient's eyes from nebulised drug. A poorly fitting mask is often the problem.

Combivent®

This is available as an inhaler containing ipratropium bromide 20 mcg with salbutamol 100 mcg per inhalation. It is indicated for bronchospasm associated with COPD, 2 puffs 4 times daily.¹⁶ The nebuliser solution contains ipratropium bromide 500 mcg with salbutamol 2.5 mg per 2.5 ml.¹⁷ It is normally used 3-4 times daily. It is not recommended for children under 12 years.