Short Acting Muscarinic Antagonists

Short acting muscarinic antagonists, of which ipratropium is the main drug, block M1 to M3 receptors in the airway for 4 to 6 hours. They are given by pressurised inhaler or nebuliser for COPD and for acute severe asthma.

Mechanism. Ipratropium is a quaternary derivative of atropine that antagonises acetylcholine at M3 receptors, relaxing smooth muscle and reducing secretion. It is non-selective for M2 receptors.

Pharmacokinetics. Onset is 15 to 30 minutes, with peak at 1 to 2 hours and duration of 4 to 6 hours. Systemic absorption is very low, and half life after inhalation is about 2 hours.

Ipratropium. Pressurised inhaler 20 mcg each actuation, and nebuliser solution 250 mcg and 500 mcg.

Combination. Ipratropium 500 mcg with salbutamol 2.5 mg as a single nebuliser unit.

Differences. Ipratropium is slower than salbutamol and gives less peak bronchodilation, and its main strength is added effect with a beta 2 agonist. In COPD its response is similar to a short acting beta 2 agonist.

Representative regimens.

• Stable COPD or asthma: 20 to 40 mcg (1 to 2 puffs) by pressurised inhaler three to four times daily.
• COPD exacerbation: 500 mcg nebulised every 4 to 6 hours, with salbutamol.
• Severe or life-threatening asthma in adults: 500 mcg nebulised with salbutamol in the first hour, then every 4 to 6 hours.
• Severe asthma in children: 250 mcg nebulised, repeated every 20 to 30 minutes for up to three doses in the first hour, then every 4 to 6 hours.

Selection. Preferred reliever when beta 2 agonists are not tolerated, and for exacerbations with both agents. Stop regular use when a long acting antimuscarinic is started, because the effects duplicate.

Adverse effects. Dry mouth, bitter taste, cough, urinary retention, constipation. Acute angle closure glaucoma follows nebulised drug reaching the eye, so use a mouthpiece rather than a face mask where possible.

Contraindications and cautions. Hypersensitivity to atropine or its derivatives. Caution in narrow angle glaucoma, prostatic hypertrophy and bladder outlet obstruction.

Interactions. Added anticholinergic effect with other antimuscarinic drugs. Beta 2 agonists add bronchodilation.

Monitoring. Response, urinary and eye symptoms, and technique.

Special groups. Pregnancy and breastfeeding: low systemic exposure, may be used when needed. Older adults: urinary retention and constipation more likely. Renal impairment: no adjustment for inhaled use.

Referral and escalation. Failure of bronchodilators in acute asthma or COPD, including peak flow under 50 percent of best or predicted or oxygen saturation under 92 percent, needs admission. Eye pain after nebulisation needs urgent ophthalmology review.