Ipratropium

Ipratropium is a short acting quaternary ammonium antimuscarinic given by inhalation or nasal spray. It relieves bronchospasm and rhinorrhoea with little systemic effect. Its main uses are acute severe asthma (added to salbutamol), acute exacerbations of chronic obstructive pulmonary disease, and watery rhinorrhoea.

Classification. Short acting muscarinic antagonist; quaternary ammonium derivative of atropine.

Mechanism. Blocks M3 receptors on airway smooth muscle and submucosal glands, reducing vagal bronchoconstriction and mucus secretion. It does not block M2 autoreceptors selectively, which limits peak bronchodilation.

Pharmacodynamics. Onset 15 to 30 minutes, peak 1 to 2 hours, duration 4 to 6 hours. Bronchodilation is smaller than with beta agonists but additive to them.

Pharmacokinetics. Poorly absorbed from lung and gut (under 10%), so systemic effects are rare. Does not cross the blood brain barrier. Elimination half life about 2 hours; excreted in urine and faeces.

Acute severe or life threatening asthma, adult.

• Ipratropium 500 micrograms nebulised, added to salbutamol, every 20 to 30 minutes for the first 3 doses, then every 4 to 6 hours as needed.

• Continue the antimuscarinic only while the attack is severe; usually stop within 24 to 48 hours.

Acute severe asthma, children. Under 12 years: 250 micrograms nebulised; 12 years and over: 500 micrograms. Same interval as adults, three doses in the first hour, then every 4 to 6 hours as needed.

Acute exacerbation of chronic obstructive pulmonary disease, adult. 500 micrograms nebulised every 4 to 6 hours, with or without salbutamol. Usual maximum 2 mg daily on regular nebulisation.

Maintenance in chronic obstructive pulmonary disease, adult (where long acting agents are unavailable). Metered dose inhaler 20 micrograms a puff: 2 puffs (40 micrograms) three or four times daily through a spacer. Maximum 12 puffs (240 micrograms) in 24 hours. Stop once a long acting antimuscarinic is started.

Rhinorrhoea (perennial rhinitis, common cold), adult and child over 12. Nasal spray 0.03%: 2 sprays (42 micrograms each) in each nostril two or three times daily; 0.06%: 2 sprays in each nostril three or four times daily for up to 4 days in the common cold.

Contraindications. Hypersensitivity to ipratropium, atropine or its derivatives.

Warnings. Paradoxical bronchospasm; stop and treat if it occurs. Spray or mist reaching the eye can cause mydriasis, blurred vision and, in narrow angles, acute angle closure glaucoma; use a mouthpiece rather than a face mask for nebulisation, and protect the eyes. Caution in bladder outflow obstruction, prostatic hypertrophy and cystic fibrosis (gut motility).

Adverse effects. Dry mouth, cough, throat irritation, headache, nausea, tachycardia, urinary retention, constipation, nasal dryness and epistaxis with nasal use.

Interactions. Additive anticholinergic effects with oral antimuscarinics, tricyclic antidepressants and antihistamines. Combined use with beta agonists is intended. Xanthines and beta agonists raise the risk of tachycardia and hypokalaemia in combination.

Special groups.

• Pregnancy: acceptable; negligible systemic exposure.

• Breastfeeding: compatible.

• Children: dose by age in asthma; ipratropium adds most in severe attacks.

• Older adults: watch for urinary retention and glaucoma.

• Kidney and liver impairment: no adjustment.

Formulations. Nebuliser solution 250 micrograms/mL (500 micrograms in 2 mL); metered dose inhaler 20 micrograms a puff; nasal spray 0.03% and 0.06%.

Nebulisation. Can be mixed with salbutamol in the same chamber for immediate use. Driven by oxygen at 6 to 8 litres/minute in acute asthma; use air in chronic obstructive pulmonary disease with hypercapnia.

Monitoring. Peak flow or FEV1, respiratory rate, oxygen saturation, heart rate. Review eyes and bladder symptoms in older adults.

Stopping. Stop when the exacerbation resolves and inhaled maintenance therapy is established.

Common prescribing errors. Continuing regular ipratropium together with tiotropium or another long acting antimuscarinic; using a face mask without eye protection; giving it alone for an acute asthma attack instead of with salbutamol.