Introduction

Ipratropium bromide (Atrovent®)and Oxitropium bromide (Oxivent®) are anticholinergic agents that are used in the treatment of asthma and the reversible element of chronic obstructive airways disease. Oxitropium has only been on the market for a few years and is a long acting form of Ipratropium and thus the subsequent information is based on Ipratropium, but the same can be said of Oxitropium.

Pharmacology

Ipratropium is a competitive muscarinic acetylcholine receptor antagonist. When given intravenously, is most potent at inhibition of bronchial receptors less so of salivary receptors, and minimal effects on cardiac and urinary bladder receptors. When given by the inhaled route, even in high dosage, the systemic effects are negligible. It produces a dose related inhibition of bronchoconstriction to a variety of inhaled bronchoconstrictors including methacholine and also to exercise induced asthma. Its effects are dose related but is a less potent bronchodilator than the ß2-agonists in asthma but may be more effective than ß2-agonists in patients with COAD and in the elderly. In patients with asthma, the combination of ipratropium and a ß2-agonist may be synergistic.

Pharmacokinetics

The onset of action of ipratropium when given by the inhaled route is slower than that of the ß2-agonists, being in region of 30-60 minutes and its effects last up to 4-6 hours and 6-8 hours for Oxitropium. Very little of the drug is absorbed following inhalation or ingestion so hepatic or renal impairment has little effect on its therapeutic use. There is no evidence of tolerence with prolonged use.

Therapeutic Use

Ipratropium is used the management of patients with asthma whose symptoms are poorly controlled on prophylactic therapy with high dose inhaled corticosteroids and regular ß2-agonists. It may be used before or after the addition of theophylline, but because of its slower onset of action, it is not recommended used as a first line therapy in the management of mild asthma. In acute severe asthma, nebulised ipratropium (250-500 g 2-4 hourly) in conjunction with nebulised ß2-agonists can be used when patients fail to respond satisfactorily to initial treatment with high doses of nebulised ß2-agonists and intravenous corticosteroids. Ipratropium is more commonly used in the management of COAD, especially in those who respond poorly to inhaled ß2-agonists alone. Ideally, a demonstrable improvement in an index of lung function following inhalation of ipratropium should be sought before commencing a patient on treatment with the drug, although in practise, this is rarely done. The use of nebulised ipratropium (250-500 g 4-6 hourly) in combination with a nebulised ß2-agonist is common in patients with severe COAD using home nebuliser therapy. Care should be taken with treatment with nebulised ipratropium as paradoxical bronchoconstriction has been reported. Initially, this was thought to be due to the preservatives used (benzalkonium chloride and EDTA) or the hypotonic nature of the nebuliser solution, but there have been similar reports with the unpreserved isotonic preparation.

Side effects and Overdosage

These are rare as there is little systemic absorption. Some patients may report a dry mouth due to effects on the salivary glands. Drying of bronchial secretions with difficulty with expectoration, glaucoma and acute urinary retention are theoretically possible. However, systemic effects are rarely seen even with high dose nebulised therapy.

Further Reading

Barros MJ, Rees PJ. Bronchodilator responses to salbutamol followed by ipratropium bromide in partially reversible airflow obstruction. Respiratory Medicine. 1990;84:371-375.

Grandordy BM, Thomas V, de Lauture D, Marsac J. Cumulative dose-response curves for assessing combined effects of salbutamol and ipratropium bromide in chronic asthma. European Respiratory Journal. 1988;1:531-5.

Ullah MI, Newman GB, Saunders KB. Influence of age on response to ipratropium and salbutamol in asthma. Thorax. 1981;36:523-9.

Ward MJ, Fentem PH, Roderick Smith WH, Davies D. Ipratropium bromide in acute asthma. British Medical Journal 1981;282:598-600.