indication

For maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema.

pharmacology

Ipratropium bromide, a synthetic ammonium compound structurally similar to atropine, is used as a bronchodilator in the management of cholinergic-mediated bronchospasm associated with chronic obstructive pulmonary disease and in the treatment of rhinorrhea associated with the common cold or with allergic or nonallergic seasonal rhinitis.

mechanism of action

Ipratropium bromide is an anticholinergic agent. It blocks muscarinic cholinergic receptors, without specificity for subtypes, resulting in a decrease in the formation of cyclic guanosine monophosphate (cGMP). Most likely due to actions of cGMP on intracellular calcium, this results in decreased contractility of smooth muscle.

toxicity

LD₅₀=1001mg/kg (orally in mice)

biotransformation

Partially metabolized to at least 8 metabolites formed primarily via hydrolysis and conjugation. The main metabolites are N-isopropylnortropium methobromide, which is formed by enzymatic hydrolysis of the ester; α-phenylacrylic acid-N-isopropylnortropine-ester methobromide, which is formed by enzymatic loss of a water; and phenylacetic acid-N-isopropylnortropine-ester methobromide, which is formed by enzymatic loss of a CH₃OH-group. These metabolites appear to be inactive.

absorption

Inhalation (local)-minimal; Nasal-rapid and minimal

half life

2-4 hours after administration orally, IV or by oral inhalation (radiolabeled ipratropium bromide assay measures parent drug and its metabolites). Using a radioreceptor assay that measures only unchanged ipratropium bromide, the initial distribution-phase half-life (t_{1/2 α}) and terminal elimination-phase half-life (t_{1/2 β}) were 0.07 and 1.6 hours, respectively, following a single 2 mg IV dose of the drug in healthy adults.

route of elimination

Primarily eliminated renally via active secretion.

drug interactions

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Ipratropium, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Trimethobenzamide: Trimethobenzamide and Ipratropium, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Triprolidine: Triprolidine and Ipratropium, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trospium: Trospium and Ipratropium, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.