Pharmacology Of Ipratropium bromide

Indication	For maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema.
Pharmacodynamics	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.
Absorption	Inhalation (local)-minimal; Nasal-rapid and minimal
Volume of distribution	4.6 L/kg
Protein binding	Minimally (0 to 9% in vitro) bound to plasma albumin and α1-acid glycoproteins
Metabolism	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.
Route of elimination	Primarily eliminated renally via active secretion.
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 (t1/2 α) and terminal elimination-phase half-life (t1/2 β) were 0.07 and 1.6 hours, respectively, following a single 2 mg IV dose of the drug in healthy adults.
Clearance	2.3 L/min (total clearance of active ingredient)
Toxicity	LD50=1001mg/kg (orally in mice)