Unii-0eb439235f

Absorption

33% of an inhaled solution reaches systemic circulation, while oral solutions have a bioavailability of 2-3%. A dry powder for inhalation is 19.5% bioavailable. Tiotropium metered spray for inhalation reaches a maximum concentration in 5-7 minutes.

Toxicity

Symptoms of overdose include altered mental status, tremors, abdominal pain, and severe constipation. However, doses of up to 282μg did not lead to systemic anticholinergic effects in a trial of 6 patients. In case of overdose, stop tiotropium and being symptomatic and supportive therapy.

Background

Tiotropium is a long-acting, antimuscarinic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD) and asthma. Tiotropium acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation and bronchodilation.
Tiotropium is more specific for the subset of muscarinic receptors commonly found in the lungs than ipratropium.
Tiotropium was granted FDA approval on 30 January 2004.

Indications

Tiotropium powder for inhalation is indicated for the maintenance of bronchospasm in COPD and to prevent exacerbations of COPD. A combination tiotropium and olodaterol metered inhalation spray is indicated for maintenance of COPD. A tiotropium inhalation spray is indicated for the maintenance of bronchospasm in COPD, to prevent exacerbations of COPD, and to treat asthma in patients 12 or more years old. A tiotropium metered inhalation spray is indicated for the maintenance of bronchospasm in COPD, to prevent exacerbations of COPD, and to treat asthma in patients 6 or more years old.

Definition

ChEBI: A quaternary ammonium ion obtained by methylation of the tertiary amino group of (1alpha,2beta,4beta,5alpha,7beta)-7-[(hydroxydi-2-thienylacetyl)oxy]-9-methyl-3-oxa-9-azon atricyclo[3.3.1.02,4]nonane. Used (in the form of the bromide hydrate) for maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease.

Pharmacokinetics

Tiotropium is a long acting antimuscarinic that causes bronchodilation. The effects of tiotropium last over 24 hours and there is a wide therapeutic index as overdoses are uncommon even at doses well above the recommended maximum.

Metabolism

Tiotropium is not heavily metabolized in the body. 74% of an intravenous dose is excreted in the urine as unchanged drug. Tiotropium is nonenzymatically cleaved to the inactive metabolites N-methylscopine and dithienylglycolic acid. In vitro experiments show cytochrome P-450 dependent oxidation and glutathione conjugation to further metabolites.