Introduction
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.
Uses
Tiotropium is a long-acting bronchodilator used in the management of chronic obstructive pulmonary disease (COPD).
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.
Associated Conditions
Pharmacodynamics
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.
Mechanism of Action
Tiotropium is an antagonist of muscarinic receptors M1 to M5. Inhibition of the M3 receptor in the smooth muscle of the lungs leads to relaxation of smooth muscle and bronchodilation.
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.
Volume of Distribution
The volume of distribution of tiotropium is 32L/kg.
Protein Binding
Tiotropium is 72% protein bound in plasma.
Route of Elimination
74% of intravenous tiotropium was excreted unchanged in urine. 14% of a dry powder inhalation dose was excreted unchanged in the urine. 24 hour urinary excretion after 21 days of 5µg once daily inhalation in patients with COPD is 18.6% and in patients with asthma is 12.8%.
Half Life
The terminal half life of tiotropium is 24 hours in patients with COPD and 44 hours in patients with asthma.
Clearance
The total clearance of tiotropium is 880mL/min in healthy subjects receiving 5µg daily. The renal clearance of tiotropium was 669mL/min. Patients 2 This decreased clearance is not associated with increased AUC or Cmax.
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.
Food Interactions
- Take with or without food. Food is not expected to interfere with absorption.
Dosage
The contents of the Tiotropium Dry Powder Inhaler capsules are only for oral inhalation and should only be used with the device.
No dosage adjustment is required for geriatric, hepatically-impaired, or renally-impaired patients. However, patients with moderate to severe renal impairment given Tiotropium capsule should be monitored closely for anticholinergic effects.
