1. Mode of Action

2. This information is from an international website which is intended for healthcare professionals not located in the United States of America (US) and the United Kingdom (UK). SPIRIVA® Respimat® (tiotropium) is subject to country-specific regulations and the approved product label may vary from country to country. Information on this website is derived from the approved European Summary of Product Characteristics. Please refer to your local product label for full details.
©Boehringer Ingelheim International GmbH This document and its contents are property of Boehringer Ingelheim (third party sources are indicated) and are, inter alia, protected by copyright law. Complete or partial passing on to third parties as well as copying, reproduction, publication or any other use by third parties is not permitted.

3. This short animated video shows the mode of action (MoA) of SPIRIVA® Respimat® (tiotropium) in the treatment of asthma.
Binding to M3 receptors, SPIRIVA® Respimat® blocks acetylcholine, which plays a significant role in the pathophysiology of asthma, and antagonises the bronchoconstrictive effects, resulting in bronchial smooth muscle relaxation.

4. Mode of Action
Acetylcholine is the primary parasympathetic neuro-transmitter in the airways and plays a significant role in the pathophysiology of asthma1.

5. When released acetylcholine
Mode of Action
When released acetylcholine

6. stimulates muscarinic M3 receptors
Mode of Action
stimulates muscarinic M3 receptors

7. on airway smooth muscle2,
Mode of Action
on airway smooth muscle2,

8. Mode of Action
On submucosal glands,2

9. And on inflammatory cells3
Mode of Action
And on inflammatory cells3

10. Mode of Action
In asthma patient’s activation of M3 receptors by acetylcholine leads to smooth muscle contraction4,5

11. resulting in bronchoconstriction,3
Mode of Action
resulting in bronchoconstriction,3

12. with mucus secretion into the airway lumen,4 and mucus over secretion4
Mode of Action
with mucus secretion into the airway lumen,4 and mucus over secretion4

13. Mode of Action
and inflammatory cell activation5which contributes to airway inflammation4,5 and remodelling in asthma animal models4,5

14. Mode of Action

15. Mode of Action SPIRIVA® (tiotropium) Respimat® is an anticholinergic6
and binds to the M3 receptors, for more than 24 hours, antagonising the effects of acetylcholine1,2,3,5

16. resulting in increased airflow3
Mode of Action
resulting in increased airflow3

17. Mode of Action reducing mucus secretion1,2
and may have effects in airway remodeling and inflammation1,4

18. SPIRIVA® Respimat®, approved for asthma.6
Mode of Action
SPIRIVA® Respimat®, approved for asthma.6

19. References
1. Moulton BC and Fryer AD, Br J Pharmacol. 2011; 163(1): 44–52
2. Kistemaker LEM, et al. Trends Pharmacol Sci 2015; 36:3, 164–171
3. Buels KS and Fryer AD Handb Exp Pharmacol. 2012; (208):
4. Kistemaker LEM, et al. Life Sci 2012;91:1126–1133
5. Gosens R, et al. Respir Res 2006;7:73
6. Summary of Product Characteristics. SPIRIVA Respimat®. 13 Jan 2017

20. Spiriva Respimat 2.5 microgram, inhalation solution Active substance: tiotropium bromide Qualitative and quantitative composition: The delivered dose is 2.5 microgram tiotropium per puff (2 puffs comprise one medicinal dose). List of excipients: benzalkonium chloride; disodium edetate; water, purified; 1M hydrochloric acid (for pH adjustment) Indication: Spiriva Respimat is indicated as an add-on maintenance bronchodilator treatment in adult patients with asthma who are currently treated with the maintenance combination of inhaled corticosteroids (≥800 µg budesonide/day or equivalent) and long-acting ß2 agonists and who experienced one or more severe exacerbations in the previous year. Contraindications: Hypersensitivity to tiotropium bromide or to any of the excipients listed above or to atropine or its derivatives, e.g. ipratropium or oxitropium. Undesirable effects: Common: dry mouth. Uncommon: dizziness; headache; insomnia; palpitations; cough; pharyngitis; dysphonia; bronchospasm; oropharyngeal candidiasis. Rare: constipation; gingivitis; stomatitis; rash; pruritus; angioneurotic oedema; urticaria; hypersensitivity (including immediate reactions). Not known: dehydration; glaucoma; intraocular pressure increased; vission blurred; aterial fibrillation; supraventricular tachycardia; tachycardia; epistaxix; laryngitis; sinusitis; dysphagia; gastrooesophageal reflux disease; dental caries; glossitis; intestinal obstruction, including ileus paralytic; nausea; skin infection/skin ulcer; dry skin; anaphylactic reaction; joint swelling; urinary retention; dysuria; urinary tract infection. 
Medicinal product subject to medical prescription. Marketing Authorisation Holder: Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, D Ingelheim am Rhein, Germany. Date of revision of text: 13 Jan 2017

21. For more information visit: www.spirivaglobal.com/asthma