Tiotropium bromide

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Tiotropium bromide
Tiotropium bromide.svg
Tiotropium-3D-balls.png
Clinical data
Trade names Spiriva, others
AHFS/Drugs.com Monograph
MedlinePlus a604018
License data
Pregnancy
category
Routes of
administration 		By mouth, inhalation by mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 19.5% (inhalation)
Metabolism Liver 25%
(CYP2D6, CYP3A4)
Elimination half-life 5–6 days
Excretion Kidney
Identifiers
  • (1α,2β,4β,7β)-
    7-[(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl-
    3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane bromide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.234.575 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H22BrNO4S2
Molar mass 472.41 g·mol−1
3D model (JSmol)
  • C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C.[Br-]

  • C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C
  • InChI=1S/C19H22NO4S2.BrH/c1-20(2)12-9-11(10-13(20)17-16(12)24-17)23-18(21)19(22,14-5-3-7-25-14)15-6-4-8-26-15;/h3-8,11-13,16-17,22H,9-10H2,1-2H3;1H/q+1;/p-1/t11?,12-,13+,16-,17+; Yes check.svgY
  • Key:DQHNAVOVODVIMG-RGECMCKFSA-M Yes check.svgY

  • InChI=1S/C19H22NO4S2/c1-20(2)12-9-11(10-13(20)17-16(12)24-17)23-18(21)19(22,14-5-3-7-25-14)15-6-4-8-26-15/h3-8,11-13,16-17,22H,9-10H2,1-2H3/q+1/t11?,12-,13+,16-,17-/m0/s1 Yes check.svgY
  • Key:LERNTVKEWCAPOY-FPISHFTHSA-N Yes check.svgY
   (verify)

Tiotropium bromide, sold under the brand name Spiriva among others, is a long-acting bronchodilator (LAMA: long acting muscarinic antagonist) used in the management of chronic obstructive pulmonary disease (COPD) and asthma. [10] [11] Specifically it is used during periods of breathing difficulty to prevent them from getting worse, rather than to prevent them from happening. [10] It is used by inhalation through the mouth. [10] Onset typically begins within half an hour and lasts for 24 hours. [10]

Contents

Common side effects include a dry mouth, runny nose, upper respiratory tract infection, shortness of breath and headache. [10] Severe side effects may include angioedema, worsening bronchospasm, and QT prolongation. [10] Tentative evidence has not found harm during pregnancy, however, such use has not been well studied. [1] It is an anticholinergic medication and works by blocking acetylcholine action on smooth muscle. [10]

Tiotropium was patented in 1989, and approved for medical use in 2002. [12] It is on the World Health Organization's List of Essential Medicines. [13] In 2021, it was the 134th most commonly prescribed medication in the United States, with more than 4 million prescriptions. [14] [15]

Medical uses

Tiotropium is used as maintenance treatment of chronic obstructive pulmonary disease (COPD). [16] [17] It may also be used as an add-on therapy in people with moderate-to-severe asthma on medium to high dose inhaled corticosteroids (ICS). [18] [19] It is not however approved for acute exacerbations of COPD or acute worsening of asthma. [10]

Tiotropium is also used in a combination inhaler with olodaterol, a long-acting beta-agonist, for the treatment of COPD, under the brand names Stiolto and Spiolto among others. [20] [21] [22]

Adverse effects

Adverse effects are mainly related to its antimuscarinic effects. Common adverse drug reactions (≥1% of people) include: dry mouth and/or throat irritation. Rarely (<0.1% of patients) treatment is associated with: urinary retention, constipation, acute angle closure glaucoma, palpitations (notably supraventricular tachycardia and atrial fibrillation) and allergy (rash, angioedema, anaphylaxis). [23] A 2006 review found the increase in bronchospasm was small and did not reach statistical significance. [24]

Data regarding some serious side effects is mixed as of 2020. [10] In September 2008 a review found that tiotropium and another member of its class ipratropium may be linked to increased risk of heart attacks, stroke and cardiovascular death. [25] The US FDA reviewed the concern and concluded in 2010 that this association was not supported. [16] [26] A 2011 review of the tiotropium mist inhaler (Respimat), however, still found it associated with an increase in all cause mortality in people with COPD. [27] [28]

Mechanism of action

Tiotropium is a muscarinic receptor antagonist, often referred to as an antimuscarinic or anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors, when topically applied it acts mainly on M3 muscarinic receptors [29] located on smooth muscle cells and submucosal glands. This leads to a reduction in smooth muscle contraction and mucus secretion and thus produces a bronchodilatory effect.[ citation needed ]

Society and culture

Tiotroprium is available in two inhaler formats: a soft mist inhaler (Respimat) and a dry powder inhaler (HandiHaler). [30] The safety and efficacy profiles of both devices are comparable and people's preference should play a role in determining inhaler choice. [30] There is no significant difference in all-cause mortality between tiotropium soft mist inhalers compared to dry powder inhalers, however caution needs to be taken in people with severe heart or kidney problems. [31]

Related Research Articles

A bronchodilator or broncholytic is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs. Bronchodilators may be originating naturally within the body, or they may be medications administered for the treatment of breathing difficulties, usually in the form of inhalers. They are most useful in obstructive lung diseases, of which asthma and chronic obstructive pulmonary disease are the most common conditions. Although this remains somewhat controversial, they might be useful in bronchiolitis and bronchiectasis. They are often prescribed but of unproven significance in restrictive lung diseases.

<span class="mw-page-title-main">Ipratropium bromide</span> Type of anticholinergic

Ipratropium bromide, sold under the trade name Atrovent among others, is a type of anticholinergic medication which is applied by different routes: inhaler, nebulizer, or nasal spray, for different reasons.

<span class="mw-page-title-main">Budesonide/formoterol</span> Medication for asthma & chronic obstructive pulmonary disease

Budesonide/formoterol, sold under the brand name Symbicort among others, is a fixed-dose combination medication used in the management of asthma or chronic obstructive pulmonary disease (COPD). It contains budesonide, a steroid and formoterol, a long-acting β2-agonist (LABA). The product monograph does not support its use for sudden worsening or treatment of active bronchospasm. However, a 2020 review of the literature does support such use. It is used by breathing in the medication.

<span class="mw-page-title-main">Inhaler</span> Medical device used to deliver medicines into lungs

An inhaler is a medical device used for delivering medicines into the lungs through the work of a person's breathing. This allows medicines to be delivered to and absorbed in the lungs, which provides the ability for targeted medical treatment to this specific region of the body, as well as a reduction in the side effects of oral medications. There are a wide variety of inhalers, and they are commonly used to treat numerous medical conditions with asthma and chronic obstructive pulmonary disease (COPD) being among the most notable.

Beta<sub>2</sub>-adrenergic agonist Compounds that bind to and activate adrenergic beta-2 receptors

Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.

Ipratropium bromide/salbutamol, sold under the brand name Combivent among others, is a combination medication used to treat chronic obstructive pulmonary disease (COPD). It contains ipratropium and salbutamol.

<span class="mw-page-title-main">Bronchoconstriction</span> Constriction of the terminal airways in the lungs

Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath.

<span class="mw-page-title-main">Long-acting beta-adrenoceptor agonist</span> Drug prescribed for asthma patients

Long-acting β adrenoceptor agonists (LABAs) are beta-adrenergic agonists usually prescribed for moderate-to-severe persistent asthma and chronic obstructive pulmonary disease (COPD).

<span class="mw-page-title-main">Indacaterol</span> Chemical compound

Indacaterol is an ultra-long-acting beta-adrenoceptor agonist developed by Novartis. It needs to be taken only once a day, unlike the related drugs formoterol and salmeterol. It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD). It is delivered as an aerosol formulation through a dry powder inhaler.

<span class="mw-page-title-main">Aclidinium bromide</span> Chemical compound

Aclidinium bromide (INN) is a long-acting, inhaled muscarinic antagonist (LAMA) approved in the United States in July 2012 as a maintenance treatment for chronic obstructive pulmonary disease (COPD).

<span class="mw-page-title-main">Olodaterol</span> Chemical compound

Olodaterol is an ultra-long-acting β adrenoreceptor agonist (ultra-LABA) used as an inhalation for treating people with chronic obstructive pulmonary disease (COPD). It is manufactured by Boehringer Ingelheim.

<span class="mw-page-title-main">Vilanterol</span> Asthma drug – β2 adrenoreceptor agonist

Vilanterol is an ultra-long-acting β2 adrenoreceptor agonist (ultra-LABA), which was approved in May 2013 in combination with fluticasone furoate for sale as Breo Ellipta by GlaxoSmithKline for the treatment of chronic obstructive pulmonary disease (COPD).. The combination is also approved for the treatment of asthma in Canada, Europe, Japan and New Zealand.

<span class="mw-page-title-main">Fluticasone furoate/vilanterol</span> Pharmaceutical drug formulation

Fluticasone furoate/vilanterol, sold under the brand name Breo Ellipta among others, is a combination medication for the treatment of chronic obstructive pulmonary disease (COPD) and asthma. It contains fluticasone furoate, an inhaled corticosteroid, and vilanterol, an ultra-long-acting β2 agonist (ultra-LABA).

<span class="mw-page-title-main">Umeclidinium bromide/vilanterol</span> Pharmaceutical medication

Umeclidinium bromide/vilanterol, sold under the brand name Anoro Ellipta, among others, is a fixed-dose combination medication for the treatment of chronic obstructive pulmonary disease (COPD). It is administered by inhalation.

<span class="mw-page-title-main">Indacaterol/glycopyrronium bromide</span> Combination drug

Indacaterol/glycopyrronium bromide, sold under the brand name Ultibro Breezhaler among others, is a fixed-dose combination medication for inhalation consisting of the following two active ingredients:

Aclidinium bromide/formoterol, sold under the brand names Duaklir and Brimica, is a fixed-dose combination medication for inhalation, used in the management of chronic obstructive pulmonary disease (COPD). It consists of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol, a long-acting β2 agonist.

<span class="mw-page-title-main">Beclometasone/formoterol/glycopyrronium bromide</span> Combination drug

Beclometasone/formoterol/glycopyrronium, sold under the brand name Trimbow among others, is an inhalable fixed-dose combination medication for the treatment of chronic obstructive pulmonary disease (COPD) and asthma. It contains beclometasone dipropionate, formoterol fumarate dihydrate, and glycopyrronium bromide.

Fluticasone furoate/umeclidinium bromide/vilanterol, sold under the brand name Trelegy Ellipta among others, is a fixed-dose combination inhaled medication that is used for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The medications work in different ways: fluticasone furoate is an inhaled corticosteroid (ICS), umeclidinium is a long-acting muscarinic antagonist (LAMA), and vilanterol is a long-acting beta-agonist (LABA).

Beclometasone/formoterol, sold under the brand name Fostair, is an inhalable fixed-dose combination drug for the treatment of asthma and chronic obstructive pulmonary disease (COPD). It contains beclometasone dipropionate and formoterol fumarate dihydrate. It is inhaled.

Budesonide/glycopyrronium bromide/formoterol, sold under the brand name Breztri Aerosphere among others, is an inhalable fixed-dose combination medication for the treatment of chronic obstructive pulmonary disease (COPD). It contains budesonide, glycopyrronium bromide, and formoterol fumarate dihydrate. It is inhaled.

References

  1. 1 2 "Tiotropium Use During Pregnancy". Drugs.com. Archived from the original on 31 January 2019. Retrieved 31 January 2019.
  2. 1 2 "AusPAR: Tiotropium bromide". Therapeutic Goods Administration (TGA). 29 November 2016. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  3. ↑ https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=E07D6674E971FA91CA258752004228AF&agid=(PrintDetailsPublic)&actionid=1 [ dead link ]
  4. ↑ "Tiotropium bromide". Therapeutic Goods Administration (TGA). Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  5. ↑ "Spiriva 18 microgram inhalation powder, hard capsule - Summary of Product Characteristics (SmPC)". (emc). 15 January 2019. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  6. ↑ "Spiriva Respimat 2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC)". (emc). 14 January 2021. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  7. ↑ "Tiogiva 18 microgram, inhalation powder, hard capsule - Summary of Product Characteristics (SmPC)". (emc). 2 June 2021. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  8. ↑ "Spiriva Handihaler- tiotropium bromide capsule". DailyMed. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  9. ↑ "Spiriva Respimat- tiotropium bromide inhalation spray spray, metered". DailyMed. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  10. 1 2 3 4 5 6 7 8 9 "Tiotropium Bromide Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 14 October 2018. Retrieved 31 January 2019.
  11. ↑ British national formulary : BNF 76 (76th ed.). Pharmaceutical Press. 2018. pp. 247–248. ISBN   9780857113382.
  12. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 447. ISBN   9783527607495.
  13. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  14. ↑ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  15. ↑ "Tiotropium - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  16. 1 2 Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M (October 2008). "A 4-year trial of tiotropium in chronic obstructive pulmonary disease". The New England Journal of Medicine. 359 (15): 1543–1554. doi:10.1056/nejmoa0805800. hdl: 2437/111564 . PMID   18836213.
  17. ↑ Pocket Guide to COPD Diagnosis, Management and Prevention [Internet] Fontana, WI The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 [Cited 12 April 2020] Available from: https://goldcopd.org/wp-content/uploads/2020/03/GOLD-2020-POCKET-GUIDE-ver1.0_FINAL-WMV.pdf Archived 12 July 2020 at the Wayback Machine
  18. ↑ Rodrigo GJ, Castro-Rodríguez JA (February 2015). "What is the role of tiotropium in asthma?: a systematic review with meta-analysis". Chest. 147 (2): 388–396. doi:10.1378/chest.14-1698. PMID   25322075.
  19. ↑ Global Strategy for Asthma Management and Prevention (2020 update) (PDF). GOLD. 2020. Archived (PDF) from the original on 19 May 2020. Retrieved 10 May 2020.
  20. ↑ "Spiolto Respimat 2.5 microgram/2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC)". (emc). 14 January 2021. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  21. ↑ "Yanimo Respimat 2.5 microgram/2.5 microgram, inhalation solution - Summary of Product Characteristics (SmPC)". (emc). 14 January 2021. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  22. ↑ "Stiolto Respimat- tiotropium bromide and olodaterol spray, metered". DailyMed. Archived from the original on 1 October 2021. Retrieved 30 September 2021.
  23. ↑ Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide.{{cite book}}: CS1 maint: location missing publisher (link)
  24. ↑ Kesten S, Jara M, Wentworth C, Lanes S (December 2006). "Pooled clinical trial analysis of tiotropium safety". Chest. 130 (6): 1695–1703. doi:10.1378/chest.130.6.1695. PMID   17166984.
  25. ↑ Singh S, Loke YK, Furberg CD (September 2008). "Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis". JAMA. 300 (12): 1439–1450. doi:10.1001/jama.300.12.1439. PMID   18812535.
  26. ↑ "Follow-Up to the October 2008 Updated Early Communication about an Ongoing Safety Review of Tiotropium (marketed as Spiriva HandiHaler)". U.S. Food and Drug Administration (FDA). 14 January 2010. Archived from the original on 2 November 2017. Retrieved 20 December 2019.
  27. ↑ Singh S, Loke YK, Enright PL, Furberg CD (June 2011). "Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials". BMJ. 342: d3215. doi:10.1136/bmj.d3215. PMC   3114950 . PMID   21672999.
  28. ↑ "Tiotropium bromide". Australian Prescriber. Retrieved 11 July 2024.
  29. ↑ Kato M, Komamura K, Kitakaze M (December 2006). "Tiotropium, a novel muscarinic M3 receptor antagonist, improved symptoms of chronic obstructive pulmonary disease complicated by chronic heart failure". Circulation Journal. 70 (12): 1658–1660. doi: 10.1253/circj.70.1658 . PMID   17127817.
  30. 1 2 Dahl R, Kaplan A (October 2016). "A systematic review of comparative studies of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease: does inhaler choice matter?". BMC Pulmonary Medicine. 16 (1): 135. doi: 10.1186/s12890-016-0291-4 . PMC   5057252 . PMID   27724909.
  31. ↑ Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, et al. (October 2013). "Tiotropium Respimat inhaler and the risk of death in COPD". The New England Journal of Medicine. 369 (16): 1491–1501. doi: 10.1056/NEJMoa1303342 . PMID   23992515.
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