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Tiotropium Trade names Spiriva MedlinePlus a604018 Pregnancy category Routes of administration Inhalation (oral) ATC code Legal status
AU : S4 (Prescription only)
UK : POM (Prescription only)
US : ℞-only
Bioavailability 19.5% (inhalation) Metabolism Hepatic 25% (CYP2D6 , CYP3A4 )Elimination half-life 5–6 days Excretion Renal
(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 ChEMBL CompTox Dashboard (EPA ) ECHA InfoCard 100.234.575 Formula C 19 H 22 Br N O 4 S 2 Molar mass 472.416 g/mol g·mol−1 3D model (JSmol )
C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C.[Br-]
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
Y Key:LERNTVKEWCAPOY-MCGYIYAPSA-N
Y
(verify)
Tiotropium bromide , originally marketed as Spiriva ,[ 1] is a long-acting, 24-hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD).
Tiotroprium was discovered in 1991 by Boehringer Ingelheim and came to market in 2004.[ 2]
Medical uses
Tiotropium is used for maintenance treatment of chronic obstructive pulmonary disease (COPD) which includes chronic bronchitis and emphysema.[ 3] It is not however used for acute exacerbations .[ 3]
Adverse effects
Adverse effects are mainly related to its antimuscarinic effects. Common adverse drug reactions (≥1% of patients) associated with tiotropium therapy 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/or allergy (rash, angioedema , anaphylaxis ).[ 4]
Tiotropium and another member of its class ipratropium were linked to increased risk of heart attacks, stroke and cardiovascular death.[ 5] The FDA requested further trials; these are now complete, and adequately resolve the previous safety concerns.[ 6]
Tiotropium mist inhaler (Respimat ) has been found to be associated with an increase of all cause mortality in people with COPD.[ 7]
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[ 8] 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.
References
^ "Tiotropium bromide" . AdisInsight . Retrieved 8 March 2017 .
^ Corey, E.J. (2012). "Tiotropium bromide". Molecules and Medicine . John Wiley & Sons. ISBN 9781118361733 .
^ a b "Spiriva Handihaler" . The American Society of Health-System Pharmacists . Retrieved 3 April 2011 .
^ Rossi S, ed. (2006). Australian Medicines Handbook . Adelaide. {{cite book }}
: CS1 maint: location missing publisher (link )
^ 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): 1439–50. doi :10.1001/jama.300.12.1439 . PMID 18812535 .
^ FDA. Follow-Up to the October 2008 Updated Early Communication about an Ongoing Safety Review of Tiotropium (marketed as Spiriva HandiHaler). FDA 2010
^ Singh, S; Loke, YK; Enright, PL; Furberg, CD (Jun 14, 2011). "Mortality associated with tiotropium mist inhaler in patients with chronic obstructive pulmonary disease: systematic review and meta-analysis of randomised controlled trials" . BMJ (Clinical research ed.) . 342 : d3215. doi :10.1136/bmj.d3215 . PMC 3114950 . PMID 21672999 .
^ 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" . Circ. J . 70 (12): 1658–60. doi :10.1253/circj.70.1658 . PMID 17127817 .
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