Tiotropium bromide

Tiotropium
Clinical data
Trade names	Spiriva
MedlinePlus	a604018
Pregnancy; category	AU: B1; ;
Routes of; administration	Inhalation (oral)
ATC code	R03BB04 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	19.5% (inhalation)
Metabolism	Hepatic 25%; (CYP2D6, CYP3A4)
Elimination half-life	5–6 days
Excretion	Renal
Identifiers
	IUPAC name (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	136310-93-5 ; 186691-13-4 (cation);
PubChem CID	5487426;
IUPHAR/BPS	367;
DrugBank	DB01409;
ChemSpider	10482095 ;
UNII	XX112XZP0J;
ChEMBL	ChEMBL1201307;
CompTox Dashboard (EPA)	DTXSID5044281 ;
ECHA InfoCard	100.234.575
Chemical and physical data
Formula	C19H22BrNO4S2
Molar mass	472.416 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C.[Br-];
	InChI 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 ; Key:LERNTVKEWCAPOY-MCGYIYAPSA-N ;
	(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.

External links

[1] "Tiotropium bromide". AdisInsight. Retrieved 8 March 2017.

[2] Corey, E.J. (2012). "Tiotropium bromide". Molecules and Medicine. John Wiley & Sons. ISBN 9781118361733.

[AHFS-3] "Spiriva Handihaler". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.

[4] Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide.{{cite book}}: CS1 maint: location missing publisher (link)

[5] 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.

[6] FDA. Follow-Up to the October 2008 Updated Early Communication about an Ongoing Safety Review of Tiotropium (marketed as Spiriva HandiHaler). FDA 2010

[7] 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.

[pmid17127817-8] 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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