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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/28 08:26:14」(JST)

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Tiotropium bromide (INN) is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). Tiotropium bromide capsules for inhalation are co-promoted by Boehringer-Ingelheim and Pfizer under the trade name Spiriva. It is also manufactured and marketed by Cipla under trade name Tiova.

Medical uses[edit]

Tiotropium is used for maintenance treatment of chronic obstructive pulmonary disease (COPD) which includes chronic bronchitis and emphysema.^[1] It is not however used for acute exacerbations.^[1]

Adverse effects[edit]

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).^[2]

Tiotropium and another member of its class ipratropium were linked to increased risk of heart attacks, stroke and cardiovascular death.^[3] The FDA requested further trials; these are now complete, and adequately resolve the previous safety concerns.^[4]

Tiotropium mist inhaler (Respimat) has been found to be associated with an increase of all cause mortality in people with COPD.^[5]

Dosage[edit]

The standard dose of Tiotropium is 18 mcg which is administered by a HandiHaler inhalation device.^[6]

Mechanism of action[edit]

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^[7] 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.

Mode of delivery[edit]

The patient removes one tiotropium capsule from the blister pack, places it into the piercing chamber of the inhalation device and closes the mouthpiece.

The capsule is manually pierced, and the medication is inhaled through the mouthpiece. It is recommended that inhalations are repeated 2 to 3 times to ensure all medication is drawn from the capsule. When properly done, the capsule will make a distinctive flutter or rattle, audible to the patient.

Once the powder capsules are removed from the blister pack, it should be taken immediately via the inhalation device. If a capsule is exposed to the air, it will rapidly degrade to the point the dose will become ineffective. Any previously exposed capsules should be discarded.

The capsules cannot be taken orally - they will not be effective as respiratory medication if absorbed through the gastrointestinal tract and may have side effects if absorbed via this route.

Front view

A previously pierced Spiriva capsule

Open (cleaning) view

References[edit]

^ ^a ^b "Spiriva Handihaler". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
^ Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide.
^ 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 (2011 Jun 14). "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. PMID 21672999. Check date values in: |date= (help)
^ Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, et al. Tiotropium respimat inhaler and the risk of death in COPD. N Engl J Med. 2013 08/30; 2013/10.
^ 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[edit]

Official SPIRIVA Site
Thomson CenterWatch

UpToDate Contents

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1. 慢性閉塞性肺疾患（COPD）における抗コリン療法の役割 role of anticholinergic therapy in copd
2. 思春期および成人における重症喘息の治療 treatment of severe asthma in adolescents and adults
3. 安定した慢性閉塞性肺疾患（COPD）のマネージメント management of stable chronic obstructive pulmonary disease
4. 思春期および成人における中等度持続型喘息の治療 treatment of moderate persistent asthma in adolescents and adults
5. 慢性閉塞性肺疾患（COPD）患者における肺過膨張 dynamic hyperinflation in patients with copd

English Journal

Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model.

Trifilieff A1, Ethell BT1, Sykes DA2, Watson KJ1, Collingwood S1, Charlton SJ2, Kent TC3.
Toxicology and applied pharmacology.Toxicol Appl Pharmacol.2015 Aug 15;287(1):9-16. doi: 10.1016/j.taap.2015.05.012. Epub 2015 May 27.
Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of ti
PMID 26026369

Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus higher dose ICS for adults with asthma.

Evans DJ1, Kew KM, Anderson DE, Boyter AC.
The Cochrane database of systematic reviews.Cochrane Database Syst Rev.2015 Jul 21;7:CD011437. [Epub ahead of print]
BACKGROUND: Long-acting muscarinic antagonists (LAMA), a class of drugs with proven effectiveness in chronic obstructive pulmonary disease (COPD), are being considered as an add-on option for adults with asthma whose condition is uncontrolled on inhaled corticosteroids (ICS). It is important to asse
PMID 26196545

Ligand Residence Time at GPCRs - Why We Should Take Our Time to Study It.

Hoffmann C1, Castro M2, Rinken A3, Leurs R4, Hill SJ5, Vischer HF4.
Molecular pharmacology.Mol Pharmacol.2015 Jul 7. pii: mol.115.099671. [Epub ahead of print]
Over the past decade the kinetics of ligand binding to a receptor have received increasing interest. The concept of drug-target residence time is becoming an invaluable parameter for drug optimization. It holds great promise for drug-development and its optimization is thought to reduce off-target e
PMID 26152198

Japanese Journal

気管支喘息診療におけるチオトロピウムの位置づけ

呼吸器内科 = Respiratory medicine 28(4), 315-320, 2015-10
NAID 40020638071

慢性閉塞性肺疾患に対するチオトロピウムとインダカテロールの併用療法からグリコピロニウム/インダカテロール配合剤への切り替えの検討 : 単施設での自己対照比較研究

呼吸器内科 = Respiratory medicine 28(3), 256-262, 2015-09
NAID 40020599206

特発性肺動脈性肺高血圧に対する学童期渡航生体肺葉移植の15年後に片側肺葉に発症した閉塞性細気管支炎

移植 50(6), 651-656, 2015
NAID 130005114868

Related Pictures

★リンクテーブル★

リンク元	「チオトロピウム」
拡張検索	「tiotropium bromide」

「チオトロピウム」

Tiotropium
Systematic (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
Clinical data
MedlinePlus	a604018
Pregnancy cat.	B1 (AU)
Legal status	Prescription Only (S4) (AU) POM (UK) ℞-only (US)
Routes	Inhalation (oral)
Pharmacokinetic data
Bioavailability	19.5% (inhalation)
Metabolism	Hepatic 25%; (CYP2D6, CYP3A4)
Half-life	5–6 days
Excretion	Renal
Identifiers
CAS number	136310-93-5; 186691-13-4 (cation)
ATC code	R03BB04
PubChem	CID 5487426
IUPHAR ligand	367
DrugBank	DB01409
ChemSpider	10482095
UNII	XX112XZP0J
ChEMBL	CHEMBL1201307
Chemical data
Formula	C19H22BrNO4S2
Mol. mass	472.416 g/mol
	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 ;
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　　[★]

英: tiotropium
化: 臭化チオトロピウム tiotropium bromide、
商: スピリーバ

抗コリン薬;慢性閉塞性肺疾患治療;長時間持続型

「tiotropium bromide」

　　[★]

臭化チオトロピウム

関: tiotropium

[AHFS-1] "Spiriva Handihaler". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.

[2] Rossi S, ed. (2006). Australian Medicines Handbook. Adelaide.

[3] 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.

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

[5] Singh, S; Loke, YK, Enright, PL, Furberg, CD (2011 Jun 14). "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. PMID 21672999. Check date values in: |date= (help)

[6] Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B, et al. Tiotropium respimat inhaler and the risk of death in COPD. N Engl J Med. 2013 08/30; 2013/10.

[pmid17127817-7] 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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