Tiotropium Systematic ( IUPAC) name (1α,2β,4β,7β)- 7-[(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl- 3-oxa-9-azoniatricyclo[220.127.116.11 2,4]nonane bromide Clinical data MedlinePlus a604018 Pregnancy cat. Legal status 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 R03 BB04 PubChem CID 5487426 IUPHAR ligand 367 DrugBank DB01409 ChemSpider 10482095 UNII XX112XZP0J ChEMBL CHEMBL1201307 Chemical data Formula C 19 H 22 Br N O 4 S 2 Mol. mass 472.416 g/mol C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C.[Br-]
Key:LERNTVKEWCAPOY-MCGYIYAPSA-N (what is this?) (verify) 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. It is not however used for [1 ] 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. The FDA requested further trials; these are now complete, and adequately resolve the previous safety concerns. [3 ] [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 M muscarinic receptors 3 located on smooth muscle cells and submucosal glands. This leads to a reduction in [7 ] 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 be 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.
A previously pierced Spiriva capsule
References [edit ] ^ a b "Spiriva Handihaler". The American Society of Health-System Pharmacists . Retrieved 3 April 2011. ^ Rossi S, ed. (2006). . Adelaide. Australian Medicines Handbook ^ 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. ^ 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 ]
Agonists: 77-LH-28-1 AC-42 AC-260,584 Aceclidine Acetylcholine AF30 AF150(S) AF267B AFDX-384 Alvameline AQRA-741 Arecoline Bethanechol Butyrylcholine Carbachol CDD-0034 CDD-0078 CDD-0097 CDD-0098 CDD-0102 Cevimeline Choline cis-Dioxolane Ethoxysebacylcholine Itameline LY-593,039 L-689,660 LY-2,033,298 McNA343 Methacholine Milameline Muscarine NGX-267 Ocvimeline Oxotremorine PD-151,832 Pilocarpine RS86 Sabcomeline SDZ 210-086 Sebacylcholine Suberyldicholine Talsaclidine Tazomeline Thiopilocarpine Vedaclidine VU-0029767 VU-0090157 VU-0152099 VU-0152100 VU-0238429 WAY-132,983 Xanomeline YM-796 Antagonists: 3-Quinuclidinyl Benzilate 4-DAMP Aclidinium Bromide Anisodamine Anisodine Atropine Atropine Methonitrate Benactyzine Benzatropine/Benztropine Benzydamine BIBN 99 Biperiden Bornaprine CAR-226,086 CAR-301,060 CAR-302,196 CAR-302,282 CAR-302,368 CAR-302,537 CAR-302,668 CS-27349 Cyclobenzaprine Cyclopentolate Darifenacin DAU-5884 Dimethindene Dexetimide DIBD Dicyclomine/Dicycloverine Ditran EA-3167 EA-3443 EA-3580 EA-3834 Etanautine Etybenzatropine/Ethylbenztropine Flavoxate Himbacine HL-031,120 Ipratropium bromide J-104,129 Hyoscyamine Mamba Toxin 3 Mamba Toxin 7 Mazaticol Mebeverine Methoctramine Metixene N-Ethyl-3-Piperidyl Benzilate N-Methyl-3-Piperidyl Benzilate Orphenadrine Otenzepad Oxybutynin PBID PD-102,807 PD-0298029 Phenglutarimide Phenyltoloxamine Pirenzepine Piroheptine Procyclidine Profenamine RU-47,213 SCH-57,790 SCH-72,788 SCH-217,443 Scopolamine/Hyoscine Solifenacin Telenzepine Tiotropium bromide Tolterodine Trihexyphenidyl Tripitamine Tropatepine Tropicamide WIN-2299 Xanomeline Zamifenacin; Others: 1st Generation Antihistamines ( Brompheniramine chlorphenamine cyproheptadine dimenhydrinate diphenhydramine doxylamine mepyramine/ pyrilamine phenindamine pheniramine tripelennamine triprolidine, etc) Tricyclic Antidepressants ( Amitriptyline doxepin trimipramine, etc) Tetracyclic Antidepressants ( Amoxapine maprotiline, etc) Typical Antipsychotics ( Chlorpromazine thioridazine, etc) Atypical Antipsychotics ( Clozapine olanzapine, etc.) Agonists: 5-HIAA A-84,543 A-366,833 A-582,941 A-867,744 ABT-202 ABT-418 ABT-560 ABT-894 Acetylcholine Altinicline Anabasine Anatoxin-a AR-R17779 Butinoline Butyrylcholine Carbachol Choline Cotinine Cytisine Decamethonium Desformylflustrabromine Dianicline Dimethylphenylpiperazinium Epibatidine Epiboxidine Ethanol Ethoxysebacylcholine EVP-4473 EVP-6124 Galantamine GTS-21 Ispronicline Levamisole Lobeline MEM-63,908/RG-3487 Morantel Nicotine NS-1738 PHA-543,613 PHA-709,829 PNU-120,596 PNU-282,987 Pozanicline Rivanicline RJR-2429 Sazetidine A Sebacylcholine SIB-1508Y SIB-1553A SSR-180,711 Suberyldicholine Suxamethonium/Succinylcholine TC-1698 TC-1734 TC-1827 TC-2216 TC-5214 TC-5619 TC-6683 Tebanicline Tropisetron UB-165 Varenicline WAY-317,538 XY-4083 Antagonists: 18-Methoxycoronaridine α-Bungarotoxin α-Conotoxin Alcuronium Amantadine Anatruxonium Atracurium Bupropion Chandonium Chlorisondamine Cisatracurium Coclaurine Coronaridine Dacuronium Decamethonium Dextromethorphan Dextropropoxyphene Dextrorphan Diadonium DHβE Dihydrochandonium Dimethyltubocurarine/Metocurine Dipyrandium Dizocilpine/MK-801 Doxacurium Esketamine Fazadinium Gallamine Hexafluronium Hexamethonium/Benzohexonium Hydroxybupropion Ibogaine Isoflurane Ketamine Kynurenic acid Laudexium/Laudolissin Levacetylmethadol Malouetine Mecamylamine Memantine Methadone ( Levomethadone) Methorphan/Racemethorphan Methyllycaconitine Metocurine Mivacurium Morphanol/Racemorphan Neramexane Nitrous Oxide Pancuronium Pempidine Pentamine Pentolinium Phencyclidine Pipecuronium Radafaxine Rapacuronium Rocuronium Surugatoxin Thiocolchicoside Toxiferine Trimethaphan Tropeinium Tubocurarine Vecuronium Xenon