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Ipratropium bromide (INN, trade names Atrovent, Apovent, Ipraxa, Aerovent and Rinatec) is a drug that relieves bronchial spasms. It is an anticholinergic drug used for the treatment of chronic obstructive pulmonary disease and acute asthma. It blocks the muscarinic acetylcholine receptors in the smooth muscles of the bronchi in the lungs, opening the bronchi.^[1]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[2]

Medical uses

Ipratropium is administered by inhalation for the treatment of chronic obstructive pulmonary disease (COPD). For that purpose it is supplied in a canister for use in an inhaler or in single dose vials for use in a nebulizer.^[3]

It is also used to treat and prevent minor and moderate bronchial asthma, especially asthma that is accompanied by cardiovascular system diseases.^{[citation needed]}

It is also combined with salbutamol (albuterol, USA) under the trade names Combivent (metered-dose inhaler or MDI) and Duoneb (nebulizer) for the management of COPD and asthma, and with fenoterol (trade names Duovent and Berodual N) for the management of asthma.

Ipratropium as a .03% nasal solution sprayed into the nostrils can reduce rhinorrhea but will not help nasal congestion.^[4]

Contraindications

There are no contraindications for inhaled ipratropium, apart from hypersensitivity to atropine and related substances. For oral administration, contraindications are similar to other anticholinergics; they include narrow angle glaucoma and obstructions in the gastrointestinal tract and urinary system.^[5]^[6]

Peanut allergy

Previously atrovent inhalers used chlorofluorocarbon (CFC) as a propellant and contained soy lecithin in the propellant ingredients. In 2008 all CFC inhalers were phased out and hydrofluoroalkane (HFA) inhalers replaced them. Allergy to peanuts was noted for the inhaler as a contraindication but now is not. It has never been a contraindication when administered as a nebulized solution.^[7]

Side effects

If ipratropium is inhaled, side effects resembling those of other anticholinergics are minimal. However, dry mouth and sedation have been reported. Also, effects such as skin flushing, tachycardia, acute angle-closure glaucoma, nausea, palpitations and headache have been observed. Inhaled ipratropium does not decrease mucociliary clearance.^[6] The inhalation itself can cause headache and irritation of the throat in a few percent of patients.^[5]

Urinary retention has been reported in patients receiving doses by nebulizer. As a result, caution may be warranted, especially by men with prostatic hypertrophy.^[8]

Interactions

Combination with beta-adrenergic agonists, as well as theophylline and other xanthine derivatives, increases the dilating effect on the bronchi. Interactions with other anticholinergics like tricyclic antidepressants, antiparkinson drugs and quinidine, which theoretically increase side effects, are clinically irrelevant when ipratropium is administered as an inhalant.^[5]^[6]

Pharmacology

Ipratropium exhibits broncholytic action by reducing cholinergic influence on the bronchial musculature. It blocks muscarinic acetylcholine receptors, without specificity for subtypes, and therefore promotes the degradation of cyclic guanosine monophosphate (cGMP), resulting in a decreased intracellular concentration of cGMP.^[9] Most likely due to actions of cGMP on intracellular calcium, this results in decreased contractility of smooth muscle in the lung, inhibiting bronchoconstriction and mucus secretion. It is a nonselective muscarinic antagonist,^[5] and does not diffuse into the blood, which prevents systemic side effects. Ipratropium is a derivative of atropine^[10] but is a quaternary amine and therefore does not cross the blood–brain barrier, which prevents central side effects (anticholinergic syndrome). Ipratropium is not considered a short-acting bronchodilator and should never be used in place of albuterol (salbutamol) as a rescue medication.

Synthesis

Ipratropium bromide, 3α-hydroxy-8-isopropyl-1αH,5αH-tropanium bromide, can be synthesized by reacting equimolar amounts of atropine and 2-bromopropane.

K. Zeile, W. Schulz, R. Bonholzer, H. Wick, U.S. Patent 3,505,337 (1967).
K. Zeile, W. Schulz, R. Bonholzer, H. Wick, S. Afr. Pat., 67 07.766 (1968).
W. Schulz, R. Banholzer, K.H. Pook, Arznei.-Forsch., 26, 960 (1976).

References

^ Baigelman W, Chodosh S (March 1977). "Bronchodilator action of the anticholinergic drug, ipratropium bromide (Sch 1000), as an aerosol in chronic bronchitis and asthma". Chest 71 (3): 324–8. doi:10.1378/chest.71.3.324. PMID 138578.
^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
^ Ipratropium Oral Inhalation PubMed Health Retrieved May 28, 2012
^ Atrovent Nasal Spray Drugs.com Retrieved May 28, 2012
^ ^a ^b ^c ^d Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 3-85200-196-X.
^ ^a ^b ^c Dinnendahl, V, Fricke, U, ed. (2010). Arzneistoff-Profile (in German) 2 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
^ Ipratropium Soybean and Nuts Allergy EMSMedRx Retrieved April 6, 2013
^ Afonso, A. S. M.; Verhamme, K. M. C.; Stricker, B. H. C.; Sturkenboom, M. C. J. M.; Brusselle, G. G. O. (2011). "Inhaled anticholinergic drugs and risk of acute urinary retention". BJU International 107 (8): 1265–1272. doi:10.1111/j.1464-410X.2010.09600.x. PMID 20880196. edit
^ Ipratropium Drugs.com
^ Yamatake Y, Sasagawa S, Yanaura S, Okamiya Y (1977). "[Antiallergic asthma effect of ipratropium bromide (Sch 1000) in dogs (author's transl)]". Nippon Yakurigaku Zasshi (in Japanese) 73 (7): 785–91. doi:10.1254/fpj.73.785. PMID 145994.

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. 小児における喘息の急性増悪：救急外来によるマネージメント acute asthma exacerbations in children emergency department management
3. 12歳未満の小児における慢性喘息：初回評価および診断 asthma in children younger than 12 years rescue treatment for acute symptoms
4. 成人における感冒：治療および予防 the common cold in adults treatment and prevention
5. 成人における亜急性および慢性咳嗽の治療 treatment of subacute and chronic cough in adults

English Journal

Republished: Pro-arrhythmic and pro-ischaemic effects of inhaled anticholinergic medications.

Singh S1, Loke YK, Enright P, Furberg CD.Author information 1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.AbstractThe majority of deaths in COPD are from cardiovascular causes. Several large randomized controlled trials demonstrate that inhaled anticholinergic agents ipratropium and tiotropium increase the risk of serious cardiovascular events, including cardiovascular mortality. Tiotropium Respimat is associated with a statistically significant increased risk of mortality (RR 1.52; 95% CI 1.06 to 2.16) and cardiovascular death (RR 2.05; 95% CI 1.06 to 3.99) compared with placebo in a meta-analysis of clinical trials. In the largest study, the subgroup of patients with COPD in the Respimat group with known rhythm and cardiac disorders at baseline had an especially high risk for cardiac death (RR 8.6; 95% CI 1.1 to 67.2). Although there was no significantly increased risk of mortality (HR 0.89; 95% CI 0.79 to 1.02) or myocardial infarction (MI) (RR 0.73; 95% CI 0.53 to 1.00) with tiotropium handihaler in the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, the reported excess of angina (RR 1.44; 95% CI 0.91 to 2.26), imbalance in strokes related to ischaemia and rates of supraventricular tachyarrhythmias are consistent with the pro-ischemic and pro-arrhythmic effects. The subjects at greatest risk of cardiovascular death, such as those with a recent history of MI, unstable or life-threatening cardiac arrhythmias or hospitalisation with heart failure, were excluded from the UPLIFT trial. The Prevention of Exacerbations with Tiotropium in COPD trial showed an excess of serious coronary ischaemic events of angina, myocardial ischaemia and MI with the tiotropium Handihaler compared with salmeterol. The authors urge caution in prescribing inhaled anticholinergics for patients with pre-existing arrhythmias or cardiac disorders.
Postgraduate medical journal.Postgrad Med J.2014 Apr;90(1062):205-7. doi: 10.1136/postgradmedj-2011-201275rep.
The majority of deaths in COPD are from cardiovascular causes. Several large randomized controlled trials demonstrate that inhaled anticholinergic agents ipratropium and tiotropium increase the risk of serious cardiovascular events, including cardiovascular mortality. Tiotropium Respimat is associat
PMID 24643260

Ipratropium bromide-mediated myocardial injury in in vitro models of myocardial ischaemia/reperfusion.

Harvey KL1, Hussain A, Maddock HL.Author information 1Department of Biomolecular and Sports Sciences, Coventry University, Cox Street, Coventry, CV1 5FB, UK.AbstractIpratropium bromide, a nonselective muscarinic antagonist, is widely prescribed for the treatment of chronic obstructive pulmonary disease (COPD). Analyses of COPD patients, with underlying ischaemic heart disease, receiving anticholinergics, have indicated increased risk of severity and occurrence of cardiovascular events (including myocardial infarction). The present study explored whether ipratropium bromide induces myocardial injury in nonclinical models of simulated myocardial ischaemia/reperfusion injury. Adult Sprague Dawley rat hearts/primary ventricular myocytes were exposed to simulated ischaemia/hypoxia prior to administration of ipratropium at the onset of reperfusion/reoxygenation. Infarct to risk ratio and cell viability was measured via triphenyl tetrazolium chloride staining and thiazolyl blue tetrazolium bromide (MTT) assay. The involvement of apoptosis and necrosis was evaluated by flow cytometry. Mitochondrial-associated responses were detected by tetramethylrhodamine methyl ester fluorescence and myocyte contracture. Ipratropium (1 × 10(-11) M - 1 × 10(-4) M) significantly increased infarct/risk ratio and decreased cell viability in a dose-dependent manner. Increased levels of necrosis and apoptosis were observed via flow cytometry, accompanied by increased levels of cleaved caspase-3 following ipratropium treatment. Levels of endogenous myocardial acetylcholine were verified via use of an acetylcholine assay. In these experimental models, exogenous acetylcholine (1 × 10(-7) M) showed protective properties, when administered alone, as well as abrogating the exacerbation of myocardial injury during ischaemia/reperfusion following ipratropium coadministration. In parallel experiments, under conditions of myocardial ischaemia/reperfusion, a similar injury was observed following atropine (1 × 10(-7) M) administration. These data demonstrate for the first time in a nonclinical setting that ipratropium exacerbates ischaemia/reperfusion injury via apoptotic- and necrotic-associated pathways.
Toxicological sciences : an official journal of the Society of Toxicology.Toxicol Sci.2014 Apr;138(2):457-67. doi: 10.1093/toxsci/kfu001. Epub 2014 Jan 15.
Ipratropium bromide, a nonselective muscarinic antagonist, is widely prescribed for the treatment of chronic obstructive pulmonary disease (COPD). Analyses of COPD patients, with underlying ischaemic heart disease, receiving anticholinergics, have indicated increased risk of severity and occurrence
PMID 24431217

Stress-induced cardiomyopathy associated with ipratropium bromide therapy in a patient with chronic obstructive pulmonary disease.

Melão F1, L Nunes JP2, Vasconcelos M3, Dias P3, Almeida PB3, Rodrigues R3, Pinho T3, Madureira A4, Maciel MJ2.Author information 1Serviço de Cardiologia, Centro Hospitalar São João, Porto, Portugal. Electronic address: filipamelao@gmail.com.2Serviço de Cardiologia, Centro Hospitalar São João, Porto, Portugal; Faculdade de Medicina da Universidade do Porto, Portugal.3Serviço de Cardiologia, Centro Hospitalar São João, Porto, Portugal.4Serviço de Radiologia, Centro Hospitalar São João, Porto, Portugal.AbstractStress-induced cardiomyopathy, also known as 'broken heart syndrome' or Takotsubo cardiomyopathy, is characterized by transient systolic dysfunction of the apical and/or mid segments of the left ventricle, in the absence of significant coronary artery disease. We report the case of a 56-year-old male patient with chronic obstructive pulmonary disease (COPD), with stress-induced cardiomyopathy associated with the use of ipratropium bromide, administered in the context of an acute exacerbation of COPD.
Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology.Rev Port Cardiol.2014 Mar 26. pii: S0870-2551(14)00052-3. doi: 10.1016/j.repc.2013.10.012. [Epub ahead of print]
Stress-induced cardiomyopathy, also known as 'broken heart syndrome' or Takotsubo cardiomyopathy, is characterized by transient systolic dysfunction of the apical and/or mid segments of the left ventricle, in the absence of significant coronary artery disease. We report the case of a 56-year-old mal
PMID 24680554

Japanese Journal

Ipratropium bromide (Atrovent nasal spray) reduces the nasal response to methacholine

BAROODY FM.
J Allergy Clin Immunol. 89, 1065-1075, 1992
NAID 30016519581

アトロベント^[○!R]の気道過敏性と肺Muscarinic Acetylcholine Receptorにおよぼす影響について

鈴木隆二郎,野坂博行,塚脇雅夫,高木健三,佐竹辰夫
アレルギー 35(5), 349-355, 1986-05-30
アトロベント^[○!R]がモルモットの気道過敏性と肺muscarinic acetylcholine receptor (mAchR)におよぼす影響について検討した.この実験では, アセチルコリン吸入テストで経皮酸素分圧を指標として気道過敏性を測定した.さらに, ムスカリン拮抗剤である^3H-quinuclidinyl benzilateを使用し, 直接肺のmAchRの測定を実施し, 以下の成績を …
NAID 110002414837

Effect of an anticholinergic agent, ipratropium bromide, on nasal ciliary epithelium.

斎藤等,坪川俊仁,斎藤武久
耳鼻咽喉科臨床 79(1), 151-159, 1986
… Nasal septal mucosa of C3H mice was employed for morphological observation by a scanning electron microscope.It was found that 40μg of IpBr sprayed twice into each nostril, which is the recommended dose of Atrovent®, was harmless. …
NAID 130001809984

Related Pictures

Drugs reference index « Atrovent » atrovent inhaler.jpg Atrovent HFA 17 mcg/Actuation Aerosol Ipratropium bromide Brand names: Atrovent Atrovent Inhaler Dosage

★リンクテーブル★

リンク元	「イプラトロピウム」

「イプラトロピウム」

Ipratropium bromide
Systematic (IUPAC) name
	[8-methyl-8-(1-methylethyl)- 8-azoniabicyclo[3.2.1] oct-3-yl] 3-hydroxy-2-phenyl-propanoate
Clinical data
Trade names	Atrovent, Apovent, Ipraxa, Aerovent, Rinatec
AHFS/Drugs.com	monograph
Pregnancy; category	US: B;
Legal status	UK: POM; US: ℞-only;
Routes	Inhalation
Pharmacokinetic data
Protein binding	0 to 9% in vitro
Metabolism	Hepatic
Half-life	2 hours
Identifiers
CAS number	22254-24-6; 60205-81-4 (cation)
ATC code	R01AX03 R03BB01
PubChem	CID 657308
IUPHAR ligand	325
DrugBank	DB00332
ChemSpider	10481997
UNII	GR88G0I6UL
ChEMBL	CHEMBL1464005
Chemical data
Formula	C20H30BrNO3
Molecular mass	412.37 g/mol
	SMILES CC(C)[N+]1([C@@H]2CC[C@H]1C[C@H](C2)OC(=O)C(CO)C3=CC=CC=C3)C.[Br-];
	InChI InChI=1S/C20H30NO3.BrH/c1-14(2)21(3)16-9-10-17(21)12-18(11-16)24-20(23)19(13-22)15-7-5-4-6-8-15;/h4-8,14,16-19,22H,9-13H2,1-3H3;1H/q+1;/p-1/t16-,17+,18+,19?,21?;; Key:LHLMOSXCXGLMMN-WDTICOSOSA-M ;
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　　[★]

英: ipratropium
化: 臭化イプラトロピウム ipratropium bromide
商: アトロベント Atrovent

ムスカリン受容体拮抗薬
アトロピンの誘導体
四級アンモニウム塩

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気管支拡張薬・気管支収縮予防薬
吸入エアロゾル

適応

慢性閉塞性肺疾患

商品名である。

[pmid138578-1] Baigelman W, Chodosh S (March 1977). "Bronchodilator action of the anticholinergic drug, ipratropium bromide (Sch 1000), as an aerosol in chronic bronchitis and asthma". Chest 71 (3): 324–8. doi:10.1378/chest.71.3.324. PMID 138578.

[2] "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.

[3] Ipratropium Oral Inhalation PubMed Health Retrieved May 28, 2012

[4] Atrovent Nasal Spray Drugs.com Retrieved May 28, 2012

[AustriaCodex-5] Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 3-85200-196-X.

[Arzneistoff-Profile-6] Dinnendahl, V, Fricke, U, ed. (2010). Arzneistoff-Profile (in German) 2 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.

[7] Ipratropium Soybean and Nuts Allergy EMSMedRx Retrieved April 6, 2013

[8] Afonso, A. S. M.; Verhamme, K. M. C.; Stricker, B. H. C.; Sturkenboom, M. C. J. M.; Brusselle, G. G. O. (2011). "Inhaled anticholinergic drugs and risk of acute urinary retention". BJU International 107 (8): 1265–1272. doi:10.1111/j.1464-410X.2010.09600.x. PMID 20880196. edit

[Drugs.com-9] Ipratropium Drugs.com

[10] Yamatake Y, Sasagawa S, Yanaura S, Okamiya Y (1977). "[Antiallergic asthma effect of ipratropium bromide (Sch 1000) in dogs (author's transl)]". Nippon Yakurigaku Zasshi (in Japanese) 73 (7): 785–91. doi:10.1254/fpj.73.785. PMID 145994.

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Atrovent