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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" (PDF). 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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English Journal

An Asthma Protocol Improved Adherence to Evidence-Based Guidelines for Pediatric Subjects With Status Asthmaticus in the Emergency Department.

Miller AG1, Breslin ME2, Pineda LC3, Fox JW3.
Respiratory care.Respir Care.2015 Dec;60(12):1759-64. doi: 10.4187/respcare.04011. Epub 2015 Jun 23.
BACKGROUND: In our institution's pediatric emergency department, adherence to evidence-based asthma guidelines was noted to be suboptimal for patients with asthma exacerbations. We hypothesized that an evidence-based asthma protocol would improve time to treatment and adherence to National Institute
PMID 26106203

The safety of anticholinergic bronchodilators for the treatment of chronic obstructive pulmonary disease.

Tashkin DP1.
Expert opinion on drug safety.Expert Opin Drug Saf.2015 Nov;14(11):1759-72. doi: 10.1517/14740338.2015.1093621. Epub 2015 Sep 24.
INTRODUCTION: Poorly absorbable quaternary ammonium-inhaled muscarinic antagonists both as the short-acting ipratropium and as long-acting (12 - 24 h) agents (tiotropium, glycopyrronium, aclidinium and umeclidinium) have all demonstrated statistically and clinically significant efficacy in chronic o
PMID 26401729

Immuno-detection of OCTN1 (SLC22A4) in HeLa cells and characterization of transport function.

Pochini L1, Scalise M1, Indiveri C2.
International immunopharmacology.Int Immunopharmacol.2015 Nov;29(1):21-6. doi: 10.1016/j.intimp.2015.04.040. Epub 2015 Apr 29.
OCTN1 was immuno-detected in the cervical cancer cell HeLa, in which the complete pattern of acetylcholine metabolizing enzymes is expressed. Comparison of immuno-staining intensity of HeLa OCTN1 with the purified recombinant human OCTN1 allowed measuring the specific OCTN1 concentration in the HeLa
PMID 25937167

Japanese Journal

Comparative Characterization of Lung Muscarinic Receptor Binding After Intratracheal Administration of Tiotropium, Ipratropium, and Glycopyrrolate

Ogoda Masaki,Niiya Ryo,Koshika Tadatsura,Yamada Shizuo
Journal of Pharmacological Sciences 115(3), 374-382, 2011
… The aim of the current study was to characterize comparatively the binding of muscarinic receptor in the lung of rats intratracheally administered anticholinergic agents (tiotropium, ipratropium, glycopyrrolate) used clinically to treat chronic obstructive pulmonary disease (COPD) and asthma. … Binding parameters of [N-methyl-3H]scopolamine methyl chloride ([3H]NMS) were determined in tissues (lung, bladder, submaxillary gland) of rats intratracheally administered tiotropium, ipratropium, and glycopyrrolate. …
NAID 130000663400

Effects of Muscarinic Receptor Antagonists With or Without M_2 Antagonist Activity on Cholinergic Reflex Bronchoconstriction in Ovalbumin-Sensitized and-Challenged Mice

HIROSE Hiroyasu,JIANG Jian,NISHIKIBE Masaru
Journal of pharmacological sciences 92(3), 209-217, 2003-07-01
… Ipratropium (0.03 – … Although ipratropium (0.03 – … 1 mg/ml) dose-dependently inhibited SO2-induced responses on Day 31, ipratropium at a dose of 0.1 mg/ml significantly increased SO2-induced responses on Day 37 (162.2% of the corresponding control). …
NAID 130000073648

Related Pictures

★リンクテーブル★

リンク元	「ムスカリン受容体拮抗薬」「イプラトロピウム」「気管支拡張薬」
拡張検索	「ipratropium bromide」「ipratropium with albuterol」

「ムスカリン受容体拮抗薬」

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 (No risk in non-human studies);
Legal status	UK: Prescription-only (POM); US: ℞-only;
Routes of; administration	Inhalation
Pharmacokinetic data
Protein binding	0 to 9% in vitro
Metabolism	Hepatic
Biological half-life	2 hours
Identifiers
CAS Registry Number	22254-24-6; 60205-81-4 (cation)
ATC code	R01AX03 R03BB01
PubChem	CID: 657308
IUPHAR/BPS	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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