Editing Ipratropium bromide

{{Short description|Type of anticholinergic}}
{{Use dmy dates|date=January 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 408942572
| image = Ipratropium bromide.svg
| image_class = skin-invert-image
| width = 
| alt = 
| caption = 

<!-- Clinical data -->
| pronounce = 
| tradename = Atrovent, others
| Drugs.com = {{drugs.com|monograph|ipratropium_bromide}}
| MedlinePlus = a618013
| DailyMedID = Ipratropium bromide
| pregnancy_AU = B1
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[Inhalation]], [[intranasal]]
| class = [[Anticholinergic]] ([[muscarinic antagonist]])
| ATC_prefix = R01
| ATC_suffix = AX03
| ATC_supplemental = {{ATC|R03|BB01}}

| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_NZ = Prescription only
| legal_UK = POM
| legal_US = Rx-only

<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 0–9% ''in vitro''
| metabolism = [[Liver]]
| metabolites = 
| onset = 15–30 minutes
| elimination_half-life = 2 hours
| duration_of_action = 3–5 hours
| excretion = 

<!-- Identifiers -->
| index2_label = Ipratropium
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 22254-24-6
| CAS_supplemental = 
| CAS_number2_Ref = {{cascite|correct|CAS}}
| CAS_number2 = 60205-81-4
| PubChem = 657308
| PubChemSubstance = 
| IUPHAR_ligand = 325
| DrugBank = DBSALT002739
| DrugBank2 = DB00332
| ChemSpiderID = 10481997
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = J697UZ2A9J
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = GR88G0I6UL
| KEGG = D02212
| ChEBI = 46659
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 2134724
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = 

<!-- Chemical and physical data -->
| IUPAC_name = [8-methyl-8-(1-methylethyl)- 8-azoniabicyclo[3.2.1] oct-3-yl] 3-hydroxy-2-phenyl-propanoate
| C = 20
| H = 30
| Br = 1
| N = 1
| O = 3
| SMILES = CC(C)[N+]1(C2CCC1CC(C2)OC(=O)C(CO)C3=CC=CC=C3)C.[Br-]
| StdInChI = 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?;
| StdInChI_comment = 
| StdInChIKey = LHLMOSXCXGLMMN-WDTICOSOSA-M
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

<!-- Definition and medical uses -->
'''Ipratropium bromide''', sold under the trade name '''Atrovent''' among others, is a type of [[anticholinergic]] medication which is applied by different routes: [[inhaler]], [[nebulizer]], or [[nasal spray]], for different reasons.<ref>[http://www.rxlist.com/search/rxl/atrovent Rxlist.com: Search Atrovent]</ref><ref name="rxipra">[http://www.rxlist.com/ipratropium/generic-drug.htm Rx.com: Ipratropium]</ref> 

The inhalant [[bronchodilator|opens up the medium and large airways in the lungs]].<ref name="AHFS2015">{{cite web|title=Ipratropium Bromide|url=https://www.drugs.com/monograph/ipratropium-bromide.html|publisher=The American Society of Health-System Pharmacists|access-date=2 December 2015|url-status=live|archive-url=https://web.archive.org/web/20151208163623/http://www.drugs.com/monograph/ipratropium-bromide.html|archive-date=8 December 2015}}</ref> It is used to treat the symptoms of [[chronic obstructive pulmonary disease]] (COPD) and [[asthma]].<ref name="AHFS2015" /> It is used by [[metered-dose inhaler|inhaler]] or [[nebulizer]].<ref name="AHFS2015" /> Onset of action is typically within 15 to 30 minutes and lasts for three to five hours.<ref name="AHFS2015" /> 

The nasal spray prevents the glands in the nose from producing large amounts of fluid.<ref name=mayoroute>[http://www.mayoclinic.org/drugs-supplements/ipratropium-nasal-route/description/drg-20064390 Mayo Clinic: Ipratropium (Nasal Route)]</ref><ref name=cleveland>[http://my.clevelandclinic.org/health/drugs/20227-ipratropium-nasal-spray Cleveland Clinic: Ipratropium Nasal Spray]</ref> It is used to treat [[rhinorrhea]] (runny nose) caused by [[allergic rhinitis]], [[nonallergic rhinitis]],<ref name=mayoroute /> and the common cold.<ref name=rxnasalspray>[http://www.rxlist.com/atrovent-nasal-spray-drug.htm Rxlist.com: Atrovent Nasal Spray]</ref><ref name=rxipra /> It is used by metered-dose manual pump spray. Onset of action is within an hour.<ref name=rxnasalspray /> 

<!-- Side effects and mechanism -->
Common side effects of inhalant use include [[dry mouth]], [[cough]], [[bronchitis|inflammation of the airways]],<ref name=AHFS2015 /> and [[Dyspnea|shortness of breath]].<ref name= rxhfa>[http://www.rxlist.com/atrovent-hfa-drug.htm#side_effects RxList.com: Atrovent HFA]</ref> Potentially serious side effects include [[urinary retention]], worsening spasms of the airways, and a [[anaphylaxis|severe allergic reaction]].<ref name=AHFS2015 /> It appears to be safe in [[pregnancy]] and [[breastfeeding]].<ref name=AHFS2015 /><ref>{{cite book| vauthors = Briggs G, Freeman RK, Yaffe SJ |title=Drugs in pregnancy and lactation : a reference guide to fetal and neonatal risk|date=2011|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-1-60831-708-0|page=763|edition=9th|url=https://books.google.com/books?id=OIgTE4aynrMC&q=Ipratropium%20discovery%201986&pg=PA763}}</ref> Ipratropium is a short-acting [[muscarinic antagonist]],<ref>{{Cite book| vauthors = Ritter J, Flower RJ, Henderson G, Loke YK, MacEwan DJ, Rang HP |url=https://www.worldcat.org/oclc/1081403059|title=Rang and Dale's pharmacology|date=2020|isbn=978-0-7020-8060-9|edition=9th|location=Edinburgh|pages=377|oclc=1081403059}}</ref> which works by causing [[smooth muscle]]s to relax.<ref name=AHFS2015 />

Common side effects of nasal spray may include [[headache]], dry nose, dry mouth or throat, nasal or throat irritation, [[Nosebleed|nosebleeds]], bad taste in mouth, [[nausea]], [[dizziness]], or [[constipation]].<ref name=rxnasalspray /> Potentially serious side effects are unusual, but include severe allergic reaction, eye pain or change in vision, or urinary retention. It is considered safe during pregnancy, but it can pass into breast milk and may harm a nursing baby.<ref name=drugscom>[http://www.drugs.com/mtm/ipratropium-nasal.html Drugs.com: Ipratropium nasal]</ref>  

<!-- Society and culture -->
Ipratropium bromide was patented in 1966, and approved for medical use in 1974.<ref>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=446 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA446 }}</ref> It is on the [[World Health Organization's List of Essential Medicines]], the most important medicines needed in a [[health system]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO }}</ref> Ipratropium is available as a generic medication.<ref name=AHFS2015 /> In 2022, it was the 219th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Ipratropium Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Ipratropium | access-date = 30 August 2024 }}</ref>

== Medical uses ==
Ipratropium as an inhalant can be used for the treatment of [[chronic obstructive pulmonary disease]] (COPD) and [[asthma]] exacerbation.<ref>{{cite journal | vauthors = Aaron SD | title = The use of ipratropium bromide for the management of acute asthma exacerbation in adults and children: a systematic review | journal = The Journal of Asthma | volume = 38 | issue = 7 | pages = 521–530 | date = October 2001 | pmid = 11714074 | doi = 10.1081/jas-100107116 | s2cid = 7335677 }}</ref> It is supplied in a canister for use in an [[inhaler]] or in single dose vials for use in a [[nebulizer]].<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000965/|title=Ipratropium Oral Inhalation|archive-url=https://web.archive.org/web/20120902155604/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000965/ |archive-date=2 September 2012|work=PubMed Health|access-date= 28 May 2012}}</ref>

It is also used to treat and prevent minor and moderate bronchial asthma, especially asthma that is accompanied by cardiovascular system diseases, as it has been shown to produce fewer cardiovascular side effects.<ref>{{Cite web|date=2004|title=Ipratropium Bromide 0.5 mg/Albuterol Sulfate 3.0 mg|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020950s032lbl.pdf|archive-url=https://web.archive.org/web/20170227231534/http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020950s032lbl.pdf|url-status=dead|archive-date=27 February 2017|access-date=4 January 2021|website=FDA}}</ref>

Combination with [[Beta2-adrenergic agonist|beta-adrenergic agonists]] increases the dilating effect on the bronchi, as when [[Ipratropium/salbutamol|ipratropium is combined with salbutamol]] ([[albuterol]] — [[United States Adopted Name|USAN]]) under the trade names Combivent (a non-aerosol [[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 nasal solution sprayed into the nostrils can reduce [[rhinorrhea]] (runny nose) but will not help [[nasal congestion]].<ref>{{cite web|url=http://www.drugs.com/pro/atrovent-nasal-spray.html|title=Atrovent Nasal Spray|archive-url=https://web.archive.org/web/20120111005137/http://www.drugs.com/pro/atrovent-nasal-spray.html|archive-date=11 January 2012|website=Drugs.com|access-date=28 May 2012|url-status=live}}</ref> It is supplied in a metered-dose manual pump spray.<ref name=rxnasalspray />

== Contraindications ==
The main contraindication for ipratropium in any form is [[hypersensitivity]] to [[atropine]] and related substances.<ref name="AustriaCodex">{{cite book|title=Austria-Codex|editor=Haberfeld, H|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2009|edition=2009/2010|isbn=978-3-85200-196-8|language=de}}</ref><ref name="Arzneistoff-Profile">{{cite book|title=Arzneistoff-Profile|editor=Dinnendahl, V |editor2=Fricke, U|publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|year=2010|edition=23|volume=2|isbn=978-3-7741-9846-3|language=de}}</ref> 

Conditions such as narrow-angle glaucoma, prostatic hyperplasia, or bladder neck obstruction are not necessarily contraindicators, but should be taken into account, particularly if the patient is receiving an anticholinergic by another route.<ref name=rxipra />

=== 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. [[Peanut allergy|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.<ref>{{cite web|url=https://emsmedrx.wordpress.com/2011/03/21/ipratropium-soybean-and-nuts-allergy-myth-dispelled/ |title=Ipratropium Soybean and Nuts Allergy|archive-url=https://web.archive.org/web/20120513115025/http://emsmedrx.wordpress.com/2011/03/21/ipratropium-soybean-and-nuts-allergy-myth-dispelled/ |archive-date=13 May 2012|work=EMSMedRx|access-date= 6 April 2013|date=21 March 2011}}</ref>

== Side effects ==
If ipratropium is inhaled, side effects resembling those of other [[anticholinergic]]s 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]].<ref name="Arzneistoff-Profile" /> The inhalation itself can cause headache and irritation of the throat in a few percent of patients.<ref name="AustriaCodex" />

Urinary retention has been reported in patients receiving doses by nebulizer. As a result, caution may be warranted, especially by men with prostatic hypertrophy.<ref>{{cite journal | vauthors = Afonso AS, Verhamme KM, Stricker BH, Sturkenboom MC, Brusselle GG | title = Inhaled anticholinergic drugs and risk of acute urinary retention | journal = BJU International | volume = 107 | issue = 8 | pages = 1265–1272 | date = April 2011 | pmid = 20880196 | doi = 10.1111/j.1464-410X.2010.09600.x | s2cid = 29516074 | doi-access =  }}</ref>

Common side effects of nasal spray are experienced at a rate of 1-6% (versus the control group of 0-3%), and may include headache, dry nose, dry mouth or throat, nasal or throat irritation, [[Nosebleed|nosebleeds]], bad taste in mouth, nausea, [[dizziness]], or [[constipation]].<ref name=rxnasalspray /><ref>[https://www.drugs.com/mtm/ipratropium-nasal.html Drugs.com: Ipratropium nasal]</ref> Potentially serious side effects from nasal spray are rare, but include severe allergic reaction, eye pain or change in vision, or difficulty urinating.<ref name=cleveland /> 

Accidental contact with the eye should be avoided. 
== Interactions ==
Interactions with other anticholinergics like [[tricyclic antidepressant]]s, [[Management of Parkinson's disease#Medication|anti-Parkinson]] drugs and [[quinidine]], which theoretically increase side effects, are clinically irrelevant when ipratropium is administered as an inhalant.<ref name="AustriaCodex" /><ref name="Arzneistoff-Profile" /> 

Ipratropium nasal spray may interact with certain medications for [[Depression (mood)|depression]], [[anxiety]], or other mental health conditions, certain medications for [[Parkinson's disease]] such as [[Benzatropine|benztropine]] and [[trihexyphenidyl]], [[atropine]], certain [[Antihistamine|antihistamines]] for [[allergy]], [[cough]], and [[Common cold|cold]], certain medications for bladder problems such as [[oxybutynin]] and [[tolterodine]], certain medications for stomach problems such as [[dicyclomine]] and [[hyoscyamine]], and certain medications for motion sickness such as [[scopolamine]].<ref name=cleveland />

== Pharmacology ==
Chemically, ipratropium bromide is a quaternary ammonium compound (which is indicated by the '''-ium''' per the [[British Approved Name|BAN]] and the [[United States Adopted Name|USAN]]) <ref>{{cite web |url=http://apps.who.int/medicinedocs/en/d/Js4895e/6.html |archive-url=https://web.archive.org/web/20120307220148/http://apps.who.int/medicinedocs/en/d/Js4895e/6.html |url-status=dead |archive-date=7 March 2012 |title= The Use of Common Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances|author=<!--Not stated--> |date=2000 |website=who.int |publisher=World Health Organization |access-date=18 July 2018 }}</ref> obtained by treating [[atropine]] with [[2-bromopropane|isopropyl bromide]], thus the name: '''i'''so'''pr'''opyl + '''atrop'''ine.{{citation needed|date=May 2017}} It is chemically related to components of the plant ''[[Datura stramonium]]'', which was used in ancient India for asthma.<ref>{{cite web
 |url=http://www.allergyandasthma.com/home/articles/history-of-asthma
 |title=History of Asthma
 |date=21 December 2017
|website=Allergy And Asthma
 |access-date=2 September 2020
|quote=...&nbsp;India, smoking the herb stramonium (an anticholinergic agent related to ipratropium and tiotropium currently used in inhalers) was used to relax the lungs.
 |archive-date=11 November 2020
|archive-url=https://web.archive.org/web/20201111221428/http://www.allergyandasthma.com/home/articles/history-of-asthma
 |url-status=dead
 }}</ref>

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.<ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/pro/ipratropium.html |title=Ipratropium|archive-url=https://web.archive.org/web/20120519210114/http://www.drugs.com/pro/ipratropium.html |archive-date=19 May 2012|website=Drugs.com}}</ref> 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]] [[Receptor antagonist|antagonist]],<ref name="AustriaCodex" /> and does not diffuse into the blood, which prevents systemic side effects. Ipratropium is a derivative of [[atropine]]<ref name="AHFS2015">{{cite web|title=Ipratropium Bromide|url=https://www.drugs.com/monograph/ipratropium-bromide.html|publisher=The American Society of Health-System Pharmacists|access-date=2 December 2015|url-status=live|archive-url=https://web.archive.org/web/20151208163623/http://www.drugs.com/monograph/ipratropium-bromide.html|archive-date=8 December 2015}}</ref> but is a [[quaternary amine]] and therefore does not cross the [[blood–brain barrier]], which prevents central side effects. Ipratropium should never be used in place of [[salbutamol]] (albuterol) as a rescue medication.

== References ==
{{Reflist}}

{{Nasal preparations}}
{{Asthma and copd rx}}
{{Muscarinic acetylcholine receptor modulators}}
{{Portal bar | Medicine}}
{{Authority control}}

{{DEFAULTSORT:Ipratropium Bromide}}
[[Category:Drugs developed by Boehringer Ingelheim]]
[[Category:Bromides]]
[[Category:Bronchodilators]]
[[Category:Isopropylamino compounds]]
[[Category:M1 receptor antagonists]]
[[Category:M2 receptor antagonists]]
[[Category:M3 receptor antagonists]]
[[Category:M4 receptor antagonists]]
[[Category:M5 receptor antagonists]]
[[Category:Primary alcohols]]
[[Category:Carboxylate esters]]
[[Category:Quaternary ammonium compounds]]
[[Category:Tropanes]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]