Ipratropium bromide

Ipratropium bromide
Names
Trade namesAtrovent, Apovent, Ipraxa, others
IUPAC name
  • [8-methyl-8-(1-methylethyl)- 8-azoniabicyclo[3.2.1] oct-3-yl] 3-hydroxy-2-phenyl-propanoate
Clinical data
Main usesCOPD, asthma[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
    Routes of
    use    		Inhalation, nasal
    Onset of action15 to 30 min[1]
    Duration of action3 to 5 hours[1]
    Defined daily dose0.12 to 0.3 mg[2]
    External links
    AHFS/Drugs.comInhaled: Monograph
    Nose: Monograph
    MedlinePlusa618013
    Legal
    License data
    Legal status
    Pharmacokinetics
    Protein binding0 to 9% in vitro
    MetabolismLiver
    Elimination half-life2 hours
    Chemical and physical data
    FormulaC20H30BrNO3
    Molar mass412.368 g·mol−1
    3D model (JSmol)
    SMILES
    • CC(C)[N+]1(C2CCC1CC(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

    Ipratropium bromide, sold under the trade name Atrovent among others, is a medication which opens up the medium and large airways in the lungs.[1] It is used to treat the symptoms of chronic obstructive pulmonary disease and asthma.[1] It is used by inhaler or nebulizer.[1] Onset of action is typically within 15 to 30 minutes and lasts for three to five hours.[1]

    Common side effects include dry mouth, cough, and inflammation of the airways.[1] Potentially serious side effects include urinary retention, worsening spasms of the airways, and a severe allergic reaction.[1] It appears to be safe in pregnancy and breastfeeding.[1][3] Ipratropium is a muscarinic antagonist, a type of anticholinergic, which works by causing smooth muscles to relax.[1]

    Ipratropium bromide was patented in 1966, and approved for medical use in 1974.[4] It is on the World Health Organization's List of Essential Medicines.[5] Ipratropium is available as a generic medication and is not expensive.[6] The wholesale price in the developing world is about 6.60 USD for a 200 dose inhaler.[7] In the United States, a month worth of medication costs 100 to 200 USD.[8] In 2017, it was the 216th most commonly prescribed medication in the United States, with more than two million prescriptions.[9][10]

    Medical uses

    Ipratropium is administered by inhalation for the treatment of chronic obstructive pulmonary disease (COPD) and asthma exacerbation. For that purpose, it is supplied in a canister for use in an inhaler or in single dose vials for use in a nebulizer.[11]

    It is also used to treat and prevent minor and moderate bronchial asthma, especially asthma that is accompanied by cardiovascular system diseases.

    It is also combined with salbutamol (albuterol — 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 but will not help nasal congestion.[12]

    Combination with beta-adrenergic agonists increases the dilating effect on the bronchi.

    Dosage

    The defined daily dose is 0.12 to 0.3 mg.[2] For those over the age of twelve 0.5 mg may be nubulized every 20 to 30 minutes.[13] In those 1 month to 12 years old the dose is 0.25 mg by nebulisation.[13]

    Contraindications

    The main contraindication for inhaled ipratropium is 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.[14][15]

    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.[16]

    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.[15] The inhalation itself can cause headache and irritation of the throat in a few percent of patients.[14]

    Urinary retention has been reported in patients receiving doses by nebulizer. As a result, caution may be warranted, especially by men with prostatic hypertrophy.[17]

    Interactions

    Interactions with other anticholinergics like tricyclic antidepressants, anti-Parkinson drugs and quinidine, which theoretically increase side effects, are clinically irrelevant when ipratropium is administered as an inhalant.[14][15]

    Pharmacology

    Chemically, ipratropium bromide is a quaternary ammonium compound (which is indicated by the -ium per the BAN and the USAN) [18] obtained by treating atropine with isopropyl bromide, thus the name: isopropyl + atropine.

    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.[19] 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,[14] and does not diffuse into the blood, which prevents systemic side effects. Ipratropium is a derivative of atropine[20] but is a quaternary amine and therefore does not cross the blood–brain barrier, which prevents central side effects (anticholinergic syndrome). Ipratropium should never be used in place of salbutamol (albuterol) as a rescue medication.

    SSociety and culture

    Cost

    The wholesale price in the developing world is about 6.60 USD for a 200 dose inhaler.[7] In the United States, a month worth of medication costs 100 to 200 USD.[8] In 2017, it was the 216th most commonly prescribed medication in the United States, with more than two million prescriptions.[9][10]

    • Ipratropium costs (US)
      Ipratropium costs (US)
    • Ipratropium prescriptions (US)
      Ipratropium prescriptions (US)

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 "Ipratropium Bromide". The American Society of Health-System Pharmacists. Archived from the original on 8 December 2015. Retrieved 2 December 2015.
    2. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 21 January 2021. Retrieved 30 August 2020.
    3. ↑ Yaffe, Gerald G. Briggs, Roger K. Freeman, Sumner J. (2011). Drugs in pregnancy and lactation : a reference guide to fetal and neonatal risk (9th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 763. ISBN 978-1-60831-708-0. Archived from the original on 5 March 2016. Retrieved 5 December 2015.
    4. ↑ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 446. ISBN 978-3-527-60749-5. Archived from the original on 1 March 2019. Retrieved 28 February 2019.
    5. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    6. ↑ Hitchings, Andrew; Lonsdale, Dagan; Burrage, Daniel; Baker, Emma (2019). The Top 100 Drugs: Clinical Pharmacology and Practical Prescribing (2nd ed.). Elsevier. pp. 72–73. ISBN 978-0-7020-7442-4. Archived from the original on 22 May 2021. Retrieved 9 November 2021.
    7. 1 2 "Ipratropium Bromide". International Drug Price Indicator Guide. Retrieved 5 December 2015.
    8. 1 2 Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 455. ISBN 978-1-284-05756-0.
    9. 1 2 "The Top 300 of 2020". ClinCalc. Archived from the original on 12 February 2021. Retrieved 11 April 2020.
    10. 1 2 "Ipratropium - Drug Usage Statistics". ClinCalc. Archived from the original on 2 July 2020. Retrieved 11 April 2020.
    11. ↑ "Ipratropium Oral Inhalation". PubMed Health. Archived from the original on 2 September 2012. Retrieved 28 May 2012.
    12. ↑ "Atrovent Nasal Spray". Drugs.com. Archived from the original on 11 January 2012. Retrieved 28 May 2012.
    13. 1 2 "IPRATROPIUM bromide nebuliser solution - Essential drugs". medicalguidelines.msf.org. Archived from the original on 26 November 2020. Retrieved 30 August 2020.
    14. 1 2 3 4 Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 978-3-85200-196-8.{{cite book}}: CS1 maint: unrecognized language (link)
    15. 1 2 3 Dinnendahl, V; Fricke, U, eds. (2010). Arzneistoff-Profile (in German). Vol. 2 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.{{cite book}}: CS1 maint: unrecognized language (link)
    16. ↑ "Ipratropium Soybean and Nuts Allergy". EMSMedRx. 21 March 2011. Archived from the original on 13 May 2012. Retrieved 6 April 2013.
    17. ↑ 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.
    18. ↑ "The Use of Common Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances". who.int. World Health Organization. 2000. Archived from the original on 10 March 2018. Retrieved 18 July 2018.
    19. ↑ "Ipratropium". Drugs.com. Archived from the original on 19 May 2012.
    20. ↑ Yamatake Y, Sasagawa S, Yanaura S, Okamiya Y (1977). "Ipratropium Bromide (Sch1000) の抗アレルギー性喘息効果" [Antiallergic asthma effect of ipratropium bromide (Sch 1000) in dogs]. Nippon Yakurigaku Zasshi (in Japanese). 73 (7): 785–91. doi:10.1254/fpj.73.785. PMID 145994.{{cite journal}}: CS1 maint: unrecognized language (link)
    Identifiers:
    • "Ipratropium bromide". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 21 December 2019. Retrieved 21 December 2019.
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