Chemistry:Oxymetazoline

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Short description: Topical decongestant
Oxymetazoline
Oxymetazoline.svg
Clinical data
Trade namesAfrin, Ocuclear, Rhofade, others
AHFS/Drugs.comMonograph
Dependence
liability		Moderate
Routes of
administration		Intranasal, eye drop, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
MetabolismKidney (30%), fecal (10%)
Elimination half-life5–6 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC16H24N2O
Molar mass260.381 g·mol−1
3D model (JSmol)
Melting point301.5 °C (574.7 °F)
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Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eyedrops to treat eye redness due to minor irritation, and (in the United States) as a prescription topical cream to treat persistent facial redness due to rosacea in adults. Its effects begin within minutes and last for up to six hours. Intranasal use for longer than three days may cause congestion to recur or worsen, resulting in physical dependence.

Oxymetazoline is a derivative of imidazole.[1] It was developed from xylometazoline at Merck by Wolfgang Fruhstorfer and Helmut Müller-Calgan in 1961.[2] A direct sympathomimetic, oxymetazoline binds to and activates α1 adrenergic receptors and α2 adrenergic receptors, most notably.[1] One study classified it in the following order: α(2A) > α(1A) ≥ α(2B) > α(1D) ≥ α(2C) >> α(1B), but this is not universally agreed upon.[3] There is little consistency across the (relatively large) number of in-vitro studies with respect to binding affinity/selectivity.

Another study classified it with selectivity ratios in alpha 2 adrenergic receptors of 200 for a2A vs a2B, 7.1 a2A vs a2C, and 28.2 a2B vs a2C.[4] Making it a highly selective a2A agonist.

In 2021, it was the 292nd most commonly prescribed medication in the United States, with more than 600,000 prescriptions.[5][6]

Medical uses

Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays.[7]

In the United States, oxymetazoline 1% cream is approved by the Food and Drug Administration for topical treatment of persistent facial erythema (redness) associated with rosacea in adults.[8]

Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleeds[9][10] and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops). [citation needed] [11]

In July 2020, oxymetazoline received approval by the FDA for the treatment of acquired drooping eyelid.[12]

Side effects

Rebound congestion

Rebound congestion, or rhinitis medicamentosa, may occur. A 2006 review of the pathology of rhinitis medicamentosa concluded that use of oxymetazoline for more than three days may result in rhinitis medicamentosa and recommended limiting use to three days.[13]

Australian regulatory submission

In a submission to the Therapeutic Goods Administration, a Novartis representative concluded, "The justification was not based on evidence." Citing an existing extensive body of evidence and noting a range of recommended periods from five to ten days, Novartis recommended the established five day period for its use for self-medication without medical consultation as it coincides with the typical duration of the common cold.[14]

Use in pregnancy

The Food and Drug Administration places oxymetazoline in category C, indicating risk to the fetus cannot be ruled out. While it has been shown that a single dose does not significantly alter either maternal or fetal circulation,[15] this subject has not been studied extensively enough to draw reliable conclusions.[original research?]

Overdose

If accidentally ingested, standard methods to remove unabsorbed drugs should be considered.[clarification needed] There is no specific antidote for oxymetazoline, although its pharmacological effects may be reversed by an adrenergic antagonists such as phentolamine. In the event of a possibly life-threatening overdose (such as a hypertensive crisis), benzodiazepines should be considered to decrease the likelihood of seizures and convulsions, as well as reduce anxiety and to lower blood pressure. In children, oxymetazoline may produce profound central nervous system depression due to stimulation of central α2 receptors and imidazoline receptors, much like clonidine.[citation needed]

Pharmacology

Pharmacodynamics

Oxymetazoline is a sympathomimetic that selectively agonizes α1 and, partially, α2 adrenergic receptors.[16] Since vascular beds widely express α1 receptors, the action of oxymetazoline results in vasoconstriction. In addition, the local application of the drug also results in vasoconstriction due to its action on endothelial postsynaptic α2 receptors; systemic application of α2 agonists, in contrast, causes vasodilation because of centrally-mediated inhibition of sympathetic tone via presynaptic α2 receptors.[17] Vasoconstriction of vessels results in relief of nasal congestion in two ways: first, it increases the diameter of the airway lumen; second, it reduces fluid exudation from postcapillary venules.[18] It can reduce nasal airway resistance (NAR) up to 35.7% and reduce nasal mucosal blood flow up to 50%.[19] Also, Oxymetzoline and Xylometazoline are strong HT1a, HT1b, HT1c and HT2b agonists.

Pharmacokinetics

Since imidazolines are sympathomimetic agents, their primary effects appear on α adrenergic receptors, with little if any effect on β adrenergic receptors.[20] Like other imidazolines, Oxymetazoline is readily absorbed orally.[20] Effects on α receptors from systemically absorbed oxymetazoline hydrochloride may persist for up to 7 hours after a single dose.[21] The elimination half-life in humans is 5–8 hours.[22] It is excreted unchanged both by the kidneys (30%) and in feces (10%).[21]

History

The oxymetazoline brand Afrin was first sold as a prescription medication in 1966. After finding substantial early success as a prescription medication, it became available as an over-the-counter drug in 1975. Schering-Plough did not engage in heavy advertising until 1986.[23]

Society and culture

Brand names

Brand names include Afrin,[24] ClariClear, Dristan, Drixine, Drixoral, Nasivin, Nasivion, Nezeril, Nostrilla, Logicin, Vicks Sinex, Visine L.R., Sudafed OM, Otrivin[25] Oxy, SinuFrin, Upneeq, and Mucinex Sinus-Max.[26]

References

  1. ↑ 1.0 1.1 "Oxymetazoline". PubChem. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/Oxymetazoline. 
  2. ↑ Fruhstorfer W, Müller-Calgan H, "2-(2,6-dimethyl-3-hydroxy-4-tert-butyl-benzyl)-2-imidazoline,and acid addition salts thereof,and process for their manufacture", DE patent 1117588, issued 23 November 1961, assigned to E Merck AG.
  3. ↑ "Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline". Fundamental & Clinical Pharmacology 24 (6): 729–739. December 2010. doi:10.1111/j.1472-8206.2009.00805.x. PMID 20030735. 
  4. ↑ Proudman, Richard G. W.; Akinaga, Juliana; Baker, Jillian G. (October 2022). "The signaling and selectivity of α‐adrenoceptor agonists for the human α2A , α2B and α2C ‐adrenoceptors and comparison with human α1 and β‐adrenoceptors" (in en). Pharmacology Research & Perspectives 10 (5). doi:10.1002/prp2.1003. ISSN 2052-1707. PMID 36101495. PMC 9471048. https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.1003. 
  5. ↑ "The Top 300 of 2021". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  6. ↑ "Oxymetazoline - Drug Usage Statistics". https://clincalc.com/DrugStats/Drugs/Oxymetazoline. 
  7. ↑ "Oxymetazoline". Lexi-Comp: Merck Manual Professional. Merck.com. http://www.merck.com/mmpe/lexicomp/oxymetazoline.html. 
  8. ↑ "Oxymetazoline hydrochloride cream for facial erythema associated with rosacea". Expert Review of Clinical Pharmacology 10 (10): 1049–1054. October 2017. doi:10.1080/17512433.2017.1370370. PMID 28837365. 
  9. ↑ "A comparison of cocaine, lidocaine with epinephrine, and oxymetazoline for prevention of epistaxis on nasotracheal intubation". Journal of Clinical Anesthesia 2 (1): 16–20. 1990. doi:10.1016/0952-8180(90)90043-3. PMID 2310576. 
  10. ↑ "Use of oxymetazoline in the management of epistaxis". The Annals of Otology, Rhinology, and Laryngology 104 (9 Pt 1): 704–706. September 1995. doi:10.1177/000348949510400906. PMID 7661519. 
  11. ↑ "VISINE Original Red Eye Drops | VISINE products". Visine.com. http://www.visine.com/product-visine-original.jsp. 
  12. ↑ "UPNEEQ Label". accessdata.fda.gov. 8 July 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/0212520s000lbl.pdf. 
  13. ↑ "Rhinitis medicamentosa". Journal of Investigational Allergology & Clinical Immunology 16 (3): 148–155. 2006. PMID 16784007. http://www.jiaci.org/summary/vol16-issue3-num52. 
  14. ↑ "Consultation submission: OTC nasal decongestant preparations for topical use: proposed advisory statements for medicines". Novartis Consumer Health Australasia. 2014. https://www.tga.gov.au/sites/default/files/consult-otc-nasal-decongestant-140328-submission-novartis.pdf. 
  15. ↑ "Uterine and fetal Doppler flow changes from a single dose of a long-acting intranasal decongestant". Obstetrics and Gynecology 76 (2): 180–182. August 1990. PMID 2196495. http://journals.lww.com/greenjournal/Abstract/1990/08000/Uterine_and_Fetal_Doppler_Flow_Changes_From_a.6.aspx. 
  16. ↑ "Chapter 6. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems". Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). http://www.accessmedicine.com/content.aspx?aID=954433. Retrieved 24 January 2015. "Anatomy and General Functions of the Autonomic and Somatic Motor Nervous Systems" .
  17. ↑ "Chapter 9. Adrenoceptor Agonists & Sympathomimetic Drugs". Basic & Clinical Pharmacology (11th ed.). http://www.accessmedicine.com/content.aspx?aID=4520412. Retrieved 30 November 2011. 
  18. ↑ "Microvascular anatomy of the nose". Allergy 52 (40 Suppl): 7–11. 1997. doi:10.1111/j.1398-9995.1997.tb04877.x. PMID 9353554. 
  19. ↑ "Vascular effects of topical oxymetazoline on human nasal mucosa". The Journal of Laryngology and Otology 100 (3): 285–288. March 1986. doi:10.1017/S0022215100099151. PMID 3950497. 
  20. ↑ 20.0 20.1 Clinical veterinary toxicology. St. Louis, Mo.: Mosby. 2004. ISBN 978-0-323-01125-9. OCLC 460904351. https://www.worldcat.org/oclc/460904351. 
  21. ↑ 21.0 21.1 "Decongestants (Toxicity) - Toxicology" (in en-US). https://www.merckvetmanual.com/toxicology/toxicities-from-human-drugs/decongestants-toxicity. 
  22. ↑ Veterinary toxicology for Australia and New Zealand. Amsterdam, Netherlands. 2017. ISBN 978-0-12-799912-8. OCLC 992119220. https://www.worldcat.org/oclc/992119220. 
  23. ↑ "Advertising; Afrin Goes After Users Of Nasal Decongestants". The New York Times. 20 October 1986. https://www.nytimes.com/1986/10/20/business/advertising-afrin-goes-after-users-of-nasal-decongestants.html. 
  24. ↑ "Afrin". https://www.afrin.com. 
  25. ↑ "Otrivin" (in en-CA). https://www.otrivin.ca/en-ca/. 
  26. ↑ "Mucinex Cold and Flu Relief in Canada | Mucinex Canada" (in en). http://www.mucinex.ca/en/. 



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