Oxymetazoline

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Oxymetazoline
Oxymetazoline.svg
Clinical data
Trade names Afrin, others
AHFS/Drugs.com Monograph
Dependence
liability 		Moderate
Routes of
administration 		Intranasal, eye drop, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 5–6 hours
Excretion Kidney: 30% Feces: 10%
Identifiers
  • 3-(4,5-Dihydro-1H-imidazol-2-ylmethyl)-2,4-dimethyl-6-tert-butyl-phenol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.014.618 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C16H24N2O
Molar mass 260.381 g·mol−1
3D model (JSmol)
Melting point 182 °C (360 °F)
  • Oc1c(c(c(cc1C(C)(C)C)C)CC/2=N/CCN\2)C
  • InChI=1S/C16H24N2O/c1-10-8-13(16(3,4)5)15(19)11(2)12(10)9-14-17-6-7-18-14/h8,19H,6-7,9H2,1-5H3,(H,17,18) Yes check.svgY
  • Key:WYWIFABBXFUGLM-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 eye drops 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 to five days may cause congestion to recur or worsen, resulting in physical dependence.

Contents

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]

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]

In 2022, it was the 305th most commonly prescribed medication in the United States, with more than 300,000 prescriptions. [5]

Medical uses

Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays. [6]

Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleeds [7] [8] and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops).[ citation needed ]

In the United States, oxymetazoline 1% cream was approved by the Food and Drug Administration (FDA) in January 2017 for topical treatment of persistent facial erythema (redness) associated with rosacea in adults. [9] [10]

In July 2020, oxymetazoline received approval by the FDA for the treatment of acquired blepharoptosis (drooping eyelid). [11] [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]

Nosebleeds

Although Oxymetazoline can be used for treatment of nosebleeds, it can also cause them under certain conditions, especially when nasal passages are dry. Oxymetazoline is a nasal decongestant that constricts blood vessels in the nasal mucosa, thereby reducing swelling and improving airflow. However, its use can lead to dryness and irritation of the nasal lining, which can increase the likelihood of nosebleeds.[ citation needed ]

Australian regulatory submission

Novartis recommended a five day maximum usage period, rather than three days, in a submission to the Therapeutic Goods Administration. Novartis suggested that "The justification [for 3 days] was not based on evidence" and cited an extensive body of evidence, and noting a range of recommended periods from five to ten days, which coincides with the typical duration of the common cold. [14]

Overdose

There is no specific antidote for oxymetazoline, although its pharmacological effects may be reversed by an adrenergic antagonists such as phentolamine.[ medical citation needed ]

Pharmacology

Pharmacodynamics

Oxymetazoline is a sympathomimetic that selectively agonizes α1 and, partially, α2 adrenergic receptors. [15] 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. [16] 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. [17] It can reduce nasal airway resistance (NAR) up to 35.7% and reduce nasal mucosal blood flow up to 50%. [18]

When used for treating acquired blepharoptosis, oxymetazoline is believed to work by stimulating the α1 and α2 adrenergic receptors of Müller's muscle, which helps to lift the eyelid and improve vision. [12]

Pharmacokinetics

Since imidazolines are sympathomimetic agents, their primary effects appear on α adrenergic receptors, with little if any effect on β adrenergic receptors. [19] Like other imidazolines, Oxymetazoline is readily absorbed orally. [19] Effects on α receptors from systemically absorbed oxymetazoline hydrochloride may persist for up to 7 hours after a single dose. [20] The elimination half-life in humans is 5–8 hours. [21] It is excreted unchanged both by the kidneys (30%) and in feces (10%). [20]

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. [22]

Society and culture

Brand names

Brand names for Oxymetazoline include Afrin, ClariClear, Dristan, Drixine, Drixoral, Nasivin, Nasivion, Nezeril, Nostrilla, Logicin, Vicks Sinex, Visine L.R., Sudafed OM, Otrivin, Oxy, SinuFrin, Vicks Sinex Severe (Spray), and Mucinex Sinus-Max.[ citation needed ] A topical cream formulation is sold under the brand name Rhofade. [23] Oxymetazoline ophthalmic solution for the treatment of acquired blepharoptosis is marketed as Upneeq. [11] [12]

References

  1. 1 2 "Oxymetazoline". PubChem. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information. CID 4636.
  2. ↑ DE 1117588,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",issued 23 November 1961, assigned to E Merck AG.
  3. ↑ Haenisch B, Walstab J, Herberhold S, Bootz F, Tschaikin M, Ramseger R, et al. (December 2010). "Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline". Fundamental & Clinical Pharmacology. 24 (6): 729–739. doi:10.1111/j.1472-8206.2009.00805.x. PMID   20030735. S2CID   25064699.
  4. ↑ Proudman RG, Akinaga J, Baker JG (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". Pharmacology Research & Perspectives. 10 (5): e01003. doi:10.1002/prp2.1003. PMC   9471048 . PMID   36101495.
  5. ↑ "Oxymetazoline Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  6. ↑ "Oxymetazoline". Lexi-Comp: Merck Manual Professional. Merck.com. Retrieved 15 April 2013.
  7. ↑ Katz RI, Hovagim AR, Finkelstein HS, Grinberg Y, Boccio RV, Poppers PJ (1990). "A comparison of cocaine, lidocaine with epinephrine, and oxymetazoline for prevention of epistaxis on nasotracheal intubation". Journal of Clinical Anesthesia. 2 (1): 16–20. doi:10.1016/0952-8180(90)90043-3. PMID   2310576.
  8. ↑ Krempl GA, Noorily AD (September 1995). "Use of oxymetazoline in the management of epistaxis". The Annals of Otology, Rhinology, and Laryngology. 104 (9 Pt 1): 704–706. doi:10.1177/000348949510400906. PMID   7661519. S2CID   37579139.
  9. ↑ Han DH (19 January 2017). "New Topical Cream Approved for Persistent Redness with Rosacea". MPR. Retrieved 21 February 2025.
  10. ↑ Patel NU, Shukla S, Zaki J, Feldman SR (October 2017). "Oxymetazoline hydrochloride cream for facial erythema associated with rosacea". Expert Review of Clinical Pharmacology. 10 (10): 1049–1054. doi:10.1080/17512433.2017.1370370. PMID   28837365. S2CID   19930755.
  11. 1 2 "UPNEEQ Label" (PDF). accessdata.fda.gov. 8 July 2020.
  12. 1 2 3 Newland M, Eberly H, Ma C, Lighthall JG (January 2025). "The Use of Oxymetazoline 0.1% Ophthalmic Solution for Acquired Blepharoptosis: A Systematic Review". The Laryngoscope. 135 (1): 8–14. doi: 10.1002/lary.31723 . ISSN   1531-4995. PMC   11635132 . PMID   39172003.
  13. ↑ Ramey JT, Bailen E, Lockey RF (2006). "Rhinitis medicamentosa". Journal of Investigational Allergology & Clinical Immunology. 16 (3): 148–155. PMID   16784007.
  14. ↑ Nguyen TM (2014). "Consultation submission: OTC nasal decongestant preparations for topical use: proposed advisory statements for medicines" (PDF). Novartis Consumer Health Australasia.
  15. ↑ Westfall TC, Westfall DP. "Chapter 6. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems". In Brunton LL, Lazo JS, Parker KL (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). Archived from the original on 30 September 2011. Retrieved 24 January 2015– via AccessMedicine. Anatomy and General Functions of the Autonomic and Somatic Motor Nervous Systems.
  16. ↑ Biaggioni I, Robertson D. "Chapter 9. Adrenoceptor Agonists & Sympathomimetic Drugs". In Katzung BG (ed.). Basic & Clinical Pharmacology (11th ed.). Archived from the original on 30 September 2011. Retrieved 30 November 2011.
  17. ↑ Widdicombe J (1997). "Microvascular anatomy of the nose". Allergy. 52 (40 Suppl): 7–11. doi:10.1111/j.1398-9995.1997.tb04877.x. PMID   9353554. S2CID   46018611.
  18. ↑ Bende M, Löth S (March 1986). "Vascular effects of topical oxymetazoline on human nasal mucosa". The Journal of Laryngology and Otology. 100 (3): 285–288. doi:10.1017/S0022215100099151. PMID   3950497. S2CID   37998936.
  19. 1 2 Plumlee KH (2004). Clinical veterinary toxicology. St. Louis, Mo.: Mosby. ISBN   978-0-323-01125-9. OCLC   460904351.
  20. 1 2 "Decongestants (Toxicity) - Toxicology". Merck Veterinary Manual. Retrieved 3 April 2023.
  21. ↑ Dalefield R (2017). Veterinary toxicology for Australia and New Zealand. Amsterdam, Netherlands: McGraw Hill LLC. ISBN   978-0-12-799912-8. OCLC   992119220.
  22. ↑ Dougherty PH (20 October 1986). "Advertising; Afrin Goes After Users Of Nasal Decongestants". The New York Times . Retrieved 30 March 2015.
  23. ↑ "Oxymetazoline cream (Rhofade) for rosacea". The Medical Letter on Drugs and Therapeutics. 59 (1521): 84–86. May 2017. PMID   28520699.
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