Oxymetazoline: A Versatile Treatment for Nasal Congestion, Rosacea, and Droopy Eyelid

I. Introduction

Oxymetazoline is a derivative of imidazole, which is also a building block of purines in DNA and hormones such as histidine and histamine. (Tudek, 2003) (Li, 2023) It is a selective α1-Adrenergic Receptor Agonist in the order α1A > α1D = α1B. (Perez, 2023) This pharmaceutical was developed from xylometazoline at Merck by Wolfgang Fruhstorfer and Helmut Müller-Calgan in 1961. (Fruhstorfer, 1961)

II. The α1-Adrenergic System

The alpha Adrenergic Receptors (ARs) are activated by adrenaline-type catecholamines such as adrenaline and noradrenaline. (Perez, 2021) These hormones are involved in the "fight or flight" response. (Cannon, 1915) ARs are members of the G-protein-coupled receptor (GPCR) superfamily. 

The α1-adrenergic receptors play a critical role in regulating several physiological responses that are integral to the fight or flight response, including vasoconstriction, (Moraga, 2021) pupil dilation, (Kordasz, 2014) and bronchodilation (Deeney, 2022). Activation of α1-ARs regulates the body's response to perceived threats or danger.

III. Nasal Congestion Relief

Oxymetazoline is commonly used as a nasal spray for its vasoconstrictive properties. It works by constricting the blood vessels in the nasal passages, thereby reducing blood flow to the swollen nasal tissues and alleviating nasal congestion for up to 12 hours. (Druce, 2018) This reduction in swelling of the nasal mucosa makes breathing easier for individuals with conditions such as the common cold, allergies, or sinusitis.

When used as a nasal spray, oxymetazoline typically provides rapid relief from nasal congestion, with effects noticeable within minutes of application. (Baroody, 2011) This quick onset of action makes it a popular choice for individuals seeking immediate relief from nasal congestion symptoms.

Unlike some other decongestants, oxymetazoline generally does not cause drowsiness or sedation when used as directed. (Cleveland Clinic) This non-sedating property makes it suitable for use during the day, allowing individuals to carry on with their daily activities without experiencing significant drowsiness.

Many formulations of oxymetazoline nasal sprays are available over the counter without a prescription, making it a convenient option for individuals seeking relief from nasal congestion without needing to visit a healthcare provider.

Oxymetazoline nasal sprays are not effective as part of the management plan for acute sinusitis. In fact, oxymetazoline may interfere with normal immune function during bacterially induced sinusitis, possibly due to a decrease in mucosal blood flow. (Bende, 1996) (Wiklund, 1994)

However, it's essential to use oxymetazoline nasal sprays as directed and for short-term relief only. Prolonged or excessive use can lead to rebound congestion, where the nasal passages become more congested when the medication wears off. Additionally, individuals with certain medical conditions, such as high blood pressure or heart disease, should consult a healthcare professional before using oxymetazoline nasal spray.

IV. Topical treatment for rosacea

Rosacea is a common and chronic inflammatory skin condition that primarily affects the face, causing redness, visible blood vessels, and sometimes small, red bumps or pustules. It typically begins with episodes of flushing or transient redness, which may eventually become persistent and more pronounced over time. (Geng, 2024)

The exact cause of rosacea is not fully understood, but it is believed to involve a combination of genetic, environmental, and vascular factors. Certain triggers, such as sun exposure, hot or cold weather, spicy foods, alcohol, stress, and certain medications, may exacerbate symptoms or cause flare-ups in individuals with rosacea. (Geng, 2024)

The use of oxymetazoline for rosacea is relatively new, and it was initially approved by the U.S. Food and Drug Administration (FDA) for the treatment of persistent facial erythema (redness) associated with rosacea in adults. It provides a rapid reduction in redness, often within 30 minutes of application, and the effects can last for up to 12 hours. (Allergan, 2024)

One of the main advantages of oxymetazoline is its targeted action on blood vessels in the skin, which helps to minimize systemic side effects. However, like any medication, it may cause some side effects, such as skin dryness, itching, or a burning sensation at the application site. These side effects are usually mild and temporary.

V. Treatment for droopy eyelid

The latest use of oxymetazoline to be approved by the FDA is for the cosmetic treatment of drooping eyelid (blepharoptosis). (RVL, 2020) Drooping eyelid can result from factors such as aging, trauma, or muscular dysfunction. In 2020, an oxymetazoline hydrochloride ophthalmic solution at a concentration of 0.1% became the first and only non-surgical treatment available for the condition.  

Oxymetazoline acts selectively on Müller's muscle within the eyelid by stimulating the alpha-adrenergic receptors present in this muscle. (Bacharach, 2021) This stimulation induces the contraction of Müller's muscle, resulting in the elevation of the upper eyelid. This mechanism provides a temporary and reversible alleviation of drooping of the upper eyelid. Typically, the effects of oxymetazoline last for approximately 8 hours following the application of a single drop daily. (Bacharach, 2021) This duration provides a window of relief for individuals experiencing ptosis, enhancing both the aesthetic appearance and functional aspects of the eyelid.

VI. Conclusion

In conclusion, oxymetazoline offers rapid and targeted relief for conditions such as nasal congestion, persistent facial erythema associated with rosacea, and droopy eyelid. While its efficacy and safety profile make it a valuable treatment option, proper adherence to usage guidelines is crucial to avoid potential side effects and complications. Further research and clinical trials may provide additional insights into oxymetazoline's therapeutic potential and expand its applications in medical practice.

VII. Sources

https://www.pharmasources.com/products/searchKey-Oxymetazoline

Tudek, B. (2003). Imidazole ring-opened DNA purines and their biological significance. BMB Reports, 36 (1), 12-19. https://doi.org/10.5483/BMBRep.2003.36.1.012

Li, S.-R., Tan, Y.-M., Zhang, L., & Zhou, C.-H. (2023). Comprehensive insights into medicinal research on imidazole-based supramolecular complexes. Pharmaceutics, 15 (5), 1348. https://doi.org/10.3390/pharmaceutics15051348

Fruhstorfer, W., & Müller-Calgan, H. (n.d.). (1961, November 23). Patent: DE1117588B Verfahren zur Herstellung eines neuen Imidazolinderivates. Retrieved from https://worldwide.espacenet.com/patent/search/family/007305675/publication/DE1117588B

RVL Pharmaceuticals plc. (2020). Osmotica Pharmaceuticals plc receives FDA approval for Upneeq? (oxymetazoline hydrochloride ophthalmic solution), 0.1% for acquired blepharoptosis (droopy eyelid) in adults. GlobeNewswire News Room. https://www.globenewswire.com/news-release/2020/07/09/2059809/0/en/Osmotica-Pharmaceuticals-plc-Receives-FDA-Approval-for-Upneeq-oxymetazoline-hydrochloride-ophthalmic-solution-0-1-for-Acquired-Blepharoptosis-Droopy-Eyelid-in-Adults.html

Bacharach, J., Wirta, D. L., Smyth-Medina, R., Korenfeld, M. S., Kannarr, S. R., Foster, S., Jaros, M. J., & Slonim, C. B. (2021). Rapid and sustained eyelid elevation in acquired blepharoptosis with oxymetazoline 0.1%: Randomized Phase 3 trial results. Clinical Ophthalmology, 15, 2743-2751. https://doi.org/10.2147/OPTH.S306155

Perez, D. M. (2023). α1-Adrenergic receptors: Insights into potential therapeutic opportunities for COVID-19, heart failure, and Alzheimer's disease. International Journal of Molecular Sciences, 24 (4), Article 4188. https://doi.org/10.3390/ijms24044188

Perez, D. M. (2021). Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism. Frontiers in Cell and Developmental Biology, 9. https://doi.org/10.3389/fcell.2021.652152

Cannon, W. B. (1915). Bodily changes in pain, hunger, fear, and rage - an account of recent researches into the function of emotional excitement (p. 211). New York and London: D. Appleton and Company.

Kordasz, M. L., Manicam, C., Steege, A., Goloborodko, E., Amato, C., Laspas, P., Brochhausen, C., Pfeiffer, N., & Gericke, A. (2014). Role of α1-Adrenoceptor Subtypes in Pupil Dilation Studied With Gene-Targeted Mice. Investigative Ophthalmology & Visual Science, 55 (12), 8295-8301. https://doi.org/10.1167/iovs.14-15706

Moraga, F. A., Reyes, R. V., Ebensperger, G., López, V., & Llanos, A. J. (2021). Enhanced Vasoconstriction Mediated by α1-Adrenergic Mechanisms in Small Femoral Arteries in Newborn Llama and Sheep Gestated at Low and High Altitudes. Frontiers in Physiology, 12. https://doi.org/10.3389/fphys.2021.697211

Deeney, B. T., Cao, G., Orfanos, S., Lee, J., Kan, M., Himes, B. E., Parikh, V., Koziol-White, C. J., An, S. S., & Panettieri Jr, R. A. (2022). Epinephrine evokes shortening of human airway smooth muscle cells following β2 adrenergic receptor desensitization. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2, L142-L151. https://doi.org/10.1152/ajplung.00444.2021

Druce, H. M., Ramsey, D. L., Karnati, S., & Carr, A. N. (2018). Topical nasal decongestant oxymetazoline (0.05%) provides relief of nasal symptoms for 12 hours. Rhinology Journal, 56(4), 343-350. https://doi.org/10.4193/Rhin17.150

Baroody, F. M., Brown, D., Gavanescu, L., DeTineo, M., & Naclerio, R. M. (2011). Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. Journal of Allergy and Clinical Immunology, 127(4), 927-934. https://doi.org/10.1016/j.jaci.2011.01.037

Cleveland Clinic. (n.d.). Oxymetazoline nasal spray. Retrieved from https://my.clevelandclinic.org/health/drugs/18562-oxymetazoline-nasal-spray

Bende, M., Fukami, M., Arfors, K. E., Mark, J., Sterna, P., & Intaglietta, M. (1996). Effect of oxymetazoline nose drops on acute sinusitis in the rabbit. Annals of Otology, Rhinology & Laryngology, 105(3), 222-225. https://doi.org/10.1177/000348949610500309

Wiklund, L., Stierna, P., Berglund, R., Westrin, K.-M., & T?nnesson, M. (1994). The efficacy of oxymetazoline administered with a nasal bellows container and combined with oral phenoxymethyl-penicillin in the treatment of acute maxillary sinusitis. Acta Oto-Laryngologica, 114(sup515), 57-64. https://doi.org/10.3109/00016489409124326

Geng, R. S. Q., Bourkas, A. N., Mufti, A., & Sibbald, R. G. (2024). Rosacea: Pathogenesis and Therapeutic Correlates. Journal of Cutaneous Medicine and Surgery, 28 (2), 178-189. https://doi.org/10.1177/12034754241229365

Allergan. (2024). Allergan Announces FDA Approval Of RHOFADE? (Oxymetazoline Hydrochloride) Cream, 1% For The Topical Treatment Of Persistent Facial Erythema Associated With Rosacea In Adults. PR Newswire. https://www.prnewswire.com/news-releases/allergan-announces-fda-approval-of-rhofade-oxymetazoline-hydrochloride-cream-1-for-the-topical-treatment-of-persistent-facial-erythema-associated-with-rosacea-in-adults-300393385.html

About the Author:

David Orchard-Webb

David  Orchard-Webb, Ph.D., is a technical writer with broad interests including  health & technology writing, plus extensive training and knowledge of  biomedicine and microbiology. My Ph.D. and postdoc were in oncology and  developing cancer medicines. I provide technical medical and other writing  services for projects ranging from “knowledge automation” to pure pharma, to  food safety, to the history of science, and everything in between. I also  provide white papers, ebooks, meta-analysis reviews, editing, consulting,  business, and market research-related activities in biomedicine, technology,  and health. In addition to its well-known role in the development of  medicines, I am a big believer in biotechnology’s ability to revolutionize  industries such as food-tech, agtech, textiles & fashion.