Oxymetazoline

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Oxymetazoline
Oxymetazoline.svg
Clinical data
Trade names Afrin, Ocuclear, Rhofade, others
AHFS/Drugs.com Monograph
Dependence
liability 		Moderate
Routes of
administration 		Intranasal, eye drop, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Kidney (30%), fecal (10%)
Elimination half-life 5–6 hours
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 301.5 °C (574.7 °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 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. It is esimated that 700,000 people in Norway could be dependent on nasal sprays. [1]

Contents

Oxymetazoline is a derivative of imidazole. [2] It was developed from xylometazoline at Merck by Wolfgang Fruhstorfer and Helmut Müller-Calgan in 1961. [3] A direct sympathomimetic, oxymetazoline binds to and activates α1 adrenergic receptors and α2 adrenergic receptors, most notably. [2] 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. [4] 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. [5] 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. [6] [7]

Medical uses

Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays. [8]

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. [9]

Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleeds [10] [11] and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops). [ citation needed ] [12]

In July 2020, oxymetazoline received approval by the FDA for the treatment of acquired drooping eyelid. [13]

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. [14]

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. [15]

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, [16] 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. [17] 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. [18] 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. [19] It can reduce nasal airway resistance (NAR) up to 35.7% and reduce nasal mucosal blood flow up to 50%. [20] 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. [21] Like other imidazolines, Oxymetazoline is readily absorbed orally. [21] Effects on α receptors from systemically absorbed oxymetazoline hydrochloride may persist for up to 7 hours after a single dose. [22] The elimination half-life in humans is 5–8 hours. [23] It is excreted unchanged both by the kidneys (30%) and in feces (10%). [22]

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. [24]

Society and culture

Brand names

Brand names include Afrin, [25] ClariClear, Dristan, Drixine, Drixoral, Nasivin, Nasivion, Nezeril, Nostrilla, Logicin, Vicks Sinex, Visine L.R., Sudafed OM, Otrivin [26] Oxy, SinuFrin, Upneeq, and Mucinex Sinus-Max. [27]

Related Research Articles

<span class="mw-page-title-main">Adrenergic receptor</span> Class of G protein-coupled receptors

The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example.

<span class="mw-page-title-main">Xylometazoline</span> Nasal decongestant

Xylometazoline, also spelled xylomethazoline, is a medication used to reduce symptoms of nasal congestion, allergic rhinitis, and sinusitis. Use is not recommended for more than seven days. Use is also not recommended in those less than three months of age and some say not less than 6 years of age. It is used directly in the nose as a spray or drops.

Definition A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine. Intranasal corticosteroids can also be used as decongestants and antihistamines can be used to alleviate runny nose, nasal itch, and sneezing.

A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors, or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms. Common uses of parasympathomimetics include glaucoma, Sjögren syndrome and underactive bladder.

<span class="mw-page-title-main">Nasal spray</span> Spray that delivers medications locally in the nasal cavities or systemically

Nasal sprays are used to deliver medications locally in the nasal cavities or systemically. They are used locally for conditions such as nasal congestion and allergic rhinitis. In some situations, the nasal delivery route is preferred for systemic therapy because it provides an agreeable alternative to injection or pills. Substances can be assimilated extremely quickly and directly through the nose. Many pharmaceutical drugs exist as nasal sprays for systemic administration. Other applications include hormone replacement therapy, treatment of Alzheimer's disease and Parkinson's disease. Nasal sprays are seen as a more efficient way of transporting drugs with potential use in crossing the blood–brain barrier.

<span class="mw-page-title-main">Phenylephrine</span> Decongestant medication

Phenylephrine is a medication used as a decongestant for uncomplicated nasal congestion, used to dilate the pupil, used to increase blood pressure, and used to relieve hemorrhoids. It can be taken by mouth, as a nasal spray, given by injection into a vein or muscle, or applied to the skin.

An adrenergic agonist is a drug that stimulates a response from the adrenergic receptors. The five main categories of adrenergic receptors are: α1, α2, β1, β2, and β3, although there are more subtypes, and agonists vary in specificity between these receptors, and may be classified respectively. However, there are also other mechanisms of adrenergic agonism. Epinephrine and norepinephrine are endogenous and broad-spectrum. More selective agonists are more useful in pharmacology.

<span class="mw-page-title-main">Naphazoline</span> Chemical compound

Naphazoline is a medicine used as a decongestant, and a vasoconstrictor added to eye drops to relieve red eye. It has a rapid action in reducing swelling when applied to mucous membranes. It is a sympathomimetic agent with marked alpha adrenergic activity that acts on alpha-receptors in the arterioles of the conjunctiva to produce constriction, resulting in decreased congestion.

<span class="mw-page-title-main">Prazosin</span> Antihypertensive drug

Prazosin, sold under the brand name Minipress among others, is a medication used to treat high blood pressure, symptoms of an enlarged prostate, and nightmares related to post-traumatic stress disorder (PTSD). It is an α1 blocker. It is a less preferred treatment of high blood pressure. Other uses may include heart failure and Raynaud syndrome. It is taken by mouth.

<span class="mw-page-title-main">Rhinitis medicamentosa</span> Medical condition

Rhinitis medicamentosa is a condition of rebound nasal congestion suspected to be brought on by extended use of topical decongestants and certain oral medications that constrict blood vessels in the lining of the nose, although evidence has been contradictory.

<span class="mw-page-title-main">Labetalol</span> Medication used to treat high blood pressure

Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.

<span class="mw-page-title-main">Brimonidine</span> Chemical compound

Brimonidine is an α2 agonist medication used to treat open-angle glaucoma, ocular hypertension, and rosacea. In rosacea it improves the redness. It is used as eye drops or applied to the skin.

The alpha-2 (α2) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α2-adrenergic receptor in the central and peripheral nervous systems.

<span class="mw-page-title-main">Alpha-adrenergic agonist</span> Class of drugs

Alpha-adrenergic agonists are a class of sympathomimetic agents that selectively stimulates alpha adrenergic receptors. The alpha-adrenergic receptor has two subclasses α1 and α2. Alpha 2 receptors are associated with sympatholytic properties. Alpha-adrenergic agonists have the opposite function of alpha blockers. Alpha adrenoreceptor ligands mimic the action of epinephrine and norepinephrine signaling in the heart, smooth muscle and central nervous system, with norepinephrine being the highest affinity. The activation of α1 stimulates the membrane bound enzyme phospholipase C, and activation of α2 inhibits the enzyme adenylate cyclase. Inactivation of adenylate cyclase in turn leads to the inactivation of the secondary messenger cyclic adenosine monophosphate and induces smooth muscle and blood vessel constriction.

<span class="mw-page-title-main">Cirazoline</span> Chemical compound

Cirazoline is a full agonist at the α1A adrenergic receptor, a partial agonist at both the α1B and α1D adrenergic receptors, and a nonselective antagonist to the α2 adrenergic receptor. It is believed that this combination of properties could make cirazoline an effective vasoconstricting agent.

<span class="mw-page-title-main">Adrenergic antagonist</span>

An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β1, β2, and β3 receptors. The second group contains the alpha (α) adrenoreceptors. There are only α1 and α2 receptors. Adrenergic receptors are located near the heart, kidneys, lungs, and gastrointestinal tract. There are also α-adreno receptors that are located on vascular smooth muscle.

A sympatholytic (sympathoplegic) drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, they may be used as antihypertensives. They are also used to treat anxiety, such as generalized anxiety disorder, panic disorder and PTSD. In some cases, such as with guanfacine, they have also shown to be beneficial in the treatment of ADHD.

Imidazoline receptors are the primary receptors on which clonidine and other imidazolines act. There are three main classes of imidazoline receptor: I1 is involved in inhibition of the sympathetic nervous system to lower blood pressure, I2 has as yet uncertain functions but is implicated in several psychiatric conditions, and I3 regulates insulin secretion.

<span class="mw-page-title-main">Alpha blocker</span> Class of pharmacological agents

Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).

<span class="mw-page-title-main">Tiamenidine</span> Chemical compound

Tiamenidine (BAN, USAN, INN, also known as thiamenidine, Hoe 440) is an imidazoline compound that shares many of the pharmacological properties of clonidine. It is a centrally-acting α2 adrenergic receptor agonist (IC50 = 9.1 nM). It also acts as an α1-adrenergic receptor agonist to a far lesser extent (IC50 = 4.85 μM). In hypertensive volunteers, like clonidine, it significantly increased sinus node recovery time and lowered cardiac output. It was marketed (as tiamenidine hydrochloride) by Sanofi-Aventis under the brand name Sundralen for the management of essential hypertension.

References

  1. ↑ https://www.newsendip.com/in-norway-700000-people-are-addicted-to-nasal-sprays/
  2. 1 2 "Oxymetazoline". PubChem. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information. CID 4636.
  3. ↑ 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.
  4. ↑ Haenisch B, Walstab J, Herberhold S, Bootz F, Tschaikin M, Ramseger R, Bönisch H (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.
  5. ↑ 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". Pharmacology Research & Perspectives. 10 (5): e01003. doi:10.1002/prp2.1003. ISSN   2052-1707. PMC   9471048 . PMID   36101495.
  6. ↑ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  7. ↑ "Oxymetazoline - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  8. ↑ "Oxymetazoline". Lexi-Comp: Merck Manual Professional. Merck.com. Retrieved 15 April 2013.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ "VISINE Original Red Eye Drops | VISINE products". Visine.com. Archived from the original on 2 December 2010. Retrieved 15 April 2013.
  13. ↑ "UPNEEQ Label" (PDF). accessdata.fda.gov. 8 July 2020.
  14. ↑ Ramey JT, Bailen E, Lockey RF (2006). "Rhinitis medicamentosa". Journal of Investigational Allergology & Clinical Immunology. 16 (3): 148–155. PMID   16784007.
  15. ↑ Nguyen TM (2014). "Consultation submission: OTC nasal decongestant preparations for topical use: proposed advisory statements for medicines" (PDF). Novartis Consumer Health Australasia.
  16. ↑ Rayburn WF, Anderson JC, Smith CV, Appel LL, Davis SA (August 1990). "Uterine and fetal Doppler flow changes from a single dose of a long-acting intranasal decongestant". Obstetrics and Gynecology. 76 (2): 180–182. PMID   2196495.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. 1 2 Plumlee KH (2004). Clinical veterinary toxicology. St. Louis, Mo.: Mosby. ISBN   978-0-323-01125-9. OCLC   460904351.
  22. 1 2 "Decongestants (Toxicity) - Toxicology". Merck Veterinary Manual. Retrieved 3 April 2023.
  23. ↑ Dalefield R (2017). Veterinary toxicology for Australia and New Zealand. Amsterdam, Netherlands. ISBN   978-0-12-799912-8. OCLC   992119220.{{cite book}}: CS1 maint: location missing publisher (link)
  24. ↑ Dougherty PH (20 October 1986). "Advertising; Afrin Goes After Users Of Nasal Decongestants". The New York Times . Retrieved 30 March 2015.
  25. ↑ "Afrin".
  26. ↑ "Otrivin". www.otrivin.ca. Retrieved 14 June 2023.
  27. ↑ "Mucinex Cold and Flu Relief in Canada | Mucinex Canada". www.mucinex.ca. Retrieved 14 June 2023.
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