Oxymetazoline

Oxymetazoline

Clinical data
Trade names	Afrin, Ocuclear, Drixine, Rhofade
AHFS/Drugs.com	Monograph
Pregnancy category	C
Dependence liability	Moderate
Routes of administration	Intranasal, Eye drop
ATC code	D11AX27 (WHO) R01AA05 (WHO), R01AB07 (WHO) (combinations), S01GA04 (WHO)
Legal status
Legal status	UK: General sales list (GSL, OTC) US: OTC (nasal spray) ℞ only (topical cream)
Pharmacokinetic data
Metabolism	Kidney (30%), fecal (10%)
Elimination half-life	5–6 hours
Identifiers
IUPAC name 3-(4,5-Dihydro-1H-imidazol-2-ylmethyl)-2,4-dimethyl-6-tert-butyl-phenol
CAS Number	1491-59-4 Y
PubChem CID	4636
IUPHAR/BPS	124
DrugBank	DB00935 Y
ChemSpider	4475 Y
UNII	8VLN5B44ZY
KEGG	D08322 Y
ChEBI	CHEBI:7862 N
ChEMBL	ChEMBL762 Y
CompTox Dashboard (EPA)	DTXSID3040691
ECHA InfoCard	100.014.618
Chemical and physical data
Formula	C16H24N2O
Molar mass	260.381 g·mol−1
3D model (JSmol)	Interactive image
Melting point	301.5 °C (574.7 °F)
SMILES Oc1c(c(c(cc1C(C)(C)C)C)CC/2=N/CCN\2)C
InChI 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) Y Key:WYWIFABBXFUGLM-UHFFFAOYSA-N Y
NY (what is this?)

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 6 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 E. Merck Darmstadt 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.^[3] 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.

Medical uses[]

Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays such as Otrivin, Afrin, Operil, Dristan, Dimetapp, Oxyspray, Facimin, Nasivin, Nostrilla, Utabon, Sudafed OM, Vicks Sinex, Zicam, SinuFrin, Drixoral^[5] and Mucinex Full Force.^[6]

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.^[7]

Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleeds^[8][9] and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops).^{[citation needed] [10]}

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

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.^[12] 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.^[13]

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,^[14] 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 α 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.^[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]

Pharmacokinetics[]

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

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.^[19]

From the mid 1980s to mid 1990s, the brand Sinex was featured in many television advertisements. Some of these commercials showed men, women, and children using other brands of nasal sprays, and then standing upside down on a sidewalk, or against a wall, etc or hanging upside down from various playground equipment to prevent their nasal spray from dripping out. This was juxtaposed with Sinex users not having to hang upside side down or stand on their heads as it didn't drip out.

Brand names[]

Brand names include Afrin, Drixine, Dristan, Nasivin, Nasivion, Nezeril, Nostrilla, Logicin, Vicks Sinex, Visine L.R., Sudafed OM, Zicam, Otrivin Oxy, SinuFrin, Upneeq, and Mucinex Sinus-Max.

References[]