Oxymetazoline, sold under the brand name Afrin among others, is a
topical decongestant Topical decongestants are decongestants applied directly to the nasal cavity. Their effectiveness by themselves in the common cold appears to have a small benefit in adults.
Topical decongestants should only be used by patients for a maximum of 5†...
and
vasoconstrictor
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...
medication. It is available
over-the-counter
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
as a
nasal spray
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 syst ...
to treat
nasal congestion
Nasal congestion is the blockage of nasal breathing usually due to membranes lining the nose becoming swollen from inflamed blood vessels.
Background
In about 85% of cases, nasal congestion leads to mouth breathing rather than nasal breathin ...
and
nosebleeds
A nosebleed, also known as epistaxis, is bleeding from the nose. Blood can flow down into the stomach, and cause nausea and vomiting. In more severe cases, blood may come out of both nostrils. Rarely, bleeding may be so significant that low bloo ...
, 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
Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarg ...
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
Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
.
Oxymetazoline is a derivative of imidazole.
[PubChem nternet Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 4636, Oxymetazoline; ited 2021 Apr. 18 Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Oxymetazoline] It was developed from
xylometazoline
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 m ...
at
E. Merck Darmstadt by Wolfgang Fruhstorfer and Helmut Müller-Calgan in 1961. A direct sympathomimetic, oxymetazoline binds to and activates
α1 adrenergic receptors and
α2 adrenergic receptors, most notably.
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. 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 Topical decongestants are decongestants applied directly to the nasal cavity. Their effectiveness by themselves in the common cold appears to have a small benefit in adults.
Topical decongestants should only be used by patients for a maximum of 5†...
in the form of oxymetazoline
hydrochloride
In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative n ...
in
nasal spray
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 syst ...
s such as Otrivin, Afrin, Operil, Dristan, Dimetapp, Oxyspray, Facimin, Nasivin, Nostrilla, Utabon, Sudafed OM,
Vicks Sinex
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 d ...
, Zicam, SinuFrin, Drixoral
and Mucinex Full Force.
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.
Due to its vasoconstricting properties, oxymetazoline is also used to treat
nose bleeds and eye redness due to minor irritation (marketed as
Visine L.R. in the form of eye drops).
In July 2020, oxymetazoline received approval by the FDA for the treatment of acquired
drooping eyelid.
Side effects
Rebound congestion
Rebound congestion, or
rhinitis medicamentosa
Rhinitis medicamentosa (or RM) is a condition of rebound nasal congestion suspected to be brought on by extended use of topical decongestants (e.g., oxymetazoline, phenylephrine, xylometazoline, and naphazoline nasal sprays) and certain oral med ...
, 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.
Australian regulatory submission
In a submission to the
Therapeutic Goods Administration
The Therapeutic Goods Administration (TGA) is the medicine and therapeutic regulatory agency of the Australian Government. As part of the Department of Health and Aged Care, the TGA regulates the quality, supply and advertising of medicines, p ...
, a
Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
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.
Use in pregnancy
The
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
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, this subject has not been studied extensively enough to draw reliable conclusions.
Overdose
If accidentally ingested, standard methods to remove unabsorbed drugs should be considered. There is no specific antidote for oxymetazoline, although its pharmacological effects may be reversed by an adrenergic antagonists such as
phentolamine
Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α- adrenergic antagonist.
Mechanism
Its primary action is vasodilation due to α1 blockade.
Non-selective α-blockers can cause a much more pronounced ...
. In the event of a possibly life-threatening overdose (such as a
hypertensive crisis
Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of 120—sometimes termed malignant or accelerated hypertension) is referred to as a hypertensive crisis, as blood pressure at this level confers a high risk ...
),
benzodiazepines should be considered to decrease the likelihood of
seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
and
convulsions
A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
, 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 α
2 receptors and
imidazoline receptor 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 y ...
s, much like
clonidine.
Pharmacology
Pharmacodynamics
Oxymetazoline is a
sympathomimetic that selectively agonizes
α1 and, partially,
α2 adrenergic receptors.
[Westfall Thomas C, Westfall David P, "Chapter 6. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems" (Chapter). Brunton LL, Lazo JS, Parker KL: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e: .] Since vascular beds widely express α
1 receptors, the action of oxymetazoline results in
vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...
. In addition, the local application of the drug also results in vasoconstriction due to its action on endothelial postsynaptic α
2 receptors; systemic application of α
2 agonists, in contrast, causes
vasodilation
Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...
because of centrally-mediated inhibition of sympathetic tone via presynaptic α
2 receptors.
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. It can reduce nasal airway resistance (NAR) up to 35.7% and reduce nasal mucosal blood flow up to 50%.
Pharmacokinetics
Since imidazolines are sympathomimetic agents, their primary effects appear on α adrenergic receptors, with little if any effect on
β adrenergic receptors.
Like other imidazolines, Oxymetazoline is readily absorbed orally.
Effects on α receptors from systemically absorbed oxymetazoline hydrochloride may persist for up to 7 hours after a single dose. The elimination half-life in humans is 5–8 hours. It is excreted unchanged both by the kidneys (30%) and in feces (10%).
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
Schering-Plough Corporation was an American pharmaceutical company. It was originally the U.S. subsidiary of the German company Schering AG, which was founded in 1851 by Ernst Christian Friedrich Schering. As a result of nationalization, it beca ...
did not engage in heavy advertising until 1986.
From the mid-1980s to mid-1990s, the brand Sinex was featured in many
television advertisement
A television advertisement (also called a television commercial, TV commercial, commercial, spot, television spot, TV spot, advert, television advert, TV advert, television ad, TV ad or simply an ad) is a span of television programming produce ...
s. 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,
Dristan, Drixine, Drixoral, Nasivin, Nasivion, Nezeril, Nostrilla, Logicin, Vicks Sinex,
Visine L.R., Sudafed OM,
Zicam
Zicam is a branded series of products marketed for cold and allergy relief whose original formulations included the element zinc. The Zicam name is derived from a portmanteau of the words "zinc" and "ICAM-1" (the receptor to which a rhinovirus bin ...
, Otrivin Oxy, SinuFrin, Upneeq, and Mucinex Sinus-Max.
References
External links
*
{{Adrenergic receptor modulators
Alpha-1 adrenergic receptor agonists
Alpha-2 adrenergic receptor agonists
Bayer brands
Imidazolines
Merck & Co. brands
Phenols
Schering-Plough brands
Tert-butyl compounds
Topical decongestants
Vasoconstrictors