Oxymetazoline
Encyclopedia
Oxymetazoline is a selective alpha-1 agonist and partial alpha-2 agonist topical decongestant
, used in the form of Oxymetazoline hydrochloride
, in products such as Afrin, Dristan, Nasivin, Logicin, Vicks Sinex
, Visine
L.R., Sudafed OM, and Zicam
. It was developed from Xylometazoline at E.Merck Darmstadt by Fruhstorfer in 1961 (German Patent 1,117,588). Oxymetazoline is generally available as a nasal spray
.
in the form of oxymetazoline hydrochloride
in nasal spray
s such as Afrin, Sudafed OM, Dristan, Dimetapp, Vicks Sinex
, and Mucinex Full Force. It was developed from xylometazoline
at E.Merck Darmstadt by Fruhstorfer in 1961 (German Patent 1,117,588).
Oxymetazoline is also used to treat epistaxis and eye redness due to minor irritation (marketed as Visine
L.R. in the form of eye drops).
. 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. 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.
congestion, or rhinitis medicamentosa
, may occur. Patients that continue to use oxymetazoline beyond this point may become reliant on the medication to relieve their chronic congestion.
, a common additive to oxymetazoline nasal sprays, may damage nasal epithelia
and exacerbate rhinitis medicamentosa. However, the majority of studies find benzalkonium chloride to be a safe preservative.
, 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.
. In children, oxymetazoline may produce profound central nervous system depression due to stimulation of central alpha-2 receptors and imidazoline receptor
s, much like clonidine
.
. The reaction of this with ethylene diamine
gives oxymetazoline.
Topical decongestant
Topical decongestants are decongestants applied directly to the nasal cavity. By applying them directly to the site of action, topical decongestants relieve nasal congestion while reducing the side effects associated with systemically-acting decongestants, such as high blood pressure...
, used in the form of Oxymetazoline hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
, in products such as Afrin, Dristan, Nasivin, Logicin, Vicks Sinex
Vicks Sinex
Vicks Sinex is a brand of topical nasal decongestant spray produced by Vicks, a division of Procter & Gamble. The active ingredient contained in the Sinex nasal spray is Oxymetazoline which acts to relieve blocked nasal passages. The recommended dosage is 2–3 sprays in each nostril every 10–12...
, Visine
Visine
Visine is a brand of eye drops produced by Johnson & Johnson. Johnson & Johnson acquired Visine, along with Pfizer's entire consumer healthcare portfolio, in December 2006.-Visine Original:...
L.R., Sudafed OM, and Zicam
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 combination of the words "zinc" and "ICAM-1" . It is marketed as an "unapproved homeopathic" product.Zicam was invented by Charles B...
. It was developed from Xylometazoline at E.Merck Darmstadt by Fruhstorfer in 1961 (German Patent 1,117,588). Oxymetazoline is generally available as a nasal spray
Nasal spray
Nasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
.
Clinical uses
Oxymetazoline is available over-the-counter as a topical decongestantTopical decongestant
Topical decongestants are decongestants applied directly to the nasal cavity. By applying them directly to the site of action, topical decongestants relieve nasal congestion while reducing the side effects associated with systemically-acting decongestants, such as high blood pressure...
in the form of oxymetazoline hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
in nasal spray
Nasal spray
Nasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
s such as Afrin, Sudafed OM, Dristan, Dimetapp, Vicks Sinex
Vicks Sinex
Vicks Sinex is a brand of topical nasal decongestant spray produced by Vicks, a division of Procter & Gamble. The active ingredient contained in the Sinex nasal spray is Oxymetazoline which acts to relieve blocked nasal passages. The recommended dosage is 2–3 sprays in each nostril every 10–12...
, and Mucinex Full Force. It was developed from xylometazoline
Xylometazoline
Xylometazoline is a drug which is used as a topical nasal decongestant. It is applied directly into the nose, either as a spray or as drops....
at E.Merck Darmstadt by Fruhstorfer in 1961 (German Patent 1,117,588).
Oxymetazoline is also used to treat epistaxis and eye redness due to minor irritation (marketed as Visine
Visine
Visine is a brand of eye drops produced by Johnson & Johnson. Johnson & Johnson acquired Visine, along with Pfizer's entire consumer healthcare portfolio, in December 2006.-Visine Original:...
L.R. in the form of eye drops).
Mechanism of action
Oxymetazoline is an adrenomimetic that nonselectively agonizes α1 and α2 adrenergic receptorsAdrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
. Since vascular beds widely express α1 receptors, the action of oxymetazoline results in vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
. 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
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
because of centrally-mediated inhibition of sympathetic tone via presynaptic α2 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.
Rebound congestion
It is recommended that oxymetazoline not be used for more than three days, as reboundRebound effect
The rebound effect, or rebound phenomenon, is the tendency of some medications, when discontinued suddenly, to cause a return of the symptoms it relieved, and that, to a degree stronger than they were before treatment first began...
congestion, or rhinitis medicamentosa
Rhinitis medicamentosa
Rhinitis medicamentosa is a condition of rebound nasal congestion brought on by extended use of topical decongestants that work by constricting blood vessels in the lining of the nose.-Presentation:This condition typically occurs after 5 to 7 days of use of such medications...
, may occur. Patients that continue to use oxymetazoline beyond this point may become reliant on the medication to relieve their chronic congestion.
Effects of benzalkonium chloride
Some studies have found that benzalkonium chlorideBenzalkonium chloride
Benzalkonium chloride, also known as alkyldimethylbenzylammonium chloride and ADBAC, is a mixture of alkylbenzyldimethylammonium chlorides of various even-numbered alkyl chain lengths. This product is a nitrogenous cationic surface-acting agent belonging to the quaternary ammonium group...
, a common additive to oxymetazoline nasal sprays, may damage nasal epithelia
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
and exacerbate rhinitis medicamentosa. However, the majority of studies find benzalkonium chloride to be a safe preservative.
Use in pregnancy
The Food and Drug Administration places oxymetazoline in category CPregnancy category
The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does not include any risks conferred by pharmaceutical agents or their metabolites that are present in breast...
, 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 alpha adrenergic antagonists such as phentolaminePhentolamine
Phentolamine is a reversible nonselective alpha-adrenergic antagonist. -Mechanism:Its primary action is vasodilation due to α1 blockade....
. In children, oxymetazoline may produce profound central nervous system depression due to stimulation of central alpha-2 receptors and imidazoline receptor
Imidazoline receptor
Imidazoline receptors are receptors for clonidine and other imidazolines.-Classes:There are three classes of imidazoline receptors:* I1 receptor – mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure, * I2 receptor – an allosteric binding site of monoamine oxidase and is...
s, much like clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
.
Blood Pressure
While Oxymetazoline is a non-selective alpha agonist and does increase blood pressure when used systemically, when used in moderate doses via direct nasal application, the net raise should be small or insignificant. Ingesting or using an excessive amount of the drug intra-nasally would however cause the drug to eventually be absorbed into the blood stream and would hypothetically cause an increase in blood pressure. Hypertensive patients are recommended to seek the advice of their physician before using.Chemistry
Oxymetazoline, 6-tert-butyl-3(2-imidazolin-2-ilmethyl)-2,4-dimethylphenol, is synthesized by chloromethylation of 6-tert-butyl-2,4-dimethylphenol and the further transformation of the resulting chloromethyl derivative into a nitrileNitrile
A nitrile is any organic compound that has a -C≡N functional group. The prefix cyano- is used interchangeably with the term nitrile in industrial literature. Nitriles are found in many useful compounds, one example being super glue .Inorganic compounds containing the -C≡N group are not called...
. The reaction of this with ethylene diamine
Ethylene diamine
Ethylenediamine is the organic compound with the formula C2H42. This colorless liquid with an ammonia-like odor is a strongly basic amine. The liquid fumes upon contact with humid air...
gives oxymetazoline.
- W. Fruhstorher, H. Muller-Calgan, (1964).
- W. Fruhstorher, H. Muller-Calgan, (1961).