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, Nezeril, Nostrilla, Logicin, Vicks Sinex, Visine L.R., Sudafed OM, Zicam and SinuFrin. It was developed from xylometazoline at E. Merck Darmstadt by Fruhstorfer in 1961. Oxymetazoline is generally available as a nasal spray.
Clinical uses
Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays such as Afrin, Operil, Dristan, Dimetapp, oxyspray, Facimin, Nasivin, Nostrilla, Sudafed OM, Vicks Sinex, Zicam, SinuFrin, and Mucinex Full Force. It was developed from xylometazoline at E. Merck Darmstadt by Fruhstorfer in 1961.
Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleed and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops).
Pharmacokinetics
Imidazolines are sympathomimetic agents, with primary effects on α-adrenergic receptors and little if any effect on β-adrenergic receptors. Oxymetazoline is readily absorbed orally. Effects on α-receptors from systemically absorbed oxymetazoline hydrochloride may persist for up to 7 hr after a single dose. The elimination half-life in people is 5â€"8 hr. It is excreted unchanged both by the kidneys (30%) and in feces (10%).
Mechanism of action
Oxymetazoline is a sympathomimetic that selectively agonizes α1 and partially α2 adrenergic receptors. 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. It can reduce Nasal Airway Resistance (NAR) up to 35.7% and Nasal mucosal blood flow up to 50%.
Side-effects and special considerations
Rebound congestion
It is recommended that oxymetazoline not be used for more than three days, as rebound congestion, or rhinitis medicamentosa, may occur. Patients who 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 chloride, 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.
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, 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 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 alpha-2 receptors and imidazoline receptors, much like clonidine.
Chemistry
Oxymetazoline is synthesized by chloromethylation of 6-tert-butyl-2,4-dimethylphenol and the further transformation of the resulting chloromethyl derivative into a nitrile. The reaction of this with ethylene diamine gives oxymetazoline.