Oxymetazoline

Oxymetazoline

Systematic (IUPAC) name
3-(4,5-dihydro-1H-imidazol-2-ylmethyl)- 2,4-dimethyl-6-tert-butyl-phenol
Clinical data
Trade names	Afrin, Dristan12-hrnasalspray, Ocuclear
AHFS/Drugs.com	monograph
Pregnancy cat.	C
Legal status	?
Pharmacokinetic data
Half-life	5-6 hours
Identifiers
CAS number	1491-59-4
ATC code	R01AA05 R01AB07, S01GA04
PubChem	CID 4636
IUPHAR ligand	124
DrugBank	APRD01158
ChemSpider	4475 Y
UNII	8VLN5B44ZY Y
KEGG	D08322 Y
ChEMBL	CHEMBL762 Y
Chemical data
Formula	C16H24N2O
Mol. mass	260.375 g·mol−1
SMILES	eMolecules & PubChem
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
Physical data
Melt. point	301.5 °C (575 °F)
Y(what is this?)  (verify)

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.

Clinical uses

Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays such as Afrin, Sudafed OM, Dristan, Dimetapp, Vicks Sinex, and Mucinex Full Force.^[1] 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^[2][3] and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops).^[4]

Mechanism of action

Oxymetazoline is an adrenomimetic that nonselectively agonizes α1 and α2 adrenergic receptors.^[5] 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.^[6] 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.^[7]

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.^[8] 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 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.^[9]

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,^[10] 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 children, oxymetazoline may produce profound central nervous system depression due to stimulation of central alpha-2 receptors and imidazoline receptors, much like clonidine^{[citation needed]}.

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 nitrile. The reaction of this with ethylene diamine gives oxymetazoline.

• W. Fruhstorher, H. Muller-Calgan, U.S. Patent 3,147,275 (1964).
• W. Fruhstorher, H. Muller-Calgan, DE 1117588  (1961).

References

1. ^ http://www.merck.com/mmpe/lexicomp/oxymetazoline.html
2. ^ Katz, R.I., et al., A comparison of cocaine, lidocaine with epinephrine, and oxymetazoline for prevention of epistaxis on nasotracheal intubation. J Clin Anesth, 1990. 2(1): p. 16-20
3. ^ 13. Krempl, G.A. and A.D. Noorily, Use of oxymetazoline in the management of epistaxis. Ann Otol Rhinol Laryngol, 1995. 104(9 Pt 1): p. 704-6.
4. ^ http://www.visine.com/product-visine-original.jsp
5. ^ 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: http://www.accessmedicine.com/content.aspx?aID=954433.
6. ^ Biaggioni Italo, Robertson David, "Chapter 9. Adrenoceptor Agonists & Sympathomimetic Drugs" (Chapter). Katzung BG: Basic & Clinical Pharmacology, 11e: http://www.accessmedicine.com/content.aspx?aID=4520412.
7. ^ J. Widdicombe. Microvascular anatomy of the nose. Allergy 52 (1997), pp. 7–11.
8. ^ JT Ramey, E Bailen, RF Lockey. Rhinitis medicamentosa. J Investig Allergol Clin Immunol 2006; Vol. 16(3): 148-155.
9. ^ Marple B, Roland P, Benninger M. Safety review of benzalkonium chloride used as a preservative in intranasal solutions: an overview of conflicting data and opinions. Otolaryngol Head Neck Surg. 2004 Jan;130(1):131-41.
10. ^ Rayburn WF, Anderson JC, Smith CV, Appel LL, Davis SA. Uterine and fetal Doppler flow changes from a single dose of a long-acting intranasal decongestant. Obstet Gynecol. 1990 Aug;76(2):180-2.