Oxymetazoline

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Oxymetazoline
Oxymetazoline.svg
Oxymetazoline 3d.gif
Systematic (IUPAC) name
3-(4,5-dihydro-1H-imidazol-2-ylmethyl)- 2,4-dimethyl-6-tert-butyl-phenol
Clinical data
Trade namesAfrin, Ocuclear, Drixine
AHFS/Drugs.commonograph
Pregnancy cat.C
Legal statusGSL (UK) OTC (US)
Pharmacokinetic data
Half-life5-6 hours
Identifiers
CAS number1491-59-4 YesY
ATC codeR01AA05
R01AB07 (combinations), S01GA04
PubChemCID 4636
IUPHAR ligand124
DrugBankDB00935
ChemSpider4475 YesY
UNII8VLN5B44ZY YesY
KEGGD08322 YesY
ChEMBLCHEMBL762 YesY
Chemical data
FormulaC16H24N2O 
Mol. mass260.375 g·mol−1
Physical data
Melt. point301.5 °C (575 °F)
 YesY (what is this?)  (verify)
 
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Oxymetazoline
Oxymetazoline.svg
Oxymetazoline 3d.gif
Systematic (IUPAC) name
3-(4,5-dihydro-1H-imidazol-2-ylmethyl)- 2,4-dimethyl-6-tert-butyl-phenol
Clinical data
Trade namesAfrin, Ocuclear, Drixine
AHFS/Drugs.commonograph
Pregnancy cat.C
Legal statusGSL (UK) OTC (US)
Pharmacokinetic data
Half-life5-6 hours
Identifiers
CAS number1491-59-4 YesY
ATC codeR01AA05
R01AB07 (combinations), S01GA04
PubChemCID 4636
IUPHAR ligand124
DrugBankDB00935
ChemSpider4475 YesY
UNII8VLN5B44ZY YesY
KEGGD08322 YesY
ChEMBLCHEMBL762 YesY
Chemical data
FormulaC16H24N2O 
Mol. mass260.375 g·mol−1
Physical data
Melt. point301.5 °C (575 °F)
 YesY (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, 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[edit]

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, Sudafed OM, Vicks Sinex, Zicam, SinuFrin, and Mucinex Full Force.[1] It was developed from xylometazoline at E. Merck Darmstadt by Fruhstorfer in 1961.[2]

Due to its vasoconstricting properties, Oxymetazoline is also used to treat nose bleed[3][4] and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops).[5]

Mechanism of action[edit]

Oxymetazoline is a sympathomimetic that selectively agonizes α1 and partially α2 adrenergic receptors.[6] 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.[7] 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.[8]

Side-effects and special considerations[edit]

Rebound congestion[edit]

It is recommended that oxymetazoline not be used for more than three days, as rebound congestion, or rhinitis medicamentosa, may occur.[9] Patients who continue to use oxymetazoline beyond this point may become reliant on the medication to relieve their chronic congestion.

Effects of benzalkonium chloride[edit]

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.[10]

Use in pregnancy[edit]

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,[11] this subject has not been studied extensively enough to draw reliable conclusions.

Overdose[edit]

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]

Chemistry[edit]

Oxymetazoline is synthesized by chloromethylation of 6-tert-butyl-2,4-dimethylphenol and the further transformation of the resulting chloromethyl derivative into a nitrile.[12][13] The reaction of this with ethylene diamine gives oxymetazoline.

Oxymetazoline synthesis.png

References[edit]

  1. ^ "Oxymetazoline: Drug Information Provided by Lexi-Comp: Merck Manual Professional". Merck.com. Retrieved 2013-04-15. 
  2. ^ German Patent 1,117,588
  3. ^ Katz, R.I. et al. (1990). "A comparison of cocaine, lidocaine with epinephrine, and oxymetazoline for prevention of epistaxis on nasotracheal intubation". J Clin Anesth 2 (1): 16–20. doi:10.1016/0952-8180(90)90043-3. PMID 2310576. 
  4. ^ Krempl, G.A. and A.D. Noorily (1995). "Use of oxymetazoline in the management of epistaxis". Ann Otol Rhinol Laryngol 104 (9 Pt 1): 704–6. PMID 7661519. 
  5. ^ "VISINE® Original Red Eye Drops | VISINE® products". Visine.com. Retrieved 2013-04-15. 
  6. ^ 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.
  7. ^ 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.
  8. ^ J. Widdicombe (1997). "Microvascular anatomy of the nose". Allergy 52 (40 Suppl): 7–11. doi:10.1111/j.1398-9995.1997.tb04877.x. PMID 9353554. 
  9. ^ JT Ramey, E Bailen, RF Lockey (2006). "Rhinitis medicamentosa". J Investig Allergol Clin Immunol 16 (3): 148–155. PMID 16784007. 
  10. ^ Marple B, Roland P, Benninger M (2004). "Safety review of benzalkonium chloride used as a preservative in intranasal solutions: an overview of conflicting data and opinions". Otolaryngol Head Neck Surg 130 (1): 131–141. doi:10.1016/j.otohns.2003.07.005. PMID 14726922. 
  11. ^ Rayburn WF, Anderson JC, Smith CV, Appel LL, Davis SA (1990). "Uterine and fetal Doppler flow changes from a single dose of a long-acting intranasal decongestant". Obstet Gynecol 76 (2): 180–182. PMID 2196495. 
  12. ^ W. Fruhstorher, H. Muller-Calgan, U.S. Patent 3,147,275 (1964)
  13. ^ W. Fruhstorher, H. Muller-Calgan, DE 1117588  (1961).