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, Ocuclear, Drixine
AHFS/Drugs.com monograph
Pregnancy
category
  • C
Dependence
liability		 Moderate
Routes of
administration		 Intranasal
Legal status
Legal status
Pharmacokinetic data
Metabolism Kidney (30%), fecal (10%)
Biological half-life 5–6 hours
Identifiers
CAS Number 1491-59-4 YesY
ATC code R01AA05 (WHO)
R01AB07 (combinations), S01GA04
PubChem CID 4636
IUPHAR/BPS 124
DrugBank DB00935 YesY
ChemSpider 4475 YesY
UNII 8VLN5B44ZY YesY
KEGG D08322 YesY
ChEBI CHEBI:7862 N
ChEMBL CHEMBL762 YesY
Chemical data
Formula C16H24N2O
Molar mass 260.375 g·mol−1
Physical data
Melting point 301.5 °C (574.7 °F)
 NYesY (what is this?)  (verify)

Oxymetazoline is a selective α1 adrenergic receptor agonist and α2 adrenergic receptor partial agonist. It is a 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, SinuFrin and Mucinex Sinus-Max. It was developed from xylometazoline at E. Merck Darmstadt by Fruhstorfer in 1961.[1] 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.[2]

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

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 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%).

Mechanism of action

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] It can reduce nasal airway resistance (NAR) up to 35.7% and nasal mucosal blood flow up to 50%.[9]

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.[10] Patients who continue to use oxymetazoline beyond this point may become dependent 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.[11]

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,[12] 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 α 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 α2 receptors and imidazoline receptors, much like clonidine.

References

  1. ↑ German Patent 1,117,588
  2. ↑ "Oxymetazoline: Drug Information Provided by Lexi-Comp: Merck Manual Professional". Merck.com. Retrieved 2013-04-15.
  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. ↑ The Journal of Laryngology & Otology, Volume 100 , Issue 03, pp 285-288
  10. ↑ JT Ramey, E Bailen, RF Lockey (2006). "Rhinitis medicamentosa". J Investig Allergol Clin Immunol 16 (3): 148–155. PMID 16784007.
  11. ↑ 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.
  12. ↑ 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.
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