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用户:DoroWolf/沙盒/羟甲唑啉

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DoroWolf/沙盒/羟甲唑啉
临床资料
商品名（英语：Drug nomenclature）Afrin, Ocuclear, Rhofade, others
AHFS/Drugs.comMonograph
依赖性Moderate
给药途径Intranasal, Eye drop, topical
ATC码
法律规范状态
法律规范
药物动力学数据
药物代谢Kidney (30%), fecal (10%)
生物半衰期5–6 hours
识别信息
  • 3-(4,5-Dihydro-1H-imidazol-2-ylmethyl)-2,4-dimethyl-6-tert-butyl-phenol
CAS号1491-59-4  checkY
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
化学信息
化学式C16H24N2O
摩尔质量260.38 g·mol−1
3D模型（JSmol（英语：JSmol））
熔点301.5 °C（574.7 °F）
  • Oc1c(c(c(cc1C(C)(C)C)C)CC/2=N/CCN\2)C
  • 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) checkY
  • Key:WYWIFABBXFUGLM-UHFFFAOYSA-N checkY

Oxymetazoline, sold under the brand name Afrin among others, is a topical decongestant and vasoconstrictor medication. It is available over-the-counter as a nasal spray to treat nasal congestion and nosebleeds, as eyedrops to treat eye redness due to minor irritation, and (in the United States) as a prescription topical cream to treat persistent facial redness due to rosacea in adults. Its effects begin within minutes and last for up to six hours. Intranasal use for longer than three days may cause congestion to recur or worsen, resulting in physical dependence. Oxymetazoline is a derivative of imidazole.[1] It was developed from xylometazoline at E. Merck Darmstadt by Wolfgang Fruhstorfer and Helmut Müller-Calgan in 1961.[2] A direct sympathomimetic, oxymetazoline binds to and activates α1 adrenergic receptors and α2 adrenergic receptors, most notably.[1] One study classified it in the following order: α(2A) > α(1A) ≥ α(2B) > α(1D) ≥ α(2C) >> α(1B), but this is not universally agreed upon.[3] There is little consistency across the (relatively large) number of in-vitro studies with respect to binding affinity/selectivity.

Medical uses

Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays.[4] In the United States, oxymetazoline 1% cream is approved by the Food and Drug Administration for topical treatment of persistent facial erythema (redness) associated with rosacea in adults.[5] Due to its vasoconstricting properties, oxymetazoline is also used to treat nose bleeds[6][7] and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops). [来源请求] [8]

In July 2020, oxymetazoline received approval by the FDA for the treatment of acquired drooping eyelid.[9]

Side effects

Rebound congestion

Rebound congestion, or rhinitis medicamentosa, may occur. A 2006 review of the pathology of rhinitis medicamentosa concluded that use of oxymetazoline for more than three days may result in rhinitis medicamentosa and recommended limiting use to three days.[10]

Australian regulatory submission

In a submission to the Therapeutic Goods Administration, a Novartis representative concluded, "The justification was not based on evidence." Citing an existing extensive body of evidence and noting a range of recommended periods from five to ten days, Novartis recommended the established five day period for its use for self-medication without medical consultation as it coincides with the typical duration of the common cold.[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.[原创研究？]

Overdose

If accidentally ingested, standard methods to remove unabsorbed drugs should be considered.[需要解释] There is no specific antidote for oxymetazoline, although its pharmacological effects may be reversed by an 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.[来源请求]

Pharmacology

Pharmacodynamics

Oxymetazoline is a sympathomimetic that selectively agonizes α1 and, partially, α2 adrenergic receptors.[13] 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.[14] 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.[15] It can reduce nasal airway resistance (NAR) up to 35.7% and reduce nasal mucosal blood flow up to 50%.[16]

Pharmacokinetics

Since imidazolines are sympathomimetic agents, their primary effects appear on α adrenergic receptors, with little if any effect on β adrenergic receptors.[17] Like other imidazolines, Oxymetazoline is readily absorbed orally.[17] Effects on α receptors from systemically absorbed oxymetazoline hydrochloride may persist for up to 7 hours after a single dose.[18] The elimination half-life in humans is 5–8 hours.[19] It is excreted unchanged both by the kidneys (30%) and in feces (10%).[18]

History

The oxymetazoline brand Afrin was first sold as a prescription medication in 1966. After finding substantial early success as a prescription medication, it became available as an over-the-counter drug in 1975. Schering-Plough did not engage in heavy advertising until 1986.[20]

参考资料

  1. ^ 1.0 1.1 Oxymetazoline. PubChem. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information. CID 4636. 
  2. ^ DE 1117588,Fruhstorfer W, Müller-Calgan H,“2-(2,6-dimethyl-3-hydroxy-4-tert-butyl-benzyl)-2-imidazoline,and acid addition salts thereof,and process for their manufacture”,发行于23 November 1961,指定于E Merck AG. 
  3. ^ Haenisch B, Walstab J, Herberhold S, Bootz F, Tschaikin M, Ramseger R, Bönisch H. Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundamental & Clinical Pharmacology. December 2010, 24 (6): 729–739. PMID 20030735. S2CID 25064699. doi:10.1111/j.1472-8206.2009.00805.x. 
  4. ^ Oxymetazoline. Lexi-Comp: Merck Manual Professional. Merck.com. [15 April 2013]. 
  5. ^ Patel NU, Shukla S, Zaki J, Feldman SR. Oxymetazoline hydrochloride cream for facial erythema associated with rosacea. Expert Review of Clinical Pharmacology. October 2017, 10 (10): 1049–1054. PMID 28837365. S2CID 19930755. doi:10.1080/17512433.2017.1370370. 
  6. ^ Katz RI, Hovagim AR, Finkelstein HS, Grinberg Y, Boccio RV, Poppers PJ. A comparison of cocaine, lidocaine with epinephrine, and oxymetazoline for prevention of epistaxis on nasotracheal intubation. Journal of Clinical Anesthesia. 1990, 2 (1): 16–20. PMID 2310576. doi:10.1016/0952-8180(90)90043-3. 
  7. ^ Krempl GA, Noorily AD. Use of oxymetazoline in the management of epistaxis. The Annals of Otology, Rhinology, and Laryngology. September 1995, 104 (9 Pt 1): 704–706. PMID 7661519. S2CID 37579139. doi:10.1177/000348949510400906. 
  8. ^ VISINE Original Red Eye Drops | VISINE products. Visine.com. [15 April 2013]. （原始内容存档于2 December 2010）. 
  9. ^ UPNEEQ Label (PDF). accessdata.fda.gov. 8 July 2020. 
  10. ^ Ramey JT, Bailen E, Lockey RF. Rhinitis medicamentosa. Journal of Investigational Allergology & Clinical Immunology. 2006, 16 (3): 148–155. PMID 16784007. 
  11. ^ Nguyen TM. Consultation submission: OTC nasal decongestant preparations for topical use: proposed advisory statements for medicines (PDF). Novartis Consumer Health Australasia. 2014. 
  12. ^ 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. Obstetrics and Gynecology. August 1990, 76 (2): 180–182. PMID 2196495. 
  13. ^ Westfall TC, Westfall DP. Chapter 6. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems. Brunton LL, Lazo JS, Parker KL (编). Goodman & Gilman's The Pharmacological Basis of Therapeutics 11th. [24 January 2015]. （原始内容存档于30 September 2011） –通过AccessMedicine. Anatomy and General Functions of the Autonomic and Somatic Motor Nervous Systems .
  14. ^ Biaggioni I, Robertson D. Chapter 9. Adrenoceptor Agonists & Sympathomimetic Drugs. Katzung BG (编). Basic & Clinical Pharmacology 11th. [30 November 2011]. （原始内容存档于30 September 2011）. 
  15. ^ Widdicombe J. Microvascular anatomy of the nose. Allergy. 1997, 52 (40 Suppl): 7–11. PMID 9353554. S2CID 46018611. doi:10.1111/j.1398-9995.1997.tb04877.x. 
  16. ^ Bende M, Löth S. Vascular effects of topical oxymetazoline on human nasal mucosa. The Journal of Laryngology and Otology. March 1986, 100 (3): 285–288. PMID 3950497. S2CID 37998936. doi:10.1017/S0022215100099151. 
  17. ^ 17.0 17.1 Plumlee KH. Clinical veterinary toxicology. St. Louis, Mo.: Mosby. 2004. ISBN 978-0-323-01125-9. OCLC 460904351. 
  18. ^ 18.0 18.1 Decongestants (Toxicity) - Toxicology. Merck Veterinary Manual. [2023-04-03] （美国英语）. 
  19. ^ Dalefield R. Veterinary toxicology for Australia and New Zealand. Amsterdam, Netherlands. 2017. ISBN 978-0-12-799912-8. OCLC 992119220. 
  20. ^ Dougherty PH. Advertising; Afrin Goes After Users Of Nasal Decongestants. The New York Times. 20 October 1986 [30 March 2015]. 

外部链接

  • Oxymetazoline. Drug Information Portal. U.S. National Library of Medicine. 

Template:Nasal preparations

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