Differential Adrenoreceptor Mediated Tachyphylaxis and Upregulation

Summary

The investigators wish to evaluate the onset of tolerance to nasal decongestants like oxymetazoline (available over the counter) and the mechanism of tolerance particularly with differential effects on alpha 1 and alpha 2 adrenoreceptors on the nose. The investigators will 'tease' out by using an alpha 1 blocker called Prazosin. The investigators hypothesize that alpha 1 receptors mediate arterial constriction and this will be captured by measuring nasal blood flow. The investigators also hypothesize that alpha 2 receptors mediate venous sinusoid constriction and this the investigators will capture by airflow parameters like Peak Nasal Inspiratory Flow, Rhinomanometry, Oscillometric indices etc.

Timeline

Start

2008-05

Primary completion

2009-05

Completion

2009-05

Publications

• Background Bousquet J, Van Cauwenberge P, Khaltaev N; Aria Workshop Group; World Health Organization. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001 Nov;108(5 Suppl):S147-334. doi: 10.1067/mai.2001.118891. No abstract available.
• Background Nassef M, Shapiro G, Casale TB; Respiratory and Allergic Disease Foundation. Identifying and managing rhinitis and its subtypes: allergic and nonallergic components--a consensus report and materials from the Respiratory and Allergic Disease Foundation. Curr Med Res Opin. 2006 Dec;22(12):2541-8. doi: 10.1185/030079906x158057.
• Background Nolte H, Nepper-Christensen S, Backer V. Unawareness and undertreatment of asthma and allergic rhinitis in a general population. Respir Med. 2006 Feb;100(2):354-62. doi: 10.1016/j.rmed.2005.05.012. Epub 2005 Jul 11.
• Background Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. Clin Exp Allergy. 2004 Apr;34(4):520-6. doi: 10.1111/j.1365-2222.2004.1935.x.
• Background Ferguson BJ. Influences of allergic rhinitis on sleep. Otolaryngol Head Neck Surg. 2004 May;130(5):617-29. doi: 10.1016/j.otohns.2004.02.001.
• Background Patou J, De Smedt H, van Cauwenberge P, Bachert C. Pathophysiology of nasal obstruction and meta-analysis of early and late effects of levocetirizine. Clin Exp Allergy. 2006 Aug;36(8):972-81. doi: 10.1111/j.1365-2222.2006.02544.x.
• Background Hadley JA. Cost-effective pharmacotherapy for inhalant allergic rhinitis. Otolaryngol Clin North Am. 2003 Oct;36(5):825-36. doi: 10.1016/s0030-6665(03)00054-9.
• Background Graf P. Long-term use of oxy- and xylometazoline nasal sprays induces rebound swelling, tolerance, and nasal hyperreactivity. Rhinology. 1996 Mar;34(1):9-13.
• Background Scadding GK. Rhinitis medicamentosa. Clin Exp Allergy. 1995 May;25(5):391-4. doi: 10.1111/j.1365-2222.1995.tb01068.x. No abstract available.
• Background Ramey JT, Bailen E, Lockey RF. Rhinitis medicamentosa. J Investig Allergol Clin Immunol. 2006;16(3):148-55.
• Background Petruson B. Treatment with xylometazoline (Otrivin) nosedrops over a six-week period. Rhinology. 1981 Sep;19(3):167-72.
• Background Yoo JK, Seikaly H, Calhoun KH. Extended use of topical nasal decongestants. Laryngoscope. 1997 Jan;107(1):40-3. doi: 10.1097/00005537-199701000-00010.
• Background Watanabe H, Foo TH, Djazaeri B, Duncombe P, Mackay IS, Durham SR. Oxymetazoline nasal spray three times daily for four weeks in normal subjects is not associated with rebound congestion or tachyphylaxis. Rhinology. 2003 Sep;41(3):167-74.
• Background Andersson KE, Bende M. Adrenoceptors in the control of human nasal mucosal blood flow. Ann Otol Rhinol Laryngol. 1984 Mar-Apr;93(2 Pt 1):179-82. doi: 10.1177/000348948409300216.
• Background Corboz MR, Rivelli MA, Varty L, Mutter J, Cartwright M, Rizzo CA, Eckel SP, Anthes JC, Hey JA. Pharmacological characterization of postjunctional alpha-adrenoceptors in human nasal mucosa. Am J Rhinol. 2005 Sep-Oct;19(5):495-502.
• Background Michelotti GA, Price DT, Schwinn DA. Alpha 1-adrenergic receptor regulation: basic science and clinical implications. Pharmacol Ther. 2000 Dec;88(3):281-309. doi: 10.1016/s0163-7258(00)00092-9.
• Background Johannssen V, Maune S, Werner JA, Rudert H, Ziegler A. Alpha 1-receptors at pre-capillary resistance vessels of the human nasal mucosa. Rhinology. 1997 Dec;35(4):161-5.
• Background Wight RG, Cochrane T. A comparison of the effects of xylometazoline on nasal airflow, and on blood flux as measured by laser Doppler flowmetry. Acta Otolaryngol. 1989 Sep-Oct;108(3-4):284-9. doi: 10.3109/00016488909125529.
• Background Ruffolo RR Jr, Rosing EL, Waddell JE. Receptor interactions of imidazolines. I. Affinity and efficacy for alpha adrenergic receptors in rat aorta. J Pharmacol Exp Ther. 1979 Jun;209(3):429-36. No abstract available.
• Background Ruffolo RR Jr, Waddell JE. Receptor interactions of imidazolines: alpha-adrenoceptors of rat and rabbit aortae differentiated by relative potencies, affinities and efficacies of imidazoline agonists. Br J Pharmacol. 1982 Sep;77(1):169-76. doi: 10.1111/j.1476-5381.1982.tb09283.x.
• Background Hein P, Michel MC. Signal transduction and regulation: are all alpha1-adrenergic receptor subtypes created equal? Biochem Pharmacol. 2007 Apr 15;73(8):1097-106. doi: 10.1016/j.bcp.2006.11.001. Epub 2006 Nov 7.
• Background DeBernardis JF, Winn M, Kerkman DJ, Kyncl JJ, Buckner S, Horrom B. A new nasal decongestant, A-57219: a comparison with oxymetazoline. J Pharm Pharmacol. 1987 Sep;39(9):760-3. doi: 10.1111/j.2042-7158.1987.tb06989.x.
• Background Jaillon P. Clinical pharmacokinetics of prazosin. Clin Pharmacokinet. 1980 Jul-Aug;5(4):365-76. doi: 10.2165/00003088-198005040-00004.
• Background Bylund DB, Eikenberg DC, Hieble JP, Langer SZ, Lefkowitz RJ, Minneman KP, Molinoff PB, Ruffolo RR Jr, Trendelenburg U. International Union of Pharmacology nomenclature of adrenoceptors. Pharmacol Rev. 1994 Jun;46(2):121-36. No abstract available.
• Background Hallen H, Enerdal J, Graf P. Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa. Clin Exp Allergy. 1997 May;27(5):552-8.
• Background Davies AO, Lefkowitz RJ. Regulation of beta-adrenergic receptors by steroid hormones. Annu Rev Physiol. 1984;46:119-30. doi: 10.1146/annurev.ph.46.030184.001003. No abstract available.
• Background Brodde OE, Brinkmann M, Schemuth R, O'Hara N, Daul A. Terbutaline-induced desensitization of human lymphocyte beta 2-adrenoceptors. Accelerated restoration of beta-adrenoceptor responsiveness by prednisone and ketotifen. J Clin Invest. 1985 Sep;76(3):1096-101. doi: 10.1172/JCI112063.
• Background Tan KS, Grove A, McLean A, Gnosspelius Y, Hall IP, Lipworth BJ. Systemic corticosteriod rapidly reverses bronchodilator subsensitivity induced by formoterol in asthmatic patients. Am J Respir Crit Care Med. 1997 Jul;156(1):28-35. doi: 10.1164/ajrccm.156.1.9610113.
• Background Hamamdzic D, Duzic E, Sherlock JD, Lanier SM. Regulation of alpha 2-adrenergic receptor expression and signaling in pancreatic beta-cells. Am J Physiol. 1995 Jul;269(1 Pt 1):E162-71. doi: 10.1152/ajpendo.1995.269.1.E162.
• Background Hochban W, Althoff H, Ziegler A. Nasal decongestion with imidazoline derivatives: acoustic rhinometry measurements. Eur J Clin Pharmacol. 1999 Mar;55(1):7-12. doi: 10.1007/s002280050585.
• Results Vaidyanathan S, Williamson P, Clearie K, Khan F, Lipworth B. Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion. Am J Respir Crit Care Med. 2010 Jul 1;182(1):19-24. doi: 10.1164/rccm.200911-1701OC. Epub 2010 Mar 4.
• Vaidyanathan S, Williamson P, Lipworth B. Comparative evaluation of nasal blood flow and airflow in the decongestant response to oxymetazoline. Ann Allergy Asthma Immunol. 2012 Feb;108(2):77-80. doi: 10.1016/j.anai.2011.11.013.

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