Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound
congestion.
Author(s): Vaidyanathan S, Williamson P, Clearie K, Khan F, Lipworth B.
Affiliation(s): Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology,
University of Dundee, Dundee DD1 9SY, Scotland, UK.
Publication date & source: 2010, Am J Respir Crit Care Med. , 182(1):19-24
RATIONALE: Chronic use of intranasal decongestants, such as oxymetazoline, leads
to tachyphylaxis of response and rebound congestion, caused by alpha-adrenoceptor
mediated down-regulation and desensitization of response.
OBJECTIVES: We evaluated if tachyphylaxis can be reversed by intranasal
fluticasone propionate, and the relative alpha(1)- and alpha(2)-adrenoceptor
components of tachyphylaxis using the alpha(1)-antagonist prazosin.
METHODS: In a randomized, double-blind, placebo-controlled, crossover design, 19
healthy subjects received intranasal oxymetazoline, 200 microg three times a day
for 14 days, followed by the addition of fluticasone, 200 microg twice a day for
a further 3 days. At Days 1, 14, and 17, participants received a single dose of
oral prazosin, 1 mg, or placebo with measurements made before and 2 hours later.
MEASUREMENTS AND MAIN RESULTS: Outcomes evaluated were peak nasal inspiratory
flow, nasal resistance, blood flow, and oxymetazoline dose-response curve (DRC).
On Day 14 versus Day 1, inspiratory flow decreased (mean difference, 95%
confidence interval) (-47.9 L x min(-1); -63.9 to -31.9; P < 0.001) and the DRC
shifted downward (24.8 L x min(-1); 20.3-29.3; P < 0.001). On Day 17 versus Day
14, after fluticasone, inspiratory flow increased (45 L x min(-1); 30-61; P <
0.001) and the DRC shifted upward (26.2 L x min(-1); 21.7-30.7; P < 0.001). On
Day 1, prazosin reduced inspiratory flow (-52.6 L x min(-1); -19.2 to -86)
compared with baseline. This effect was abolished on Day 14 (7.9 L x in(-1);
-41.3 to 25.5).
CONCLUSIONS: Oxymetazoline-induced tachyphylaxis and rebound congestion are
reversed by intranasal fluticasone. Further studies are indicated to evaluate if
combination nasal sprays of decongestant and corticosteroid are an effective
strategy to obviate tachyphylaxis and rebound in rhinitis. Clinical trial
registered with www.clinicaltrials.gov (NCT 00487032).
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