Abstract | 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:
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Authors | Sriram Vaidyanathan, Peter Williamson, Karine Clearie, Faisel Khan, Brian Lipworth |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 182
Issue 1
Pg. 19-24
(Jul 01 2010)
ISSN: 1535-4970 [Electronic] United States |
PMID | 20203244
(Publication Type: Journal Article, Randomized Controlled Trial)
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Chemical References |
- Adrenergic alpha-Agonists
- Adrenergic alpha-Antagonists
- Androstadienes
- Anti-Inflammatory Agents
- Oxymetazoline
- Fluticasone
- Prazosin
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Topics |
- Administration, Intranasal
- Administration, Oral
- Adrenergic alpha-Agonists
(administration & dosage, adverse effects)
- Adrenergic alpha-Antagonists
(administration & dosage)
- Adult
- Androstadienes
(administration & dosage)
- Anti-Inflammatory Agents
(administration & dosage)
- Cross-Over Studies
- Double-Blind Method
- Female
- Fluticasone
- Humans
- Male
- Middle Aged
- Oxymetazoline
(administration & dosage, adverse effects)
- Prazosin
(administration & dosage)
- Tachyphylaxis
- Young Adult
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