Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion

Sriram Vaidyanathan, Peter Williamson, Karine Clearie, Faisel Khan, Brian Lipworth (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    39 Citations (Scopus)

    Abstract

    Rationale: Chronic use of intranasal decongestants, such as oxymetazoline, leads to tachyphylaxis of response and rebound congestion, caused by a-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 mu g three times a day for 14 days, followed by the addition of fluticasone, 200 mu g 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 . min(-1); -63.9 to -31.9; P < 0.001) and the DRC shifted downward (24.8 L min(-1); 20.3-29.3; P < 0.001). On Day 17 versus Day 14, after fluticasone, inspiratory flow increased (45 L min(-1); 30-61; P < 0.001) and the DRC shifted upward (26.2 L . min(-1); 21.7-30.7; P < 0.001). On Day 1, prazosin reduced inspiratory flow (-52.6 L min(-1); -19.2 to -86) compared with baseline. This effect was abolished on Day 14 (7.91 . 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.

    Original languageEnglish
    Pages (from-to)19-24
    Number of pages6
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume182
    Issue number1
    Early online date4 Mar 2010
    DOIs
    Publication statusPublished - 1 Jul 2010

    Keywords

    • Alpha-adrenergic receptors
    • Tachyphylaxis
    • Oxymetazoline
    • Fluticasone
    • Up-regulation
    • Human nasal mucosa
    • Seasonal allergic rhinitis
    • Acoustic rhinometry
    • Spray
    • Medicamentosa
    • Prazosin
    • Subtypes
    • Disease

    Cite this

    @article{339deb7ea250436c884d81a3cdfb88e7,
    title = "Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion",
    abstract = "Rationale: Chronic use of intranasal decongestants, such as oxymetazoline, leads to tachyphylaxis of response and rebound congestion, caused by a-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 mu g three times a day for 14 days, followed by the addition of fluticasone, 200 mu g 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 . min(-1); -63.9 to -31.9; P < 0.001) and the DRC shifted downward (24.8 L min(-1); 20.3-29.3; P < 0.001). On Day 17 versus Day 14, after fluticasone, inspiratory flow increased (45 L min(-1); 30-61; P < 0.001) and the DRC shifted upward (26.2 L . min(-1); 21.7-30.7; P < 0.001). On Day 1, prazosin reduced inspiratory flow (-52.6 L min(-1); -19.2 to -86) compared with baseline. This effect was abolished on Day 14 (7.91 . 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.",
    keywords = "Alpha-adrenergic receptors, Tachyphylaxis, Oxymetazoline, Fluticasone, Up-regulation, Human nasal mucosa, Seasonal allergic rhinitis, Acoustic rhinometry, Spray, Medicamentosa, Prazosin, Subtypes, Disease",
    author = "Sriram Vaidyanathan and Peter Williamson and Karine Clearie and Faisel Khan and Brian Lipworth",
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    Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion. / Vaidyanathan, Sriram; Williamson, Peter; Clearie, Karine; Khan, Faisel; Lipworth, Brian (Lead / Corresponding author).

    In: American Journal of Respiratory and Critical Care Medicine, Vol. 182, No. 1, 01.07.2010, p. 19-24.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion

    AU - Vaidyanathan, Sriram

    AU - Williamson, Peter

    AU - Clearie, Karine

    AU - Khan, Faisel

    AU - Lipworth, Brian

    PY - 2010/7/1

    Y1 - 2010/7/1

    N2 - Rationale: Chronic use of intranasal decongestants, such as oxymetazoline, leads to tachyphylaxis of response and rebound congestion, caused by a-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 mu g three times a day for 14 days, followed by the addition of fluticasone, 200 mu g 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 . min(-1); -63.9 to -31.9; P < 0.001) and the DRC shifted downward (24.8 L min(-1); 20.3-29.3; P < 0.001). On Day 17 versus Day 14, after fluticasone, inspiratory flow increased (45 L min(-1); 30-61; P < 0.001) and the DRC shifted upward (26.2 L . min(-1); 21.7-30.7; P < 0.001). On Day 1, prazosin reduced inspiratory flow (-52.6 L min(-1); -19.2 to -86) compared with baseline. This effect was abolished on Day 14 (7.91 . 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.

    AB - Rationale: Chronic use of intranasal decongestants, such as oxymetazoline, leads to tachyphylaxis of response and rebound congestion, caused by a-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 mu g three times a day for 14 days, followed by the addition of fluticasone, 200 mu g 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 . min(-1); -63.9 to -31.9; P < 0.001) and the DRC shifted downward (24.8 L min(-1); 20.3-29.3; P < 0.001). On Day 17 versus Day 14, after fluticasone, inspiratory flow increased (45 L min(-1); 30-61; P < 0.001) and the DRC shifted upward (26.2 L . min(-1); 21.7-30.7; P < 0.001). On Day 1, prazosin reduced inspiratory flow (-52.6 L min(-1); -19.2 to -86) compared with baseline. This effect was abolished on Day 14 (7.91 . 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.

    KW - Alpha-adrenergic receptors

    KW - Tachyphylaxis

    KW - Oxymetazoline

    KW - Fluticasone

    KW - Up-regulation

    KW - Human nasal mucosa

    KW - Seasonal allergic rhinitis

    KW - Acoustic rhinometry

    KW - Spray

    KW - Medicamentosa

    KW - Prazosin

    KW - Subtypes

    KW - Disease

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    JO - American Journal of Respiratory and Critical Care Medicine

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