Effects of the Inverse Alpha-Agonist Doxazosin in Allergic Rhinitis

Clin Exp Allergy. 2016 May;46(5):696-704. doi: 10.1111/cea.12700.

Abstract

Background: We examined the paradoxical hypothesis that the alpha-receptor inverse agonist doxazosin might produce beneficial effects in allergic rhinitis.

Objectives: To evaluate single and chronic dosing effects of doxazosin on nasal airflow and symptoms in allergic rhinitis.

Methods: Fifteen patients randomized to receive 3-5 weeks of oral doxazosin 4 mg daily or placebo in crossover fashion. Measurements were taken at baseline and after first and last doses.

Results: There was a fall in peak nasal inspiratory flow (PNIF) between baseline vs. first dose of doxazosin: mean difference -19 L/min (95% CI -35 to -2) P = 0.03, with recovery between first and last doses: 21 L/min (95% CI 7-34) P = 0.006. Nasal visual analogue scale (VAS) and blockage scores were worse between baseline vs. first dose of doxazosin: mean difference VAS -10 mm (95% CI -18 to -2) P = 0.02, blockage -0.7 (95% CI -1.3 to -0.1) P = 0.02, with recovery between first and last doses: VAS 15 mm (95% CI 4-25) P = 0.009, blockage 1.1 (95% CI 0.5-1.6) P = 0.001. The oxymetazoline dose-response for PNIF was blunted after single vs chronic dosing with doxazosin: mean difference -17 L/min (95% CI -30 to -4) P = 0.01. Heart rate and diastolic blood pressure showed the same pattern. There was a significant difference between doxazosin and placebo for nasal blockage score and heart rate after single but not chronic dosing.

Conclusions: There was a disconnect between single and chronic dosing effects of doxazosin for nasal symptoms, oxymetazoline response and cardiovascular outcomes, in turn suggesting alpha-1 receptor up-regulation.

Trial registration: ClinicalTrials.gov NCT01946035.

Keywords: Allergic rhinitis; alpha-receptor antagonist; alpha-receptor inverse agonist; doxazosin; peak nasal inspiratory flow.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / administration & dosage
  • Adrenergic alpha-1 Receptor Antagonists / adverse effects
  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use*
  • Biomarkers
  • Doxazosin / administration & dosage
  • Doxazosin / adverse effects
  • Doxazosin / therapeutic use*
  • Female
  • Humans
  • Male
  • Nasal Provocation Tests
  • Rhinitis, Allergic / diagnosis
  • Rhinitis, Allergic / drug therapy*
  • Rhinitis, Allergic / immunology
  • Rhinitis, Allergic / metabolism
  • Skin Tests
  • Treatment Outcome

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Biomarkers
  • Doxazosin

Associated data

  • ClinicalTrials.gov/NCT01946035