Effects of Alfuzosin, an α 1 -Adrenergic Antagonist, on Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders

Subhankar Chakraborty, Kelly Feuerhak, Anjani Muthyala, William S. Harmsen, Kent R. Bailey, Adil Eddie Bharucha

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Some patients with defecatory disorders (DD) have high anal pressures that may impede rectal evacuation. Alpha-1 adrenoreceptors mediate as much as 50% of anal resting pressure in humans. We performed a randomized, placebo-controlled study of the effects of alfuzosin, an alpha1-adrenergic receptor antagonist, on anal pressures alone in healthy women and also on bowel symptoms in women with DD. Methods: In a double-blind study performed from March 2013 through March 2017, anal pressures were evaluated before and after 36 women with DD (constipation for at least 1 year) and 36 healthy women (controls) were randomly assigned (1:1) to groups given oral alfuzosin (2.5 mg immediate release) or placebo. Thereafter, patients were randomly assigned (1:1) to groups given oral alfuzosin (10 mg extended release) or placebo each day for 2 weeks. Participants kept daily diaries of bowel symptoms for 2 weeks before (baseline) and during administration of the test articles (treatment). Weekly questionnaires recorded the overall severity of constipation symptoms, bloating, abdominal pain, nausea, and vomiting; overall satisfaction with treatment of constipation was evaluated at weeks 2 and 4. The primary endpoint was the change in the number of spontaneous (SBMs) and complete SBMs (CSBMs) between the treatment and baseline periods. We evaluated relationships between stool form, passage, and complete evacuation. Results: Alfuzosin reduced anal resting pressure by 32 ± 3 mm Hg versus 16 ± 3 mm Hg for placebo (P =.0001) and anal pressure during evacuation by 26 ± 3 mm Hg versus 16 ± 3 mm Hg for placebo, (P =.03). However, alfuzosin did not significantly increase the rectoanal gradient, SBMs or CSBMs compared with placebo. Both formulations of alfuzosin were well tolerated. Hard stools and the ease of passage during defecation accounted for 72% and 76% of the variance in the satisfaction after defecation, respectively, during baseline and treatment periods. Conclusions: In a randomized trial, alfuzosin reduced anal pressure at rest and during simulated evacuation in healthy and constipated women, compared with placebo, but did not improve bowel symptoms in constipated women. This could be because the drug does not improve stool form or dyssynergia, which also contribute to DD. ClinicalTrials.gov number, NCT 01834729.

Original languageEnglish (US)
JournalClinical Gastroenterology and Hepatology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Adrenergic Antagonists
Habits
Placebos
Pressure
Constipation
Defecation
Ataxia
Therapeutics
alfuzosin
Double-Blind Method
Nausea
Abdominal Pain
Vomiting
Pharmaceutical Preparations

Keywords

  • Anal Manometry
  • Anismus
  • Biofeedback
  • Sympathetic Nervous System

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Effects of Alfuzosin, an α 1 -Adrenergic Antagonist, on Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders . / Chakraborty, Subhankar; Feuerhak, Kelly; Muthyala, Anjani; Harmsen, William S.; Bailey, Kent R.; Bharucha, Adil Eddie.

In: Clinical Gastroenterology and Hepatology, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Harmsen, William S.

AU - Bailey, Kent R.

AU - Bharucha, Adil Eddie

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