Tags

Type your tag names separated by a space and hit enter

Effects of Alfuzosin, an α1-Adrenergic Antagonist, on Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders.
Clin Gastroenterol Hepatol. 2019 05; 17(6):1138-1147.e3.CG

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.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: bharucha.adil@mayo.edu.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30130627

Citation

Chakraborty, Subhankar, et al. "Effects of Alfuzosin, an α1-Adrenergic Antagonist, On Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders." Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, vol. 17, no. 6, 2019, pp. 1138-1147.e3.
Chakraborty S, Feuerhak K, Muthyala A, et al. Effects of Alfuzosin, an α1-Adrenergic Antagonist, on Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders. Clin Gastroenterol Hepatol. 2019;17(6):1138-1147.e3.
Chakraborty, S., Feuerhak, K., Muthyala, A., Harmsen, W. S., Bailey, K. R., & Bharucha, A. E. (2019). Effects of Alfuzosin, an α1-Adrenergic Antagonist, on Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders. Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association, 17(6), 1138-e3. https://doi.org/10.1016/j.cgh.2018.08.036
Chakraborty S, et al. Effects of Alfuzosin, an α1-Adrenergic Antagonist, On Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders. Clin Gastroenterol Hepatol. 2019;17(6):1138-1147.e3. PubMed PMID: 30130627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of Alfuzosin, an α1-Adrenergic Antagonist, on Anal Pressures and Bowel Habits in Women With and Without Defecatory Disorders. AU - Chakraborty,Subhankar, AU - Feuerhak,Kelly, AU - Muthyala,Anjani, AU - Harmsen,William S, AU - Bailey,Kent R, AU - Bharucha,Adil E, Y1 - 2018/08/18/ PY - 2018/04/19/received PY - 2018/08/08/revised PY - 2018/08/09/accepted PY - 2018/8/22/pubmed PY - 2020/9/24/medline PY - 2018/8/22/entrez KW - Anal Manometry KW - Anismus KW - Biofeedback KW - Sympathetic Nervous System SP - 1138 EP - 1147.e3 JF - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JO - Clin. Gastroenterol. Hepatol. VL - 17 IS - 6 N2 - 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. SN - 1542-7714 UR - https://www.unboundmedicine.com/medline/citation/30130627/Effects_of_Alfuzosin_an_α1_Adrenergic_Antagonist_on_Anal_Pressures_and_Bowel_Habits_in_Women_With_and_Without_Defecatory_Disorders_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1542-3565(18)30874-7 DB - PRIME DP - Unbound Medicine ER -