| Tadalafil for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia: pathophysiology and mechanism(s) of action. | |
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MedLine Citation:
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PMID: 21284024 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The PDE5 inhibitor tadalafil is investigation for the treatment of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Several clinical studies of tadalafil and other PDE5 inhibitors have reported significant symptom reduction but limited urinary flow rate improvement. This manuscript reviews the published literature describing the pathophysiology of male LUTS, with an emphasis on mechanisms that may be modulated or improved by phosphodiesterase type 5 (PDE5) inhibition. METHODS: Literature (through March 2010) was obtained via Medline searches and from the individual reviewers files. Articles were selected for review based on describing in vitro, preclinical, or clinical studies of pathological processes contributing to LUTS, or possible effects of PDE5 inhibition in the lower urinary tract. RESULTS: Major mechanisms contributing to LUTS include: reduced nitric oxide/cyclic guanosine monophosphate signaling; increased RhoA kinase pathway activity; autonomic overactivity; increased bladder afferent activity; and pelvic ischemia. Tadalafil and other PDE5 inhibitors have demonstrated beneficial effects on smooth muscle relaxation, smooth muscle and endothelial cell proliferation, nerve activity, and tissue perfusion that may impact LUTS in men. CONCLUSIONS: The pathophysiology of male LUTS is complex and not completely understood. LUTS may occur independently of BPH or secondary to BPH but in both cases involve obstructive or irritative mechanisms with substantial pathophysiological overlap. While the precise mechanism remains unclear, inhibition of PDE5 seems to have an effect on several pathways that may impact LUTS. |
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Authors:
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Karl-Erik Andersson; William C de Groat; Kevin T McVary; Tom F Lue; Mario Maggi; Claus G Roehrborn; Jean Jacques Wyndaele; Thomas Melby; Lars Viktrup |
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Publication Detail:
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Type: Journal Article; Review Date: 2011-01-31 |
Journal Detail:
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Title: Neurourology and urodynamics Volume: 30 ISSN: 1520-6777 ISO Abbreviation: Neurourol. Urodyn. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-17 Completed Date: 2011-06-30 Revised Date: 2012-08-10 |
Medline Journal Info:
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Nlm Unique ID: 8303326 Medline TA: Neurourol Urodyn Country: United States |
Other Details:
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Languages: eng Pagination: 292-301 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
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Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. karl-erik.andersson@klinfarm.lu.se |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Carbolines
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therapeutic use* Evidence-Based Medicine Humans Male Phosphodiesterase 5 Inhibitors / therapeutic use* Prostatic Hyperplasia / complications*, physiopathology Recovery of Function Signal Transduction / drug effects Treatment Outcome Urodynamics / drug effects Urologic Diseases / drug therapy*, etiology, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/Carbolines; 0/Phosphodiesterase 5 Inhibitors; 0/tadalafil |
| Comments/Corrections | |
Comment In:
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Neurourol Urodyn. 2012 Jun;31(5):706
[PMID:
22488565
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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