Combination of alfuzosin and tadalafil exerts an additive relaxant effect on human detrusor and prostatic tissues in vitro.
Eur Urol
; 57(4): 699-707, 2010 Apr.
Article
em En
| MEDLINE
| ID: mdl-19428174
ABSTRACT
BACKGROUND:
Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are highly prevalent in aging men and are strongly linked. Alpha1-blockers such as alfuzosin are effective monotherapies for LUTS. Phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil are the first-line treatment for ED. Both drugs act by two different mechanisms of action on common urogenital target organs and, thus, may have additive effects.OBJECTIVES:
We evaluated in vitro the effects of alfuzosin, tadalafil, and the combination of both on human detrusor and prostatic smooth muscle. DESIGN, SETTING, ANDPARTICIPANTS:
Prostatic and bladder tissue were obtained from patients (n=20 and n=17, respectively) undergoing cystoprostatectomy for bladder cancer. MEASUREMENTS In organ baths, isolated prostatic strips and isolated bladder strips were incubated with vehicle, tadalafil (10â»6 M and 10â»5 M), alfuzosin (3×10â»8 M or 10â»6 M and 10â»5 M) or a combination. Concentration-response curves (CRCs) to norepinephrine were generated on prostatic strips and detrusor strips precontracted with carbachol. Strips were also submitted to electrical field stimulation (EFS). RESULTS ANDLIMITATIONS:
When alfuzosin and tadalafil were combined, the maximal relaxation to norepinephrine on carbachol-precontracted detrusor strips was significantly increased compared with tadalafil alone, and EFS-induced detrusor contractions were better inhibited compared with each compound alone. Tadalafil significantly inhibited norepinephrine-induced prostatic strip contractions by reducing the maximal effect, whereas alfuzosin shifted the CRC of norepinephrine to the right. Combining both tadalafil and alfuzosin resulted in a greater relaxant effect. Likewise, the combination was more effective at reducing EFS-induced contractions compared with each compound alone.CONCLUSIONS:
The combination of alfuzosin and tadalafil exerts an additive effect of inhibiting adrenergic smooth muscle tone of prostatic tissue and EFS-induced detrusor contractions and conversely, of enhancing adrenergic relaxation of detrusor precontracted with carbachol. These experiments provide experimental support for the clinical investigation of the combination of α1-blockers and PDE5 inhibitors in the treatment of LUTS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Próstata
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Quinazolinas
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Bexiga Urinária
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Carbolinas
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Inibidores da Fosfodiesterase 5
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Antagonistas de Receptores Adrenérgicos alfa 1
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Relaxamento Muscular
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Músculo Liso
Limite:
Aged
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Humans
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Male
Idioma:
En
Revista:
Eur Urol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França
País de publicação:
CH
/
SUIZA
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SUÍÇA
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SWITZERLAND