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- Andersson, Karl-Erik, et al.
(författare)
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Phosphodiesterases (PDEs) and PDE inhibitors for treatment of LUTS
- 2007
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Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 26:6, s. 928-933
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Tidskriftsartikel (refereegranskat)abstract
- Lower urinary tract (LUT) smooth muscle can be relaxed by drugs that increase intracellular concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both of these substances are degraded by phosphodiesterases (PDEs), which play a central role in the regulation of smooth muscle tone. The distribution and functional significance of PDE enzymes vary in different tissues of the LUT. Targeting specific PDE isoenzymes should thus allow organ selectivity. PDE 4 and 5 appear to predominate in the prostate, PDE 1 and 4 are thought to influence detrusor smooth muscle function, and PDE 5 may be functionally important in the urethra and vasculature. Studies on the use of PDE inhibitors to treat various LUT symptoms (LUTS), have yielded favorable results. Thus, positive effects of the PDE 5 inhibitors sildenafil and tadalafil on symptoms and quality of life in men with LUTS, erectile dysfunction, and BPH have also been demonstrated. These effects may be due to effects on cGMP signaling and/or modification of afferent input from bladder, urethral, and prostate tissue. This review gives an update on the distribution of PDEs in structures relevant for LUT function, and discusses how inhibition of these enzymes can contribute to beneficial effects on LUTS. Information for the review was obtained from searches of the PubMed database, and from the authors' files.
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- Hashim, Hashim, et al.
(författare)
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Desmopressin, as a "Designer-Drug," in the Treatment of Overactive Bladder Syndrome
- 2009
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Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 28:1, s. 40-46
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study looked at whether oral desmopressin, by decreasing kidney urine production, would prolong bladder filling-time thereby increasing the time to reach maximum capacity, thus reducing overactive bladder (OAB) symptoms, and providing an alternative method of treatment to OAB sufferers. Methods: An investigator-initiated, 2-week, multi-national, multi-centre, "proof-of-concept," phase IIb, double-blind, placebo-controlled, prospective, randomized, cross-over study was conducted using 0.2 mg of oral desmopressin in adults suffering with OAB. Patients were included in the trial period if they had >= 4 voids in the first 8-hr of the day after rising, excluding the first morning void. The primary endpoint was evaluation of effectiveness of desmopressin in increasing the time to the first OAB symptom episodes during the first 8-hr following treatment. Results: Time to first void was 8-min later on the drug than on placebo (P = 0.27). However, the drug led to one less void (3.2 vs. 4.2) in the same period (P < 0.001). There was an increase in the time to first urgency episode with a decrease in the number of urgency episodes in the drug days compared to placebo (P < 0.003). There was a subjective improvement in frequency and urgency and overall quality-of-life as measured by the ICIQ-OAB. Twenty-seven people reported adverse events which were all mild, headache being the commonest and no hyponatremia was recorded. Conclusions: Antidiuresis, using oral desmopressin tablets, is a novel, feasible and safe (short-term basis) method of treatment for adults with OAB, and could be considered in the armamentarium of drugs available for the treatment of OAB. Neurourol. Urodynam. 28:40-46, 2009. (C) 2008 Wiley-Liss, Inc.
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- Jiang, Chonghe, et al.
(författare)
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Gating of the Micturition Reflex by Tonic Activation of Bladder Cold Receptors in the Cat
- 2009
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Ingår i: NEUROUROLOGY AND URODYNAMICS. - : Wiley. - 0733-2467 .- 1520-6777. ; 28:6, s. 555-560
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To determine whether C afferents can modify the gating of the A delta micturition reflex in order to identify the neuronal site of interaction of the two afferent systems. Methods: Adult female cats, anaesthetized with a.-chloralose, had their bladder and urethra catherized through a slit in the proximal urethra. Micturition threshold volume was assessed by cystometry and bladder efferent activity recorded simultaneously. The bladder was filled at a slow rate (1.2-3.5 ml/min) with either body-warm saline (control) or menthol solution (0.06 mM) or by cold saline (4 degrees C). Results: Of 14 trial sessions in 5 animals, the threshold volume of the A delta micturition reflex was consistently reduced by menthol infusions from a control median (md) value of 16.8 to 10.2 ml (P andlt; 0.01). The threshold pressure was also somewhat decreased from and 0.7 to 0.5 kPa (P andlt; 0.05), while the peak pressure or pressure slope did no differ in two situations. Similar results were obtained with slow cold infusions into the bladder (nine sessions in three animals). The threshold volume decreased from and 19.8 to 17.4 ml (P andlt; 0.05). The bladder reflex response to slow menthol or cold infusions had the typical features of an A delta micturition reflex in that the efferent activity was largely abolished by the bladder A delta mechanoreceptor unloading. Conclusions: Gradual tonic activation of bladder cold receptors lowers the threshold volume of the ordinary A delta micturition, pointing to a segmental spinal mechanism for the gating of the micturition reflex. Neurourol. Urodyrzam. 28:555-560, 2009.
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- Lee, Tack, et al.
(författare)
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Simultaneous registration of intraabdominal and intravesical pressures during cystometry in conscious rats-effects of bladder outlet obstruction and intravesical PGE(2)
- 2008
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Ingår i: Neurourology and Urodynamics. - : John Wiley and Sons, Ltd. - 0733-2467 .- 1520-6777. ; 27:1, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: A method was developed and evaluated to simultaneously register intraabdominal pressure (IAP) and intravesical pressure (IVP) during cystometry in conscious rats. In addition, IAP and IVP were recorded in rats with experimental detrusor overactivity (DO).METHODS: Sprague Dawley rats (n = 24) were used. Six female rats were subjected to partial bladder outlet obstruction for 2 weeks. A catheter was implanted into the bladder to record the IVP, and a balloon-fitted catheter was positioned in the abdominal cavity to record the IAP. PGE(2) was given intravesically to induce DO. Detrusor pressure (DP) was defined as the IVP corrected for IAP.RESULTS: Recorded as increases in IAP, all rats of both sexes exhibited abdominal straining during every void. In controls, a maximal IAP of 6.0 +/- 1.4 cmH(2)O (range 3-15 cmH(2)O) was registered (n = 12) at the time of the flow pressure (FP). Intravesical administration of PGE(2) or BOO did not affect the IAP at basal pressure, FP or micturition pressure. Changes in IAP due to movement or non-voiding-related straining were subtracted from IVP to generate DP and to visualize DO after BOO or intravesical PGE(2).CONCLUSIONS: The conscious rat uses abdominal straining during voiding, and maximal IAP is recorded at the onset of urinary flow. Simultaneous registration of IAP and IVP during the micturition cycle in conscious rats is a convenient method for accurate quantification of pressures inside the bladder and for studying "true" DO without interference from movement artifacts
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