Alpha-adrenergic Blockers for Bladder Emptying

A variety of alpha adrenergic blockers have been used to treat SCI bladder dysfunction. These drugs have been used to target alpha adrenoreceptor blocker subtypes which may be implicated in a variety of mechanisms including bladder neck dysfunction, increased bladder outlet resistance, detrusor-sphincter dyssynergia, autonomic hyperreflexia or upper tract stasis.

Table: Summary of Alpha Adrenergic Blockers

Discussion

Tamsulosin is an alpha1 adrenoreceptor antagonist that has been used to treat SCI bladder neck dysfunction by causing smooth muscles in the bladder neck to relax and improve urine flow rate. A large scale (n=263) study conducted by Abrams et al. (2003), provided evidence for decreased micturition frequency and improvement in urinary leakage parameters for individuals with SCI. This study consisted of a 4 week RCT followed by a longer-term open-label period conducted over a year in persons with overactive bladder with or without dyssynergia. Maximal urethral pressure determined via urethral pressure profilometry was reduced significantly with the longer-term trial (p<0.001) although only a trend was apparent during the one month RCT with 0.4 mg dose (p=0.183) but not with a dose of 0.8 mg (p=0.443). In the 1 year open-label investigation tamsulosin also was associated with several improved cystometry parameters related to bladder storage and emptying, and also resulted in increased mean voided volume values as reported in a patient diary. Given that most positive outcomes were more apparent with the open-label phase, which consisted of a pre-post trial design, this trial has been assigned as level 4 evidence.

Moxisylyte is an alpha adrenoreceptor blocker used commonly in the treatment of Raynaud’s disease where narrowing of the blood vessels in the hands causes numbness and pain in the fingers. Costa et al. (1993) in an n=20 RCT investigated the off-label use of moxisylyte in the treatment of SCI bladder neck dysfunction. With its smooth muscle relaxant property, the decrease in urethral closure pressure was found to be dose related and significant when compared to placebo, with the maximum reduction of 47.6% occurring at 10 minutes after 0.75mg/kg in individuals with SCI.

Terazosin is often used to treat hypertension. However, this alpha-adrenergic blocker is also useful in treating bladder neck dysfunction by relaxing the bladder neck muscles and easing the voiding process. Perkash (1995) reported that although 82% of patients (N=28), with absent detrusor sphincter dyssynergia, perceived improvement in voiding; only 42% registered meaningful objective decreases in maximum urodynamic voiding pressure. Side effects, tolerance and required additional urodynamic monitoring may be deterrents to the wide-spread adoption of terazosin as an alternative treatment for bladder neck dysfunction in SCI individuals. The specificity of terazosin action on the bladder neck, exclusive of the external sphincter, was demonstrated by Chancellor et al. (1993) in a subgroup of SCI patients who had persistent voiding difficulty after previous sphinterotomy subsequent to failed initial terazosin treatment.

Phenoxybenzamine is an antihypertensive usually chosen to treat autonomic symptoms of pheochromocytomas such as high blood pressure or excess sweating. Al-Ali et al. (1999) undertook to utilize the autonomic effects of phenoxybenzamine to treat bladder dysfunction which is in part under autonomic control. Treatment with phenoxybenzamine (n=46 with 41 completers) resulted in a reduction of bladder outlet resistance, detrusor-sphincter dyssynergia or autonomic hyperreflexia in some subjects while no benefits were recorded for areflexive bladders. Phenoxybenzamine can be beneficial as an adjunct treatment for neuropathic bladder following SCI, when tapping or crede is unable to achieve satisfactory residual urine volumes of <100 mL. The lack of efficacy in those with bladder neck dysfunction was specifically noted in this study. Since statistically significant results were not reported in this study, further appropriately sized RCTs would be helpful in providing sufficient evidence for the use of phenoxybenzamine in the treatment of SCI neuropathic bladder.

The pyelouretheral smooth muscle responsible for urethral peristalsis and movement of the urine from the kidneys to the bladder via the ureters is also a potential site of action for alpha 1-receptor antagonist therapy. Linsenmeyer et al. (2002), in a small (n=10) retrospective chart review found that in men with upper tract (i.e. kidneys and ureters) stasis secondary to SCI at or above T6, 6 months of alpha1-blocker therapy provided improvement in upper tract stasis in 80% of subjects who used reflex voiding to manage their bladder as measured by significant decreases of the duration of uninhibited bladder contractions. Firm conclusions about effectiveness and the optimum duration of treatment can only be validated with further RCT trials.

Conclusion

  • Level 1 evidence from a single study suggests that moxisylyte decreases maximum urethral closure pressure by 47.6% at 10 minutes after an optimum dose of 0.75mg/kg in individuals with SCI.
  • There is level 4 evidence from a single study that suggests that tamsulosin may improve bladder neck relaxation and subsequent urine flow in SCI individuals.
  • There is level 4 evidence (two studies, n=28 & 9) that supports terazosin as an alternative treatment for bladder neck dysfunction in SCI individuals provided that side effects and drug tolerance are monitored.
  • There is level 4 evidence derived from a single, case series study involving 46 subjects (41 completers) that indicates some potential for phenoxybenzamine as an adjunct treatment for neurogenic bladder following SCI, when tapping or crede is insufficient to achieve residual urine volume of <100mL. Further evidence is required.
  • Level 4 evidence from 1 small retrospective chart review suggests that 6 months of alpha 1-blocker therapy may improve upper tract stasis secondary to SCI in men by decreasing the duration of involuntary bladder contractions.
     
  • Tamsulosin may improve urine flow in SCI individuals with bladder neck dysfunction.

     

    Mosixylyte is likely able to decrease maximum urethral closure pressure at
    a dose of 0.75mg/kg in individuals with SCI.

     

    Terazosin may be an alternative treatment for bladder neck dysfunction in individuals with SCI. but side effects and drug tolerance should be monitored.

     

    Phenoxybenzamine may be useful as an adjunct therapy for reducing residual
     urine volume in SCI neuropathic bladders maintained by crede or tapping.

     

    Six months of alpha 1-blocker therapy in male SCI patients may improve upper tract stasis.