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Other Pharmaceutical Treatments for Bladder Emptying

Beyond the typical alpha adrenergic and botulinum toxin approaches to improving bladder emptying, other pharmaceutical interventions have been explored. While these approaches still are few in number, this section describes primarily the use of 4-Aminopyridine (Grijalva et al. 2010) and isosorbide dinitrate (Reitz et al. 2004). 4-Aminopyridine prepared in various commercial formulations for the treatment of MS-related walking difficulties is also known as fampridine [ampyra, fampyra]. Most SCI specific studies involving 4-Aminopyridine assess bladder sensation and/ or control with respect to outcomes relevant to bladder management; often conducting more global assessments of function following treatment. This section reports only on bladder specific outcomes.

Table 10 Other Pharmaceutical Treatments for Bladder Emptying

Author Year

Country
Score
Research Design
Total Sample Size

MethodsOutcome
Grijalva et al. 2010

Mexico

Phase 1: RCT; N=14

Phase 2: Pre-Post

PEDro=9

N=12

Population: AIS A; Mean age=29 years; male=10, female=4; Level of injury: C=7, T=7; Time since injury=6.21 years

Intervention: 30 mg of 4-aminopyridine per day

Outcome Measures: Scores of the ASIA motor and sensory scales, the SCIM, sphincter control and somatosensory evoked potentials

1.     3 individuals were able to walk without assistance and 1 individual changed to an incomplete injury.

2.     In terms of bladder sensation and control, 5 individuals reported an improvement while 4 out of 9 male individuals had psychogenic erection.

3.     7 individuals showed improvement in somatosensory evoked potentials.

4.     1 individual suffered epileptic seizures and another had persistent anxiety and insomnia.

Reitz et al. 2004

Switzerland

Pre-Post

N=12

Population: Mean age: 32 yr (range 29-36 yr); Gender: males=12, females=0.

Intervention: Following a bladder emptying by clean intermittent catheterization (n=6) and suprapubic tapping (n=6), individuals were sublingually administered 10 mg of isosorbide dinitrate.

Outcome Measures: Maximal bladder pressure, external urethral sphincter pressure, reflex volume, and residual volume.

1.     External urethral sphincter pressure at both rest and dyssynergic contraction reduced significantly after nitric oxide treatment (p<0.05; p<0.05); however, bladder pressures at rest and during contraction as well as reflex volume remain unchanged.

2.     In the individuals who used suprapubic tapping for bladder emptying the mean post triggering residual volume was significantly reduced (p<0.05).

Discussion

4-Aminopyridine is a potassium channel blocker, prolonging action potentials and increasing neurotransmitter release at the neuromuscular junction. Only one study to date, Grijalva et al. (2010), has explicitly commented on bladder function following administration of fampridine. During the open-label portion of the study where dosage levels of fampridine peaked, 3 of 12 participants regained both sensation and control of the bladder sphincter, and 1 of 12 regained sensation only. The paucity of literature in this area does not yet warrant fampridine as a primary treatment of bladder management in SCI.

Isosorbide dinitrate is a drug typically used to prevent angina attacks. However, it has been studied for the use of improving bladder function among 12 males post SCI (Reitz et al. 2004). In this single pre-post study, it was found that isosorbide dinitrate reduced external urethral sphincter pressure along with dyssynergic contraction; however, bladder pressures remained unchanged.

Conclusion

There is level 4 evidence (from one pre-post study; Reitz et al. 2004) that isosorbide dinitrate may be effective in reducing eternal urethral pressure and dyssynergic contraction.

There is level 4 evidence (from one pre-post study; Griljava et al. 2010) that 4-aminopyridine, at sufficient dosage, may be effective in restoring sensation and/ or control of the bladder sphincter.

Isosorbide dinitrate may improve control of the bladder post SCI; although, more evidence is needed to support this as a treatment option.

4-Aminopyridine at sufficient dosage may return sensation and control of the bladder sphincter following SCI; more evidence is needed to support this as a treatment option.