無抑制型神経因性膀胱の薬物療法 -尿水力学的検査法によるTimepidium Bromideの薬理効果の検討-

Abstract

Thirty patients with recurrent urinary tract infection or urinary incontinence were diagnosed as reflex neurogenic bladder including uninhibited neurogenic bladder or unstable bladder by a series of tests including urological routine tests, roentgenography (mainly, voiding cysto-urethrography), urodynamic and electrophysiologic examinations, urethral pressure profile, and endoscopic examinations, and by EEG and myelography for some cases. Some of them were treated with timepidium bromide, an anti-cholinergic agent, and the effects were evaluated by urodynamic examinations before and after the treatment. Other patients were subcutaneously injected with bethanecol chloride and 30 minutes later subjected to urodynamic examinations. Then, they were intramuscularly injected with timepidium bromide, and again subjected to urodynamic examination 30 minutes later. The latter trial was an attempt to make vesical and urethral smooth muscles more unstable and in these conditions to probe the efficacy of timepidium more clearly. The urodynamic examinations used in this series were Lewis' cystometrogram for the bladder filling phase and the voiding urodynamic examination (VUD) for the voiding phase with a 6 channel polygraph that simultaneously measured the vesical, urethral and intra-abdominal pressures, tonus and E M G of the anal sphincter, and urinary flow rate. The subjects studied consisted of 6 males and 24 females from the age 6 to 65 (22 children and 8 adults), and of 13 cases of unstable bladder and 17 cases of uninhibited neurogenic bladder. Timepidium bromide was very effective in 63%, and only moderately effective in 20% of the treated patients. The effects of the drug were evaluated on the three voiding parameters, i. e. the bladder volumes at the first desire to void, maximal desire to void and maximal vesical voiding pressure before and after administration of the drug, and analyzed by Student "t" test to give the following results; the first two parameters were greater with P<0.001 and the last parameter smaller with 0.01 >P>0.001 after than before the treatment. This indicates that the vesical capacity increased and the voiding pressure decreased after the treatment with timepidium with high degrees of statistical significance. In other words, the lowered vesical capacity and the hypertonic condition in uninhibited neurogenic bladder were alleviated by the treatment with timepidium. Comparison of the urodynamic patterns on the 6 channel polygraph between pre- and post-administration measurements revealed a decrease or complete disappearance of the involuntary detrusor contractions during the filling phase after the drug treatment. It was worthy of note that the secondary spastic condition of the pelvic floor musculature due to the involuntary contractions of the detrusor decreased or nearly disappeared after the treatment. This latter aspect seemed to be the one of the most important actions in the mechanism for the prevention of recurrent urinary tract infection and enuresis. The urodynamic patterns during the voiding phase indicated that the treatment with timepidium diminished or eliminated the fluctuations of the vesical and the urethral pressures observed before and after the voiding phase. Improvement of dyssynergia between detrusor and external urethral sphincter was not clearly observed. In conclusion, the treatment with anti-cholinergic agents such as timepidium should constitute the standard therapy for uninhibited neurogenic bladder and unstable bladder, and such an agent may be indicated in combination with other drugs according to symptoms. For example, the use of timepidium with tolperisone hydrochloride or diazepam should be taken into consideration when the spasm of the pelvic floor musculature appears. Large doses of an anti-cholinergic agent may be necessary for the uninhibited neurogenic bladder as a sequel of cerebral infantile paralysis or other brain diseases. In these cases, combined medication with flavoxate or imipramine should be warranted.