The effect of drugs on isolated detrusor muscle contraction.

Detrusor instability is the commonest type of urinary incontinence in the elderly and is present in up to 50% of patients attending continence clinics. Treatment of this condition, aimed at reducing uncontrollable detrusor contractions, is at present unsatisfactory. For example, calcium antagonists are cliniclly disappointing and studies were carried out to investigate why they are ineffective. Rats were treated with nimodipine for 8 days or with a single dose. Treatment for 8 days had no effect on isolated detrasor contraction but a single dose reduced detrasor contractile response. It is propossed that chronic treatment with nimodipine caused an up-regulation of calcium channels as a compensatory mechanism. Oestrogens have been shown to have an inhibitory effect on detrusor muscle contraction after in vitro and in vivo treatment. In post-menopausal women with a uterus unopposed oestrogens should not be given, but progesterone has anti-oestrogenic actions. When rats were treated with oestrogen and progesterone for 8 days, there was no effect on rat detrasor contractile response. An anti-oestrogenic effect of progesterone has therefore been demonstrated in rat detrusor smooth muscle. Caffeine has been shown to increase detrasor pressme on bladder filling in patients with detrusor instability. The effect of low concentrations of caffeine on the contractile response of isolated human and rat detrusor muscle was therefore determined. Caffeine was found to have only a slight potentiating effect on isolated human and rat detruosr muscle contraction. The results in this thesis have important clinical imphcations for the treatment of detrusor instability. It may be more effective to administer calcium antagonists in an intermittent manner. Oestrogens are better given alone or with the lowest possible dose of progestogens. Caffeine would not be contraindicated in patients with detrusor instability.