Urinary incontinence

The bladder serves as a reservoir for the continual production of urine by the kidney (Fig. 3.31.1). Failure to store and empty urine appropriately gives rise to urge urinary incontinence (UUI) and stress urinary incontinence (SUI), respectively.

Fig. 3.31.1 Bladder control.

There is a strong desire to void in UUI as a result of an overactive bladder arising from a neurogenic dysfunction (e.g. Alzheimer’s disease, Parkinson’s disease, stroke and spinal cord injury). Muscarinic antagonists are used to reduce bladder contractility. Oxybutynin is a potent non-selective competitive muscarinic antagonist and is metabolized in the liver to the N-desethyl metabolite. Newer muscarinic antagonists show greater selectivity for the bladder over the salivary glands (tolterodine, darifenacin) and, therefore, offer better tolerability.

In SUI, the urethral smooth muscle and sphincter are unable to generate sufficient resistance to retain urine in the bladder. The most common cause is weakness in the sphincter, which may arise from childbirth, pelvic surgery or in postmenopausal women because of a lack of oestrogen. In men, it can arise following prostate surgery. Norepinephrine from sympathetic nerves innervating urethral smooth muscle activates a number of α-adrenoceptor subtypes including α_1A-, α_1B– and α_1D-adrenoceptors, thereby contracting smooth muscle and increasing resistance, which reduces the flow of urine.

Midodrine (Portugal and Finland) and phenylpropanolamine (USA) are non-selective α-agonists and have limited usefulness because of a lack of selectivity for the bladder, with potential for unacceptable increase in blood pressure. An alternative approach is to enhance the activity of serotonin pathways within the CNS, which is known to exert an inhibitory action on parasympathetic input to the bladder and thereby reduce voiding. Duloxetine a specific inhibitor of serotonin and norepinephrine uptake, increases the activation of 5HT_1A inhibitory pathways, thereby reducing voiding. A peripheral mechanism may also contribute toward the effects of this drug by preventing reuptake of norepinephrine in the bladder and thereby increasing the concentration of norepinephrine at neuroeffector sites in urethral smooth muscle and increasing urethral pressure.