The main abnormalities that require treatment are:
• Unstable bladder or detrusor instability, characterised by uninhibited, unstable contractions of the detrusor which may be of unknown aetiology or secondary to an upper motor neuron lesion or bladder neck obstruction.
• Decreased bladder activity or hypotonicity due to a lower motor neuron lesion or overdistension of the bladder or to both.
• Urethral sphincter dysfunction which is due to various causes including weakness of the muscles and ligaments around the bladder neck, descent of the urethrovesical junction and periurethral fibrosis; the result is stress incontinence.
• Atrophic change affects the distal urethra in females.
Drugs that may be used to alleviate abnormal micturition
Antimuscarinic drugs such as oxybutynin and flavoxate are used to treat urinary frequency; they increase bladder capacity by diminishing unstable detrusor contractions. Both drugs may cause dry mouth and blurred vision and may precipitate glaucoma. Oxybutynin has a high level of unwanted effects which limits its use; the dosage needs to be carefully assessed, particularly in the elderly. Flavoxate has less marked side effects but is also less effective. Propiverine, tolterodine and trospium are also antimuscarinic drugs which have been introduced for urinary frequency, urgency and incontinence. Propantheline was formerly widely used in urinary incontinence but had a low response rate and a high incidence of adverse effects; it is now used mainly for adult enuresis. The need for continuing antimuscarinic drug therapy should be reviewed after 6 months.
Tricyclic antidepressants. Imipramine, amitripty-line and nortriptyline are effective, especially for nocturnal but also for daytime incontinence. Their parasympathetic blocking (antimuscarinic) action is probably in part responsible but imipramine may also benefit by altering the patient's sleep profile.
Oestrogens either applied locally to the vagina or taken by mouth may benefit urinary incontinence due to atrophy of the urethral epithelium in menopausal women.
Parasympathomimetic drugs, e.g. bethanechol, car-bachol and distigmine, may be used to stimulate the detrusor when the bladder is hypotonic, e.g. due to an upper motor neuron lesion. Distigmine, which is an anticholinesterase, is preferred but, as its effect is not sustained, intermittent catheterisation is also needed when the hypotonia is chronic.
BENIGN PROSTATIC HYPERPLASIA (BPH)
One of the commonest problems in men older than 50, BPH was for a long time helped only by surgical interventions, which themselves were an outstanding example of the different (usually absent) rules that apply in the assessment of surgical compared to pharmacological treatments. Many are the men who would have opted for continuing micturition frequency in preference to the impotence, incontinence or pulmonary emboli that awaited them after transurethral resection; few are the drugs which would survive such complications, whatever the benefits. Now there is a limited choice between medical and surgical approaches, although these have never been formally compared, and the drugs are not a substitute for surgery if urinary retention has occurred. The prostate gland is a mixture of capsular and stromal tissue, rich in a^-adrenoceptors, and glandular tissue under the influence of androgens. Both these, the a-receptors and androgens, are targets for drug therapy. Because the bladder itself has few a-receptors, it is possible to use selective «.j-blockade without affecting bladder contraction.
Alpha-adrenoceptor antagonists. Prazosin, afluzosin, indoramin, terazosin and doxazosin are all a-adrenoceptor blockers, with selectivity for the a,-subtype. They cause significant increases (compared to placebo) in objective measures such as maximal urine flow rate, and drugs also improve semi-objective symptoms scores. In normotensive men, they cause generally negligible falls in blood pressure; in hypertensive patients, the fall in pressure can be regarded as an added bonus (provided concurrent treatment is adjusted accordingly). These drugs can cause dizziness and asthenia even in the absence of marked changes in blood pressure. Nasal stuffiness can be a problem — especially in patients who resort to a agonists (e.g. pseudoephedrine) for rhinitis. These adverse events are avoided by using tamsulosin. This is selective for the alc-subclass of adrenoceptors, and therefore does not block the vascular aj-receptor responsible for the undesired effects of other a blockers. It is taken as a single 400 microgram dose each day.
Finasteride. An alternative drug for such prostatic symptoms is the type II 5a-reductase inhibitor, finasteride, which inhibits conversion of testosterone to its more potent metabolite, dihydrotestoster-one. Finasteride does not affect serum testosterone, or most nonprostatic responses to testosterone. It reduces prostatic volume by about 20% and increases urinary flow rates by a similar degree. These changes translate into only modest clinical benefits. Finasteride has a t1/2 of 6 h, and is taken as a single 5mg tablet orally each day. The improvement in urine flow appears over 6 months (as the prostate shrinks in size) and in 5-10% of patients may be at the cost of some loss of libido. The serum concentration of prostate-specific antigen is approximately halved. While this may reflect a real reduction in risk of prostatic cancer, in patients receiving finasteride it is safer to regard as abnormal, values of the antigen in the upper half of the usual range. Lower doses of finasteride have been used successfully to halt the development of baldness.5 Other antiandrogens, such as the gonadorelin agonists, are used in the treatment of prostatic cancer, but the need for parenteral administration makes them less suitable for BPH.
5 Paradoxically, it has also been used as a treatment for hirsutism in women. Tartagni M et al 2000 Fertility and Sterility 73: 718-723.
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