Thursday, 12 July 2012

Drugs In The Management of Incontinence

Drugs commonly used for the management of female urinary incontinence can be categorized into the following categories:-

1.     Drugs for overactive Bladder ( OAB)
2.     Drugs for Hypocontractile Bladder
3.     Drugs for Stress Urinary Incontinence
4.  Drugs Acting Outside The Urinary Tract

1.     Detrusor Overactivity ( OAB)

The mainstay of treatment should be behavioural and pelvic floor therapy. When these therapies are ineffective then pharmacological therapy should be added. These pharmacological therapies include:

Anticholinergic Drugs

The drugs of choice are the antimuscarinic drugs. Drugs that are available in Malaysia are:– oxybutynin 2.5-5mg bd/tds (Ditropan ®), Tolteridine 4mg daily ( Detrusitol ®), Fesoteradine (4 and 8 mg), solifenacin 5-10mg daily ( Vesicare ®), Trospium 20mg ( Spasmolyt ®) and  Propantheline Bromide 15md-30mg bd/tds.

This drugs has side effects of parasympathetic blokage like: the complaint of dry mouth which may lead to the undesirable tendency to drink more. It may also cause drowsiness, tachycardia , constipation  and blurred vision. It is therefore contraindicated in patients with acute angle glaucoma and cardiac arrythmia.
In patients with neurogenic detrusor overactivity (detrusor hyper-reflexia) the dosages of these drugs can be increased till the desired inhibition of detrusor contraction is achieved or until intolerable side effects occur.  In some cases, oxybutynin can also be instilled directly into the bladder (5mg tablet crushed into 30mls of saline, instilled 3 times per day and retained for 30 minutes each time)

Oxybutynin has the advantage that it can be used in children above the ages of 5 but must be used with caution in the elderly and in those with heart disease. Both drugs are contraindicated in pregnancy, with breast feeding, in patients with glaucoma and myasthenia gravis. Toleradine and fesoteradine newer antimuscarinic agents which as efficacious as oxybutynin and higher tolerability rate among patients. 

Other quarternary ammonium compounds with antimuscarinic activities include propantheline (Pro-Banthine ®), emepromium and hyoscyamine (Buscopan®). However these drugs are limited by their unpredictable pharmacokinetics and are not commonly used for detrusor overactivity.


Tricyclic Antidepressants

Tricyclic antidepressants have both anticholinergic and alpha adrenergic effects. These drugs are useful for detrusor overactivity and will at the same time increase the urethral sphincter tone. Their central sedative effect is also an advantage especially in patients who are unduly anxious. Imipramine  (25mg od-tds) is usually used. The dose can be increased by 2.5mg/ week until the desired effects are seen or until intolerable side effects occur. Abrupt cessation of the drug must be avoided because of its rebound tendency. side-effects include hepatic dysfunction, mania, cardivascular events.

Flavoxates

Flavoxates (Genurin®, Urispas ®) has no appreciable anticholinergic effects but has anti spasmodic activity on the smooth muscles of the urogenital tract. They also have local analgesics effects and are suitable for symptomatic relief of symptoms of irritable bladder syndrome ie cystitis. High doses (400mg tds) can be used for detrusor overactivity. Side effects are few but can cause drowsiness and must be used with caution in patients with glaucoma and obstructive uropathy.

Other Drugs

Other drugs that can be used for detrusor hyperactivity include intravesical capsaisin (substance P antagonist), beta adrenalgic agonists (terbutaline), calcium channel blockers (nifedipine : Adalat®) have been reported with limited success. These drugs are best considered as adjunct to first line therapy.

2.     Detrusor Hypocontractility

Poor detrusor contractility leads to high residual volume and can lead to overflow incontinence. Treatment is directed at improving bladder emptying.

Parasympathomimetic Agents

These are the agents of choice for improving detrusor contractions. Bethanechol chloride (Urecholine®) was the main agent of choice but is not available locally. The alternative is the cholinesterase inhibitor Ubretid ®. This drug can be given with an initial loading dose of 5 to 10mg followed by 5 mg every other day. It should not be used in patients with circulatory insufficiency and bronchial asthma.

3.      Stress Urinary Incontinence and Uretheric Sphincter Incompetence

For the management of Urethreric sphincter incompetency and strees urinary incontinence:  pelvic floor exercises, vaginal devices, injectables and  surgery has always been considered the main modality of treatment. However several types of pharmacological agents have been found to be of some benefits. There are alpha adrenalgic receptors on the bladder neck and on the smooth muscle portion of the external urethral spincter and alpha adrenalgic agonists appear to increase the tone of these smooth muscles at the bladder neck. Other pharmacological agents include the Serotonin Norepinephrine Reuptake Inhibitors.

Alpha adrenalgic agonist

Drugs available include epinephrine, pseudoephedrine and phenylpropanolamine. These are commonly found in cough mixtures and nasal decongestants. They should be viewed as adjunct treatment to the other established modalities of treatment for urethric sphincter incompetence.

Serotonin Norepinephrine Reuptake Inhibitor (SNRI)

Duloxetine hydrochloride (Cymbalta ®, Yentreve®) is a drug that primarily targets major depressive disorders and pain related to diabetic peripheral neuropathy. It is now found to be effective in the management of stress urinary incontinence. Using 40mg twice daily, the drug has been proven to reduce incontinence episodes by up to 50% in most individuals. Side effects include nausea, fatigue, dry mouth and insomnia. This drug is not available locally and currently not popular simply because it is expensive and for it's long term usage. Availability of sling ( SUS) operation with good results further retards it's usage.

4.     Drugs Acting Outside The Urinary Tract

Oestrogens

Topical and oral oestrogens have been noted to exert a trophic effect on the uroepithelium of the urethra and trigone. It is therefore useful in the incontinent women when the urethral mucosal seal in defective. It does not appear to have any effect with incontinence secondary to bladder neck hypermobility. oestraogen ( oestradiol valerate 0.5gm biweekly for 2 months does help in older women with urogenital atrophy (UGA)

Anti-diuretic Hormone (ADH)

Desmopressin (Minirin dDAVP®) is a synthetic vasopressin that increases distal renal tubules reabsorbtion of water. It is effective in the treatment of enuresis where a deficiency of nocturnal ADH is present. It is also useful in the elderly patient with nocturia. It can be taken orally in doses of between 0.2 to 0.4mg at night and at these doses, there will be between 8 to 20 hours of antidiuresis. Its use is contraindicated in those patients with unstable angina and cardiac failure.


Dr Aruku Naidu MD FRCOG CU

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