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Medical Management of Voiding Dysfunctions

WHEC Practice Bulletin and Clinical Management Guidelines for healthcare providers. Educational grant provided by Women's Health and Education Center (WHEC).

Recent advances in the understanding of the neurology and neuro-pharmacology of the lower urinary tract indicate that a multiplicity of different types of drugs influence the physiological activity of the bladder and urethra. Although behavior modification improves or cures most patients with detrusor instability, pharmacologic therapy remains the most popular mode of treatment. In women between the ages of 15 to 60 years, the prevalence of voiding dysfunction is about 5-25%. 12 to 38% of women are over the age of 60. 69% of women are over the age of 18 with the symptoms of urinary incontinence, and the incidence of urge incontinence among this group is about 46%. Because the cause of detrusor instability is unknown, the response to treatment is often unpredictable and the side effects are common with effective doses. In general, drugs improve detrusor instability by inhibiting the contractile activity of the bladder.

These agents can be broadly classified into anticholinergic drugs, calcium channel blockers, tricyclic antidepressants, musculotropic drugs, and a variety of less commonly used drugs. This chapter provides the readers with information regarding the effects of drugs on the autonomic nervous system and their subsequent effects on the lower urinary tract. It also provides guidelines for the use of these drugs in specific urologic therapy.

Anticholinergic Agents:

A variety of anticholinergic drugs are effective in the management of detrusor instability, although certain agents have more specific activity on the detrusor muscle than on other cholinergically innervated organs. For many years, propantheline bromide was the treatment of choice for detrusor instability and the drug to which most other new compounds were compared. The dosage is 15 to 30 mg orally three or four times a day. In general, the maximum dose is usually determined by patient's tolerance to side effects rather than by other forms of toxicity.
Side effects: dry mouth; blurred vision; drowsiness; tachycardia; constipation
Contraindications: glaucoma; intestinal obstruction; cardiac dysrhythmia; myasthenia gravis

Musculotropic Agents:

The mechanisms of action of these drugs in this category are smooth muscle relaxant, anticholinergic, and local anesthetic. Commonly used drugs are:

Name of Drug


1. Oxybutynin chloride (Ditropan)

2.5-5 mg bid-qid

2. Oxybutynin Chloride XL (Ditropan XL)

5-30 mg qd

3. Oxytrol patch

1 patch q 3 days

4. Tolterodine (Detrol)

2 mg bid

5. Tolterodine (Detrol LA)

4 mg qd

6. Dicyclomine hydrochloride (Bentyl)

10-20 mg/day

7. Flavoxate hydrochloride (Urispas)

100-200 mg/day

Oxybutynin chloride (Ditropan XL) is currently the most commonly used drug available for the treatment of detrusor instability. It is effective for both neuropathic and idiopathic detrusor instability. Numerous clinical trials have confirmed that symptoms of urgency, frequency, and urge incontinence are significantly improved or eradicated in a large proportion of patients using oxybutynin chloride. However, some patients are unable to tolerate its anticholinergic side effects.
Tolterodine (Detrol) is a new, potent, competitive muscarinic receptor antagonist developed specifically for the treatment of the overactive bladder. Unlike oxybutynin, however, tolterodine is far more selective for muscarinic receptors in the bladder as opposed to parotid gland, thus avoiding the side effects; particularly dry mouth.

Side Effects: anticholinergic effects - dry mouth, blurred vision, drowsiness, tachycardia, constipation
Contraindications: glaucoma, intestinal obstruction, cardiac dysrhythmia, myasthenia gravis

Tricyclic Antidepressant:

Imipramine hydrochloride (Tofranil) improves bladder storage significantly. This medication appears to improve bladder hypertonicity or compliance rather than uninhibited contractions. It has been prescribed for treatment of enuresis in children for many years. It has a complex pharmacologic action, with anticholinergic, antihistaminic, and local anesthetic properties. It also increases bladder outlet resistance through a peripheral blockade of noradrenaline uptake. Because of this dual action, the drug also may be effective for patients with combined stress incontinence and detrusor instability.
Dosage: 25 mg one to three times a day for adults and 5 to 10 mg four times a day for children. Single nightly doses can be given in patients for the treatment of nocturnal enuresis.
Side Effects: anticholinergic effects - dry mouth, blurred vision, drowsiness, tachycardia, constipation, orthostatic hypotension (especially in elderly patients), hepatic dysfunction, mania, cardiovascular effects, tremor and fatigue.
Contraindications: glaucoma, intestinal obstruction, cardiac dysrhythmia, myasthenia gravis, monoamine oxidase inhibitors are prohibited.

Calcium Channel Blockers:

Terodoline (micturin) was the most commonly prescribed drug in Europe for the treatment of detrusor instability. It was voluntarily withdrawn from the market by the manufacturer following adverse cardiac effects mainly in elderly patients. Verapamil used in combination with oxybutynin has shown improvement in symptoms and inhibits bladder contraction.
Side effects: palpitation, weakness, rash, nausea, constipation, dizziness, headache, facial flushing, hypotension, and abdominal discomfort.

Other Agents:

Other drugs that have been shown to possibly inhibit bladder contractility include beta-adrenergic agonists, such as clenbuterol and terbutaline. These drugs have been shown in animal studies to increase bladder capacity; however, their role in the management of detrusor instability in humans is uncertain. In addition, alpha-adrenergic antagonists and prostaglandin synthetase inhibitors reduce bladder capacity in animals however; no significant benefit has been reported in humans.

Synthetic vasopressin, DDAVP (1-desamino-8-D-arginine vasopressin), decreases urine production. It is given in doses of 20 to 40 micro g intranasally as a spray or snuff at bedtime. This dosage has been shown to decrease urine production by up to 50 %. DDVP is helpful in patients with troublesome nocturnal urinary symptoms.
Side Effects: headache, nausea, nasal congestion, rhinitis, flushing, and mild abdominal cramps.
Contraindications: coronary artery disease, hypertension, heart failure or epilepsy.

Estrogen Therapy:

Although abundant literature exists regarding estrogen therapy and lower urinary tract dysfunction, there have been very few placebo-controlled trials using standard outcome measures. No studies have shown that estrogen therapy improved incontinence caused by detrusor instability. However, sensory urgency is improved by estrogen therapy, which is thought to raise the sensory threshold of the bladder.
Dosage: oral tablet strength ranges from 0.3-1.25 mg/ day. It can also be administered transdermally, subcutaneously, or topically. A new silicone ring impregnated with estradiol is being introduced for vaginal use. This new device offers a continuous delivery over a 90 day period, and has shown to be acceptable in certain women.
Side Effects: increased risk of breast and uterine cancer, deep vein thrombosis, hypertension.
Contraindications: breast and genital tract cancers, cardiac diseases, liver disorders, hypertension, deep vein thrombosis, undiagnosed uterine dysfunctional bleeding.

Intravesical Agents:

Intravesical drugs delivery has theoretical and real advantages for patients who can not tolerate oral anticholinergic agents or in patients who require higher levels of local drug delivery to achieve effect. Advantageous effects of intravesical instillation of atropine, phentolamine, verapamil, lidocaine, and bupivaciane have been reported in detrusor dysfunction. Although most studies indicate a substantial improvement in tolerability with intravesical oxybutynin administration; some studies have shown similar side effect profiles as compared to oral administration with this route. Intravesical delivery systems utilize a physiologic solution containing oxybutynin, and have shown consistent drug serum levels, reflecting improved bioavailability. Current intravesical pump delivery systems utilize a reservoir with a thirty day dwell time within the bladder, but require cystoscopic insertion and removal. Other types of sustained release delivery systems utilize fibrinogen based adhesive with active agents co-mingled with the adhesive, to enhance drug delivery to target areas.

Intravesical delivery of two new agents provides a promising future treatment alternative. Capsaicin is derived from the capsicum peppers. It is a vinillyl amide and interacts with vanilloid receptors within the urinary bladder. Resiniferatoxin (RTX) derived from the cactus relative euphorbia resinifera shares a vanilloid configuration with capsaicin and is an analog with much higher potency. Intrvesical delivery allows site-specific drug delivery with a reduced side effect profile as compared to oral delivery systems either by avoiding first pass metabolism or by obtaining a local effect.


Certain considerations should always be kept in mind regarding the drug therapy for detrusor instability; each drug should be given for at least 6 weeks before it is deemed a failure, as the onset of benefit may at times be delayed. The drug doses must be titrated based on subjective response and the presence or absence of side effects. If one drug is not beneficial, it is worth trying other drugs with different modes of action or combining drugs. Placebo effects are high and may be present in as many as 50 % of patients. The detrusor instability is a relapsing and remitting condition and treatment may need to be adjusted accordingly.

Suggested Reading:

  1. Stewart WF, Van Rooyen JB, Cundiff GW et al. Prevalence and burden of overactive bladder in the United States. World J Urol 2003;20:327-336
  2. Wein AJ, Rovner ES. Definition and epidemiology of overactive bladder. Urology 2002;60 suppl:7-12
  3. Jick SS, Kaye JA, Vasilakis-Scaramozza LA, et al. Validity of the general practice research database. Pharmacotherpy 2003;23:686-689
  4. Lewis JD, Schinnar R, Bilker WB et al. Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf 2007;16:393-401
  5. Diokno AC, Appell RA, Sank PK et al. Prospective, randomized, double-blind study of the efficacy and tolerability of the extended release formulations of oxybutynin and tolterodine for overactive bladder: result of the OPERA trial. Mayo Clin Proc 2003;78:687-695
  6. Roxburgh C, Cook J, Dublin N. Anticholinergic drugs versus other medications for overactive bladder syndrome in adults. The Cochrane Database of Systematic Reviews 2007, Issue 4 Art. No.: CD003190. DOI: 10.1002/14651858. CD003190
  7. van Wijk BI, Avorn J, Solomon DH et al. Rates and determinants of reinitiating antihypertensive therapy after prolonged stoppage: a population based study. J Hypertens 2007;25:689-697
  8. Gopal M, Haynes K, Bellamy SL et al. Discontinuation rates of anticholinergic medications used for the treatment of lower urinary tract symptoms. Obstet Gynecol 2008;112:1311-1318

Published: 9 February 2009

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