Voiding Dysfunction Medication

Pharmacologic therapy of voiding dysfunction in children usually centers on treating uninhibited detrusor contractions during filling and, at times, decreasing bladder outflow resistance. Most of the neurohumoral stimulus for bladder contraction is the stimulation of muscarinic-cholinergic receptor sites on bladder smooth muscle. Anticholinergic agents can depress uninhibited bladder contractions, but effects on normal contractions with subsequent incomplete bladder emptying and retention must also be considered. In addition, certain anticholinergic medications may exacerbate constipation, as they also may affect the intestinal musculature. In rare instances, bladder outlet resistance is increased because of stimulation of alpha1-adrenergic receptors in the bladder neck, and this effect may be decreased by the use of alpha1-adrenoreceptor blockers.

• Oxybutynin is approved by the US Food and Drug Administration (FDA) for treatment of OAB in children and has traditionally been the treatment of choice.

  • Despite the prevalence and significance of pediatric daytime incontinence, few prospective randomized trials assessing treatments have been published. This problem was documented by a 2003 review of studies of pediatric incontinence that found only one randomized controlled study that evaluated currently used treatment; that study reported no benefit in the combination of biofeedback and oxybutynin.^[12]
  • One of the larger studies of oxybutynin evaluated 144 children, two thirds of whom were treated with anticholinergic medication.^[1] Follow-up averaged 3.2 years. The study reported symptom resolution or improvement in 91% of children with daytime urinary incontinence, and 56% of those with UTI stopped having infections.
  • In an attempt to define predictive factors that affect the continence outcome in children with daytime wetting, a study evaluated 81 children treated with oxybutynin for an average of 1.2 years; at the last visit while taking oxybutynin, 38% of patients were dry, 31% of patients were significantly improved, 24% of patients were slightly improved, and 7% of patients were unchanged in their symptoms.^[13] The only variable significantly associated with improvement in daytime wetting with oxybutynin was the frequency of wetting episodes; those who presented with fewer wetting episodes were more likely to become dry.
• An extended-release formulation of oxybutynin (Ditropan XL) is taken once per day.

  • One study reviewed 27 children who were changed from immediate-release oxybutynin to extended-release.^[14] All patients had persistent incontinence while taking regular oxybutynin. Of children with persistent wetting, 48% became dry or had significant improvement in the frequency of wetting by the next visit after changing to the extended-release formulation. Voided volume and bladder capacity were also improved.
  • Studies of oxybutynin extended-release reported fewer adverse effects.^[15]

Class Summary

These drugs inhibit the binding of acetylcholine to the cholinergic receptor, thereby suppressing involuntary bladder contraction of any etiology. In addition, they increase the volume of the first involuntary bladder contraction, decrease the amplitude of the involuntary bladder contraction, and, possibly, increase bladder capacity.

Oxybutynin (Ditropan, Ditropan XL)

Synthetic tertiary amine; like atropine, antagonizes muscarinic actions of acetylcholine. Direct spasmolytic effect on detrusor muscle and small intestine and local anesthetic action. Reduces incidence of uninhibited detrusor contractions.

Class Summary

These agents are used to decrease smooth muscle tone in the bladder outlet.

One study of doxazosin in dysfunctional voiding associated with urinary retention showed an 88% reduction in residual urine, whereas a placebo-controlled trial did not show an objective benefit.^[16]

Doxazosin mesylate (Cardura)

Selective inhibitor of alpha1-adrenergic receptors. Blockade of these receptors in bladder neck decreases outflow resistance. Available as tablet.

Terazosin hydrochloride (Hytrin)

Selective inhibitor of alpha1-adrenergic receptors. Blockade of these receptors in bladder neck decreases outflow resistance. Available only as capsule.

Class Summary

These agents are useful when treating constipation and detrusor instability.

Polyethylene glycol-3350 powder for PO solution (Miralax, GlycoLax)

PEG solution is an osmotic agent that causes water to be retained in stool. Despite lack of specific recommendations, widely given to children with voiding dysfunction by primary care physicians, pediatric gastroenterologists, and pediatric nephrologists caring for children. Recommended for occasional constipation in adults.