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CPD ACTIVITY 59 Enuresis Algorithm A ‘3-System’ Approach Primary Enuresis (Mono Symptomatic) • History1 • Physical Examination2 • Urine Dipstix → +UTI → Treat • Constipation → Treat Secondary Enuresis & (Primary NON-Mono Symptomatic Enuresis) Treat Appropriately Key History1: Red flags - Dysuria, genital/rectal pain or discharge, straining to urinate, haematuria, daytime incontinence, sleep apnoea or snoring. Physical Examination2: Red flags - Adeno-tonsillar hypertrophy, spinal pathology, neurological symptoms, abnormal gait, enlarged bladder or kidneys febrile. Urotherapy3: Diet modification, fluid modification, pelvic floor rehabilitation, biofeedback. Consider along with behavioural modification. Noradrenergics3,6 The β-3 adrenergic agonist mirabegron (Betmiga), is used in adults with detrusor overactivity but is not approved for use in children. Antidepressants3,6 Imipramine is third line for enuresis if other therapies are unsuccessful. The mechanism of action of impramine is multifactorial, involving noradrenergic, serotoninergic and anticholinergic action on the bladder, arousal systems and urine production.3 The studies show a 30-50 per cent success rate in therapy-resistant children, with an increase in efficacy if desmopressin is added.3 The limiting factor of imipramine is the danger of cardiotoxicity. A detailed cardiovascular evaluation of the child and family needs to be undertaken to dismiss any issues with cardiac conditions before prescribing. Unexplained syncope, palpitations, or a positive family history of sudden cardiac death would rule imipramine out.3 At the time of writing (December 2020), imipramine must be ordered via a special ordering system which limits access. The most limiting adverse effects for imipramine are: • Tolerance – may develop over time (drug free periods may reduce this). Large voided amounts, Before/Around Midnight 1. Night-Time Polyuria • Urotherapy3 • Desmopressin OR Desmopressin & Alarm therapy Bladder Diary Variable voided amounts, multiple episodes, through the night 2. OAB / Small capacity bladder • Urotherapy3 • Anticholinergic treatment No improvement (3 month review) Refer to Specialist Early morning voids. Reluctance to leave the bed. 3. Lack of Arousel • Urotherapy3 • Alarm therapy Figure 3. South African guidelines on enuresis (2017) \\\\\\\\\\\\\\\[OAB = overactive bladder\\\\\\\\\\\\\\\] years before tapering the dose. • Desmopressin is not considered curative, but a tool to achieving dryness. Anticholinergics3 • Oxybutynin (Ditropan and generics – the only example approved for use in children in Australia). • Tolterodine (Detrusitol). • Solifenacin (Vesicare and generics). • Fesoterodine (Toviaz – seen in Australian research papers but not yet registered in Australia). Detrusor muscle overactivity is an important pathogenic mechanism in enuresis, especially in NMSE or enuresis unresponsive to desmopressin.3 Anticholinergics relax the detrusor muscle and bladder contractions to decrease urinary urgency and frequency. Anticholinergic therapy should be used cautiously as it may worsen the problem. Anticholinergics can only be given if constipation and faecal overload have been excluded and there is no history of post-void residual volume in the bladder. Anticholinergic therapy may be given alone or in combination with desmopressin. There is good evidence from randomised controlled trials to support the use of anticholinergics in enuresis therapy with or without desmopressin.3 Anticholinergic adverse effects seen in adults are rarely seen in children.3 The most important clinical adverse effects witnessed in children are: • Constipation, which can cause lower urinary tract function abnormalities. • Post-void residual volume, which in turn increases the risk of infection. • Dry mouth, which increases the risk of dental issues and mouth ulcers. • Behavioural and psychiatric adverse effects, such as mood swings (seen with oxybutynin). These adverse effects will diminish once the anticholinergic is ceased.3 Adverse effects can be monitored and managed if the anticholinergic is considered necessary. Anticholinergics should be given at bedtime and continued for one to two months to evaluate safety and efficacy. The effect may not be seen immediately, which is why the evaluation needs to occur over a longer period. If no effect is seen, either the dose needs to be increased or desmopressin can be added.3 The prescriber may decide to start with combination therapy and then wean with the desmopressin.3 The family should be supported to trial reducing the medication every three months or so if the child becomes dry and maintains dryness.3 Regular surveillance for increased residual volume and urinary tract infections is important with anticholinergics. If initial therapy response is good but wet nights recur, the patient should be investigated for constipation or faecal overload.3 • Nausea. • Mood swings. TO PAGE 60 RETAIL PHARMACY • JAN/FEB 2021