Pharm: UI and pediatric enuresis

Which receptors are responsible for PNS innervation of the detrusor muscle?

cholinergic muscarinic

Which receptors are responsible for SNS innervation of the detrusor muscle and internal urethral sphincter?

Detrusor: beta2 and beta3 adrenergic

Internal urethral sphincter: alpha1 adrenergic

What neurotransmitters are important in maintaining smooth m tone or the urethra and internal urethral sphincter during filling?

Serotonin and Norepinephrine

Nonpharm Tx of UI

Weight loss, treat constipation and cough (stress UI)

Pelvic muscle exercises (kegels, for urge and stress UI)

Manage fluid intake, avoid caffeine and EtOH

Try lifestyle changes for 3 months prior to Pharm treatment

Duloxetine MOA, for ___ UI, indications, S.E.

MOA: SNRI, increases smooth m tone of urethra and internal urethral sphincter. May be useful for pts w/ concomitant depression

For Stress UI

Indications: diabetic neuropathy, fibromyalgia, GAD

S.E.: drug interactions due to CP450 metabolism, nausea, hepatotoxicity

Estrogen cream indications

Stress and Urge UI

Use if local signs of estrogen deficiency (like in atrophic vaginitis in postmenopausal women)

Can use intravaginally or around urethral meatus

1st and 2nd line pharm for urge incontinence

1st: antimuscarinics 2nd: beta-adrenergics (Mirabegron)

Examples of antimuscarinics used for Urge incontinence (same as those used for irritative Sx of BPH) (6)

Darifenacin, Fesoterodine, Oxybutinin/Ditropan (available in an OTC patch), Solifenacin, Tolterodine, Trospium

C.I. of antimuscarinics

C.I. in pts w/ gastric retention, in pts w/ angle-closure glaucoma

Mirabegron class, MOA, CrCl requirements, S.E.

Class: Beta-3 adrenergic agonist

MOA: relaxes the detrusor during filling via SNS stimulation

Not recommended if CrCl<15 (ESRD)

S.E.: QT prolongation, CP450 interactions, increased HR and BP, angioedema, urinary retention

What is the most effective long-term therapy for nocturnal enuresis in children

Enuresis/bed-wetting alarms

Low relapse

What two meds can be used for nocturnal enuresis in children?

Desmopressin (synthetic ADH, not widely recommended due to hyponatremia → seizures)

Imipramine/TCAs (usually managed by a specialist at this point)