Module 4.3.1 (Drugs for Urinary Incontinence)

Question 1

How does control of bladder function work?

Answer 1

Detrusor muscle (DM)

• Muscle of micturition when DM contracts
• micturition

Internal urethral sphincter (IUS)

circular muscles in bladder neck

When the DM contracts –> sphincter –> opens

External sphincter (ES)

circular muscle that surrounds the urethra

Act as a reserve mechanism to stop micturition eps when there is high bladder pressure.

Question 2

How is control of bladder functiona achieved?

Answer 2

Parasympathetic Innervation Stimulation of M2 receptors –> DM contraction –> micturition

Sympathetic Innervation –> DM relaxation –> Increase urine storage

Somatic Motor Innervation

• Inhibition of motor efferents –> relaxation of external sphincter –> micturition
• Stimulation of motor efferents –> Contraction of external sphincter–> increase urine storage

Question 3

Exmaples of anticholinergics used for UI?

Answer 3

Darifenacin • Oxybutynin • Propantheline • Solifenacin • Tolterodine

Question 4

MOA of anticholinergics?

Answer 4

Antimuscarinic agent ™

Competitive, direct inhibition of muscarinic receptors in detrusor muscle –> muscle relaxation –> bladder relaxation ™

Indirectly enhances the internal sphincter closure

Question 5

Mirabegron MOA? PK?

Answer 5

Beta3-adrenoreceptor agonist ™

relaxes bladder muscle during the storage phase of micturition ™

Increasing bladder capacity.

> increases the amount of pee that your bladder can hold and reduces your need to pee as frequently or as urgently.

PK

• Extensively metabolised via multiple pathways and CYP3A4 and CYP2D6
• Excretion via urine and faeces
• 71% protein binding (albumin & alpha1-acid glycoprotein)
• Half life about 50h, peak at about 3.5h
• Efficacy within 8 weeks, steady state within 7 days

Question 6

AE of mirabegron?

Answer 6

Common (>1%)

increased BP (rare reports of severe hypertension including hypertensive crisis), nasopharyngitis, UTI

Infrequent (0.1–1%)

headache, tachycardia, rash, urticaria

Rare (<0.1%)

angioedema, leukocytoclastic vasculitis