URINARY INCONTINENCE

Question 1

types of urinary incontinence

Answer 1

URGE
- detrusor instability, hyperactivity + impaired bladder contractility, or involuntary sphincter relaxation

STRESS
- urethral sphincter failure (anatomic or ISD)

OVERFLOW
- hypotonic or underactive detrusor secondary to drugs, fecal impact, DM, spinal cord injury, disruption motor innervation detrusor, urethral obstruct, genital prolapse

MIXED
- combo urge, stress, MC older women

Question 2

tx approaches for urinary incontinence
- what should you typically choose first?
- testing before

Answer 2

• pharmalogical
• behavioral (wt loss, diet, smoking cessation, exercise)
• surgical

choose least invasive tx w/fewest potential ADRs for pt
- urodynamic testing before tx

Question 3

muscarinic receptors locations (M1-5)

Answer 3

M1- brain, salivary gland, SNS ganglia
M2- smooth muscle, hindbrain, cardiac
M3- smooth muscle, salivary gland, eye
M4: brain, salivary gland
M5- substantia nigra, eye

Question 4

muscarinic receptors
- effects of antagonism

Answer 4

M1- impair memory+cognition, dry mouth, impair secretion gastric acid
M2- tachy, inc gastric sphincter tone
M3- dec bladder+bowel contractility, dry eyes and mouth, abnl vision (main target for incontinence tx)
M4- unknown CNS effects
M5- unknown CNS effects, abnl vision, dec in pilocarpine induced salivation

Question 5

SNRI- Duloxetine
- MOA
- use

Answer 5

• MOA: SNRI
• use: stress incontinence

not used often due to side effects, although 50% improvement of Sx

Question 6

alpha adrenergic agonists- Phenylpropanolamine
- MOA
- use

Answer 6

• MOA: stim urethral smooth muscle contraction
• uses: stress incontinence

not used routinely–>only mildy effacacious

Question 7

anticholinergics (muscarinic receptor antagonists)
- list drug names

Answer 7

• propantheline
• oxybutynin
• oxytrol and gelnique
• tolterodine
• darifenacin
• solifenacin
• tropsium Cl

Question 8

anticholinergics

propantheline
- MOA
- precautions

Answer 8

MOA
- muscarinic blocker–> inhib involuntary detrusor musc contractions (not selective, so not used clinically)

precautions
- narrow angle glaucoma, elderly

Question 9

anticholinergics

propantheline ADRs

Answer 9

• urinary retention
• blurred vision
• dry mouth
• nausea, constipation
• tachy
• drowsy, confusion

Question 10

anticholinergics

oxybutynin
- MOA
- precautions

Answer 10

MOA
- inhibit involuntary detrusor muscle contractions
- delays desire to void
- dec urgency + freq
- direct antispasmoid effect on smooth muscle (M3>M1)

precautions
- narrow angle glaucoma, elderly

Question 11

anticholinergics

oxybutynin
- active metabolite
- ADRs
- DDIs

Answer 11

active metabolite
- N-desethyloxybutynin

ADRs (inc severity w dose)
- dry mouth, skin
- blurred vision
- sedation, change in mental status
- nausea, constipation

DDIs
- CYP3A4 substrate and inhib

Question 12

anticholinergics

oxytrol and gelnique
- formulation
- frequency
- pro

Answer 12

• apply topically for systemic effects
• bypass first pass effect, so less anticholinergic side effects
• significantly LESS DRY MOUTH

oxytrol- path apply twice weekly
gelnique- gel apply daily

Question 13

anticholinergics

tolterodine
- MOA
- Precautions
- ADRs
- DDI

Answer 13

MOA
- M3/M1 blockers, greater affinity recep in bladder than saliva

precautions
- narrow angle glaucoma, elderly

ADRs
- urinary retention, blurred vision, dry mouth, nausea, constipation, HA, drowsy, confusion

DDI
- CYP2D6 + CYP3A4 substrate

Question 14

tolterodine v. fesoterodine

Answer 14

fesoterodine
- new agent, has same active metabolite as tolterodine
- may be more effective in higher doses, but will also have more ADRs

Question 15

anticholinergics

darifenacin v. solifenacin receptor target
- precautions
- ADRs
- DDIs

Answer 15

darifenacin- selective M3 blocker
solifenacin- M3>M1

• same precautions
• ADRs: same but less severe, less CNS bc does NOT CROSS BBB (especially solif)
• DDIs: CYP450 substrate

Question 16

anticholinergics

Tropsium Cl
- MOA
- ADRs
- DDI/how is it excreted

Answer 16

MOA
- M3/m1 receptor blocker (similar to tolterodine)
- ADRs: same as others, LESS CNS side effects
- RENAL excretion, NO CYP450 drug interactions

Question 17

beta 3 agonist- Mirabegron
- MOA
- ADRs
- DDI

Answer 17

MOA
- relax smooth musc in bladder, inc storage capacity

ADRs
- HTN, tachy, HA, constipation/diarrhea

DDI
- CYP2D6 inhibitor

very expensive, new drug second line after anticholinergics (not tested to combine yet)

Question 18

TCAs
- drug names
- useful why?
- mc use

Answer 18

• imipramine, amitriptyline, doxepin
• useful for anticholinergic properties
• NOT FDA APPROVED FOR INCONTINENCE
• mc use for noctural enuresis

Question 19

CCBs
- useful why?
- name

Answer 19

• nifedipine
• may be useful bc calcium involved in urinary muscle contractions

not FDA approved

Question 20

estrogen therapy

Answer 20

• (oral or vaginal) consider as adjuvant for postmenopausal women w stress or mixed incontinence
• conjugated estrognes and medroxyprogesterone may be used

Question 21

alpha 1 antagonists
- use
- MOA

Answer 21

use to tx overflow incontinence bc will dec sphincter tone
- “azosin”

Question 22

nocturnal enuresis- pediatrics
- drug name
- MOA
- formulations + duration trial

Answer 22

desmopressin (DDAVP) nasal spray or PO
- PO may cause less hyponatremia
- try for 6 months

MOA
- enhance reabsorp of water in kidneys by inc cellular permeability of collecting ducts