PHARM2 3- URINARY BLADDER

Stress incontinence

inc abdominal pressure under stress (weak pelvic floor muscles)

Urge incontinence

involuntary contraction of bladder muscles

Overflow incontinence

d/t blockage of urethra

Neurogenic incontinence

d/t disturbed function of nervous system

age increases what for LUTS?

detrusor hyperactivity

PVR

incidence of BPH/prostate cancer

nocturia

age decreases what for LUTS?

max bladder capacity

sensation of bladder filling

bladder contraction function

urethral closure pressure

estrogen (women)

Adequate trial for behavioral tx for urinary incontinence should last?

8-12 weeks

Reversible causes of urinary incontinence

• DIAPERS

  • Delirium and dementia

  • Infections

  • Atrophic vaginitis, atrophic urethritis, atonic bladder

  • Pharm

  • Psychological (depression)

  • Excessive urinary output (DM, hypothyroidism)

  • Reduced mobility

  • Stool impaction

Drug-induced causes of urinary incontinence

• A-adrenergic agonist

• A-adrenergic antagonist

• ACEI

• Anticholinergics

• CCBs

• Cholinsterase inhibitors

• Diuretics

• Opioids

• psychotropics

AAAACCDOP

a-adrenergic agonist MOA → cause of incontinence

increase smooth muscle tone in urethra and prostate → overflow incontinence

a-adrenergic ANTAGONIST MOA → cause of incontinence

MOA: decrease muscle tone in urethra

Stress incontinence

ACEI MOA → cause of incontinence

MOA: cough

Stress incontinence

anticholinergics MOA → cause of incontinence=

MOA: impaired emptying, urinary retention, constipation, cognitive impairment

Overflow incontinence

=

CCBs MOA → cause of incontinence/

MOA: impaired emptying, urinary retention, constipation, dependent edema

Overflow incontinence

/

cholinesterase inhibitors MOA → cause of incontinence

MOA: increase bladder contractility

Urge incontinence

diuretics MOA → cause of incontinence

MOA: increased diuresis

Urge incontinence

opioids MOA → cause of incontinence

MOA: urinary incontinence, constipation, confusion, and immobility

Overflow incontinence

psychotropics MOA → cause of incontinence

MOA: confusion and impaired mobility

Functional incontinence

Most common cause of incontinence in elderly

urge incontinence

urge incontinence

Associated with detrusor muscle over-activity

tx of urge incontinence/overactive bladder (NON PHARM)

• #1: lifestyle interventions

• Behavioral interventions

• Toileting program

• Pelvic floor exercises

• E-stim

• surgery

Pharm tx of urge incontinence/overactive bladder

• First line - anticholinergic drugs

• Oxybutynin (Ditropan)*

• Tolterodine (Detrol)*

  • Flexibility with dosing

• Solifenacin (Vesicare)

• Trospium (Sanctura)

• Darifenacin

• Propantheline

• Fesoterodine

• Mirabegron (Myrbetriq) NOT ANTICHOL (B3 antagonist)

• Vibegron (Gemtesa) NOT ANTICHOL (B3 antagonist)

mirabegron and vibegron SE

HTN

HA

UTIs

nasopharyngitis

SE of anticholinergics

• Dry mouth

• Visual disturbances

• Constipation

• Dry skin

• dizziness

SE of anticholinergics is d/t wht?

SE d/t inhibition of muscarinic receptors of bladder

anticholinergic drug MOA

antagonizes acetylcholine at muscarinic receptors -> relax bladder smooth muscle, inhibit involuntary detrusor muscle contraction

big note about anticholinergic drugs

crosses BBB (except trospium)

Oxybutynin (Ditropan)* dosing

transdermal patch/gel (bypass first pass metabolism)

ER = QD, IR is multiple times a day

start elderly dose low

do NOT need renal dose adjustments

Oxybutynin (Ditropan)* SE

most anticholinergic,

highest rate of dry mouth,

this and darifenacin bad for constipation

Tolterodine (Detrol) and Solifenacin (Vesicare) SE

QT prolongation

which anticholinergic drugs for OAB is NOT renally dosed?

oxybutynin

darifenacin

what OAB drug does NOT cross BBB = less SE?

Trospium (Sanctura)

what OAB drugs cause constipation?

oxybutynin

darifenacin

Fesoterodine

Metabolizes to the same metabolite as tolterodine

Mirabegron (Myrbetriq) MOA

SELECTIVELY stimulates b3 adrenergic receptors -> relaxes bladder

Parasympathetic (Cholinergic control)

“blocks” muscarinic receptor -> no contraction -> delayed voiding

Sympathetic (Adrenergic control)

“activates” muscarinic receptor -> relaxation -> inc storage capacity + dec voiding freq

IR vs. ER SE

IR has more

Go-to tx for stress incontinence

pelvic floor muscle exercises (Kegels)

meds for stress incontinence

• Estrogen replacement

  • Alora (patch)

  • Estrace (cream)

  • Vagifem (vaginal tablets)

SE of estrogen replacement meds for stress incontinence

rash

when is estrogen replacement therapy for stress incontinence CI?

hx of thromboembolic disorders

breast cancer

uterine cancer

vaginal cream estrogen replacement for stress incontinence admin

BIW

Overflow Incontinence

Straining, dribbling, weak urinary stream, hesitancy, frequency, nocturia

drug groups for overflow incontinence

1. a-adrenergic blockers

2. 5-a reductase inhibitors

go-to for overflow obstruction and OAB

Tamsulosin (Flomax)*

usage of Tamsulosin (Flomax)

BPH b/c it is more selective for the a-1 receptors (only FDA indication)

Tamsulosin (Flomax) dosing

0.4 mg BID -> 0.8 mg at night, works faster

Tamsulosin (Flomax) SE

=

floppy iris syndrome

=

list of a-adrenergic blockers for overflow incontinence

1. tamsulosin

2. Alfuzosin

3. Prazosin

4. Terazosin

5. Doxazosin

Doxazosin SE

syncope (1st dose effect)

orthostasis (ortho hypotension)

palpitations

for overflow incontinence, what drugs are MEN ONLY?

5-a reductase inhibitors - finasteride (proscar) and dutasteride (avodart)

dutaseride (avodart) SE

gynecomastia

dec libido

MOA of 5-a reductase inhibitors (full)

inhibits type II 5-a reductase -> inhibition of conversion of testosterone -> dihydrotestosterone to shrink prostate

urge/OAB UI tx

1. Lifestyle interventions (non-pharm first)

2. Behavioral interventions

3. Toileting program

4. Pelvic floor muscle

5. Exercises

6. e-stim/biofeedback

7. Pharm (antimuscarinics or mirabegron if initial tx does NOT work)

8. If still no improvement -> neuro-based therapy

Stress UI tx

1. Lifestyle intervention (non-pharm first)

2. Toilet program

3. Pelvic floor muscle

4. Exercises

5. Intravaginal support devices

6. Pharm (pessaries or surgery if not improved)

Overflow UI tx

1. Tx constipation

2. Pharm

3. Intermittent catheterization

4. Indwelling urinary catheter

Functional UI tx

1. Environmental changes

2. Toileting program

3. PT/OT

Guidelines of Tx urinary incontinence

1. Preferred MONOtherapy (consider combo therapy w/ antimuscarinic AND b3 agonist if pt is refractory to monotherapy)

2. Use non-pharm tx first! (anti-muscarinics or b3 is 2nd line)

3. Similar efficacy between oral muscarinics (ER better d/t lower dry mouth)

4. Trial 4-8 weeks to assess drug efficacy

Tx of UTI in children

1st gen cephalosporin (cephalexin)

3rd gen cephalosporin (cefixime, cefdinir)

1st gen cephalosporin (cephalexin) dosing

weight-based

TID x 10 days

when do use 3rd gen ceph instead of 1st gen ceph for UTI tx in children

PCN allergy

cephalosporins SE

GI*, angioedema

cephalosporin interactions

iron supplements

cefixime dosing

14 days total

poor renal function -> reduce freq of admin

Cefpodoxime dosing

BID

cefdinir dosing

PO QD

acute complicated UTI sx

fever/chills

flank pain

costovertebral angle tenderness

pelvic pain

UTI sx

dysuria*

flank/suprapubic/testicular pain

freq/urgency

hematuria

non-uti sx

confusion/change in mental status*

new falls

foul smelling/cloudy urine

lobe criteria w/o catheter

acute dysuria alone or FEVER* and:

1. new/worsening urinary urgency/freq

2. suprapubic pain

3. hematuria

4. CVA tenderness

5. incontinence

lobe criteria w/ catheter

1 of the following:

1. fever

2. CVA tenderness

3. rigors

4. delirium

mcgeer criteria no catheter

3 of following:

1. fever*

2. burning pain/freq/urgency

3. change in character of urine

4. tenderness

mcgeer criteria w/ catheter

2 of following:

1. fever*

2. flank pain/tenderness

3. change in character of urine

4. worsening mental status

tx for UTI

• fluids!

• vit C

• AZO (pyridine) (treats dysuria)

revised mcgeer criteria for UTI

1. positive urine culture

2. localizing s/sx to GU

general criteria of UTI W/O catheter

s/sx: acute dysuria, fever, leukocytosis

if no fever, 2 of these: CVA/suprapubic pain, hematuria, incontinence, urgency, freq

urine culture W/O catheter = UTI

105 cfu/mL of <2 species

102 cfu/mL of organisms

general criteria for UTI W/ catheter

s/sx: no alternate site of infection, AMS change w/ no alternate diagnosis and leukocytosis

most frequent microbial cause of simple cystitis

e coli

other species of enterobacteria causing UTI

kleb

proteus

staph

ciprofloxacin interactions

antacids

iron supp

aluminum

ertapenem, gentamicin, imipenem is used in UTI for

e coli if PCN resistance

rate limiting factor of gentamicin in hospital

renal impairment

reasons NOT to use nitrofurantoin for UTI

if pt is preg

renal function

reasons to NOT use bactrim for UTI

sulfa allergy

renal function

Empiric Tx of cystitis

1. nitro*

2. Sulfamethoxazole/Trimethoprim (Bactrim)

3. Fosfomycin

go-to empiric tx for cystitis

nitrofurantoin

nitrofurantoin dosing for cystitis

100 mg PO BID x 5 days, renal function

Sulfamethoxazole/Trimethoprim (Bactrim) dosing for cystitis

PO BID x 5 days, renally dosed

Fosfomycin for cystitis dosing

NOT renally dosed, 3g of powder in water

Tx for Complicated UTI

PO FLQ (cipro/levo)

bad choices for tx of complicated UTI

nitro, bactrim, fosfomycin, oral beta-lactams

why are nitro, bactrim, fosfomycin, oral beta-lactams bad choices for tx complicated UTI?

high prevalence of resistance

simple cystitis tx - can’t take nitro, bactrim, fosfo, what next?

beta lactam

if that doesn’t work, FLQ

complicated UTI tx - FLQ isn’t enough, what next?

irtapenem

if you can’t use FLQ for first-line complicatd UTI tx, what can you use instead?

bactrim

augmentin

adult cystitis tx

Nitro* or Bactrim (e. Coli resistance common)

RENALLY DOSED

pyelonephritis tx

Cipro

ceftriaxone

IV therapy (FLQ, aminoglycoside, cephalosporin, PCN, carbapenem)

RENALLY DOSED

Higher gen of ceph treats gram ___ better

negative