Download Urinary Incontinence Drugs

Urinary Incontinence Drugs
Urge Incontinence- Detrusor Instability, Detrusor Hyperactivity w/ impaired bladder contractility or involuntary sphincter relaxation.
Stress Incontinence (ST)- urethral sphincter failure – due to either anatomic changes or intrinsic sphincter deficiency (ISD).
Overflow Incontinence- hypotonic or underactive detrusor due to drugs, fecal impaction, DM, lower spinal cord injury, disruption of motor innervation of detrusor, urethral obstruction or genital prolapse
Mixed Incontinence- combination of urge and stress incontinence, especially common in older women.
Tx: Pharmacological, Behavioral, Surgical. 1st choice should be the least invasive treatment w/ fewest potential adverse CI’s. Before tx- complete evaluation & appropriate urodynamic testing.
Muscarinic
Receptors – Role
in treatment of
Incontinence
Muscle Receptor
Location
Effects of Antagonism
MI
Brain, salivary gland, SNS ganglia
Impairment of memory & cognition, dry mouth, impaired secretion of gastric acid
M2
Smooth muscle, hindbrain, cardiac
Tachycardia,  gastric sphincter tone
M3 – Primary receptor for overactive Bladder
Smooth muscle, salivary gland, eye
 Bladder and bowel contractility, dry eyes and mouth, abnormal vision
M4
Brain, salivary gland
Unknown CNS effects
M5
Substantia Nigra, eye
Unknown CNS effects, abnormal vision,  in pilocarpine-induced salivation
1. Oxybutynin (Ditropan, Ditropan

MOA – inhibits involuntary detrusor muscle contractions, delays desire to void,  urgency & frequency, direct antispasmodic effect on smooth muscle.
XL, Oxytrol) (B)

Precautions – narrow angle glaucoma, elderly. DDI – CYP3A4 substrate & inhibitor

Active metabolite – N-desethyloxybutynin

ADRs – dry mouth, dry skin, blurred vision, sedation, change in mental status, nausea, constipation (severity of ADRs increases w/ dosage)
2. Oxytrol transdermal System
(Expensive)


Dose: 3.9 mg/day system applied 2x/ week (every 3-4 days), Because of dosing delivery, less incidence of dry mouth than other oxybutynin products.
applied to dry, intact skin on abdomen, hip, or buttock, application site should be rotated w/ each application, avoiding re-application to the same site w/in seven days.
3. Oxybutynin (Investigational)


UROS Infusor – uses a balloon reservoir filled w/ oxybutynin. This device is inserted into the bladder and releases drug over a period of several weeks.
impregnated ring for intravaginal use. The drug would be released during a 28 day period.
4. Propantheline (ProBanthine)(C)



MOA – inhibit involuntary detrusor muscle contractions. Prototype for Anticholinergic agents used for urologic conditions.
Precautions – Narrow angle glaucoma, elderly
ADRs – urinary retention, blurred vision, dry mouth, nausea, constipation, tachycardia, drowsiness & confusion
5. Tolterodine (Detrol,
Detrol XL) (C)



MOA – inhibits involuntary detrusor muscle contractions. Has greater affinity for muscarinic receptors in bladder than saliva
ADRs – urinary retention, blurred vision, dry mouth, nausea, constipation, headache, drowsiness and confusion. Precautions – narrow angle glaucoma, elderly
DDIs: CYP2D6 & CYP3A4 substrate
6. Darifenacin (Enablex) &
Solifenacin (Vesicare)


MOA – selective M3 receptor antagonist. Same precautions as other Anticholinergics
ADRs – same as others, but less severs. Less CNS effects b/c does not cross blood brain barrier (especially solifenacin). DDis – CYP450 substrate
7. Tropsium Cl (Sanctura)


MOA – M2 and M3 receptor blocker (similar to tolterodine)
ADRs – same as others, less CNS side effects. Renally excreted – NO CYP450 drug interactions
8. Dicyclomine (Bentyl) (B)


MOA – Direct Antispasmodic Smooth Muscle Relaxan t.
Not as effective as other Anticholinergic agents. More often used for GI disorders like Irritable Bowel Syndrome.
Tricyclic Antidepressants:
Imipramine (Tofranil)



More commonly used to treat nocturnal enuresis
Useful b/c have Anticholinergic properties
Not FDA-approved for incontinence
Calcium Channel Blockers:
Nifedipine (Procardia)


May be useful b/c calcium is involved in urinary muscle contractions. Not FDA approved, not many clinical studies
Nifedipine often used for Urinary Incontinence
Estrogen Therapy


Estrogen (oral or vaginal) as adjunct for postmenopausal women w/ stress incontinence or mixed incontinence.
Conflicting data – some trials suggest hormone therapy may contribute to incontinence. Conjugated estrogens and medroxyprogesterone may be used.
Alpha – 1 antagonists

Used to treat overflow incontinence b/c will decrease sphincter tone. “azosin” drugs
Nocturnal Enuresis – Pediatrics
Desmopressin (DDAVP) (nasal
spray) (PO)


MOA – Enhances reabsorption of water in kidneys by increasing cellular permeability of the collecting ducts
Dose: 100 mcg/mL nasal solution – Administer 10 – 40 mcg (0.1 – 0.4 ml) at bedtime. Give ½ the dose in each nostril. Usually tried for up to 6 months
Doxepin (Sinequan)
Amitriptyline (Elavil)