LIWANAG, Genecarlo 2-D Urinary Incontinence - Any involuntary leakage of urine.

- Usually results from either instability of bladder contractions and/or diminished bladder neck contraction. - There is either an increased stimulus to void or decreased ability to prevent voiding. - It is a loss of bladder control - Symptoms can range from mild leaking to uncontrollable wetting - Becomes more common with age - Most bladder control problems happen when muscles are too weak or too active

More common in women than men Older > younger White race Multiparity Obesity

Normal Physiology of Micturition and Continence: Continence and micturition involve a balance between urethral closure and detrusor muscle activity. urethral pressure normally exceeds that of the bladder pressure, resulting in urine remaining in the bladder. the proximal urethra and bladder are both within the pelvis. intraabdominal pressure increases (whenever a person coughs or sneezes), and is then transmitted to both urethra and bladder equally, resulting in continence. normal voiding is the result of changes in both pressure factors: urethral pressure decreases while bladder pressure increases.

Pathophysiology of Urinary Incontinence: According to Melmon and Morelli there are four types of urinary incontinence: 1. Stress incontinence

a. Due to dysfunction of bladder outlet. i. Causes include urethral sphincter as occurs in postmenopausal women with estrogen deprivation and decreased bladder neck support as in multiparity. ii. If the muscle that keeps the bladder closed is weak iii. Failure of the sphincteric mechanism to remain closed when there is sudden increase in intraabdominal pressure, such as cough or sneeze. iv. In women, this condition is due to insufficient strength of the pelvic floor muscles. v. In men, it is almost exclusively secondary to prostate surgery. 2. Urge incontinence

a. Due to uninhibited bladder contractions i. Causes include CNS lesions that impair inhibition of bladder contractions, infection, tumors, and idiopathic causes. ii. This is the loss of urine accompanied by sudden sensation of need to urinate. iii. Patient may feel a strong urge to go to the bathroom even if there is only little urine in the bladder

iv. This is due to detrusor muscle overactivity (lack of inhibition) due to loss of neurologic control. 3. Overflow incontinence

a. Due to overdistended bladder i. Causes include impaired detrusor contraction due to neurologic abnormalities and outflow obstruction due to medications, tumors, strictures, and prostatic hypertrophy. ii. It is as if the patients bladder is continually overflowing even after frequent urination iii. Characterized by urinary dribbling, either constantly or for some period after urination. iv. Due to impaired detrusor muscle contractility (secondary to denervation, like in Diabetes) or bladder outlet obstruction (due to hypertrophy of the prostate in men and cystocele in women.) 4. Mixed incontinence a. Due to combination of factors.

Medications: Classified according to mechanism of action. Decrease bladder contraction:

 Prophantheline Br (7.5-30 mg at least TID) Oxybutynin Cl (2.5-5 mg TID or QID) Dicyclo mine HCl (10-20 mg TID) Flavoxalate HCl (100-200 mg TID or QID Increase Bladder outlet contraction Phenylpropanolamine 25-100 mg BID Pseudoephedrine 15-30 mg TID Nonspecific: Estrogens TCAs (Imipramine, Amitriptyline) Desmopressin Anticholinergics / Anti-muscarinics For overactive bladder, characterized by abnormal bladder contractions. Anticholinergic drugs block the action of a chemical messenger acetylcholine that sends the signals that trigger these contractions. 1. Oxybutynin (Ditropan) a. Oxybutynin is used to control urgent, frequent, or uncontrolled urination in people who have overactive bladder. b. The full effect of this drug can be experienced in six to eight weeks. c. It completely antagonizes the M1, M2, and M3 receptors. d. Direct spasmolytic effects on the bladder smooth muscle. e. Usually taken BID, TID, or four times a day, PO. f. DOC for STRESS INCONTINENCE 2. Propantheline Bromide a. By relaxing the gut muscle, propantheline can relieve pain in conditions caused by spasm of the muscle in the gut. Relaxing the smooth muscle in the bladder prevents the involuntary spasms that can allow leakage of urine from the bladder (known as enuresis). Can also be used to treat hyperhidrosis and excessive lacrimation. b. Antimuscarinic. Antispasmodic. Propantheline works by blocking the action of ACh to muscarinic receptors in smooth muscle tissues (bladder smooth muscle) causing a decrease in smooth muscle contraction. 3. Dicyclomine HCl a. Used to treat intestinal hyper motility, symptoms of IBS or Spastic colon. Relieves muscle spasms and cramps, smooth muscle relaxant. 4. Flavoxalate a. Used to treat urinary bladder spasms. Indicated for symptomatic relief of interstitial cystitis, dysuria, urgency, suprapubic pain, frequency and incontinence as may occur in cystitis, prostatitis, urethritis, urethrocystitis, urethrotrigonitis. b. Antimuscarinic. Similar to Prophantheline Br and Dicyclomine HCl. c. Anticholinergic effects, can potentially cause severe vomiting, GI upset, dry mouth/throat, blurred vision, eye pain, photosensitivity.

d. CI: obstructive conditions such as pyloric or duodenal obstruction, obstructive intestinal lesions, ileum, achalasia, GI hemorrhage, obstructive uropathies of lower urinary tract.

5. Tolterodine a. Tolterodine is used to relieve urinary difficulties, including frequent urination and inability to control urination. b. Tolterodine acts on M1, M2, M3, M4 and M5 receptors. c. It works by preventing bladder contraction. d. Usually taken BID 6. Darifenacin (Enablex) a. Darifenacin is used to treat an overactive bladder b. It works by relaxing the bladder muscles to prevent urgent, frequent, or uncontrolled urination. c. Works on the M3 receptor, which is primarily responsible for bladder muscle contractions. d. Comes in an extended-release form, taken OD. 7. Fesoterodine a. Fesoterodine is used to treat overactive bladder b. It works by relaxing the bladder muscles to prevent urgent, frequent, or uncontrolled urination. c. Fesoterodine is a produrg. It is broken down into its active metabolite, 5-hydroxymethyl-tolterodine, by plasma esterases d. Comes in an extended-release form, taken OD. e. It may take up to 12 weeks before full effect is seen. 8. Solifenacin a. Solifenacin is used to treat overactive bladder b. Acts on the M3 receptor c. It works by relaxing the bladder muscles to prevent urgent, frequent, or uncontrolled urination. 9. Trospium Chloride a. Trospium is used to treat an overactive bladder b. Comes in an extended-release form, taken OD. c. The tablet is usually taken twice a day on an empty stomach or one hour before meals,or is sometimes taken once a day at bedtime Side Effects: Xerostomia Constipation Heart burn Blurry vision Tachycardia Increased body temperature Mydriasis Flushed skin

 Impaired memory Confusion Urinary retention Decreased mucus production Increased IOP Photophobia Antidepressants: 1. Imipramine (Tofranil) a. It makes the bladder muscle relax, while causing the smooth muscles at the bladder neck to contract. b. It inhibits norepinephrine re-uptake, to a lesser extent, that of serotonin. c. It may be used to treat mixed urge and stress incontinence. d. May cause drowsiness, so it's often taken at night. e. Useful for nighttime incontinence f. Imipramine is usually not a good fit for older adults. 2. Amitriptyline (Elavil) Side Effects:

Rare but include CV problems Irregular heartbeat Dizziness Fainting from hypotension Weight loss/gain Urinary retention Exacerbation of glaucoma Rarely, agranulocytosis Children and older adults are more susceptible to the above side-effects

Other Drugs: 1. Desmopressin a. A synthetic version of a natural body hormone called anti-diuretic hormone (ADH). b. This hormone decreases the production of urine. c. In children, bed-wetting may be caused by a shortage of nighttime production of ADH. d. Commonly used to treat bed-wetting in children. e. May also reduce urinary incontinence in adult women. Side Effects: Uncommon, but there is a risk of water retention that results in a low sodium level in the blood (hyponatremia). In rare cases led to seizures, brain swelling and death. 2. Phenylpropanolamine a. used as a stimulant, decongestant, and anorectic agent, cough and cold preparation, urinary incontinence. b. Act as potent and selective releasing agent of NE and Epi. Also acts as dopamine releasing agent to a lesser extent. Mimic effects of endogenous catecholamines such as Epi and NE and to a lesser degree, Dopamine.

Side Effects: Sympathetic effects. "fight or flight responses such as Increase HR, BP, pupil dilation, drying of mucous membranes, sweating. 3. Estrogen a. Synthetic hormone indicated in treating post-menopausal women, used to treat urinary incontinence in females. b. Important side effect to watch out for is thrombosis in the form of DVT.

References: Harrisons Principles of Internal Medicine 18th Edition. Melmon and Morellis Clinical Pharmacology 4th Edition. http://www.drugs.com/monograph/dicyclomine-hydrochloride.html retrieved on July 17, 12.