Urinary incontinence(UI)Anticholinergic effects, α-antagonist effects •Alcohol Polyuria,...

Urinary incontinence(UI)

Hozan Jaza

MSc Clinical Pharmacy

College of Pharmacy

5/ 2/ 2020

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Urinary incontinence(UI) is the complaint of involuntary leakage of urine.

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Etiology and Pathophysiology • Aging affects the lower urinary tract in several ways , including

both structural and functional changes. Age-Related Changes in Urologic Function ↓ Bladder capacity ↑ Residual urine ↑ Uninhibited bladder contractions ↑ Nocturnal sodium and fluid excretion ↓ Urethral resistance in women ↑ Urethral resistance in men Weakness of pelvic floor muscles in women • Involuntary bladder contractions (detrusor motor instability) is

The most common age-related change, in both women and men.

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For women

These changes are correlated with the postmenopausal decline of estrogen production.

Estrogen has trophic effects on the epithelium and on tissues lining and surrounding the urethra, bladder outlet, and vagina.

Atrophy of these tissues can result in inflammation, susceptibility to infection, diminished periurethral blood flow, and prolapse of pelvic structures.

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For men

The age-related changes in the prostate gland are responsible for many of the changes in urination.

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Classification of Urinary incontinence

There are two types of urinary incontinence include

Acute (or transient) and reversible incontinence

Chronic and persistent incontinence

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Acute incontinence The causes of Acute incontinence include the following: cystitis, atrophic vaginitis, and urethritis heart failure polyuria from diabetes delirium and acute confusional states immobility medication side effects . The management of acute forms of urinary incontinence depends on the identification and elimination of the reversible factor.

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Medication that lead to urinary incontinence include • Diuretics Polyuria, frequency, urgency • α-Receptor antagonists Urethral relaxation and stress urinary incontinence in women • α-Receptor agonists Urethral constriction and urinary retention in men • Calcium channel blockers Urinary retention • Narcotic analgesics Urinary retention from impaired contractility • Sedative hypnotics Functional incontinence caused by delirium, immobility

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• Antipsychotic agents Anticholinergic effects and urinary retention • Anticholinergics Urinary retention • Antidepressants Anticholinergic effects, α-antagonist effects • Alcohol Polyuria, frequency, urgency, sedation, delirium • ACEIs Cough as a result of ACEIs may aggravate stress urinary incontinence by increasing intra-abdominal pressure

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Persistent urinary incontinence (PUI)

It which refers to incontinence that is not acute and occurs for a long time, can be classified further into four subgroups:

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Bladder overactivity is known as urge UI (UUI)

It is associated with increased urinary frequency and urgency, with or without urge incontinence.

The detrusor muscle is overactive and contracts inappropriately during the filling phase.

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Urethral underactivity is known as stress UI (SUI)

• It occurs during activities such as exercise, lifting, coughing, and sneezing.

• Stress incontinence is common in elderly women but uncommon in men (unless the sphincter has been damaged during a transurethral resection of the prostate [TURP] or a prostatectomy).

• Stress incontinence can be diagnosed by the “tissue test” in which a tissue is placed just below the urethra and the patient is asked to cough, resulting in the loss of a small amount of urine.

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Urethral overactivity and/or bladder underactivity is known as overflow incontinence.

The bladder is filled to capacity but is unable to empty, causing urine to leak from a distended bladder.

Common causes of urethral overactivity include benign prostatic hyperplasia, prostate cancer and urethral stricture , in women, cystocele formation.

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Leakage of small amounts of urine (dribbling) is common throughout the day and night.

The patient may complain of hesitancy, diminished and interrupted flow, a need to strain to void, and a sense of incomplete emptying.

The bladder usually is palpable, and the residual urine volume is large.

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Mixed incontinence includes the combination of bladder overactivity and urethral underactivity is known as Functional incontinence.

It occurs when a continent individual is unable or unwilling to reach the toilet to urinate.

Common causes are musculoskeletal disorders, muscle weakness, impaired mental status, psychological impairment, and medications (e.g., sedatives, neuroleptics).

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Clinical presentation

Signs and symptoms of UI depend on the underlying pathophysiology :

Patients with SUI generally complain of urine leakage with physical activity,

whereas those with UUI complain of frequency, urgency, high-volume incontinence, and nocturia and nocturnal incontinence.

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Urethral overactivity and/or bladder underactivity is a rare but important cause of UI. Patients complain of lower abdominal fullness, hesitancy, straining to void, decreased force of stream, interrupted stream, and sense of incomplete bladder emptying. Patients can also have urinary frequency, urgency, and abdominal pain.

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Diagnosis

• A complete medical history, physical examination (ie, abdominal examination to exclude distended bladder, pelvic examination in women looking for evidence of prolapse or hormonal deficiency, and prostate examination in men).

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• For SUI, the preferred diagnostic test is observation of urethral meatus while the patient coughs or strains.

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• For UUI, the preferred diagnostic tests are urodynamic studies. Perform urinalysis and urine culture to rule out urinary tract infection.

• For urethral overactivity and/or bladder underactivity, perform digital rectal examination or transrectal ultrasound to rule out prostate enlargement. Perform renal function tests to rule out renal failure.

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Non-pharmacologic Therapy

• The first step is to educate patients about bladder function, appropriate fluid intake, and avoidance of caffeine and other bladder irritants.

• The patient can then keep a bladder diary in which they record their fluid intake, voiding pattern, and incontinence episodes.

• Bladder training refers to scheduled voiding, urge-suppression techniques, and pelvic muscle exercises ( kegel exercise).

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Pharmacologic Therapy

Bladder overactivity (UUI) •The first choice for treatment of UUI is anticholinergic/antispasmodic drugs, which antagonize muscarinic cholinergic receptors. Oxybutynin It is available as an oral immediate-release tablet, an

extended-release tablet, a transdermal system, and a topical gel.

The oral dosage of oxybutynin chloride suggested for the elderly is 2.5 mg up to 3 times a day; in some cases, the dosage may need to be increased to 5 mg 3 times a day.

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Once-daily, controlled-release oxybutynin at doses of 5 to 30 mg reduced the number of incontinence.

The transdermal system is available both in a prescription and over-the-counter version and contains 36 mg of active drug and delivers 3.9 mg of oxybutynin per day when dosed twice a week. The transdermal system should be protected from moisture and humidity. Common side effects from the transdermal system at the application site are pruritus and redness.

Oxybutynin gel is also available for daily use.

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Tolterodine Tartrate

It is considered first-line therapy in patients with urinary frequency, urgency, or urge incontinence.

Dosage adjustment is recommended in the presence of renal or hepatic impairment and during concurrent therapy with drugs that inhibit cytochrome P-450 (CYP) 2D6 and CYP3A4 isozymes.

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The common adverse effects of it include dry mouth, dyspepsia, headache, constipation, and dry eyes.

The usual dose for the elderly is 1 to 2 mg twice daily of the immediate release or 2 to 4 mg once daily of the long acting formulation

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Fesoterodine

The recommended starting dosage of fesoterodine is 4 mg once daily and may be increased to 8 mg in patients with an insufficient response.

Patients with severe renal impairment (creatinine clearance <30 mL/minute) or those taking a strong CYP3A4 inhibitor should not take more than 4 mg/day.

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Trospium Chloride

• It is used for the management of overactive bladder and urge incontinence.

• The hydrophilic properties of trospium minimize the passage of the drug through the blood–brain barrier, thereby causing fewer CNS and cognitive adverse events.

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• The medication should be administered at a dose of 20 mg twice daily or 60 mg of the extended-release product once daily.

• For patients with severe renal insufficiency (creatinine clearance <30 mL/minute), the dose should be reduced to 20 mg once daily.

• Trospium should be taken on an empty stomach to avoid decreasing absorption.

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Darifenacin

It is indicated for the treatment of overactive bladder with symptoms of urinary incontinence, urgency, and frequency.

The recommended starting dose is 7.5 mg once daily. Based on the individual response, the dose may be increased to 15 mg daily after 2 weeks.

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Solifenacin

• It is used for the treatment of overactive bladder with symptoms of urinary incontinence.

• The recommended dose of solifenacin is 5 mg once daily, which can be increased to 10 mg once daily if needed.

• Patients with renal and hepatic impairment or on CYP3A4 inhibitors, the dose should not exceed 5 mg once daily.

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β- adrenergic agent Mirabegron • It is a first in class β3-adrenergic agonist approved

for use in overactive bladder. • Mirabegron can be used alone or in combination

with antimuscarinics for those who cannot tolerate an increase in the antimuscarinic dose or are already on a maximum dose.

• Mirabegron is initiated at 25 mg once daily and can be titrated up to 50 mg once daily in 2 to 4 weeks.

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• Patients with renal or hepatic impairment should not receive doses higher than 25 mg once daily.

• Mirabegron is also a CYP2D6 inhibitor, and drugs that are CYP2D6 substrates taken concomitantly may require dose adjustments.

• The most common adverse effects of it include Hypertension, urinary tract infection, and headache.

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Urethral underactivity:

• Treatment of SUI is aimed at improving urethral closure by stimulating α-adrenergic receptors in smooth muscle of the bladder neck and proximal urethra, or enhancing serotonin and norepinephrine effects in the micturition reflex pathways.

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α-Adrenergic receptor agonists

α-adrenergic agonists, such as pseudoephedrine and Phenylephrine.

These agents are contraindicate in patients with hypertension, tachyarrhythmias, coronary artery disease, myocardial infarction.

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Duloxetine It is a serotonin and norepinephrine reuptake

inhibitor that has shown efficacy in patients with stress incontinence.

It is used for a woman with both depression and stress incontinence

The most common adverse effect with duloxetine is nausea, which tends to resolve with time. The dose of duloxetine that has been studied for stress incontinence is 40 to 80 mg/day in one or two doses.

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Estrogens

Local and systemic estrogens have been the mainstays of pharmacologic management of SUI.

Estrogens were administered orally, intramuscularly, vaginally, or transdermally.

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Urethral overactivity and/or bladder underactivity

For treatment of Overflow α1A-blockers are used such as Prazosin, Terazosin, Indoramin, Doxazosin, Tamsulosin, and Alfuzosin.

If detrusor underactivity is the known cause of overflow incontinence, bethanechol can be used

Common adverse effects of bethanechol include flushing, tachycardia, abdominal cramps, and malaise.

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