10/19/2015

Faculty Urinary Incontinence: Pathophysiology, Jacqueline Giddens, MSN, RN Assessment and Nurse Consultant Treatment Options Bureau of Home & Community Services Nancy Bishop, RPh Satellite Conference and Live Webcast Assistant State Pharmacy Director Wednesday, October 21, 2015 2:00 – 4:00 p.m. Central Time Alabama Department of Public Health Produced by the Alabama Department of Public Health Video Communications and Distance Learning Division

Objectives Objectives • Define urinary incontinence (UI) • Discuss pharmaceutical • Describe pathophysiology and management of various types of UI clinical presentation of common • Discuss basic management options types of UI for UI symptoms and causes of UI • Discuss common medications that affect UI

Urinary Incontinence Micturation • UI is the involuntary leakage of urine • Complex function • Two times more common in • Continence is voluntary women than men • Estimated one - third of women over the age of 60 are incontinent

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Causes of Urinary Incontinence • Problem with nervous system • Weakness of the muscles Medications Linked to Urinary Incontinence • Blockage of the urethra

Medications That Cause Medications That Cause Urinary Incontinence Urinary Incontinence • Medications that may be associated – Estrogen replacement with urinary incontinence include the – Beta - mimetics following: – Sedatives – Cholinergic or anticholinergic drugs – Muscle relaxants – Alpha - blockers – Diuretics – Over - the - counter – Angiotensin - converting enzyme allergy medications (ACE) inhibitors

Medications Linked to Medications Linked to Urinary Incontinence Urinary Incontinence • Alpha blocker anti - hypertensives: • Antidepressants: Amitriptyline, Cardura, Minipres, Hytrin desipramine, nortripyline – While improving symptoms of BPH – Impairs ability of bladder to contract, in men, these medications relax causing the bladder to not empty the muscles in the bladder of completely women causing an increase in • Diuretics: Furosemide and thiazides severity of incontinence symptoms – Increase in amount of urine, worsening incontinence symptoms

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Medications Linked to Medications Linked to Urinary Incontinence Urinary Incontinence • Sedatives and Sleeping pills: • Angiotensin - converting enzyme Patients do not wake up when (ACE) inhibitors: benazepril, bladder if full captopril • Estrogens and progestin – Can cause cough and worsen combination therapy: Increased stress incontinence risk of developing urinary incontinence in women with history of cardiovascular disease

Medications Linked to Medications Linked to Urinary Incontinence Urinary Incontinence • Calcium channel blockers: diltiazem, • Antipsychotics: Haloperidol, verapamil resperidone, thioridazine, – Interfere with bladder contraction theothixene and worsen constipation, causing – Slows mobility and causes abrupt urine to be retained in the bladder urge followed by uncontrollable loss of urine

Medications Linked to Medications Linked to Urinary Incontinence Urinary Incontinence • Opioids: Morphine • H-1 antagonists: Diphenhydramine – Interferes with bladder contraction and Chlopheniramine and worsens constipation, causing – Significant degree of retention of urine anticholinergic effects • Alpha agonists: Pseudoephedrine – Tightens the urinary spincter causing urine to be retained in the bladder

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Medications Linked to Medications Linked to Urinary Incontinence Urinary Incontinence • Cholinergics: Bethanechol • Pregabalin (Lyrica): Reported in – Treatment for urinary retention clinical trials – • Donepezil (Aricept): Reported in Cause unknown clinical trials • Baclofen (Lioresal): With intrathecal – Cause unknown use • Caffeine and alcohol – Increase urine production

Types of UI Stress Incontinence • Stress • Stress Incontinence (SI): • Urge – Leakage that occurs when • Overflow laughing, sneezing, coughing, lifting heavy objects, or exerting • Functional other pressure on the bladder – Urine leaks as result if increased pressure on the bladder and weak muscles in the pelvic floor

Stress Incontinence Causes Stress Incontinence • Weak pelvic floor muscles • Affects both men and women • Weak urethral sphincter – In women, may follow childbirth • Childbirth or menopause – • Obesity In men, may follow prostate cancer treatment, such as radical • Prostate disease or surgery prostatectomy • Medications

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Urgency Incontinence Urgency or OAB • Urgency Incontinence or Over • Bladder spasms resulting in urinary Active Bladder (OAB): frequency – Loss Urgent need to pass urine • Sudden urges to go to the bathroom and the inability to get to a toilet • Having to get up at night to go to the in time bathroom • Mobility limitations

Overflow Incontinence Overflow Incontinence • Overflow Incontinence is when the • Causes of overflow incontinence: bladder does not empty properly and – Weak bladder muscles there is a slow leak, often a constant – Blockage of the urethra, such as drip or flow of urine by prostate enlargement • Often seen in men with prostate – Medical conditions, such as symptoms tumors, that cause obstruction of urine flow

Overflow Incontinence Overflow Incontinence – Constipation – Parkinson’s Disease – Pelvic trauma – Polio – Pelvic organ prolapse (women) – Other Neurological disorders – Enlarged prostate (men) – Spinal Cord injury – MS

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Functional Incontinence Causes of • The inability to hold urine due to Functional Incontinence Factors that Can Cause a Person Not reasons other than neuro - urologic to Get to the Bathroom in Time and lower urinary tract dysfunction • Physical • Functional Incontinence is when a – Arthritis person has normal functioning – bladder, but is unable to physically Muscle weakness or mentally get to the bathroom to – Stroke urinate – Muscular disease

Causes of Causes of Functional Incontinence Functional Incontinence Factors that Can Cause a Person Not Factors that Can Cause a Person Not to Get to the Bathroom in Time to Get to the Bathroom in Time • Cognitive • Cognitive – Dementia – Stroke – Alzheimer’s Disease – Mentally Challenged – Parkinson’s Disease – Brain Injury

Mixed Incontinence Mixed Incontinence • Common • Treatment may be a combination of • Symptoms of both stress and the treatments listed for stress or urgency incontinence are present urgency incontinence • • Symptoms of one type of Treatment may be directed to the incontinence may be more severe symptoms which are the most than the other bothersome to the patient

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Anti - Cholinergic Agents Anti - Muscarinic or Muscarinic Receptor Antagonists

Pharmaceutical • Treatment of urinary incontinence Management of • First line drug therapy Urinary Incontinence • Patients with more severe symptoms typically receive greater benefit

Anti - Cholinergic Agents Muscarinic Receptor Anti - Muscarinic or Muscarinic Antagonists Receptor Antagonists • Mechanism of action: • May decrease dose or try another – Depress voluntary and involuntary medication if patient has inadequate bladder contractions response or intolerable adverse – Decrease in detrusor muscle effects pressure – Targets M ₂₂₂ and M ₃₃₃ receptors in the detrusor muscle

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists – M₃₃₃ receptors are primarily • Adverse effects: – Dry / itchy eyes responsible for bladder function – Dry mouth* – Dyspepsia and direct contraction of the – Blurred vision – Urinary retention detrusor muscle – Constipation* – Decreased cognitive function *Most common

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Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists • Extended release formulations may • Absolute contraindications have lower incidence of dry mouth include closed angle glaucoma, • Caution in patients with narrow angle gastroparesis, GI obstruction, glaucoma, impaired gastric emptying pyloric stenosis, and urinary or urinary retention retention

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists • Interaction with CYP3A4 inhibitors: – Associated with dose - dependent – Increased anticholinergic effects prolongation of the QT interval with medications such as • Avoid in patients at risk for fluconazole and ketoconazole Torsades de pointes • Constipation, dry eyes, – Dose adjustment recommended dry mouth with strong CYP34A inhibitors

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists • Darifenacin (Enablex) • Solifenacin succinate (Vesicare, • Fesoterodine (Toviaz) YM905) • • Flavozate (Urispas) Tolterodine (Detrol, Detrol LA) • • Oxybutynin (Ditropan tablets, Oxytrol Trospium (Sanctura, Sanctura XR) Transdermal Patch, Gelnique Gel)

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Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists • Fesoterodine (Toviaz) – Level 2 drug interaction: – Indications: Overactive Bladder, Itraconazole, a potent CYP3A4 Urinary Incontinence, Urinary inhibitor which increases level of Urgency Toviaz, thereby increasing risk of adverse effects – Dose: Initially 4 mg by mouth daily – Interaction may be exaggerated in • May increase to 8 mg if not patients with renal or hepatic taking potent CYP3A4 inhibitor dysfunction

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists • Darifenacin (Enablex) – Dose: Initially 7.5 mg by mouth – Indications: Overactive Bladder, daily Urinary Incontinence • May increase to 15 mg if not – In theory, has fewer anti - muscarinic taking potent CYP3A4 inhibitor side effects than others because of – Level 2 drug interaction: greater affinity for M ₃₃₃ receptors Conivaptan (Vaprisol), a CYP34A inhibitor

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists – Monitor when less potent CYP34A • Flavozate (Urispas) inhibitors are given: fluconazole, – Oral urinary antispasmodic agent verapamil, diltiazem, grapefruit with direct actions of smooth juice muscle, especially of the urinary tract – Relaxes detrusor muscle and increases bladder capacity

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Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists – Has weak antihistaminic, local – Contraindications: Achalasia, anesthetic and analgesic bladder obstruction, GI Bleeding , properties GI obstruction, ileus, urethral – High doses can produce weak stricture, urinary retention, urinary anticholinergic actions tract obstruction – Level 2 drug interactions: anti - muscarinics, bethanechol

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists – Adverse reactions: nausea, • Oxybutynin – Ditropan tablets, Oxytrol vomiting, and dry mouth Transdermal Patch, Gelnique Gel – Indications: Overactive Bladder, Urinary Incontinence, Neurogenic bladder – Available as oral and transdermal formulations

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists – Oral immediate release 5 mg 2-3 – Topical: Apply 3 pumps or one times daily with maximum dose of 5 gel packet once daily mg 4 times a day • Rotate sites – Oral extended release: 5-10 mg daily – Oxytrol Transdermal is OTC – Transdermal: One patch applied approved for treatment of twice weekly overactive bladder in women 18 • Rotate patch site years of age and older

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Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists – Level 2 interactions: Potassium • Tolterodine (Detrol, Detrol LA) salts and Tegaserod (Zelnorm) due – Indications: Overactive Bladder, to decreased GI mobility Urinary Incontinence, Urinary – GI - related side effects were Urgency reported less frequently with the – Preferred in geriatric population patch and gel formulations – QT interval prolongation not observed at dose of 4 mg BID

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists – Dose immediate release 1-2 mg – Ketoconazaole requires an acidic twice a day, Extended release 4 mg pH for oral absorption which is daily diminished by tolterodine – Level 1 drug interactions: • Stagger time of administration Cisapride, Dofetilide, Dronedarone, by several hours or consider Thioridazine, Ziprasidone, alternative antifungal Pimozide, Ketoconazole, Voriconazole, Itraconazole

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists – Level 2 interactions: 70+ • Solifenacin Succinate (Vesicare) medications – Indications: Overactive Bladder, – Additional adverse effects: Urinary Incontinence dizziness and vertigo – Level 1 drug interactions due to – Most common reason for potential of QT interval discontinuation: dry mouth, prolongation resulting in torsades dizziness and headache de points

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Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists – Includes: Cisapride, Dofetilide, – Dry mouth most common reason Dronedarone, Thioridazine, for drug discontinuation Ziprasidone, Pimozide, – Dose: 10 mg daily Fluconazole, Ketoconazole, Posaconazole, Voriconazole – Level 2 drug interactions: 70+ medications

Muscarinic Receptor Muscarinic Receptor Antagonists Antagonists • Trospium (Sanctura, Sanctura XR) – Is not a substrate or inhibitor of – Indications: Overactive Bladder, cytochrome P-450 enzymes Urinary Incontinence, Neurogenic – Dose: Immediate release 20 mg bladder once or twice a day – Does not cross blood - brain • Extended release 60 mg daily in barrier like oxybutynin morning

Muscarinic Receptor Other Medications Antagonists • Mirabegron (Myrbetriq) – No level 1 drug interactions • OnabotulinumtoxinA (Botox) – Severity of dry mouth less than oxybutynin

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Other Medications Other Medications • Mirabegron (Myrbetriq) – Relaxes detrusor muscle via beta-3 – Beta-3 adrenergic receptor agonist AR activation, increasing bladder capacity during the urine storage – First in this class of agents phase – Indications: overactive bladder and – Can be alternative to anti - urinary incontinence muscarinics – First line drug therapy

Other Medications Other Medications – Common adverse reactions: – Monitor blood pressure and heart nausea, headache, hypertension, rate closely diarrhea, constipation, dizziness, – Contraindications: Severe and sinus tachycardia, UTIs uncontrolled hypertension – Dose 25 mg daily (SBP > 180 and/or DBP > 110 • May increase to 50 mg daily if – Level 2 drug interactions: tolerated Clozapine, digoxin, Doxorubicin, Eilglustat, Flecainide, MAOIs, Pimozide, Tamoxifen, Thioridazine

Other Medications Other Medications • OnabotulinumtoxinA (Botox) – Boxed Warning: risk of adverse – Indications: neurogenic bladder, effects if toxin spread beyond overactive bladder, urinary injection site (respiratory incontinence when anti - compromise and death) muscarinic agents are not – Requires Risk Evaluation and tolerated or are not providing Mitigation Strategy (REMS) and adequate response MedGuide – Injected into the detrusor muscle

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Other Medications Other Medications – Dose: 100 units (10 ml) given as 20 – Absolute contraindications: injections of 0.5 ml spaced 1 cm apart Infection, urinary retention, – Discontinue anti - platelet urinary tract infection medications at least 3 days prior to – Level 2 drug interactions: injection abobotulinumtoxinA, chloroquine, – Give antibiotics (excluding hydroxycholoroquice, aminoglycosides) 1 - 3 days prior to neuromuscular blockers, treatment and 1 - 3 days after rimabotulinumtoxinB treatment

Other Medications Over the Counter – Adverse reactions: Urinary Medications retention, UTI, hematuria, dysuria, • Azo Bladder Control with Go - Less injection site reaction, weakness in – Blend of pumpkin seed extract and muscles adjacent to the injected soy germ muscle – Pumpkin seed extract tones the muscles and maintains the strength of the detrusor and sphincter muscles

Over the Counter Over the Counter Medications Medications – Soy germ sustains the bladder • Methionine muscle and pelvic floor – Oral agent used to control odor, – Improvement seen in 2 to 6 weeks dermatitis and ulceration in – Dose: One tablet twice daily incontinent adults – – $15.86 for 27 days of therapy Creates an ammonia - free urine by raising pH of urine – Has good consumer reviews

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Over the Counter Over the Counter Medications Medications – Take with food or with milk or – Dose: 200-500 mg by mouth up to 4 other liquid times a day after meals – Contraindications: Liver disease – No significant drug interactions – Adverse reactions: Large doses can exaggerate the toxemia of liver disease

Off - Label Medications Off - Label Medications • Duloxetine - Do not use in liver – Contraindications / Precautions: Bovine failure patients hypersensitivity (including hypersensitivity to bovine collagen • Ephedra, Ma Huang products or dietary beef); history of severe • Bovine collagen implant: for UI due allergies, undergoing desensitization to to sphincter deficiency (Reserved for meat products; cystitis, urethritis, or other infection; autoimmune disease, systemic patients who have failed other connective tissue disease; intravenous therapy for at least 12 months) administration; bladder neck or urethral strictures; pregnancy; children

Off - Label Medications Off - Label Medications – Drug Interactions: • Imipramine- reserved for patients Immunosuppressive therapy, with an additional indication such as corticosteroids depression or neuralgia – Adverse Reactions: Urinary • Midodrine retention, hematuria, injection site • Propantheline reaction, worsening incontinence, • Pseudoephedrine erythema, urticaria, abscess formation

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Surgical Interventions Non - Surgical Interventions • Sling procedures • Urethral insert • Bladder neck suspension • Pessary • Prolapse surgery • Bulking material injections • Artificial urinary sphincter • Botulinum toxin type A (Botox) • Nerve stimulators • Bladder retraining

Non - Surgical Interventions Bladder Retraining Programs • Lifestyle changes • Many studies over the years have • Exercise supported the success of bladder retraining programs for both women • Management of underlying or and men experiencing symptoms of contributory factors: urge incontinence and urgency – Constipation – Hormone therapy associated with overactive bladder – Diabetes – Functional (OAB)

What Can You Do? What Can You Do? • Assist patient with – Following the individualized – Bladder / Void diary, as instructed toileting plan established by their by the nurse nurse or physician – – Bladder training, as instructed by Proper application of containment the nurse (diapers, pads, condom catheters) – To keep clear the path to the bathroom or bedside commode

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Exercises Kegel Exercises • Walking • Kegel Exercises are for men • Balance exercise and women • Abdominal (core) muscle strengthening* • Stop urination in midstream • Pelvic muscle exercise (Kegels) • Slow down the flow of urine • Can be done by both men and women • Don’t tense the muscles in your *Resource: buttocks, legs, or abdomen, and don’t hold your breath http://eldergym.com/lower-back-exercise.html

Kegel Exercises Perfect Your Technique • When you can slow or stop the flow • With the bladder empty, tighten of urine, you’ve successfully located muscles like holding in gas these muscles • Hold for 5 seconds • Relax for 5 seconds • Repeat 5 times • Work up to 10 seconds hold, 10 seconds relax and repeat 10 times

Practice What Can You Do? • Repeat for up to 3 sets per day • Encourage patient • Don’t overdue – There are ways to improve • Remember relaxation is as important their continence the nurse and as tightening! physician can provide – To drink most fluids earlier in the day

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What Can You Do? Contact Information – Restrict drinking fluids 2 hours Jacqueline Giddens, MSN, RN prior to bedtime Nurse Consultant Bureau of Home and Community Services – To do Kegel exercises as [email protected] instructed by the nurse (334) 206-5685 Nancy Bishop, RPh Assistant State Pharmacy Director [email protected] (334) 206-3014

Alabama Department of Public Health

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