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 1 10/19/2015 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 2 10/19/2015 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 3 10/19/2015 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 4 10/19/2015 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 5 10/19/2015 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 6 10/19/2015 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 7 10/19/2015 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) 8 10/19/2015 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