Drugs for Urinary Incontinence or Retention Flashcards
Anticholinergics
Darifenacin Fesoterodine Oxybutynin Solifenacin Tolterodine Trospium Botulinum Toxin
Sympathomimetics
Mirabegron
Pseudoephedrine †
Ephedra †
Ancillary Drugs
Methionine
Bovine Collagen Implant
Overactive Bladder (OAB)
Substantial medical and QOL sequelae of OAB
Treatment of Urinary Incontinence typically begins with?
Noninvasive approaches such as behavioral therapy, including patient education, fluid management, bladder retraining, pelvic floor exercises, biofeedback, and timed bladder emptying.
If noninvasive does not work?
Surgical procedures and catheterization are appropriate for some patients or add pharmacotherapy when behavioral modification fails.
Most commonly prescribed drugs?
Antimuscarinic medications: tolterodine & oxybutynin.
Reluctance in nursing home use due to?
Lack of efficacy data in these populations, often severe cognitive impairment, and risk of drug-drug interactions.
Incontinence [Urge (detrusor overactivity)]
Common Causes
Usual Symptoms
Drug Treatments
Strokes, Alzheimer Parkinson disease BPH with overflow
Urgency & frequency, day or night (nocturia)
Anticholinergics: Oxybutynin & Tolterodine
Incontinence [Stress (outlet incompetence)]
Common Causes
Usual Symptoms
Drug Treatments
Urological procedures, multigravida, Estrogen deficiency
Minimal urine loss with coughing, sneezing, running, or laughing
Topical estrogen, Alpha-agonists Non-drug method
Incontinence [Mixed]
Common Causes
Usual Symptoms
Drug Treatments
Multiple etiologic factors
Symptoms of urge and/or stress and/or overflow
Focus treatment on predominant symptoms
Incontinence [Atonic bladder]
Common Causes
Usual Symptoms
Drug Treatments
Severe diabetic neuropathy, Stroke
Complete loss of bladder control
Catheterization
Incontinence [Functional]
Common Causes
Usual Symptoms
Drug Treatments
Inability to reach bathroom, changes in mental
status, UTIs, medications
Symptoms of incontinence vary according to type
of external cause
Therapy choice to eliminate cause
Salivary glands:
Receptors
Effects of Blockage
M1, M3, M4
Dry mouth
Cardiac tissue:
Receptors
Effects of Blockage
M2
Tachycardia, palpitations
Eye (ciliary muscle, iris)
Receptors
Effects of Blockage
M3, M5
Dry eyes, blurred vision
GI tract:
Receptors
Effects of Blockage
M1, M2, M3
Slowing of transit time (constipation), effects on sphincter tone and gastric acid secretion
CNS, brain (cortex and hippo-campus):
Receptors
Effects of Blockage
M1, M2, M3, M4, M5
Effects on memory, cognition and psychomotor speed, confusion, delirium, hallucinations, sleep disruption
Bladder (detrusor muscle):
Receptors
Effects of Blockage
M2 (opposes β- receptor), M3 (direct effect)
Decreased contraction, urinary retention
Adverse Effects of Anticholinergic Drugs
Peripheral Effects
Dry mouth Mydriasis Constipation Urinary retention Tachycardia
Adverse Effects of Anticholinergic Drugs
Central Effects
Sedation Confusion/delirium Hallucinations Slowed cognitive function Sleep disruption
Tertiary Amines are?
Oxybutynin Tolterodine Fesoterodine Solifenacin Darifenacin
Quaternary Amine is?
Trospium means want effect CNS.
Which has > M3- selectivity?
Darifenacin
Oral bioavailability Poor:
Darifenacin
Oxybutynin
Trospium
CYP Metabolism only one with almost no CYP activity?
Trospium
Trospium & Fesoterodine have rapid
Urinary Excretion
Solifenacin half life:
45–68 hrs
Oxybutynin & Tolterodine both have?
Short half lives (2hrs), but have extended release formulations.
Fesoterodine is rapidly hydrolyzed to?
5-hydroxymetghyl-tolterodine; parental drug is not detectable in systemic circulation.
Elderly patients may be taking multiple anticholinergics, so monitor for adverse effects:
– Urinary retention, especially in BPH
– CV effects may include palpitations, tachycardia, & a prolonged QTc interval
– GI effects: mild constipation to severe obstructions
Elderly patients may be taking multiple anticholinergics Contraindications:
– Angle closure or narrow-angle glaucoma
– Urinary and gastric obstruction
– Need for mental alertness
– Alzheimer’s type dementia
Risk of withdrawal & dry mouth
Dry Mouth: Oxybutynin = Tolterodine > Solifenacin & Fesoterodine
Botox injections are more successful in patients with?
Anticholinergic intolerability as compared to patients with poor medication efficacy.
Botox Mechanism:
Inhibits vesicular release of excitatory neurotransmitters and axonal expression of other SNARE-complex dependent proteins in the urothelium/suburothelium mediating intrinsic or spinal reflexes thought to cause detrussor overactivity.
Sympathetic postganglionic neurons release?
Norepinephrine, which activates β3 adrenergic receptors to relax bladder smooth muscle & activates α1 adrenergic receptors to contract urethral smooth muscle.
Mirabegron Receptor binding: Oral bioavailability: CYP Metabolism: Urinary Excretion: Half-life:
β-3 agonist; increases bladder capacity by relaxing detrusor s.m.
≤ 35%; decreased by food
3A4»_space; 2D6; also butylcholinesterase, UGT, & alcohol dehydrogenase
~10% as parental drug
~50 hrs
Pseudoephedrine Receptor binding: Oral bioavailability: CYP Metabolism: Urinary Excretion: Half-life:
Direct & indirect α & β agonist; α>β effects Almost complete Minimal ≤ 75%; increase with acidic urine 9-16 hrs, depending on urinary pH
Ephedra Receptor binding: Oral bioavailability: CYP Metabolism: Urinary Excretion: Half-life:
Indirect nonselective α & β agonist ~85% Minimial Up to 99%; increase with acidic urine ~5 hrs
Mirabegron side effects?
– Increase BP; monitoring recommended, especially in hypertensives.
– Tachycardia
Pseudoephedrine side effects?
– Hypertension, tachyarrhythmia, A-fib
– Insomnia
– Anxiety, feeling nervous, restlessness
Ephedra side effects?
– Hypertension, tachyarrhythmia, CHF, MI
– Insomnia
– Symptoms of CNS stimulation
Have MAOI interaction?
Mirabegron
Pseudoephedrine
Ephedra
Check patient drug history
Methionine Mechanism & use?
• Creates ammonia-free urine by acidifying urine pH
• Used to control odor, dermatitis, and ulceration in
incontinent adults
Methionine adverse effects?
Most common adverse effects: Drowsiness; nausea and vomiting.
Bovine Collagen mechanism & use?
For incontinence due to intrinsic sphincter deficiency.
Injected into submucosal tissue of urethra and/or bladder neck & forms a soft cohesive network of fibers increasing tissue bulk around the urethral lumen.
Bovine Collagen Adverse Reactions:
Urinary retention, hematuria, injection site reaction, worsening incontinence, erythema, urticaria, abscess formation.
Management Of Urinary Retention Includes?
Assessment of post-void residual urine volume Strengthening of cholinergic-mediated detrussor
muscle contraction
Bethanechol Receptor binding: Oral bio-availability: Metabolism: Urinary Excretion: Half-life:
Muscarinic agonist in urinary bladder and GI tract Ionized; doesn’t cross BBB Poor; % undetermined Not inactivated by cholinesterases Undetermined Short duration: 1 hr orally, 2 hrs s.c.
Neostigmine Receptor binding: Oral bio-availability: Metabolism: Urinary Excretion: Half-life:
Inhibits acetylcholinesterase, augments action of Ach at both muscarinic and nicotinic receptors
Poor, ~2%
Inactivated by cholinesterases & hepatic microsomal enzymes
≤ 70% as parental drug
< 1 hr
Bethanechol side effects:
– CV: Lightheadedness, Syncope – GI: Diarrhea, Stomach cramps – Neurologic: Dizziness – Ophthalmic: Excessive tear production, miosis – Renal: Urgent desire to urinate
Neostigmine side effects:
– AV block – Bradyarrhythmia – Cardiac arrest – Cardiac dysrhythmia – Hypotension – Syncope – Tachycardia
Opiate Adverse Effects
- Urinary retention (oral, < 5% ; epidural/intrathecal, ≤ 70%)
- Cholinomimetic agents such as bethanechol may be helpful to treat urinary retention induced by opioids
