Lower Urinary Tract Pharmacological Flashcards
Overactive Bladder
- Anticholinergic Mechanism
Blocks parasympathetic signals from activating detrusor muscles
- Reduces urination (Does not cure)
Alpha vs Beta Bladder Receptors
Alpha:
- Activation causes contraction of bladder neck resulting in increased resistance (Good for stress incontinence)
Beta
- Activation causes relaxation of bladder smooth muscle
(Good for urgency incontinence)
Overactive Bladder
- Antimuscarinic Summary
Decrease number of urinations and incontinence episodes
- Have side effects that may cause patient to stop taking
–> Cognition
–> Heart
–> Glaucoma
Overactive Bladder
- Antimuscarinic Adverse Effects
Dry Mouth
Dry Eyes
Confusion
Rapid Heart Rate
Urine Retention
Skin Flushing
Constipation
Overactive Bladder
- Antimuscarinic Heart
Solifenacin, Tolterodine, and Mirabegron can cause QT Prolongation
- Bradycardia
- Electrolyte Imbalance
- Heart Disease
- Kidney/Liver Impairment
Overactive Bladder
- Antimuscarinic Cognition
Older antimuscarinic medications are more likely to cross into the brain and cause confusion
Oxybutynin > Solifenacin > Tolterodine > Darifenacin > Fesoterodine > Trospium
Overactive Bladder
- Antimuscarinic Contraindications
- Glaucoma
- Myasthenia Gravis
- GI: Obstruction, Inflammatory bowel, atony
- Urogenital: Obstruction
Overactive Bladder
- Beta-3 Adrenergic Agonist
Mirabegron
- Relaxes bladder smooth muscle preventing contractions
Overactive Bladder
- Beta-3 Adrenergic Agonist Adverse Effects
Adverse Effects:
- Nausea, Diarrhea, Constipation, Dizziness, Headache
CV Safety:
- Tachycardia, Increased BP, Prolonged QT
Antimuscarinic Drugs
Oxybutynin
Tolterodine
Fesoterodine
Propiverine
Darifenacin
Solifenacin
Trospium
Overactive Bladder
- Anticholinergic Interactions
Interacts with antihistamines and TCA
Overactive Bladder
- Cholinergic Interactions
Interacts with Cholinesterase Inhibitors for dementia
FORTA Classification
- What is it
Highlights Medications and their safety in older adults
- Class A (Absolutely)
- Class B (Beneficial)
- Class C (Careful)
- Class D (Don’t)
FORTA Classification
- Overactive Bladder
A: No drugs
B: Fesoterodine
C: Most bladder drugs fall here
D: Propiverine, Immediate release Oxybutynin
Overactive Bladder
- Off Label Drugs
TCA
Dicyclomine
Flavoxate
Overactive Bladder
- Botulinum Toxin
Helps bladder muscles relax
- Used in Refractory Overactive Bladder
- Used in Chronic Urinary Infections
- Used in Neurologic Condition
Can make bladder too flaccid after treatment
Summary: How to Treat Overactive Bladder
Antimuscarinic
Beta-3-Agonist (Mirabegron)
Botulinum Toxin
Stress Incontinence
- Alpha Agonist
Ex. Pseudoephedrine
Squeezes off bladder neck to tighten the sphincter
- Some benefits, very stimulating drug that penetrates deep into CNS
Stress Incontinence
- Alpha Agonist Considerations
Not much evidence
Only use with non-pregnant women or men
Stress Incontinence
- Alpha Agonist Adverse Effects
- Increased BP
- Cardiac Arrhythmias
- Anxiety
- Insomnia
Stress Incontinence
- Hormone Therapy Mechanism
Sensitizes alpha receptors
- Increasing bladder resistance
Minimize atrophy
- Ensures bladder muscles maintain their strength
Stress Incontinence
- Hormone Therapy Considerations
Not much evidence
Testosterone therapy in men is avoided
Stress Incontinence
- Duloxetine Mechanism
Off Label use for Urinary Incontence
- Selective 5-HT and NE reuptake inhibitor (For depression)
Increases sphincter contractility
Stress Incontinence
- Duloxetine Adverse Effects
Nausea
Stress Incontinence
- Other Options
Surgical
- Bladder Suspension
Bulking Agents
- Autologous Fat
- Silicone
Summary: How to Treat Stress Incontinence
Alpha Agonists (Little Evidence)
Hormone Therapy (Little Evidence)
Duloxetine
Overflow Urinary Incontinence (BPH Treatment)
- BPH Treatment
Surgery
Catheterization (Allows patient to relieve urine)
Pharmacotherapy
Overflow Urinary Incontinence (BPH Treatment)
- Surgery
TURP (Transurethral Resection of the Prostate)
Prostatectomy
Overflow Urinary Incontinence (BPH Treatment)
- 5-Alpha Reductase Inhibitors Drugs
Finasteride, Dutasteride
Dutasteride works faster (3 months compared to 6)
Dutasteride reduces prostate size more
Overflow Urinary Incontinence (BPH Treatment)
- 5-Alpha Reductase Inhibitors Mechanism
Prevent formation of DHT (Testosterone Analogue)
Takes a long time to show any effects (3 months)
Overflow Urinary Incontinence (BPH Treatment)
- 5-Alpha Reductase Inhibitors Adverse Effects
Impotence
Decreased Libido
Infertility
Decreased Volume of Ejaculate
Overflow Urinary Incontinence (BPH Treatment)
- 5-Alpha Reductase Inhibitors Considerations
Contraindicated in Hypersensitivity
Increased risk for breast cancer and suicide
- Monitor for mental health
Overflow Urinary Incontinence (BPH Treatment)
- Alpha Antagonists Drugs
Tamsulosin
Doxazosin
Terazosin
Alfuzosin
Silodosin
Overflow Urinary Incontinence (BPH Treatment)
- Alpha Antagonists Mechanism
Acts on alpha 1 receptors on prostate
- Induces relaxation of muscles
Overflow Urinary Incontinence (BPH Treatment)
- Alpha Antagonists Considerations
AM vs PM Dosing
- AM: May experience dizziness and other adverse effects throughout the day
- PM: Patient will sleep through adverse effects, however, may experience dizziness when they get up to urinate (risk of falls)
Overflow Urinary Incontinence (BPH Treatment)
- Alpha Antagonists Adverse Effects
Dizziness
Retrograde Ejaculation
- Bladder neck may be too relaxed, causes ejaculate to backflow
Floppy iris
Overflow Urinary Incontinence (BPH Treatment)
- PDE5-I Drugs
Tadalafil
Sildenafil
Vardenafil
Overflow Urinary Incontinence (BPH Treatment)
- PDE5-I Mechanism
Relaxes smooth muscle of prostate and bladder
- Relaxation also allows blood to flow, good for treating Erectile Dysfunction
Overflow Urinary Incontinence (BPH Treatment)
- PDE5-I Adverse Effects
Headache
Dyspepsia
NAION (Blood loss to optic nerve)
Priapism (Long lasting erection)
Overflow Urinary Incontinence (BPH Treatment)
- PDE5-I Considerations
Contraindicated in
- Cardiovascular Diseases
- Nitrates
- Non-Selective Alpha Blockers
–> May go into shock because BP gets too low
Interactions with:
- Nitrates
- Alpha-Blockers
- Antihypertensive agents
Overflow Urinary Incontinence (BPH Treatment)
- Alpha Antagonists vs PDE5-I
Quite similar
- Choice depends on patient’s comorbidities and how quick patient wants to see improvement
Tadalafil is quicker takes effect in first few weeks
Finasteride takes months
Overflow Urinary Incontinence (BPH Treatment)
- NHP Drug
Saw Palmetto
Overflow Urinary Incontinence (BPH Treatment)
- NHP Mechanism
5-Alpha Reductase Inhibition
Decreased DHT
Triggers Prostatic Cell Apoptosis
Anti-inflammatory effect
Overflow Urinary Incontinence (BPH Treatment)
- NHP Considerations
Contraindicated in Hypersensitivity
Not recommended for treatment of BPH or LUTS
Underactive Bladder
- Cholinergic Drugs
Bethanechol
Underactive Bladder
- Cholinergic Mechanism
Stimulates bladder contraction (Parasympathetic)
–> Allows for urination
Underactive Bladder
- Cholinergic Considerations
Contraindicated in:
- Bradycardia
- Uncontrolled asthma
- Active Peptic Ulcer Disease
- Seizure Disorders
Interactions with:
- Cholinesterase Inhibitors
- Anticholinergics
- Procainamide
- Quinidine
Underactive Bladder
- Cholinergic Adverse Effects
GI Motility
Salivation
Flushing
Underactive Bladder
- Other Options
PGE2 Intravesically
Cholinesterase Inhibitors
Stem Cell Therapy
Sacral Neuromodulation
Summary: How to Treat Overflow UI
BPH Treatments
- Alpha Antagonist
- 5-Alpha Reductase Inhibitors
- Phosphodiesterase 5 Inhibitors
Neurogenic Treatments
- Cholinergic Agonist
Nocturia
- Desmopressin Mechanism
Increases reabsorption of water
- Less urine produced
Nocturia
- Desmopressin Adverse Effects
Nausea
Headache
Dizziness
Hyponatremia
Nocturia
- Diuretics Mechanism
Furosemide dosed in the afternoon to urinate fluid before going to bed
Summary: How to treat Nocturia
Desmopressin
Diuretics
LUTS Monitoring
Efficacy
- How many urgent continence episodes
- How many leakage episodes
Validates Questionnaires
- ICIQ-UI
- International Prostate Symptom Score
Timeline
- Usually monthly
- Some medicines have earlier responses (Alpha Antagonists)
