Pharmacotherapy of Urinary Incontinence in the Elderly Flashcards
Causes of urge incontinence
- infection
- neurologic disorder
- diabetes
- acetylcholinesterase inhibitors
- diuretics
- lithium
- caffeine
- alcohol
Causes of functional incontinence
neurological injury
Causes of urinary retention
- Alpha 1 receptor agonist especially in men (i.e. phenylephrine, phenylpropanolamine, clonidine, guanfacine)
- Drugs with anticholinergic side effects (i.e. antihistamines, antiparkinsonian agents, antidepressants, antipsychotics)
- Beta-agonist, narcotics
Causes of urethral underactivity
- Alpha 1 receptor antagonists (in women – carvedolol, labetolol , mirtazepine, tarazosin, doxazosin)
- ACE inhibitors which induce cough
T/F; For both urge incontinence and stress incontinence, bladder training and pelvic floor muscle training are important components of therapy
True
General Principles to Guide Pharmacotherapy of Urge Incontinence (UI)
- start medications on lowest possible dose to minimize common side effects
- allow sufficient time to adequately assess efficacy
- concomitant behavioral therapy may enhance drug response
What are the anticholinergics used in UI?
- Oxybutynin
- Tolterodine
- Trospium chloride
- Solifenacin succinate (VESIcare*)
- Darifenacin hydrobromide (Enablex*)
- Fesoterodine (Toviaz*)
Oxybutynin
- Immediate Release (Ditropan* and generics) – Geriatric Patients: 2.5 to 5 mg up to three times daily. Change dose no more frequently than once per month
- Extended Release (Ditropan XL* and generics) – 5 mg once per day. Change doses no more frequently than once per month
- Transdermal patch– twice weekly (Alleged decreased anticholinergic effects)
- Gel (Gelnique*) – daily application (Alleged decreased anticholinergic effects)
Tolterodine
- Immediate Release (Detrol* and generics) – Geriatric Patients: 1 to 2 mg twice daily. Change dose no more frequently that once per month
- Extended Release (Detrol LA* and generics) – Geriatric Patients: 2 to 4 mg daily. Change dose no more frequently than once per month
Trospium chloride
- 20 mg BID
- Dose should probably be 20 mg q d in patient over 75 years of age as renal function may be decreased
- ER -> 60 mg
Solifenacin succinate (VESIcare*)
- 5mg once per day
- Drug interaction with potent 3A4 inhibitors (clarithromycin, ketoconazole, ritinovir)
Darifenacin hydrobromide (Enablex*)
- 7.5 to 15 mg once per day
- Drug interactions with potent 3A4 inhibitors
MOA of anticholinergics
Muscarinic receptor antagonists acting on the smooth muscle of the bladder to decrease bladder contractility and increase bladder capacity
Toxicity of Anticholinergics in Urge Incontinence
- Drop out rate for oxybutynin IR = 20% due most often to severe dry mouth (xerostomia) leading to taste disturbance, anorexia, difficulty chewing, esophogeal dysmotility, etc.
- Drop out rates for oxybutynin XL and the tolterodine compounds are less than 10% with dry mouth remaining the most common complaint
- Other side effects expected from anticholinergics include dry eyes, blurred vision, constipation, reflux, confusion and SVT
- Oxybutynin likely has the greatest amount anticholinergic effects
- Tolterodine probably produces troublesome CNS effects less frequently than does oxybutynin due to the fact that it is less likely to cross the blood-brain barrier
Drug interactions with the UI medicationsn
- potent CYP 3A4 inhibitors such as macrolide antibiotics (clarithromycin), imidazole antifungal agents, ritinovir –> decrease dose of tolterodine, solifenacin, darifenacin and fesoterodine by 50%
- antacids and PPIs interact with tolterodine LA
UI drug uses in other disease states
- Contraindicated in narrow angle glaucoma
- With Alzheimer’s disease -> enhanced sensitivity to CNS side effects; use of ACh-inhibitors lead to OAB
Role of Estrogens in Urge Incontinence
- Indicated for treatment of OAB associated with atrophic vaginitis or urethritis
- Oral therapy with estrogen and progestin – ineffective and may worsen OAB (Womens Health Initiative)
- Topical therapy with intravaginal estrogen tablets (63% improvement vs. 32% placebo)
- Recurrent vaginitis – estrogen cream one to two times per week
Other Agents Used in Urge Incontinence
- Tricyclic antidepressants
* Mirabegron (Myrbetriq*)
Tricyclic antidepressants
- No more effective than oxybutynin, more risk, use only as last resort
- Notripytyline (Aventyl*)
- Desipramine (Norpramin*)
What is considered ineffective for the treatment of UI?
– Flavoxate (Urispas*)
– Propantheline (Pro-Banthine*)
What has insufficient information on efficacy in UI?
– Hyoscyamine (Anaspaz*)
– Dicyclomine (Bentyl*)
Mirabegron (Myrbetriq*)
– Beta 3 receptor agonist: Relaxes detrusor muscle thereby increasing bladder capacity
– Thought to be similar in efficacy to tolterodine – No anticholinergic side effects, thus may be better tolerated
– Side effects: HTN (8%), headache (3%) – Dose: 25 mg per day, may increase to 50 mg per day after 8 week
– Inhibitor of CYP2D6 – metoprolol, flecainide
Pharmacotherapy of Stress Incontinence
• No more effective than bladder training
therapy, pelvic floor muscle training (Kegel exercises) and pessaries
• Alpha-1 receptor agonists
• Estrogen Therapy
• Combined estrogen therapy with alphaagonists better than either alone
• Last resort – tricyclic antidepressants
Pharmacotherapy of Stress Incontinence: Alpha-1 receptor agonists
– Ephedrine 25 mg bid
– Pseudoephedrine 15 to 45 mg tid
– Toxicity: CNS stimulation
– Relatively contraindicated in elderly with HTN, angina, or MI
– Contraindicated in narrow angle glaucoma
Estrogen Therapy
– No proven role for oral therapy
– Topical therapy seems logical but insufficient evidence to determine its role
Pharmacotherapy of Urinary Incontinence due to BPH
- Lifestyle modification, reduced fluid intake and identify and treat reversible causes.
- avoid exacerbating medications, alcohol and caffeine
- Alpha -1 receptor antagonists
- Antiandrogens (5- ARI)
- Saw palmetto
- Other: Tadalafil (Cialis*) – 5 mg/day
- Combination of alpha-1 receptor antagonist and antiandrogen – Improve symptoms of BPH more effectively than either agent alone, preliminary impression
Lower Urinary Tract Symptoms (LUTS)
- Mild LUTS (AUA-SI < 8) or moderate or severe LUTS (AUA-SI score ≥8) without symptoms: Watchful waiting (active surveillance) should be implemented; follow up in 1 year or as clinically indicated
- Bothersome LUTS (AUA-SI ≥ 8): Initiate basic treatment with lifestyle modifications, reduce fluid intake, and examine reversible causes (i.e., medication)
- Bothersome LUTS (AUA-SI ≥ 8) despite basic treatment: Initiate detailed drug treatment based on symptoms
- LUTS without BOO (urgency)
treatment of bothersome LUTS
– Bladder outlet obstruction (BOO) and OAB (urge incontinence): Initiate alpha-1 blocker ± anti-muscarinic agent
– BOO with small prostate size/low PSA (≤ 1.4 ng/mL): Initiate alpha-1 blocker
– BOO with large prostate size/high PSA (> 1.5 ng/ mL): Initiate alpha-1 blocker, 5-ARI, or combination
Pharmacotherapy of Urinary Incontinence due to BPH: Alpha-1 Receptor Antagonists
- MOA: Relax smooth muscle tone in bladder neck, proximal urethra and prostate
- Terazosin (Hytrin*) – 1 to 5 mg q.h.s.
- Doxazosin (Cardura) – 1 to 5 mg q.h.s. • Tamsulosin (Flomax) – 0.4 to 0.8 mg q.d. (30 minutes after the same meal each day)
- Alfuzosin (Uroxatral*) – 10 mg q.d.
- Silodosin (Rapaflo*) – 8 mg q.d. with a meal
- Response to a particular dose is typically seen within two to three weeks
- Although there are slight differences in the adverse events profiles of these agents, all four (not including silodosin) appear to have equal clinical effectiveness.
- Postural hypotension – dose related and less likely with tamsulosin and alfuzosin due to preferential binding in prostatic sites
Pharmacotherapy of Urinary Incontinence due to BPH: Alpha-1 Receptor Antagonists and Antiandrogen (5-ARI)
Dutasteride and Tamsulosin (Jalyn*)
Pharmacotherapy of Urinary Incontinence due to BPH: Antiandrogen
• Fenasteride – MOA: a 5 alpha-reductase inhibitor which inhibits the conversion of testosterone to dihydrotestosterone upon which the prostate depends for growth
– Dose: 5 mg per day – Decreases prostate volume by 24 to 27% with the greatest effect seen in patients with prostate enlargement
– Symptom improvement: 30% – Maximum benefit: 6 to 12 months – Decrease PSA by 50% (Multiply X 2), Sexual dysfunction
• Dutasteride (Avodart*)
– Dose – 0.5 mg per day
Pharmacotherapy of Urinary Incontinence due to BPH: Saw Palmetto
– MOA: Similar to fenasteride – Dose: 320 mg per day – Efficacy: Similar to fenasteride – Well tolerated > fenasteride – Non-legend drug therefore purity and potency may vary between brands
