BPH, ED & Urinary Incontinence Flashcards
(43 cards)
1
Q
Pathophys of BPH
A
- Circulating Testosterone:
- 90% from testes
- 10% from adrenal glands
- Adult males <40 yo
- prostate size stays the same ~15-20gm
- > 40 yo
- testosterone enters prostate cells
- type II 5 alpha reductase is converted to dihydrotestosterone (DH-T)
- testosterone enters prostate cells
- androgens (i.e. testosterone) has not direct effect on stromal tissue
-
overgrowth of muscle or stromal tissue around the urethra
- caused by testosterone → estrogen (in peripheral) → stimulates growth of stromal cells
-
overgrowth of muscle or stromal tissue around the urethra
2
Q
LUTS and BPH
A
lower urinary tract symptoms (LUTS)
- when pt has BPH → will eventually experience LUTS
- 3 contributing factors:
- static factors:
- anatomic obstruction
- dynamic factors:
- excessive stimulation of alpha (1A)-receptors on smooth muscle of prostate and urethra → contraction
- Detrusor Factors:
- instability of detrusor muscle due to excessive hypertrophy and outlet obstruction
- static factors:
3
Q
Symptoms of BPH
A
- obstruction due to static or dynamic factors:
- decreased force of the urinary stream
- urinary dribbling
- inability to completely empty bladder
- Detrusor instability
- irritable voiding sxs
- urinary urgency and frequency
- irritable voiding sxs
4
Q
AUA-7 Score + IPSS
A
assessing severity of the LUTS in BPH
- AUA-7
- American urologic association score
- IPSS
- international prostate symptoms score = previous 7 question + Quality of Life
- Mildly Symptomatic: 0-7
- Moderately Symptomatic: 8-19
- Severely Symptomatic: 20-35
5
Q
Treatment Algorithm for BPH
A
6
Q
Tx for Mild Sxs of BPH
A
Mild Sxs = 0-7 on IPSS
Watchful waiting
7
Q
Tx for Moderate to severe symptoms with no BPH complications
A
- prostate less than 30g?
-
alpha-adrenergic antagonist
- if response, continue
- if no response (1-2 weeks) , surgery
-
alpha-adrenergic antagonist
- Prostate ≥ 30 g?
-
5alpha-reductase inhibitor
- if response, continue
- if no response, try combo of this + alpha adrenergic antagonist or surgery
-
combo of alpha adrenergic antagonist + 5-alpha reductase inhibitor
- if response, continue
- if no response, surgery
-
5alpha-reductase inhibitor
8
Q
Tx of severe symptoms of BPH and BPH complications
A
surgery
9
Q
Alpha Antagonists Overview with BPH
A
- reduce the dynamic factor
- relax bladder neck, prostatic urethra, and prostate smooth muscle
- all agents in the class are equally effective
- onset = days - weeks
- good trial period = 1-2 weeks
- Mostly metabolized by the liver except silodosin (Rapaflo) -→ need to adjust for renal function
-
SEs:
- dose limiting hypotension, syncope
- less frequent with ER formulation and uroselective (alpha 1a blockers)
- ejaculation disorders (tamsulosin)
- dose limiting hypotension, syncope
- DDI:
- additive BP lowering effect
- +other antihypertensives
- +diuretics
- +phosphodiesterase inhibitors
- additive BP lowering effect
10
Q
Terazosin (Hytrin)
A
non-selective alpha antagonist
- dose given at bedtime
- hypotensive
- extensive metabolism by liver
- floppy iris (when undergoes cataract surgery) → no need to d/c
11
Q
Doxazosin
A
non-selective alpha blocker
- longest half life
- cardiovascular side effects
- SEs similar to terazosin:
- hypotension
- intraoperative floppy iris syndrome
12
Q
Alfuzosin (uroxatral)
A
uroselective alpha 1A +alpha1D blocker
- better absorption with food (Alf likes to eat a lot)
- caution with renal disease
- least amount of SEs
13
Q
Tamsulosin (Flomax)
A
uroselective alpha 1A + 1D blocker
- best absorbed on an empty stomach, “tammy is skinny b/c she does not eat food and is also extra floppy”
- caution in renal and hepatic impairment
- lowest hypotension
- can cause ejaculation disorder
- 40x higher risk of floppy iris than terazosin
14
Q
Silodosin (Rapaflo)
A
uroselective alpha 1A +1D blocker
- food decreases extent of absorption → less hypotensive
- SEs same as tamsulosin
- causes ejaculation disorder
- CrCl = 30-50ml/min → half dose (4mg q day)
- contraindicated in CrCl <30ml/min
15
Q
5-alpha reductase inhibitor MOA
A
prevent testosterone from being converted to DHT (DHT→which would normally promote tissue growth)
Finasteride and dutasteride
- Reduce the static factor → shrinkage of prostate by 20-25%
- 2 types of 5-alpha reductases in prostate
- type II = much more abundant than type I
16
Q
5-alpha reductase inhibitors overview
A
- slow onset
- peak shrinkage in up to 6 months
- reduce PSA levels
- need at least 6 month to demonstrate effectiveness
- relieve sxs in 30-70% of patients
- no dose adjustment needed in renal impairment
-
SEs:
- decreased libido
- erectile dysfunction
- ejaculation disorders
- gynecomastia
- breast tenderness
- contraindicated in pregnant women → feminization of male fetus
- women should handle with GLOVES
17
Q
Finasteride (Proscar)
A
- Type II 5 alpha reductase inhibitor
- inhibit 70-76% of serum dihydrotestosterone levels
-
half life slightly longer than dutasteride (6.2 hours vs 3-5 hours)
- lasts 6 years
18
Q
Dutasteride (Avodart)
A
Type I and II 5-alpha reductase inhibitor
- inhibits 90-95% of serum dihydrotestosterone levels
- shorter half life than finasteride
19
Q
Dutasteride/Tamsulosin (Jalyn)
A
5alpha reductase inhibitor + alpha blocker
-
Indications:
- high risk for BPH complications
- prostate size > 30g
- PSA > 1.5ng/mL
- relieves sxs and reduces the need for prostatectomy by 67%
- high risk for BPH complications
- may d/c alpha blocker part of medication after 6-12 month of tx
20
Q
Herbal Therapies for BPH
A
- commonly used in europe but not approved by FDA
-
Saw Palmetto
- OTC.
- no difference from placebo on:
- urinary sx scores
- urinary flow
- prostate size
21
Q
Tadalafil (Cialis) and LUTS
A
- approved for tx of LUTS
- relaxation of smooth muscle of urethra
- comparable to alpha blockers
- does not increase urinary flow rate or reduce post-void residual volume
- Best for BPH with ED
- CrCl< 30ml/min? DO NOT USE; if CrCl < 50 = reduce dose
22
Q
Erectile Dysfunction
A
- commonly occurs in men with systemic disorders such as:
- DM
- HTN
- ischemic heart disease
- increased age
- identify the underlying etiology
- medication induced? → SSRI, TCA, antipsychotics
- Identify and the CV risks:
- smoking
- obesity
- HTN
- Dyslipidemia
- initiate Therapy
- PDE-5 inhibitors → 1st line
- if ineffective → other treatments available
- vacuum devices
- penile self-injectable drugs
- intraurethral alprostadil
23
Q
MOA of PDE-5 inhibitors
A
used for erectile dysfunction
PDE-5 usually breaks down cGMP (cGMP promotes smooth muscle relaxation → increased blood flow in the corpus cavernosum) so inhibiting PDE-5 = more cGMP
24
Q
Sildenafil (Viagra)
Revatio
A
decrease dose if CrCl <30mL/min
- 30min -1 hour before activity
- Revatio = used for pulmonary artery HTN
-
SEs:
- headaches, dizziness, flushing
- nasal congestion
- UTI, diarrhea
- reversible photosensitivity → “blue vision” – PDE-6 inhibition - retina
- MI, stroke, hypotension
- hearing loss
- Priapism (prolonged erection) seizures
- DDI:
- vasodilators – ie alpha blockers
- NITRATES → ALL CONTRAINDICATED
25
Vardenafil (Levitra)
(Staxyn)
* similar onset and duration as viagra **1 hour prior to activity**
* **QT prolongation**
* high fat meals → lower peak serum concentration by 18%
* delays absorption by 1 hour
* ODT =more rapid onset
26
Tadalafil (Cialis)
**30 min before activity**
has different structure than sildenafil and vardenafil
**approved for BPH-LUTS and pulmonary artery htn**
avoid use if _CrCl \<30mL/min_
27
Avanafil (Stendra)
* **15 min before activity**
* +/- food
* _SEs_:
* HA, flushing, vertigo
* nasal congestion, nasopharyngitis
* back pain
* angina, DVT
* muscle spasms, pruritus
* _DDIs_ :
* Nitrates = contraindication
* alpha-blockers
* antihypertensives
* 3A4 inhibitors
28
Types of Urinary Incontinence
29
Treatments of SUI
* if **estrogen deficiency** (atrophic urethritis or vaginitis) → **vaginal estrogen** (tablets and rings better than cream)
* → avoid systemic estrogen as this may actually increase risk of new onset UI
* **Alpha Receptor Agonists**
* ephedrine – not recommended
* phenylephrine – lack of data
* **Pseudoephedrine** → Alpha 1 agonist
* _SEs_: HTN, HA, dry mouth, nauseam insomnia, and restlessness
* can add when estrogen alone is not working
* **Duloxetine**
* SNRI
* *off-label use*
* enhances serotonergic and adrenergic tone controlling smooth muscle and sphincters
* avoid if CrCl \<30mL/min
* can raise BP
* do not d/c abruptly → withdrawal syndrome
* avoid in narrow-angle glaucoma
* hepatotoxicity
30
Tx of Urge Urinary Incontinence (UUI)
* first line = **anticholinergic/antispasmodic**
* suppressing premature detrusor contractions (_overstimulation of M2 & M3 receptors_)
* **enhances bladder storage**
* all have similar _SEs and CIs_
* urinary retention
* gastric retention, constipation
* uncontrolled narrow angle glaucoma
* dry mouth, HA
* orthostatic hypotension
* **immediate release**:
* _oxybutynin_
* _Tolterodine_
* higher rate of ADE esp in elderly → start at lowest dose
* **Extended Release**
* oxybutynin
* trospium
* tolterodine
* fesoterodine
* darifenacin
* solifenacin
* less dry mouth compared to IR
31
Tertiary Amine AntiMuscarinic Agents
Oxybutynin (highly lipophilic), tolterodine, fesoterodine, solifenacin, darifenacin
* can penetrate BBB → CNS SEs
* sedation
* mental status change
32
Quaternary Amine Antimuscarinic Agent
Trospium (Sanctura)
* + charge → hydrophilic → **cannot cross BBB** → less CNS SEs
33
Antimuscarinic Agents DDI
* all metabolized by 3A4 and/or 2D6
* except Trospium (hydrophilic and renal clearance)
* CrCl \<30mL/min = need dose reduction
* need to reduce dose with 3A4 inhibitors
* Tolterodine
* fesoterodine
* solifenacin
* darifenacin
* avoid use with
* antagonism:
* acetylcholinesterase inhibitors
* donepezil
* additive effects
* anticholinergics
34
Mirabegron (Myrbetriq)
* MOA: selective beta-3 agonist → ***relaxes smooth muscle of bladder***
* Eliminated by the kidneys, avoid in ESRD
* indication: **overactive bladder**
* _SEs_: **HTN,** urinary retention, UTI, HA, tachycardia
* _DDI:_
* +digoxin → increased dig AUC by 27% → monitor level
* 2D6 inhibitor (moderate)
* +thioridazine → QT prolongation, urinary retention
* + anticholinergic → urinary retention
* + colchicine → increase colchicine level → toxic myopathy, rhabdomyolysis
35
Tx of Overflow urinary Incontinence due to bladder underactivity
* Cholinomimetic
* **bethanechol**
* mixed results
* SEs: muscle and abd cramps, hypersalivation, diarrhea, bradycardia, and bronchospasm
* _Alpha Blockers → help outflow_
* **prazosin, terazosin, doxazosin, tamsulosin, silodosin, alfuzosin**
* intermittent urethral cath, indwelling urethral, suprpubic cath,
36
Monitoring of BPH
reduction of sxs score ≥ 3 points
perceive symptoms as not bothersome
if response → continue drug regimen and check q 6 months
* repeat PSA and DRE annually
* if no response (weeks after alpha blockers, 6 months after 5alpha reductase inhibitors) → surgery
37
PDE-5 Inhibitors (list)
* Sildenafil (Viagra, Revatio)
* Vardenafil (Levitra, Staxyn)
* Tadalafil (Cialis, adcirca)
* Avanafil
38
Duloxetine
SNRI → **off label use = tx of _stress urinary incontinence_**
* enhances serotonergic and adrenergic tone controlling smooth muscle and sphincters
* avoid if **CrCl \<30ml/min**
* raises BP
* do not d/c abruptly → withdrawal
* avoid in uncontrolled narrow-angle glaucoma
* hepatotoxicity
39
Oxybutynin
anticholinergic/antispasmodic drug recommended for UUI
* tertiary amine
* active metabolite
* caution if CYP 3A4 inhibitors also being taken
40
Tolterodine
anticholinergic/antispasmodic drug recommended for UUI
* tertiary amine
* active metabolite
* oral Antacid interactions
41
Trospium Chloride
anticholinergic/antispasmodic drug recommended for UUI
* quaternary amine → does not cross BBB due to + charge
* foods decrease absorption, give on **empty stomach**
* altered in **renal disease → _dose reduction if CrCl \<30ml/min_**
42
Solifenacin
anticholinergic/antispasmodic drug recommended for UUI
* tertiary amine
43
Fesoterodine
anticholinergic/antispasmodic drug recommended for UUI
* tertiary amine
* pro-drug
