Men's Health Flashcards
What are the 2 main mechanisms that contribute to the pathophysiology of BPH?
What is the bladder response to the obstruction of urine?
- In the early phases, the bladder muscle is able to force urine through the narrowed urethra by contracting more forcefully
- Over time, the bladder muscle gradually becomes thicker (hypertrophy) to overcome the obstruction
- Once the detrusor muscle has achieved the highest state of hypertrophy, the muscle decompensates
- Detrusor muscle becomes irritable and/or overly sensitive (detrusor overactivity or instability), contracting abnormally in response to small amounts of urine in the bladder, resulting in a need to urinate frequently
What are some examples of obstructive symptoms & examples of irritative symptoms?
Obstructive/ Voiding Symptoms -
> Early in disease course
* Hesitancy
* Weak stream
* Sensation of incomplete emptying
* Dribbling
* Straining
* Intermittent flow
Irritative/ Storage Symptoms ->
Occurs after several years of
untreated BPH
* Dysuria
* Frequency
* Nocturia
* Urgency
* Urinary Incontinence (UI)
List and compare classes of drugs used for BPH based on the following
conditions: mechanism of action, adverse effects, and drug interactions.
- Alpha Adrenergic Antagonist: antagonize both and urinary α1 adrenergic receptors)
SE:
DDI: - 5ARIs:
MOA: Inhibits 5α reductase (Type II) → decrease conversion from testosterone to DHT→ reducing the size of prostate
3: PDE5i:
Recommend appropriate BPH therapy based on patient specific characteristics
Start if symptoms bother patient or complications occur
* When choosing a BPH treatment, consider…
* LUTS Severity (IPSS)
* Prostate size
* Concurrent comorbidities
* PSA value
* Presence of irritative/ storage symptoms
Counsel patients regarding medication and nonpharmacological therapies for the management of BPH
Non-Rx:
1. Limit fluid intake in evening
2. Minimize caffeine and alcohol intake
3. Educate patient to take time to empty their bladder completely and often
4. Avoid medications that can exacerbate symptoms
Medications:
1. Alpha Adrenergic Antagonist:
* Non Selective (antagonize both
peripheral vascular and urinary α1
adrenergic receptors):
* Doxazosin
* Terazosin
* Prazosin (not recommended for BPH)
Need to titrate slowly to
therapeutic dose (risk of
hypotension and syncope)
- Selective for urinary α1A receptors
(predominant receptor in the
prostate and the LUT): - Alfuzosin
- Tamsulosin
- Silodosin
Lesser risk of hypotension -> Dose
titration not necessary
Are effective in reducing LUTS, especially in those classified with
moderate or severe LUTS with small prostate (<40g)
* They do not reduce the prostate size and they don’t offer prevention
for progression of BPH or the need for surgery
* No effect on PSA
* Onset is fast: days to weeks
* s/s likely recur if discontinued
Alpha Adrenergic Antagonist
* Side Effect Profile:
* General side effects: muscle weakness, fatigue, ejaculatory
disturbance, headache, etc
* Bedtime administration to decrease orthostatic effects
* Non selective:
* Dizziness (most common), first dose syncope and orthostatic
hypotension
* Uroselective:
* Low to none peripheral vascular dilatation → less hypotension
or syncope
* Ejaculatory Disturbance (delayed or retrograde ejaculation)
* Silodosin > Tamsulosin > Alfuzosin
* Still related with less sexual dysfunction than 5ARI
Intraoperative Floppy Iris Syndrome (IFIS):
MOA linked to blockage of α1receptors in iris dilator muscle
* Most commonly associated with
tamsulosin
Non selective agents-
* Could be beneficial in those hypertensive patients that need additional blood
pressure (BP) lowering effect
* In BEERs List as drugs to avoid in patients with history of syncope
* Should not be used as monotherapy for a patient that has HTN and BPH
concurrently
* Selective agents may be used in patients that don’t need added BP lowering effect
- MOA: Inhibits 5α reductase (Type II) → decrease conversion
from testosterone to DHT→ reducing the size of prostate
* Slow progression of disease, decrease need for surgery
* Finasteride and Dutasteride
* Indicated for moderate or severe LUTS with large prostate (> 40g)
* Also in patients who want to avoid surgery or cannot tolerate SE of
α1 antagonist
* Can decrease PSA levels -> consider adding if initial PSA > 1.5 ng/mL
* Onset of action is slow, may take up to 6 to 12 months to decrease
prostate size
* Side effect profile
* Ejaculatory disorders (reduced semen during ejaculation or
delayed ejaculation) -> higher risk than alpha antagonist
* Decreased Libido (3 -8%)
* Erectile Dysfunction (ED) (3-16%)
* Gynecomastia and breast tenderness (1.0%)
* Lesser risk of hypotension
* Clinical pearls
* Pregnant/ child bearing age females should NOT handle
these agents
* Obtain PSA before initiating therapy -> not easily
interpretable after initiation - Phosphodiesterase 5 Inhibitor (PDE5I)
* MOA: exact mechanism for BPH unknown – some evidence to show
BPH and ED share pathophysiologic mechanism
* Only Tadalafil is FDA approved for BPH
* Usually as add on therapy, especially patients with concomitant ED
* Recall SE of 5ARIs?
* Does not affect prostate size, onset is days to weeks
* Take without regards to timing of sexual activity
* Side effects profile: significant hypotension
- Administration of tadalafil 5 mg daily as
monotherapy is justified in patients with BPH-
LUTS with or without concurrent ED - Younger age, low BMI and higher baseline
symptoms => better effect of the treatment
with PDE5 inhibitors.
For irritative Sx: Anti-muscarinics
* Add on for those patients who present irritative voiding symptoms, which mimic overactive bladder (OAB)
* MOA: Block muscarinic receptors in detrusor muscle→ decreasing involuntary contraction of the bladder
* Agents: oxybutynin, tolterodine, solifenacin, trospium, darifenacin, fesoterodine
* PVR must be less than 250 ml (or 150 ml for more conservative
guidelines)
Assessment of BPH
- Digital Rectal Exam (DRE)
- Ultrasonography
- Maximum Urinary Flow Fate (Qmax)
- Postvoid Residual (PVR)
- < 100 ml normal
- > 200 ml inadequate emptying
- Prostate specific antigen (PSA)
- Might be elevated in BPH and positively
correlated with prostate volume - Can help predict progression of BPH (>
than 1.5 ng/mL) - Higher risk for prostate cancer
- Controversial – not clear cut
Medication History:
* Anticholinergics -> decrease bladder muscle contractibility
* Antihistamines, tricyclic antidepressants (TCAs), etc
* α1 adrenergic agonist -> contraction of prostate smooth muscles
* Decongestants
* Opioid Analgesics -> increase urinary retention
* Diuretics -> increase urinary frequency
* Testosterone -> can stimulate prostate growth
MOH LUTS/BPH Guidelines 2005
slide 6
monitor:
- Watchful waiting!
- Mild symptoms (IPSS<8) or with moderate or severe symptoms
(IPSS ≥ 8) who are not bothered by symptoms (IPSS QOL <3) - Reassessment of symptoms using the IPSS, annually or more
frequent - Lifestyle changes / Non-pharm
What are the physiological/chemical
changes that are needed to cause an erection?
Sexual Health Inventory for Men (SHIM)
* Mild to no ED: 17 to 21 points
* Moderate to Severe: <11 points
What are the various risk factors that could
contribute to development of ED?
CVD, smoking, obesity, DM, psychotherapy, surgery
List and compare classes of drugs used for ED based on the following conditions: mechanism of action, adverse effects, and drug interactions
Recommend appropriate ED therapy based on patient specific characteristics.
Counsel patients regarding medication and nonpharmacological therapies for the management of ED
non-pharm:
* Addressing modifiable risk factors
* Stop smoking
* Control weight
* Control glucose / BP / lipids
* Exercise
* Decrease alcohol
* Psychotherapy
* Devices: Vacuum erection devices (VEDs)
* Surgery eg penile implant
Drug:
PDE51 - Sildenafil, Vardenafil, Tadalafil 5mg, Avanafil
MOA: Inhibit PDE 5 enzyme which induces catabolism of cGMP → enhancing cGMP activity →inducing smooth muscle relaxation→erection
A lower initial dose for:
* Patients ≥ 65y/o
* Those taking alpha blockers
* Patients with renal failure
* Taking CYP3A4 Inhibitors (e.g. erythromycin, cimetidine, ketoconazole, itraconazole, clarithromycin, grapefruit or grapefruit juice, ritonavir, saquinavir, among others), as they may increase the serum concentrations of PDE5 Inhibitors
SE: headache, rhinitis, flushing. Qtc prolongation-vardenafil, muscle pain tadalafil, prolonged erections (priapism), (v rare) sudden hearing loss with tinnitus and dizziness, ocular prob, photosensitivity, Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)
DDI: Nitrates, alcohol, Cyp3A4i
- Testosterone Replacement: Alprostadil
Prostaglandin E1 analog that stimulates adenyl cyclase cAMP→ inducing smooth muscle relaxation→ erection (do not need sexual stimulation
Restore serum testosterone levels to normal range (300–1100 ng/dL; 10.4– 38.2 nmol/L)
SE: irritability, aggressive behaviour, undesirable hair growth, incr BP,
hepatotoxicity, dyslipidemia, polycythemia, prostatic hyperplasia (CI for prostate CA)
Monitor serum testosterone within 1–3 months and at 6- to 12-month intervals -> discontinue if no improvement after 3 months
DDI: PDE5i
