PR3152 IC19 (BPH/ED) Flashcards
what is the physiology of the prostate
1) epithelial cells (glandular): growth stimulated by androgens
2) stroma cells (smooth): innervated by alpha1 adrenergic receptors
testosterone is converted into DHT by 5alpha-reductase.
what is the pathophysiology of BPH?
1) static component
- hormone factors (testosterone -> DHT) = enlargement of prostate tissue
2) dynamic component
- increase smooth muscle tissue and agonism of alpha 1 receptors = narrowing of urethra
= urethral obstruction and other s/sx
what is the pathophysiology of BPH in the long term, relating to bladder
the detrusor muscle must contract hard to force the urine out of the narrow urethra = hypertrophy = at the highest level of hypertrophy, the detrusor muscle compensates = bladder becomes irritative and highly sensitive = contract abnormally w/ smallest amounts of urine = increase urinary frequency.
what is LUTS
lower urinary tract symptoms (LUTS)
- nocturia, frequency, urgency, intermittent stream, straining, weak stream, incomplete emptying
progression of BPH in males? relate to age
more patients are asymptomatic until 65yo, where 1/3 will start to develop symptoms.
what are the two types of s/sx for BPH?
1) obstructive/voiding (typically early on)
- sensation of incomplete emptying
- dribbling
- weak stream
- intermittent stream
- hesitancy
- straining
2) irritative/storage (after several years, when detrusor starts to decompensated)
- frequency
- urgency
- nocturia
- dysuria (pain during urination)
- urinary incontinence
assessment methods for BPH
1) maximum urinary flow rate (Qmax)
2) Prostate specific antigen (PSA)
- not specific to BPH, but can monitor BPH progression. PSA ideally <1.5, may indicate risk of prostate cancer.
3) Post void residual (PVR)
- <100 = normal
- >200 = urinary retention
4) digital rectal exam (DRE)
5) ultrasonography
IPSS
7 sections, total of 5 per section, up to 35 max points
also includes QOL, up to 6 points.
MOH LUTS
4 grades
I) QOL <3, PVR < 100, treatment not needed
II) QOL ≥3 PVR <100, phx
III) QOLNIL PVR >100, Qmax<10ml/s surgical option
IV) QOLNIL, (urine retention, recurrent UTI, bladder calculi, persistent macroscopic hematuria)
surgery TURP
medication risk factors for BPH
need to remove risk factor
opioid analgesics = increases urinary retention
anticholinergics (tricyclic antidepressants eg -triptylines, antihistamines) = block acetylcholine which send signals for bladder contraction = reduces bladder muscle contractility
testosterone = increase prostate size
diruetics = increase urinary frequency
alpha 1 agonists (decongestants) = contract prostate smooth muscles
when do you not need to initiate treatment for BPH
if patient has IPSS < 8 or
mod-severe (IPSSS≥8) with QOL <3
non phx measures for bPH
1) limit fluid intake at night
2) avoid caffeine or alcohol intake
3) counsel patient to have complete and frequent urination
4) avoid meds that worsen symptoms
what to consider when initiating treatment for BPH
comorbidities
IPSS (luts severity)
prostate size
PSA
describe the alpha adrenergic antagonists (types, onset, and any specific instructions) in BPH
alpha1 adrenergic antagonists
1) non-selective: affect the peripheral vascular and urinary a1 receptors
- DTP: doxazosin, terazosin, prazosin (P not used)
- risk of hypotension and syncope = require dose titration slowly.
2) selective: selectively affect the urinary a1 receptors
- SAT: silodocin, alfuzocin, tamsulosin
- do not require dose titration.
onset is days to weeks
indication of alpha adrenergic antagonists in BPH
for patients with moderate to severe LUTS with small prostate <40g
downsides to alpha adrenergic antagonists in BPH
no effect on PSA
s/sx recur if discontinue
does not reduce prostate size or reduce progression of disease (only helps with symptomatic management)
benefits to alpha adrenergic antagonists in BPH
including onset time
fast onset of days to weeks
potentially beneficial in patients with concomitant HTN
side effect profile for alpha adrenergic antagonists in BPH
general: muscle weakness, fatigue, headache, ejaculatory abnormalities
uroselective: ejaculatory abnormalities
S>T>A
non-selective: dizziness, first dose syncope, hypotension
what medical condition to check when initiating alpha adrenergic antagonists and what to do w med admin in BPH
check for IFIS
- intraoperative floppy iris syndorms
caused by alpha adrenal blocking at the iris dilator muscle, complicates cataract surgery - likely cause = tamsulosin
to stop alpha blockers at least 14 days before surgery
administration instructions for non-selective alpha adrenergic antagonists in BPH
to take at night to reduce risk of orthostatic hypotension
what (and when) is the indication for 5ARIs in BPH
patients with moderate to severe LUTS and prostate size >40g
patients who cannot tolerate SE of alpha blockers OR do not want surgery
consider initiating if PSA >1.5
what are the 5ARI drugs in BPH
finasteride and dutasteride
benefits of 5ARI in BPH?
reduces PSA levels (consider initiating if PSA >1.5)
downsides of 5ARI in BPH?
slow onset 6-12months
side effect profile of 5ARI?
decreased libido
increased risk ejaculation abnormalities vs alpha blockers
erectile dysfunction
gynaecomastia
lesser HTN risk
5ARI increases the amount of circulating testosterone that (not converted to androgen) is now converted into estrogen, leading to development of female features = gynaecomastia
contraindications for 5ARI?
special population
women and children
additional labs to take before initiating 5ARI in BPH?
obtain PSA before starting as it is difficult to interpret after initiating
indications for PDE5i in BPH?
adjunctive therapy for BPH
administration and onset of PDE5i for BPH?
include the drug approved
include the drug used
tadalafil
adminster irregardless of sexual activity
onset days to weeks
when should monotherapy for PDE5i for BPH be initiated?
low BMI, young age, higher baseline symptoms
who are more likely to benefit from combination therapy?
moderate luts (IPSS 8-19), QOL (5-6), prostate >25g
a1 antagonist + 5ari combination for BPH?
alpha blocker onset in weeks to help manage symptoms, while 5ari onset in months to control the size of prostate
symptomatic patients with enlarged prostate
after 6 months can consider discontinuing alpha blocker.
PDE5i + 5ari combination for BPH?
help to mitigate 5ari side effects causing sexual disturbance/concomitant ED
however, risk of cardiac problems (commonly associated with ED patients)
avoid nitrate use eg GTN
a1 antagonist + PDE5i combination for BPH?
not recommended due to significant risk of LIFE THREATENING hypotension. if initiated:
start with optimising and stabilising alpha blocker dose
before adding pde5i at the lowest dose
when should antimuscarinics be added for BPH? (and initiated when)
for irritative/storage symptoms
initiate if patient PVR <250 (150 in some guidelines)
MOA of antimuscarinics for BPH
inhibits smooth muscle contraction of bladder (detrusor) by blocking muscarinic receptor = decrease involuntary contraction
name the antimuscarinic BPH agents?
SOFTT -(blaDAR)
solifenacin
oxybutinin
fesoterodine
tolerodine
trospium
darifenacin
what is the definition of erectile dysfunction (ED)?
> 6 months unable to have or maintain erection to have satisfactory sexual intercourse
what is the physiology of erection
activation of parasympathetic nervous system:
1) ach increase = increases in cGMP
2) ach and prostaglandin E increase = increase in cAMP
= combined to increase smooth muscle relaxation and vasodilation
= corpus carvenosa fills with blood (inflow increased)
= presses against the tunica albuginea (outflow decreased)
= erection
testosterone plays contributory role but should be assessed with patient symptoms. patient may have low testosterone but no ED
what are the normal testosterone levels
300- 1000 ng/dL
10.4 - 38.2 nmol/L
what is the physiology of detumescence?
parasympathetic deactivation
- PDE5 degradation of cGMP to 5GMP = reduced smooth muscle relaxation and increased vasoconstriction
sympathetic activation
- a2 adrenergic receptors = induce smooth muscle contraction = reduced blood flow
what is the etiology of ED
1) organic
2) psychogenic
3) mixed
4) others: social habits (smoking, drinking, illicit drug use), obesity
what are the factors in organic ED
1) vascular
2) hormonal
3) neurological
4) medication-related causes
what are the vascular causes in organic ED
atherosclerosis
DM
HTN
PVD
what are the hormonal causes in organic ED
related to lack of testosterone
- hypogonadism
- hyperprolactinemia (increased prolactin = decreased testosterone and sperm production)
what are the neurological causes in organic ED
primary: CNS disorders
secondary: neuropathy, DM, urethral surgery
what are the medication-related causes to organic ED (include moa)
BADSBC
1) BP medications: methydopa, betablockers (except ), thiazide diuretics = decreased blood flow
2) Anticholinergic agents: 1st gen antihistamines, tricyclic antidepressants (e.g. -triptyline) = decreased Ach activity
3) Dopamine Antagonists: metoclopramide = dopamine related to sexual arousal/stimulation
4) SSRIs = increase serotonine in brain/decrease testosterone
5) BPH meds: 5ARIs = decreases testosterone
6) CNS depressants: benzodiazepines, anticonvulsants =suppress perception of psychic stimulus
what are the causes of psychogenic ED?
Malaise
Loss of attraction
Stress
Performance anxiety
Mental Disorders
Sedation
EDdiagnosis/ evaluation criteria?
1) signs and symptoms
2) SHIM (sexual health inventory for men)
<11 = moderate to severe ED (mild is 17-21; goes up to 25 max)
3) patient medical history for underlying causes
- social history, med/medication history, surgical history, lab results (lipid, glucose, testosterone)
why should CVS evaluation be initatied in ED patients?
1) possible early symptom of unidentified CVS problems
2) sexual intercourse = increase in sympathetic activation = BP and HR = risk of myocardial infarction
CV risk factors for ED and what to do?
if unknown or not low risk: test exercise capacity using exercise stress test.
if unstable/severe symptomatic CVD: defer sexual activity until the condition stabilises
cardiac rehab and regular exercise needed to reduce the risk of CV complications with sexual activity
non phx measures for ED?
1) address modifiable RF:
control weight, BP, lipids, glucose
exercise
stop smoking
decrease alcohol
2)psychotherapy
3) vacuum erection device (ved)
4) surgery eg. penile implant
what are the PDE5i agents for ED? include special instructions
SVTA
Sildenafil
- take with food. hepatic and renal dose adjustment
Vardenafil
- take with food. hepatic adjustment
Tadalafil
- long duration of action 36h
- can be taken daily (OD)
- take irregardless food. hepatic and renal dose adjustment
Avanafil
- take irregardless food.
when to lower dose of PDE5i for ED?
if
- age >65
- taking alpha blocker
- renal failure
- cyp3a4 inhibitors e.g. macrolide, cimetidine, conazole antifungal, protease inhibitors
what are the SE for PDE5i
muscle and back pain (pde11 in MSK)
headache, rhinitis, flushing, dizziness, hypotension (relax arteries throughout body = increase flow)
priapism (for more than 4h = goA&E)
sudden hearing loss (rare) (due to increased blood flow to the ear)
ocular problems (PDE6):
- sensitivity to light
- colour discrimination problem (blue-green tinting of vision)
what are the food + drug interactions for PDE5i
X nitrates
X antihypertensives
X cyp3a4 inhibitors
X alcohol = hypotension
what are the monitoring parameters for PDE5i (efficacy and safety)
E.G. if failure reported also
efficacy
-If failure reported;
* Administration with food?
* Timingandfrequencyofdosing
* Lack of adequate sexual stimulation
* Titration to maximum dose
* If all modifiable factors are addressed, may be treated with a different PDE5 inhibitor or proceed with other more invasive therapy
safety
* BP
* Side effects
* Drug interactions
* Changes in cardiac health status
when to initiate testosterone for ED?
symptomatic gonadism with
1) reduced serum testosterone (should fall below the normal range of 300-1100ng/dl OR 10.4-38.2nmol/L)
2) decreased libido
SE of testosterone for ED?
circulatory system related
- polycythemia
- increase BP
- dyslipidemia
mood
- irritability
- aggression
other organs
- hepatotoxicity
- prostatic hyperplasia
others
- undesirable hair growth
dosage forms of testosterone for ED?
Dosage forms: IM injection, buccal, patches, topical gel, body spray, nasal spray & PO
monitoring freq of testosterone for ED?
within 1-3 months monitoring then every 3-6 months.
if no effect after 3 months = discontinue
MOA of alprostadil
prostaglindin E analog
= stimulate production of cAMP = increased vasodilation and smooth muscle relaxation = erection
no need for sexual stimulation for effect
onset, DOA, DDI, SE of alprostadil
5-10min onset
for intraurethral = 30-60min duration of action
DDI: PDE5i
SE: pain, warmth or burning sensation in the urethra, voiding difficulties, bleeding or spotting, priapism, partners may experience vaginal burning or itching
no need sexual stimulation
intraurethral alprostadil pellets vs intracavernosal alprostadil
intracarvenosal has better efficacy
BUT
higher risk of priapism, bleeding, hematoma, fibroids
+
disadvantages: fear of needles, invasiveness, lack of spontaneity, complicated administration technique
titration for alprostadil intracavernosal
titrate in healthcare setting to erection that is maintain for ≤1 hr
self administer no more than 3 times per week
what is yohimbine
alpha 2 antagonist
controversial
side effect specific to tadalafil (more likely)
muscle pain due to afinity to pde11
side effect specific to vardenafil
QTC prolongation
PDE5i more likely to cause ocular problems( what + explain reasoning)
NAOINS: nonartertic anterior ischemic optic neuropathy
- sildenafil and vardenafil
- due to PDE5i causing hypoperfusion to the optic nerve resulting in ischemia
risk factors for NAION + counselling (PDE5i induced)
non artheritic ischemic optic neuropathy
DM, smoking, htn, cvd, dyslipidemia, >50yo
if sudden vision loss/decreased vision = stop and go doctor
counselling points of PDE5i with nitrates?
12h: avanafil
24h: sildenafil and vardenafil
48h: tadalafil
