ic16, ic19 BPH, ED Flashcards
What is the prostate composed of?
Epithelial (glandular) tissue
Stimulated by DHT
Smooth muscle tissue
Contains a-1 adrenergic receptors
How does BPH occur?
1) Static component (involving epithelial tissue)
Testosterone → DHT by 5a reductase
Prostate tissue enlarges
2) Dynamic component (involving smooth muscle)
A1 receptors activated
Smooth muscle constrict, causes narrowing of urethra
1 + 2 = Urethral obstruction, Symptoms
How does bladder become over-sensitive long term?
Initially, bladder can force urine through narrowed urethra
Over time, bladder hypertrophy and decompensates
Bladder becomes overly sensitive, contract abnormally to small amounts of urine
What are some Obstructive symptoms? (6 points)
When does this occur?
Hesitancy
Weak stream
Sensation of incomplete emptying
Dribbling
Straining
Intermittent flow
Early in disease
What are some Irritative symptoms? (5 points)
When does this occur?
Dysuria (burning sensation)
Frequency
Nocturia
Urgency
Urinary Incontinence (cannot control urination)
Occurs after years of untreated BPH
What is a normal Postvoid Residual?
What is the cut-off for Anti-muscarinic use?
< 100ml
Must be < 250ml
What does Prostate Specific Antigen (PSA) help to predict?
Predict progression of BPH
but not specific, could be high due to cancer
Medications and how they contribute to BPH symptoms (5 points)
Anticholinergics (eg. antihistamines)
→ Decrease bladder contractility
Opioid analgesics
→ Increase urinary retention
Diuretics
→ Increase urinary frequency
Testosterone (DHT)
A1 adrenergic agonist
→ Contract SM
Non-pharm methods for BPH (4 points)
Limit fluid intake at night
Minimise caffeine and alcohol intake
Schedule voiding, empty completely and often
Avoid medications that can exacerbate symptoms eg. diuretics
When to treat BPH? (3 points)
When patient is bothered (QOL > 3)
→ Pharmacotherapy
When Uroflow < 10ml/s + PVR > 100ml
→Do surgery
When:
Urinary retention
Haematuria
Recurrent UTI
Bladder stones (calculi)
→Do TURP (surgery)
When do we do watchful waiting?
When patient has mild symptoms OR patient is not bothered by symptoms despite having moderate or severe symptoms
Examples of Alpha 1 Antagonists?
Where do they act on?
TeD ATaS
Non Selective (Peripheral vessels + Urinary a1 adrenergic receptors)
Terazosin
Doxazosin
Selective a1 antagonist
Alfuzosin
Tamsulosin
Silodosin
Act on the smooth muscle, cause SM relaxation and vasodilation
Difference between Non-selective A1 antagonists VS Selective
Non selective:
block peripheral vascular and urinary a1 adrenergic receptors → Cause hypotension
Selective:
Only blocks urinary receptors
Effect of Alpha 1 Antagonists
Effective in reducing obstructive symptoms with small prostate (< 40g)
Fast onset
Does not reduce prostate size or PSA
BPH can still progress and Surgery is still needed
Most common side effects for Non-selective and Selective A1 antagonists
Non-selective:
Dizziness (take medication at bedtime)
Selective:
Ejaculatory disturbances (Silodosin highest, Alfuzosin lowest)
What must we always check before dispensing A1 antagonists?
If patient is going to do cataract surgery
Tamsulosin may cause Intraoperative Floppy Iris Syndrome (IFIS)
If yes, either hold 14 days before surgery or initiate after surgery completed
Absolute contraindication with Non-selective A1 Antaognist
History of syncope
What is the MOA of 5a reductase inhibitor?
2 examples of 5ARI
Where does 5ARI act on?
Inhibit 5a reductase inhibitor (Type 2), which inhibits Testosterone → DHT
Finasteride, Dutasteride
Acts on glandular tissue, to reduce size of prostate
Who are 5ARI indicated for?
Patients with moderate or severe LUTS + Large prostate (> 40g)
if PSA > 1.5ng/mL
Effect of 5ARI (2 points)
Reduces size of prostate
Decreases PSA levels
Counselling points of 5ARI (2 points)
1) Slow onset, takes 6-12 months to decrease prostate size
2) Teratogenic
Pregnant or Females of child bearing age should NOT handle these agents
Side effects of 5ARI (3 points)
Ejaculatory disorders
Decreased libido
Erectile dysfunction
What should we do before initiating 5ARI?
Obtain baseline PSA
What does PDE5i stand for?
Which PDE5i is approved for BPH?
Dose?
Side effect of PDE5i
Phosphodiesterase 5 Inhibitor
Tadalafil 5mg OD
Significant hypotension
MOA of PDE5i in BPH
Affects smooth muscle
Does not affect prostate size
What are the 2 combination of drugs for BPH?
Alpha 1 Antagonists + 5ARI
FD DTa
Specifically:
Finasteride + Doxazosin
Dutasteride + Tamsulosin
Benefits of A1 Antagonist + 5ARI
Alpha blockers → fast onset
5ARI → slow onset
For symptomatic patients with enlarged prostate
Benefits of 5ARI + PDE5i
PDE5i helps to mitigate sexual adverse effects from 5ARI
Risk of Alpha 1 Antagonist + PDE5i
Both drugs may cause hypotension, use selective alpha blocker instead
Will not decrease prostate size
Optimise Alpha 1 Antagonist dose first before adding PDE5i
What drug should be used for irritative bladder symptoms? Example?
What is the MOA?
Anti-muscarinics
eg. Oxybutynin
Trospium
“-terodine”
“-fenacin”
MOA:
Decrease involuntary contraction of bladder
When can Anti-muscarinics be used
PVR < 250ml
Physiology of Erection
(On the tissue level)
1) Smooth muscle relaxes
→ Corpora Cavernosa fills up with blood
→ Swelling causes a compression of venules
(On the molecular level)
2) Activation of Parasympathetic system
Acetylcholine (Ach) increases Nitric Oxide
→ Increase cGMP
Prostaglandin E increases cAMP
Result: High cGMP, cAMP
→ SM relaxation and Vasodilation → Increase blood inflow
Physiology of Detumescence
Deactivate Parasympathetic system
cGMP is deactivated by PDE-5 → Cause vasoconstriction / Stop vasodilation
Activate Sympathetic system
Smooth muscle contraction via a2 adrenergic receptors → Reduction of blood flow
4 causes of ED
Organic:
Vascular
Hormonal
Nervous
Medication induced
Psychogenic:
Feelings
Mixed:
Organic + Psychogenic
Others:
Social habits eg. smoking, alcohol, drug use
What is the role of Testosterone?
Normal range of Testosterone
To encourage libido
300-1000ng/dl
When is Testosterone replacement indicated?
After giving, how to monitor Testosterone?
For patients with ED and symptomatic hypogonadism eg. decreased libido
Monitor Testosterone once at first 3 months, and every 6-12 months intervals
Stop if no improvement after 3 months!
What is PDE5i
Examples of PDE5i (4 points)
and starting doses
Phosphodiesterase 5 inhibitor
SVTA
Sildenafil 50mg
Vardenafil 10mg
Tadalafil 5mg
Avanafil 100mg
MOA of PDE5i
Inhibit PDE5 enzyme (that breaks down cGMP) → cGMP increases → arterial SM relaxation → Increased arterial flow → Erection
Still require sexual stimulation!
Which PDE5i needs to be taken daily?
Why?
Tadalafil
Duration of action is 36hrs, so does not need to be taken just before intercourse
Which PDE5i needs to be taken before food?
Sildenafil
Vardenafil
When should a lower dose of PDE5i be used? (4 points)
1) Patients > 65 yo
2) Taking alpha blockers
3) Renal failure
4) Taking CYP3A4 inhibitors → Increase serum conc of PDE5i
Side effects of PDE5i (7 points)
Headache
Hypotension
Priapism
Erection last more than 4hrs, Need to go ED
Hearing loss
QTC prolongation (Vardenafil)
Muscle pain (Tadalafil)
Ocular problems
In Sildenafil and Vardenafil
- Green blue colour discrimination
- Ischemia of optic nerve
DDI with PDE5i (4 points)
Nitrates
Can cause fatal hypotension
Space 24hrs after sildenafil or vardenafil, 48hrs after tadalafil
Alcohol
Anti-hypertensives
CYP3A4 Inhibitors
Increase conc of PDE5 inhibitors
What is Alprostadil?
MOA?
Prostaglandin E1 analogue
Increases cAMP → SM relaxation
Does not require sexual stimulation to work!
Onset of action of Alprostadil
Dosage forms of Alprostadil
5 - 10 mins
1) Intraurethral pellet
2) Intracavernosal injection
Better efficacy
Has highest risk of priapism
Who is most likely to benefit from combination therapy of Alpha 1 Antagonist + 5ARI? (3 points)
1) Moderate symptoms
IPSS >8
QOL 5-6
2) Prostate size > 25g
