Men BPH Flashcards
Define BPH
Non-malignant growth of some components of the prostate
What is the normal physiology of the prostate?
Epithelial tissues produce androgen which stimulates growth
Smooth muscle tissues contract through a1 adrenergic receptors
Testosterone is reduced by DHT with enzyme 5a reductase
DHT increases prostate size
What are the 2 components of the pathophysiology behind BPH?
Static and dynamic component
Describe the static and dynamic component of BPH
Static component
1. Hormonal factors cause an increase in testosterone
2. Increase in testosterone lead to increase in DHT
3. Increases prostate size
Dynamic component
1. Increase in smooth muscle tissue contractility due to agonism of alpha 1 receptors
2. Narrowing of urethra outlets
Both causing urethral obstruction
What is the long term pathophysiology to describe the worsening of symptoms in BPH?
In early phases, bladder muscle able to force urine through narrowed urethra by contracting more forcefully
Bladder muscle gradually becomes thicker to overcome obstruction
At highest state of hypertrophy, muscle decompensates
Muscle becomes irritable and overly sensitive and contract abnormally in response to low amount of urine causing the need to urinate frequently
What are the 2 subcategories of BPH symptoms and when do they happen?
Obstructive / voiding: early in disease
Irritative / Storage: after several years
What are obstructive symptoms of BPH?
Hesitancy
Weak stream
Dribbling
Sensation of incomplete emptying
Straining
Intermittent flow
What are the irritative symptoms of BPH?
Dysuria
Frequency
Nocturia
Urgency
Urinary incontinence
How can a diagnosis of BPH be made?
Digital rectal exam
Ultrasonography
Maximum urinary flow rate
PSA
Postvoid residual
What are the advantages and disadvantages of using PSA?
Advantage: Can predict progression of BPH and prostate cancer
Disadvantage: Not BPH specific
What is the postvoid residual value for inadequate emptying?
> 200mL
How are symptoms stratified based on their severity using the American Urologic Association score?
Mild: Less than or equal to 7
Moderate: 8-19
Severe: More than or equals to 20
What are some complications of BPH?
Recurrent UTI
Bladder stones
Hematuria
Acute urinary retention
Urinary incontinence
What are some drugs that can cause BPH and how do they exacerbate BPH?
Anticholinergics (e.g. antihistamines, tricyclic depressants) : decrease muscle contractility
Alpha 1 adrenergic agonist (e.g decongestants): Increase contraction of prostate smooth muscle
Opioid analgesics : Increase urinary retention
Diuretics : Increase urinary frequency
Testosterone: Stimulate prostate growth
What are some non pharmacological advice to give patients with BPH?
Limit fluid intake in evening
Minimize caffeine and alcohol
Educate patients to take time to empty bladder completely
Avoid medication that exacerbate symptoms
What are the indications to start BPH medications?
Bothersome symptoms
Complications
What are some factors to consider before starting BPH?
PSA value
LUTS severity
Prostate size
Concurrent comorbidities
Presence of irritative/ storage symptoms
What are the 3 agents used to treat BPH?
Alpha adrenergic antagonist
5 alpha reductase inhibitors
PDE5 inhibitors
List the selective and nonselective alpha adrenergic antagonist.
Non selective: Terazosin, Doxazosin
Selective: Alfazosin, Tamsulosin, Siludosin
What are the mechanism of action for both alpha adrenergic antagonists?
Nonselective: Antagonize both peripheral vascular and urinary alpha 1 receptors
Selective: Antagonist urinary alpha 1 receptors
What are the indications to use alpha adrenergic antagonist?
Moderate / severe LUTS with small prostate
When should non selective alpha adrenergic antagonists be considered?
Hypertensive patients needing additional BP lowering effect
Should not consider for use of monotherapy due to risk of syncope
List the DO NOT’s of alpha adrenergic antagonist.
DO NOT
- reduce prostate size
- prevent progression of BPH and need for surgery
- PSA
What are the adverse drug reactions for both selective and nonselective alpha adrenergic antagonist?
Muscle weakness; fatigue; ejaculatory disturbances; headache
What are the adverse drug reactions specific to nonselective alpha adrenergic antagonist?
Dizziness
First dose syncope
Orthostatic hypertension
What are the adverse drug reactions specific to selective alpha adrenergic antagonist?
Ejaculatory disturbances
What is a serious and major adverse event of alpha adrenergic antagonist? Why does this happen?
Intraoperative floppy iris syndrome that complicates those going for cataract surgery
Due to blockage of alpha 1 receptors in iris dilator muscle
What is a possible solution to reduce risk of IFIS?
Avoid initiation of alpha adrenergic antagonist until surgery is complete
Hold alpha adrenergic antagonist for 2-3 weeks before surgery
What is the mechanism of action for 5 alpha reductase inhibitors?
Inhibits 5 alpha reductase
Decrease conversion from testosterone to DHT
Lesser DHT –> Decreases prostate size
What are the indications of 5ARI?
Moderate/ severe LUTS with large prostate
Patients wanting to avoid surgery
Patients unable to tolerate side effects of alpha adrenergic antagonist
What are the agents of 5ARI?
Finasteride
Dutasteride
What are the adverse drug reactions of 5ARI?
Ejaculatory disturbances
Decreased libido
Erectile dysfunction
Gynecomastia and breast tenderness
What are the monitoring parameters needed for 5ARI?
PSA before initiating treatment
What is the drug that can be used for BPH and is a PDE5 inhibitor?
Tadalafil
Can PDE5 inhibitor be used for monotherapy? Why?
Can consider using but for a specific group that are
1. Young age
2. Low BMI
3. High baseline symptoms
What is the PDE5 inhibitor frequency, onset and place in therapy?
Onset in days / weeks
Can be taken without regard to timing of sexual activity
No change to prostate size
What is an important ADR of tadalafil?
Hypotension
When should combination therapy be considered?
Individuals with moderate symptoms (AUASI score 8-19)
Prostate size > 25g
What are the 3 combination regimen?
Alpha adrenergic antagonist + 5ARI
5ARI + PDE5i
Alpha adrenergic antagonist + PDE5i
Who would benefit from using the alpha adrenergic antagonist + 5ARI?
Symptomatic patients with enlarged prostate
What are the benefits towards using the alpha adrenergic antagonist and 5ARI regimen?
Onset
- Alpha adrenergic faster onset than 5ARI in helping to alleviate symptoms
Mechanism of action
- Alpha adrenergic antagonist: control smooth muscle
- 5 ARI: decrease prostate size
What are the indications to using 5ARI + PDE5 inhibitors?
Mitigate sexual adverse effects from 5ARIs
Concomitant ED with BPH
What are the risks of using 5ARI + PDE 5 inhibitors?
Most BPH patients have cardiac comorbidities
If patient on nitrates, can have significant DDI.
Why is the alpha 1 adrenergic antagonist and PDE5 inhibit combine therapy generally not recommended?
Risk of severe hypotension
Does not help with prostate size
If needed, what can you do to reduce the risk of hypotension in combined therapy of alpha adrenergic antagonist and PDE 5 inhibitor?
Select a uroselective antagonist
Optimize and stabilize alpha antagonist first before adding PDE5i
Use lowest PDE5i dose
What agent can I use to help with irritative and storage symptoms?
Anti muscarinics
When is antimuscarinics allowed
PVR < 250mL
What are the antimuscarinic agents?
Oxybutynin
Tolterodine
Solifenacin
