Pharmacologic Therapy of Benign Prostatic Hyperplasia Flashcards
Benign Prostatic Hyperplasia
- Abnormal enlargement of the prostate gland that appears to occur with aging
- Produces persistant lower urinary tract symptoms (LUTS)
Prostate Gland
- Walnut-sized gland located between bladder and penis
- Urethra runs through center of the prostate
- Prostate secretes fluid that nourishes and protects sperm
What are the three types of prostate tissue?
- Epithelial
- Stromal
- Capsule
Epithelial tissue
- Glandular tissue
- Produces ejaculate secretions
Stromal tissue
- Smooth muscle tissue
- Contains **alpha-1 adrenergic receptors **
Capsule tissue
- Outer shell
- Compromised of fibrous connective tissue with alpha-1 adrenergic receptors
5-alpha reductase
Converts testosterone and androstenedione to dihydrotestosterone (DHT) which causes prostate enlargement and growth
What are some obstructive symptoms of BPH?
- Hesitancy
- Dribbling
- Incomplete emptying
- Interrupted stream
- Impaired force or size of urinary stream
- Strain or push to urinate
- acute retention
What are some irritative symptoms of BPH?
- Frequency
- Urgency
- Nocturia
- Pain or burning on urination
What are the complications of BPH?
- Urinary retention
- Overflow urinary incontinence
- Renal insufficiency
- Urinary tract infection
- Gross hematuria
- Bladder stones
What is used to screen for prostate cancer?
Prostate specific antigen (PSA) and digital rectal exam (DRE)
* PSA > 1.4 ng/mL –> at risk for developing complications of disease
What is the peak and average urinary flow rate?
10-15 mL/sec
What are some medications that can exacerbate symptoms of BPH?
- Anticholinergics
- Bronchodilators
- Psychotropics
- Antidepressants that have anticholinergic effects
- Antiarrhythmics/antianginals that have anticholinergic effects
- Antihistamines
- OTC medications – cough and cold
What are some treatment options?
- Watchful waiting
- Behavorial interventions
- Surgery
- Prostatectomy (transurethrally “TURP” or suprapubically)
- Balloon dilation
- Pharmacologic options
- Alpha-adrenergic blockade
- 5-alpha reductase inhibition
- Phosphodiesterase-5 (PDE-5) inhibitors
Alpha-1 antagonist
- MOA: Blockade alpha-1 adrenergic receptors in the prostatic stromal tissue
- Faster at reducing LUTS
- **Do NOT reproduce prostate size **
- NO effect on PSA
- SLOW titration to treatment maintenance dose is needed
- No dosage reduction in renal failure
- Should NOT be used as a single agent in patients with BPH and HTN (ALLHAT trials)
What medications are Alpha-1 antagonist?
- Doxazosin
- Prazosin
- Terazosin
What are the adverse effects of Alpha-1 antagonist?
- Dizziness
- Syncope
- Orthostatic hypotension
- Headache
- CNS effects
Selective alpha-1 antagonists
- MOA: Selective for prostatic alpha-1A receptors WITHOUT causing peripheral vascular smooth muscle relaxation
- Take approximately** 30 minutes** AFTER the same meal every day
-Dose titration is minimal or NOT needed (only silodosin) - **Good choice for patients with CAD, volume depletion, cardiac arrhythmias, or those taking multiple BP meds **
What are the drug interactions of selective alpha-1 antagonist?
- Cimetidine and diltiazem (decrease metabolism)
- Carbamazepibe and phenytoin (increase metabolism)
What medications are selective alpha-1 antagonists?
- Alfuzosin
- Silodosin
- Tamsulosin
What are the adverse effects of alfuzosin?
- Dizziness
- Fatigue
- Ejaculatory dysfunction
- LESS hypotension
What are the adverse effects of silodosin?
- Dizziness
- Headache
- Ejaculatory dysfunction
What are the adverse effects of tamsulosin?
LESS hypotension
5-alpha reductase inhibitors
- MOA: Competitively inhibits **type 1 and/or type II 5-alpha reductase **
- **Management of moderate to severe BPH **
-
Reduces prostate size by ~25% and serum PSA levels by ~50% **
-Delayed onset of clinical effect–> 6-12 months
-First choice in patients with significantly enlarged prostate (>40 g)
-Choice for those who can not tolerate CV effects of alpha-blockers (angina, arrhythmias)
-NO renal dosage adjustments or clinically relevant DDIs
-FDA pregnancy category – X**
What medications are 5-alpha reductase inhibitors?
- Dutasteride
- Finasteride
What are the adverse effects of 5-alpha reductase inhibitors?
- Impotence
- Decreased libido
- Gynecomastia
PDE-5i
- MOA: Prevents the metabolism of **cGMP **
- NO/cGMP pathway is one of the major regulators of smooth muscle contractility
- Following NO release, cGMP formation elicits smooth muscle relaxation
- **Tadalafil (Cialis®) is the only medication in this used for BPH or BPH with ED (erectile dysfunction) **
- Renal dose adjustment
What medications are PDE-5i?
Tadalafil
What is a contraindication of tadalafil?
Any form of organic nitrate
What are some adverse effects of tadalafil?
- Headache
- Dyspepsia
- Back pain
- Myalgia
- Nasal congestion
- Flushing
- Pain in limb
What are some drug interactions of tadalafil?
- CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) INCREASE tadalafil exposure
- CYP3A4 inducers (e.g. rifampin) DECREASE tadalafil exposure
What are some warnings/precautions of tadalafil?
- Use with alpha-blockers, antihypertensives, or substantial amounts of alcohol may lead to hypotension
- Patients should seek emergency treatment for an erection **lasting > 4 hours **
- Use with caution in patients predisposed to **priapism **
- Patients should stop use and seek medical care if a sudden loss of vision occurs in one or both eyes – could be a sign of **Non-Arteritic Ischemic Optic Neuropathy (NAION) **
- Patients should stop use and seek prompt medication attention in the event of sudden decrease or loss of hearing
Floppy Iris Syndrome
- Adverse effect found to be associated with **doxazosin, silodosin, and tamsulosin **
- Patients need to tell their ophthalmologist if they are taking an alpha-1 adrenergic antagonist!
Who is the combination therapy indicated for?
- Severe symptoms
- Prostate gland > 40 g
- PSA > 1.4 ng/mL
