Benign Prostatic Hyperplasia (BPH) Flashcards
What’s the role of dihydrotestosterone (DHT)?
DHT is responsible for normal and hyperplastic growth (increase in number of cells)
How does BPH occur?
BPH results from overgrowth of stromal and epithelial cells of the prostate gland
What’s the effect of enlarged gland in prostate?
The enlarge gland contributes to lower urinary tract sx (LUTS) via direct bladder outlet obstruction (BOO) and increased smooth muscle tone and resistance
Is there a direct linear correlation between protease size and sx?
No
Does enlarged prostate increase the risk of prostate cancer?
No
What mainly causes the s/sx of BPH?
LUTS (Lower Urinary Tract Sx)
LUTS (lower urinary tract sx) may include the ff
Hesitancy, intermittency, straining or weak stream of urine
Urinary urgency and leaking or dribbling
Incomplete emptying of the bladder (bladder always feels full)
Urinary frequency, especially nocturia (urination at night)
Bladder outlet obstruction (BOO)
List drugs that may worsen BPH?
Decongestants e.g. Pseudoephrine
Anticholinergics e.g. Benztropine
Antihistamines e.g. Diphenhydramine, Chlorpheniramine
TCAs, phenothiazines and other drugs with anticholinergic properties
Caffeine (can worsen sx)
Diuretics (increase urination-be sure to take early in the day to limit nocturia)
SNRIs (affect urethral resistance)
Testosterone pdts
What guides selection of tx modality in a pt?
The patient’s perception of the severity of BPH sx guides selection of tx
List tx options of BPH
Watchful waiting (mild dx; pt returns for yearly reassessment)
Pharmacologic therapy
Surgical intervention
When are 5-alpha reductase inhibitors used in BPH?
LUTS secondary to BPH + Prostatic enlargement
T/4 don’t use if no prostatic enlargement
Why should 5 alpha-reductase inhibitors not be used if no prostatic enlargement?
5 alpha-reductase inhibitors work by decreasing prostate size
What’s a reasonable option for men w/o an elevated post void residual (PRV) urine and when LUTS are predominately irritative?
Peripheral-acting anticholinergic agent used for over active bladder e.g. Tolterodine
What’s the value of PVR for anticholinergic to be used?
< 250-300mL
What’s an option for men with both BPH and erectile dysfunction?
Tadalafil
What’s the standard BPH tx?
Alpha blockers e.g. Terazosin, Doxazosin
When is a 5 alpha-reductase inhibitor combined with alpha blockers?
Moderate sx of BPH
What’s the most popular alpha-blocker? With SE is it recently associated with?
Tamsulosin
Floppy iris syndrome
Effect of tamsulosin’s floppy iris syndrome on cataract?
Increases the risk of cataract
AND
Makes cataract surgery itself difficult (important to tell ophthalmologist that pt has ever used alpa-blocker)
List natural pdts used in BPH
Saw palmetto (prostate cancer MUST be ruled out first b4 use)
Pygeum
Beta-sitosterol
Rye grass pollen
Should pharmacists recommend natural pdts for BPH?
No.
MOA of alpha-blockers
Inhibit alpha-1 adrenergic receptors and relax the smooth muscle of the bladder neck reducing bladder outlet obstruction and improving urinary flow
List non-selective alpha-1 blockers
Terazosin (Hytrin)
Doxazosin (Cardura, Cardura XL)
Prazosin
Whats the brand name of Terazosin? (Non-selective alpha-1 blockers)
Hytrin
Whats the brand name of Doxazosin? (Non-selective alpha-1 blockers)
Cardura
Cardura XL
How are terazosin, Doxazosin, and prazosin titrated?
Slowly
What’s the associated warning with non-selective alpha-1 blockers?
Orthostatic hypotension/ Syncope (typically with 1st dose). T/4 dose QHS, especially during initiation
Floppy iris syndrome (can occur during cataract surgery)
SE of a non-selective alpha-1 blockers (terazosin, Doxazosin, prazosin)
Dizziness
Fatigue
Orthodtatic hypotension
Headache
How are non-selective alpha-1 blockers taken? Exception?
All taken at QHS to help minimize the initial orthostasis/ dizziness
Except Cardura XL, which is taken with breakfast
List types of alpha receptors
1A receptors primarily found in prostate
1B and 1D
Effect of alpha-blockers on prostate size and PSA levels?
Alpha blockers have NO effect on prostate size (they don’t shrink) and NO changes to PSA levels
List selective alpha1a blockers
Tamsulosin (Flomax)
Tamsulosin + Dutasteride (Jalyn)
Alfuzosin (Uroxatral)
Silososin (Rapaflo)
What’s the brand name of Tamsulosin? (Selective Alpha1a blocker)?
Flomax
What’s the dose of Tamsulosin (Flomax)? (Selective alpha 1a blocker)?
0.4mg daily, 30mins after the same meal each day; max 0.8mg daily
What’s the warning associated with selective alpha-1a blockers?
Floppy iris syndrome
They have lower risk of orthostatic hypotension than non-selective
What’s the cut-off CrCl for selective alpha-1a blockers use?
CrCl < 30mL/min
SE of selective alpha-1a blockers?
Dizziness
Fatigue
Hypotension
Headache
Abnormal ejaculation (esp with Tamsulosin and Silodosin)
Which selective alpha-1a blockers have a higher risk of abnormal ejaculation?
Tamsulosin (Flomax)
Silodosin (Rapaflo)
In what group of pt is Alfuzosin contra-indicated?
Don’t use in pts at risk for QT prolongation - prolongs QT-interval
What’s the off-label use of alpha-blockers in women?
Bladder outlet obstruction
What’s the concern with using PDE-5 inhibitors (Viagra/Revatio, Cialis/Adcirca, Levitra/Staxyn, Stendra) co-admin with alpha blockers?
Both are vasodilators with BP lowering effects
T/F? The selective alpha-1a blocker are all major CYP 3A4 substrates?
True
What should be avoided with Tamsulosin, Alfuzosin, Silodosin because they are CYP 3A4 substrate?
Strong 3A4 inhibitors
Ritonavir
Itraconazole
Ketoconazole
Clarithromycin
Others
What should Silodosin not be used with?
Strong P-GP inhibitors e.g. Cyclosporine
T/F? Alfuzosin can cause QT prolongation?
True
Which alpha-blocker may result in QT prolongation?
Alfuzosin (Uroxatral)
MOA of 5 alpha-reductase inhibitors?
Inhibits 5 alpha-reductase enzyme which blocks the conversion of testosterone to dihydrotestosterone (DHT)
What’s the indication for 5 alpha-reductase inhibitors use?
Tx of symptomatic BPH in men with ENLARGE PROSTATE
List 5 alpha-reductase inhibitors agents?
Finasteride (Proscar)
Dutasteride (Avodart)
Dutasteride + Tamsulosin (Jalyn)
What’s the brand name of Finasteride? (5 alpha-reductase inhibitors)
Proscar
What’s the brand name of Dutasteride? (5 alpha-reductase inhibitors)
Avodart
What’s the dose of Finasteride (Proscar) used for BPH?
5mg daily
1mg used for hair loss
Whats the contra-indication to 5 alpha-reductase inhibitors use?
Women of child-bearing potential, pregnancy, children
SE of 5 alpha-reductase inhibitors (Finasteride - Proscar; Dutasteride - Avodart)?
Impotence
Reduce libido
Ejaculation disturbances
Breast enlargement and tenderness
What’s the pregnancy category of 5 alpha-reductase inhibitors (Finasteride - Proscar; Dutasteride - Avodart)?
X
Effects of 5 alpha-reductase inhibitors (Finasteride - Proscar; Dutasteride - Avodart) on prostate size and PSA levels
They shrink prostate size and reduce PSA levels
List Phosphodiesterase-5 (PDE-5) inhibitor agent used in BPH?
Tadalafil (Cialis)
What’s the brand name of Tadalafil?
Cialis
SE of Phosphodiesterase-5 (PDE-5) inhibitor agent (Tadalafil - Cialis)?
Headache
Flushing
Dyspepsia
Color vision changes
Blurred vision
Increased sensitivity to light
Epistaxis
Erythemia
Effect of cold and allergy meds (e.g. Decongestants) and antihistamines on BPH sx?
They may worsen BPH sx
Can alpa blockers result in a painful erection erection?
Yes. But, this erection can’t be relieved with sex
How should Tamsulosin (Flomax) be used?
Appox half an hr following the same meal each day
How should Alfuzosin be taken?
Don’t crush, chew or break Alfuzosin tab. Swallow whole
Take at the same time each day with food
Why is Alfuzosin encouraged to be taken with food?
Food increases absorption
What’s the most common SE ass with Silodosin?
An orgasm with reduced or no semen (dry orgasm)
Why does 5 alpha-reductase inhibitors take a long time to work?
Bcuz they shrink the prostate slowly
Why are 5 alpha-reductase inh preg cat x?
They cause birth defects to a developing male fetus
NOTE: Semens of males using 5 alpha-reductase may also be harmful
Why are PSA levels measured with 5 alpha-reductase inhibitors (Finasteride - Proscar; Dutasteride - Avodart) and NOT alpha-blockers?
5 alpha-reductase inhibitors (Finasteride - Proscar; Dutasteride - Avodart) actually reduce PSA levels (and shrink prostate size too)
Alpha-blockers have no such effect
List the worrisome SE of 5 alpha-reductase inhibitors (Finasteride - Proscar; Dutasteride - Avodart)
Decreased sex drive
Decreased vol of ejaculate
Impotence
Breast tenderness/ enlargement
What’s testosterone metabolized to?
Dihydrotestosterone (DHT)
