Urology Flashcards
Erectile dysfunction
Many causes—vascular disease, diabetes,
medications, depression, complication of
prostate surgery, psychological causes
Many options for therapy—penile implants,
intrapenile injections or intraurethral
suppositories of Aloprostil [MUSE, Caverject,
Edex] and oral phosphodiesterase-5 [PDE-5]
inhibitors
Drugs to treat erectile dysfunction:
Phosphodiestrease-5 (PDE-5)
PDE-5 inhibitors
MOA—sexual stimulation causes smooth muscle relaxation of corpus cavernosum, which increases blood flow. The mediator is nitric oxide [NO], which
activates and helps in the formation of cyclic GMP—this then causes smooth muscle relaxation through a
reduction of intracellular Ca++
PDE-5 inhibits PDE-5 which is the isoenzyme responsible for breaking down of cGMP in the corpus cavernosum—the result is to increase the flow of blood into the corpus
cavernosum—these agents have NO effect in the absence of sexual stimulation
Examples of PDE-5 inhibitors
Sildenafil (Viagra)—protype
Tadafil (Cialis)
Vardenafil (Levitra; Staxyn)
Avanafil (Stendra)
Sildenafil (Viagra)
Brand name: viagra
Taken on empty stomach—at least 1 hour before anticipated sexual activity; dosed once a day
Metabolized by CYP3A4
Dose reduction when hepatic disease is present
Dose reduction when severe renal disease is present
ADE—headache, flushing, dyspepsia, nasal stuffiness, DISTURBANCES IN PERCEPTION OF BLUE AND GREENS, SUDDEN TRANSIENT HEARING LOSS (FROM VASODILATION) can cause
priapism
Use caution with CV disease and in those at risk for CV disease
Drug interactions/considerations with SILDENAFIL aka VIAGRA
Can potentiate hypotension [if patient on other agents that can lower BP—alpha blockers, vasodilators]
Contraindicated with nitrates, isosorbide (vasodilators)
Start at low dose and titrate up as needed for effect
Reduce dose of these agents if patient on CYP3A4 inhibitors—Biaxin, Ritonavir and other protease inhibitors
Generic: sildenafil
Brand: viagra Route: PO Onset of action: 60 minutes 1/2 life: 3-4 hours Food interaction: yes Caution with alpha blockers: +
Generic: tadalafil
Brand: cialis Route: PO Onset of action: 120 miutes 1/2 life: 18 hours Food interaction: no Caution with alphablockers: ++++
**ALSO APPROVED FOR BPH*
Generic: Vardenafil
brand: Levitra Route: PO Onset of action: 60 miutes 1/2 life: 4-5 hours Food interaction: no (do not take with WATER) Caution with alpha blockers: ++
Generic: Avanafil
Brand: Stendra Route: PO Onset of action: 30-45 minutes 1/2 life: 5 hours Food interaction: no Caution with alpha blockers: ++
Alprostadil
Synthetic prostaglandin E1
In the penile tissues, PGE1 allows relaxation of the smooth muscle of corpus cavernosum
Given intraurethral [supp] or intrapenile [injection]
Can be used 1st line—but most often used in those who are not candidates for oral agents
Acts locally, which decreases chance of ADEs
MOA—smooth muscle relaxants, exact physiological mechanism is unknown
Systemic absorption is minimal
Onset 5-10” [supp] or 2-25” [injection]—effects last 30-60”
ADEs—rare; hypotension, headache have been reported; local effects—penile pain, urethral
pain, testicular pain
Priapism may occur
BPH
Nonmaligant growth of the prostate—occurs with age
Three categories of drugs approved for treating
BPH
-Alpha Blockers
-5 Alpha Reductase Inhibitors
-PDE-5 Inhibitors
Alpha Blockers
Blocking Alpha1A & Alpha1B receptors in the prostate cause the smooth muscles in the gland to relax, which leads to improved urine outflow Selective agents only block Alpha1B—have no BP effects— nonselective ones decrease peripheral vascular resistance and lower BP Five agents in this class approved for BPH, a sixth one may be used but not FDA approved 4 nonselective and 2 selective alpha blockers—real prototype drug hard to identify
Generic Name: Terazosin
Trade name: Hytrin FDA approved for BPH: yes NONSELECTIVE alpha blocker NO food effect Metabolized in liver but not CYP450
Generic Name: Doxazosin
Trade Name: cardura FDA approved for BPH: yes NONSELECTIVE alpha blocker No food effecr CYP450 metabolism? yes
Generic Name: Alfuzosin
Trade name: Uroxatral FDA approved for BPH: yes NONSELECTIVE alpha blocker Food HELPS with absorption CYP450 metabolism? yes
Generic: Prazosin
Trade name: minipress FDA approved for BPH: NOOOO NONSELECTIVE alpha blocker No effect with food CYP450: yes
Generic: Tamulosin
Trade name: Flomax FDA approved for BPH: yes SELECTIVE alpha blocker Food helps with absorption CYP450 metabolism: yes
Generic: Silodosin
Trade name: rapaflo FDA approved for BPH: Yes SELECTIVE alpha blockers Food helps with absorption CYP450: yes** (also substrate for P-glycoprotein)
Alpha Blockers
½ life—8-22 hours
Peak effects seen in 1-4 hours
Rapaflo must be dose reduced for renal disease—avoid in severe CKD
ADEs—dizziness, fatigue, nasal congestion, HA, drowsiness and orthostatic hypotension [these effects are less with selective agents]; nonselective agents given at HS
Alpha blockers can effect ejaculatory ducts and impair smooth muscle contractions—inhibition of ejaculation and retrograde ejaculation have been reported with all of these drugs—these agents do NOT affect male sexual function severely like phenoxybenzamine and phentolamine [OraVerse]
Drug interaction with Alpha Blockers
Drugs that inhibit CYP3A4 and CYP2D6—Verapamil, Diltiazem may increase the drug levels of Cardura, Flomax, Rapaflo and Uroxatrol
Drugs that induce CYP450—Tegretol, Dilantin and St. John’s Wort may decrease the plasma concentrations of the aforementioned agents
Uroxatrol may prolong QT interval, use caution when giving other drugs that can prolong QTc—Biaxin, Levaquin, Cipro, Avelox, class III antiarrhymthics
Cyclosporine increases levels of Rapaflo because it is a
substrate for P-gp
5 Alpha Reductase Inhibitors
2 agents in this class—both agents work slowly—over 9-12 months [unlike alpha blockers that work in 7-10
days]—these agents reduce the size of the gland
Prostate MUST be enlarged for these agents to work, these agents are used in COMBINATION with alpha blockers
Types:
- finastride (proscar)
- dutasteride (avodart)
MOA of 5 alpha reductase inhibitors
inhibit 5 alpha reductase—which converts
testosterone to dihydrotestosterone[DHT], the more
potent, active compound that stimulates the prostate
to grow. By decreasing DHT the gland shrinks and urine
outflow improves.
5 Alpha Reductase Inhibitor
FINASTERIDE (Proscar)
Food does not affect absorption
½ life 6-12 hours [terminal ½ life of Avodart is 5 weeks, once the steady state is reached in 6 months]
ADEs—decreased ejaculate, decreased libido, ED, gynecomastia, oligospermia
All drugs in this category are teratogenic for women—those of child bearing age or those that are pregnant should not handle or ingest 5 alpha reductase inhibitors as they may lead to birth defects in the
genitalia of male fetus
Rare drug interactions
Finasteride is used [in small doses] for alopecia—
reduces DHT in scalp and serum which prevents hair
loss
PDE-5 inhibitors
TADALAFIL (Cialis)
FDA approved for s/s of BPH
-inhibition of PDE 5 allow vasodilation and relaxation of smooth muscles of the prostate and bladder-which improves the symptoms of BPH
Effect of BPH urethra
As the prostate enlarges, it can obstruction of the urethra
As a result, the man can present with urgency, postvoid dribbling or overflow incontinence
More common in men
Men can have urethral obstruction—from a cystocele, stricture or meatal stenosis [but most common in men]
Conservative therapy includes bladder retraining and prompted voiding, which can be used if none of the following are present
Hydronephrosis, large PVR, recurrent UTI or hematuria
Alpha blockers that decrease tone in prostatic capsule and urethra-really helpful in BPH
- Terazosin (hytrin)
- Doxazosin (cardura)
- Alfuzosin (uroxatral)
- Tamsulosin (flomax)
- Silodosin (rapaflo)
5 alpha reductase inhibitors are also added
Last resort for BPH
intermittent or indwelling catheter then can do a voiding trial and then if that does not work, surgery
Detrusor Underactivity
If the patient has a prolonged outflow obstruction, a neurogenic type situation can develop; this patient has a large PVR and overflow leakage
Goals—drain urine from the bladder; decrease UI; present hydronephrosis & urosepsis
Trial of indwelling/intermittent catheterization to decompress bladder, allowing it to recover its contractile ability; left in for 2 weeks; then removed to see if voiding recurs normally
If not, catheter can be reinserted for 4
weeks & a voiding trial reattempted;
Valsalva maneuvers can be tried to induce
bladder contractions
Bethanechol, a cholinergic agonist, can be
tried at 10-50 mg QID
Testosteron Deficiency
Evaluation of ED should include a testosterone level
Testosterone deficiency can be part of male hypogonadism and can lead to osteoporosis—in addition to sexual issues.
Refer to URL and EBG cited on slide #2; refer to detail
document that reviews testosterone products
Urinary Incontinence
Involuntary loss of urine that leads to hygienic or social problems
Affects at least 10 million Americans
UI is associated with pressure ulcers, skin irritation and falls
UI can lead to anxiety, depression, embarrassment and isolation
