GU Flashcards
When the penis is flaccid:
arterial blood flow (in)=venous blood flow (out)
With an erection:
arterial blood flow (in)>venous blood flow (out)
3 main causes of ED (broad categories)
- Organic
- Psychogenic
- Medication/drug-induced
MC cause of organic ED
decreased blood flow (d/t dz ie DM, HTN, heart dz–> vascular problems)
Organic causes of ED
- Decreased blood flow (MC)
- Hormone imbalance (low testosterone)
T or F- all people with low testosterone levels have ED?
F
Psychogenic causes of ED
stress, anxiety, depression
What meds can cause ED?
- BP meds
- Antipsychotic meds (esp 1st gens)
- Antidepressants
- BPH
- Opioids
- Nicotine
- Excessive alcohol
What specific BP meds can cause ED? (3)
BBs, clonidine, methyldopa
What specific antipsychotic meds can cause ED? (4)
1st gen antipsychotics (not 2nd gens): haloperidol, chlorpromazine, thioridazine, fluphenazine
What specific antidepressants can cause ED?
SSRIs, SNRIs
What is the #1 reason why pts stop taking their antidepressants?
ED
What specific BPH drugs can cause ED?
finasteride, dutasteride, silodosin
What specific opioids can cause ED?
ALL, especially methadone
Are 1st or 2nd gen antipsychotics more likely to cause ED?
1st gen
What is a useful tool for patient hx for pts w/ ED?
International index of erectile function (IIEF-5) questionnaire
Pt hx for ED (2 essential things to help obtain it)
- IIEF-5 questionnaire
- Past medical hx
ED physical exam findings (4)
- hypogonadism (dec testosterone)
- penile dz
- enlarged prostate
- HTN, DM (vascular dz)
What is the goal of therapy for ED?
increase QUANTITY and QUALITY of sexual intercourse
Should ED txs be used for pts w/o ED?
NO
1st step before initiating tx of ED
Identify cause- physical vs psychological
Tx algorithm for PHYSICAL ED
- 1st= Lifestyle modifications
- if no effect–> devices and medications
Tx algorithm for PSYCHOLOGICAL ED
- 1st= Lifestyle modifications
- if no effect–> medications
For an erection to happen, muscle must be ____ (contracted/relaxed)
relaxed
Physiology of an erection: starts with _____
acetylcholine
Physiology of an erection: 2 pathways after acetylcholine is released: ____ or _____
increased NO (nitric oxide) release or increased Prostaglandin E release
Physiology of an erection: When NO is released, this causes an increase of _____
cGMP
Physiology of an erection: When prostaglandin E is released, this causes an increase of _____
cAMP
Physiology of an erection: Increases in both cGMP and cAMP result in decreased _____
calcium
Physiology of an erection: When calcium is blocked, muscle_____, allowing erection
relaxes
Which side of the “erection pathway” does Alporostadil affect?
increases prostaglandin E (Alporostadil is prostaglandin E), leading to increased cAMP and dec Ca
Which side of the “erection pathway” do phosphodiesterase inhibitors affect?
Slows breakdown of cGMP, leading to increased cGMP and dec Ca
ED tx algorithm: drug-induced ED
- d/c offending agent
OR
-reduce dose of offending agent
ED tx algorithm: Organic ED–> What are the 1st line options? (2)
-Oral PDE inhibitor
or
-Vacuum erection device
Organic ED: is it a physical or psychologic cause of ED?
physical
ED tx algorithm: Organic ED–> What are the 2nd line options?
Intracavernosal therapy (injection)
ED tx algorithm: Organic ED–> What are the 3rd line options?
Intraurethral alprostadil (suppository)
ED tx algorithm: Organic ED–> What is the last line option?
penile prosthesis (surgery)
ED tx algorithm: Psychogenic ED (2)
- psychotherapy
- behavior modification
List the non pharm tx for ED (devices)
- Vacuum erection device (1st line)
- Penile prosthetic implant (last line)
2 first line therapies for ED tx
Vacuum erection devices and Oral PDE inhibitors
Vacuum erection device time of onset
30 min
How long should vacuum erection devices be used for?
only for 30-60 mins
Vacuum erection devices: what maintains erection?
tension bands
What is a downside of vacuum erection devices that you need to inform your pt of?
ejaculation won’t always occur
CIs for the 2 devices
- sickle cell anemia
- pt already on anticoagulants ie coumadin
ABSOLUTE CI for devices
sickle cell anemia
What are the 3 categories of pharmacologic tx of ED?
- phosphodiesterase inhibitors
- Prostaglandin E1
- Unapproved (rx and herbal) agents
1st line pharm therapy for ED?
phosphodiesterase inhibitors
List the phosphodiesterase inhibitors
Sildenafil, vardenafil, tadalafil
Sildenafil brand name
Viagra
vardenafil brand name
Levitra
tadalafil brand name
Cialis
which PDE inhibitors inhibit PDE-5, slowing the breakdown of cGMP?
Sildenafil, vardenafil, tadalafil
Which PDE inhibitors inhibit PDE-6?
Sildenafil, vardenafil (minimal)
Where is the enzyme PDE-6 found in the body?
the eyes around the photoreceptors
PDE-6 affects what part of your vision?
color vision, especially the color blue
What ADR can occur in drugs that inhibit PDE-6? What do you do if this occurs?
color changes can occur. Stop drug immediately before photoreceptor damage is permanent
Onset of action for vardenafil?
1 hr
Onset of action for Sildenafil?
30 min- 1 hr (shortest onset of the 3)
Onset of action for tadalafil?
2 hrs (longest onset of the 3)
Duration of action for Sildenafil?
4 hrs
Duration of action for tadalafil?
24-36 hrs (longest)
Duration of action for vardenafil?
4 hrs
What is the fatty meal effect?
absorption of the drug is affected by fatty meals, so you must take the drug on an empty stomach
Which PDE inhibitors have the fatty meal effect?
sildenafil, vardenafil
Photoreceptor damage (color changes) are most common with which PDE inhibitor?
sildenafil (viagra); vardenafil only small risk; tadalafil rare, but there’s still a warning
What is the least potent PDE inhibitor?
sildenafil (dose= 25-100 mg); others dose= 5-20 mg
Which PDE inhibitors should you take on an empty stomach?
sildenafil, vardenafil
Which PDE inhibitors can you take with or without food?
tadalafil
What is a good thing to keep in mind when deciding which ED med is best to prescribe your pt?
insurance coverage
MOA- PDE inhibitors
inhibits phosphodiesterase enzymes, slows breakdown of cGMP, allowing for depression of Ca, leading to smooth muscle relaxation and erection
What side of the erection pathway do PDE inhibitors affect?
left side (NO, cGMP)
Drug-drug interactions- PDE inhibitors
-Alcohol and nitrates
Are PDE inhibitors absolutely CI’d if pt is on nitrates?
No.
If pt is on nitrates, how long must they wait to take their nitrates after taking viagra?
24 hrs
If pt is on nitrates, how long must they wait to take their nitrates after taking cialis?
48 hrs
Are PDE inhibitors absolutely CI’d if pt drinks alcohol?
No. moderate ETOH consumption is ok (ETOH in excess=absolute CI)
ADRs- PDE inhibitors
Rare and serious:
- nonarteritic anterior optic neuropathy (NAION)
- priaprism
Other:
-change in color vision (mainly viagra)(d/t PDE-6 inhibition)
Definition: vision changes in the eye (not the same as the color changes)
nonarteritic anterior optic neuropathy (NAION)
Define priaprism
erection lasting >4 hrs
List the prostaglandin E1 drugs for tx of ED
Aprostadil
MOA- Alprostadil
Increases cAMP, decreasing Ca
What side of the erection pathway does Alprostadil affect?
right side (prostaglandin E, cAMP)
List the 2 routes of administration of Alprostadil
- Intracavernous injection
2. Intraurethral (MUSE)- suppository
Alprostadil intracavernous injection brand names (2)
Caverject, Edex
Which form of alprostadil is a suppository inserted into the urethra?
MUSE
Which form of alprostadil is preferred?
Intracavernous injection
Why is the intracavernous injection the preferred method of administration of Alprostadil?
faster absorption
Intracavernous injection of Alprostadil: ADRs? (3)
- Injection site rxn
- Fibrous deposits
- Curvature of the penis
What part of the penis is the intracavernous injection of Alprostadil injected into?
right into the penis cavernosa
What should be done to reduce fibrous deposits and injection site rxns with the intracavernous injection of Alprostadil?
rotate injection sites (switch sides of the cavernosa)
How big is the needle for the intracavernous injection?
1/2”, 27-30 gauge (prefilled syringe)
Alprostadil onset of action?
5-15 min (5 min-injection, 15 min- MUSE-slower absorption)
Alprostadil duration of action?
14-44 min for either; DOSE RELATED
What is the non-response rate w/ Alprostadil injections? (%)
30%
What are the unapproved rx agents for ED? (3)
- Pentolamine
- Papaverine
- Trazodone
Which UNAPPROVED rx agents for ED are available as injections?
Pentolamine and Papaverine
What are the unapproved herbal OTC agents for ED? (3)
- Yohimbine
- Wild yam
- DHEA (dehydroepiandosterone)
What is the problem with herbal OTC agents for tx of ED?
- Not found to be super efficacious in txing ED
- not FDA regulated
What should you always tell pts to look for on the bottles of herbal supplements, since herbals are not FDA regulated?
USP gold seal (indicates good manufacturing practices)
BPH- sex and age
males >60 yo
What is the MC benign neoplasm in men?
BPH
What % of men have enlarged prostate and BPH symptoms?
40%
What % of men require tx for BPH symptoms?
20%
Functions of the prostate (2)
- produce ejaculation fluids (40%)
2. antibacterial secretions
Layers of the prostate (3)
- Epithelial (glandular)
- Stromal (smooth muscle)
- Capsule (fibrous)
What receptors are located in the epithelial layer of the prostate?
androgen receptors
What receptors are located in the stromal layer of the prostate?
a1 receptors
What receptors are located in the capsule layer of the prostate?
a1 receptors
How many growth phases of the prostate are there?
2
Describe the growth phases of the prostate
- puberty-25yo (1st growth of the prostate)
2. 40 yo- rest of life
Size range of prostate from 1st to 2nd growth phases
1g to 25-50g
Are there more a1 adrenergic receptors in the bladder or the prostate?
Many more in the prostate
Normal prostate- ratio of stromal layer:epithelial layer
2:1
What layer of the prostate expands in BPH?
stromal layer
BPH- ratio of stromal layer:epithelial layer
5:1
BPH pathophys: epithelial tissue
Androgen receptors (5a reductase): testosterone converted into DHT–> causes prostate enlargement
BPH pathophys: stromal & capsule
a1 receptors: bind norepinephrine, cause muscle contraction
Static vs Dynamic causes of BPH
- Static= physical block-permanent enlargement of tissue
- Dynamic= muscle contraction- affect urethral lumen
BPH symptoms (7)
- urinary frequency
- urinary urgency
- urinary intermittency
- Nocturia (getting up in middle of night to pee)
- Hesitancy
- Straining
- Decreased force of stream
BPH signs (6)
- DRE- enlarged prostate
- Elevated PSA
- Elevated BUN, Scr (with obstruction)
- Increased post-void residual volume
- Decreased urine flow rate
- Weakened stream
PSA value in BPH
elevated, >1.4 ng/mL
BPH- post-void residual volume
Increased, >25-50 mL (more urine left in bladder)
BPH-urine flow rate
decreased (less than 10 ml/sec)- dec flow rate, weakened stream
Med induced BPH: meds that affect the prostate directly (2)
- Testosterone
- a-agonists- more short term/reversible, pts usu not on these meds chronically.
Med induced BPH: meds whos ADRs mimic BPH symptoms, but don’t actually change the prostate (5)
- Anticholinergics
- antihistamines (diphernhydramine-benadryl) (?like an anticholinergic?)
- phenothiazine
- TCAs
- Large doses of diuretics
How does testosterone affect the prostate?
inc testosterone= inc prostate size
List a-agonists that directly affect the prostate
pseudoephedrine, ephedrine, phenylephrine
List the complications of untreated BPH (7)
- AKI
- Gross hematuria
- Overflow urinary incontinence or unstable bladder
- Recurrent UTIs (bc of residual urine in the bladder)
- Bladder diverticula
- Bladder stones
- Long standing obstruction leading to chronic renal failure
Non-pharm tx of BPH (mild symptoms) (2)
- Watchful waiting
2. Behavior modification
What is included as part of behavior modification as a non-pharm tx of BPH? (4)
- Medication review
- Restrict fluids close to bedtime
- minimize caffeine and alcohol
- bladder training (frequent emptying)
Tx for pt w/ severe symptoms from BPH
surgery (complex, many risks)
What is the name or the survery for pts w/ BPH to determine need for tx?
AUA BPH symptom score index
How many questions are in the AUA BPH symptom score index? What is the rating scale?
- 8 questions, rate each 0-5; 0=best, 5=worst
Severity of BPH based on the AUA BPH symptom score index (actual numbers)
Mild: less than 7
Mod: 8-19
Severe: >20
BPH tx flow chart: mild sympts
Watchful waiting
BPH tx flow chart: mod sympts
- a1 antagonist OR 5a reductase inhibitor; if response- continue, if no reponse-surgery
- a1 antagonist AND 5a reductase inhibitor; if response- continue, if no reponse-surgery
BPH tx flow chart: severe sympts/complications
surgery
Pharmacologic tx for BPH: classes (3)
- a1 antagonists
- 5-a reductase inhibitors
- herbal products
a1 antagonists MOA
block a1 receptors in prostate, relaxing stromal layer
5-a reductase inhibitors MOA
block 5a reductase (epithelial layer), reducing production of androgens/testosterone
Which BPH drug class relaxes smooth muscle in the prostate?
a1 antagonists
Which BPH drug class decreases prostate size?
5-a reductase inhibitors
Which BPH drug class halts dz progress?
5-a reductase inhibitors (halts but doesn’t reverse)
Which BPH drug class is best to tx a muscle related cause of BPH?
a1 antagonists
Which BPH drug class is best to tx a pt w/ a very enlarged prostate?
5-a reductase inhibitors
Peak onset of a1 antagonists?
1-6 wks
Peak onset of 5-a reductase inhibitors?
3-6 mo (longer onset)
Efficacy of BPH drug classes?
Both a1 antagonists and 5-a reductase inhibitors are equally efficacious (++); 5-a reductase inhibitors are better for enlarged prostates, however
Which BPH drug class decreases PSA?
5-a reductase inhibitors
Which BPH class causes the most sexual dysfunction?
5-a reductase inhibitors (++) (most problems d/t dec testosterone)
a1 antagonists still cause some (+)
Which BPH drug class has cardiovascular ADRs?
a1 antagonists
How many generations of a1 antagonists are there for tx of BPH?
2- 2nd gen and 3rd gen
Which generation of a1 antagonists are the best for a pt with both HTN and BPH?
2nd gen
Which generation of a1 antagonists are the most prostate specific and have less side effects as a result?
3rd gen
List the 2nd gen a1 adrenergic antagonists for tx of BPH (5)
Prazosin, terazosin, doxazosin, doxazosin GTS (XL), alfuzosin
List the 3rd gen a1 adrenergic antagonists for tx of BPH (2)
Tamsulosin, silodosin
Indications for 2nd gen a1 adrenergic antagonists
pt w/ HTN and BPH–> less prostate specific
Indications for 3rd gen a1 adrenergic antagonists
pt w/ BPH (no HTN), with muscular cause; 3rd gens are more urospecific (prostate specific)
a1 adrenergic antagonists ADRs (6)
- Dizziness (esp 2nd gen)
- Hypotension (esp 2nd gen)
- Syncope w/ 1st dose (make sure pt lying or sitting down after taking 1st dose)
- Muscle weakness
- H/A
*Rare/serious: floppy iris syndrome- refer to opthalmologist
Describe how you should dose a1 adrenergic antagonists for tx of BPH
start low dose and titrate up based on sympts and tolerance of ADRs
T or F? a1 adrenergic antagonists affect the prostate size?
F
3 main differences btw 2nd and 3rd gen a1 adrenergic antagonists
- Time to sympt relief is decreased- 2nd gen= 2-6 wks, 3rd gen= several days (3rd gen quicker symptom relief)
- Receptor selectivity- increased uroselection in 3rd gen –> less side effects
- Frequency- 2nd gen=take multiple times/day (unless XL), 3rd gen= take once a day (better for pt compliance)
List the 5a-reductase inhibitors for tx of BPH (2)
-Finasteride, dutasteride
T or F? The 5a-reductase inhibitors will decrease prostate size?
T
Which 5a-reductase inhibitor is better tolerated/has less systemic side effects? Why?
Dutasteride; blocks more conversion leading to lower levels of DHT
Which 5a-reductase inhibitor is more selective for prostatic enzymes?
Finasteride
How often do you need to take 5a-reductase inhibitors?
once daily
5a-reductase inhibitors- ADRs
Sexual dysfunction (ED)
Which 5a-reductase inhibitor requires special handling? Why?
Finasteride- can be absorbed through skin- caution handling, must wear gloves
List the herbal products available for tx of BPH (5)
- Saw palmetto
- stinging nettle
- South african stargrass
- pumpkin seed
- African plum
MC herbal BPH tx?
Saw palmetto (widely used herbal product for BPH)
Urinary Incontinence: MC gender?
Females
UI incidence increases with ___ (both men and women)
age
Women with UI- ages and %
-less than 25 yo - 20%
-25-60 yo- 30%
60 yo- 40%
Overall % of men with UI?
9%
Normal Urinary cycle (4 steps)
- Empty Bladder
- 1/2 full (1st sensation to void)
- Full (high desire to void)
- Urination
Which muscles are contracted and relaxed during urination?
- detrusor: contracts
- pelvic floor muscles: relax
UI can be to either under or over functioning of which muscle?
detrusor
3 classifications of clinical presentations in UI
- Stress
- Urge
- Overflow
UI d/t stress is caused by:
urethral underactivity
-occurs during exertion (exercise, coughing, sneezing)
UI d/t urge is caused by:
- overactive bladder and/or detrusor muscle
- associated w/ frequency, urgency, nocturia, and eneuresis
Definition of eneuresis
involuntary urination
UI d/t overflow is caused by:
- overactive urethra and/or underactive bladder
- bladder fills but is unable to empty- strain, hesitancy, dec force of stream (similar sympts to BPH)
Meds that induce or worsen UI (6)
- Diuretics
- Alpha receptor antagonists (BPH meds)
- Sedation hypnotics
- Antidepressants (esp TCAs)
- Alcohol
- ACEIs- d/t cough (exertional)
Non-pharm txs of UI (5)
- Decrease risk factors- healthy weight, prevent constipation (straining), fluid modification (ex- if nocturia, limit fluid intake before bed), caffeine and alcohol reduction
- Bladder training- scheduled toileting (every 2 hrs)
- Pelvic floor exercises- Kegels
- Urine collection- urinals at bedside, pads, depends
- Physical therapy- improves strength
Pharm tx based on whether UI is related to ____ or _____
stress or overactive bladder
List the 2 options for pharmacologic tx of stress-related UI
- duloxetine (cymbalta)
- a-adrenergic agonists (pseudoephedrine-sudafed, phenylephrine-sudafed PE)
1st line pharm tx for stress-related UI
Duloxetine (cymbalta)
2nd line pharm tx for stress-related UI
-a-adrenergic agonists (pseudoephedrine-sudafed, phenylephrine-sudafed PE)
Duloxetine ADRs
H/A, dry mouth, fatigue; *s/e’s improve over time
a-adrenergic agonists ADRs
dizziness, confusion, urinary retention, photosensitivity
List the 2 options for pharmacologic tx of UI caused by overactive bladder
ANTICHOLINERGICS:
- Oxybutynin (ditropan)
- Tolterodine (detrol)
1st line pharm tx for OAB-related UI
Anticholinergics; oxybutinin=MC
Dosage forms of oxybutynin
- Oral- IR and XL
2. Dermal- TDS and gel
Oxybutinin ADRs (4)
- dizziness
- dry mouth* (MC, but better with XL form)
- constipation
- nausea
Dosage forms of tolterodine
Oral- IR and LA (LA=long acting)
tolterodine ADRs
dry mouth (better with LA form)
1st line tx for overactive bladder
Anticholinergics