Benign Prostatic Hypertrophy/erectile Dysfunciton

Front 1

What is the role of the spinal erection center in the brain?

Back 1

Audiovisual stimuli or fantasy initiate neuroendocrine messages from the brain to the autonomic nuclei of the spinal erection center, an area in the spinal cord in which the pelvic autonomic, sensory, and motor nerves form a reflex arc.
-spinal erection center activates the erectile process
- it sends messages via the cavernosal nerves

Front 2

What is the role of the parasympathetic NS in an erection?

Back 2

-Parasympathetic nerve fibers in the cavernosal nerves are the principle mediators of erection.
- These nerve fibers cause dilation of arteries supplying the corpora cavernosa and therefore increase blood flow into the erectile tissue.

Front 3

What is the role of the sympathetic NS in an erection?

Back 3

-Sympathetic nerve fibers in the cavernosal nerves control ejaculation and detumescence
-sympathetic nerve fibers causes constriction of the cavernosal arteries supplying the erectile tissue (no more erection)

Front 4

What two factors modulate an erection?

Back 4

- psychological factors and testosterone levels

Front 5

What is a hormonal ED?

Back 5

ED results when there are inadequate levels of the sex hormone testosterone with a resulting loss of libido and inadequate nitric oxide release from the endothelium of the blood vessels of the arterioles supplying the corpora cavernosa.

Front 6

What is the role of psychological factors in ED?

Back 6

-results when men have a loss of libido
- possible causes include:• performance anxiety
1) relationship problems
2) loss of attraction for a partner
3) stress
4) depression – ED occurs in 70% of patients with clinical depression

Front 7

What 3 endothelium derived factors and neurotransmitters can effect the Ca levels and therefore the tone of the smooth muscle?

Back 7

endothelium factors=nitrous oxide, vasoactive intestinal polypeptide, and prostaglandin E1
neurotransmitters =norepinephrine
-are able to influence intracellular calcium and thereby alter the balance between penile flaccidity and erection.

Front 8

What is the role of the mediator Nitric oxide in an erection?

Back 8

-most important neurotransmitter involved in an erectile process
Nitric oxide diffuses into the smooth muscle cells and activates a series of enzymes that produce cyclic GMP (cGMP) which causes a decrease in intracellular calcium resulting in smooth muscle relaxation and hence arteriolar vasodilation.
arteriolar vasodilation leads to engorged erectile tissue in the corpora cavernosa

Front 9

What branch of the nervous system modulates NO and What hormone enhances the release of NO?

Back 9

-parasympathetic nerve simulation releases NO from the endothelium of the inside walls of the blood vessels supplying the corpora cavernosa.
-The hormone testosterone enhances the release of nitric oxide so that when testosterone levels are low, there is less release of this neurotransmitter important to achieving an effective erection.

Front 10

What enzyme breaks down cGMP?

Back 10

Phosphodiesterase 5
-it ends the vasodilation initiated by NO release

Front 11

What is the role of vasoactive intestinal polypeptide in an erection?

Back 11

located in the endothelium of arteriolar blood vessels REDUCES intracellular calcium
- causes arteriolar VASODILATION leading to increased blood flow to the corpora cavernosa.

Front 12

What is the role of prostaglandin E in an erection?

Back 12

located in the endothelium of arteriolar blood vessels reduces intracellular calcium
- causes arteriolar vasodilation leading to increase blood flow to the corpora cavernosa.

Front 13

What is the role of norepinephrine in erection?

Back 13

-counterbalances the smooth muscle relaxation initiated by nitric oxide, VIP, and PGE1
-modulated by the sympathetic NS within the corpora cavernosa and activates alpha1-receptors on the smooth muscle
-alpha1-receptors causes increased intracellular calcium in the smooth muscles of the arteries supplying the copora cavernosa.
- As a result of this action, norepinephrine causes smooth muscle contraction and hence vasoconstriction of these arteries.
-The blood flow to the erectile tissue of the penis is therefore diminished by norephinephrine’s actions.

Front 14

What is the sequence of events in the development of an erection?

Back 14

1. audiovisual or fantasy stimuli initiate neuroendocrine messages from the brain to the autonomic nuclei of the spinal erection center,
2. spinal erection center sends messages via the cavernosa nerves to the corpus cavernosum
3. parasympathetic fibers cause increased blood flow (vasodilation) and an erection
4. sympathetic nerve fibers control ejaculation
5.Detumescence is the loss of penile erection that occurs naturally after orgasm and ejaculation. this is controlled by sympathetic nerve fibers and causes vasoconstriction

Front 15

What is the cause of neurogenic ED?

Back 15

-failure to initiate nerve impulses or when there is interrupted neural transmission to the spinal erection center and/or the penis.
(included in the broader class of organic ED)

Front 16

What are causes of neurogenic ED?

Back 16

• stroke
• Alzheimer’s disease
• spinal cord injury
• radical pelvic surgery
• diabetic neuropathy
• pelvic injury
• intervertebral disc lesion
• multiple sclerosis
• trauma

Front 17

What is a vasculogenic ED?

Back 17

results from inadequate arterial blood flow to erectile tissue in the penis

Front 18

What are some causes of vasculogenic ED?

Back 18

• atherosclerosis
• hypertension
• diabetes mellitus – ED occurs in 50% of patients with diabetes
• trauma
• pelvic irradiation
• dyslipidemia

Front 19

How does hypertension cause vasculogenic ED?

Back 19

ED occurs in 15% of patients with hypertension because of the development of arterial stenotic lesions affecting proper arterial blood flow to the penis

Front 20

How does trauma cause vasculogenic ED?

Back 20

trauma from a bicycle accident may result in stenoses of some arterioles supplying blood to the corpora cavernosa

Front 21

How can dyslipidemia cause vasculogenic ED?

Back 21

may contribute to the development of atherosclerosis in penile arteries

Front 22

What are some drugs that cause drug induced ED?

Back 22

• Antihypertensives
• Antidepressant drugs
• Anti-androgenic drugs
• Alcohol abuse – may cause alcoholic neuropathy affecting nerve stimulation important to achieving an erection
• Cigarette smoking – facilitates development of vascular insufficiency

Front 23

How do antiandrogenic drugs cause ED?

Back 23

5-alpha reductase inhibitors like finasteride (Proscar®) may decrease libido

Front 24

What are 4 other factors that can lead to ED?

Back 24

• old age – aging contributes to diminished neural and vascular function
• diabetes mellitus – affects vascular and neural functioning
• chronic renal failure – affects vascular and neural functioning
• coronary heart disease – ED occurs in 40% primarily through affects to the vascular system important to achieving and effective erection

Front 25

Is ED usually organic or psyhogenic?

Back 25

ED most commonly results from the combination of both psychogenic and organic dysfunctions, making solutions to the problem difficult to find for some patients.

Front 26

What are the tx options for ED?

Back 26

Tx should begin with identifying organic comorbidities and psychosocial factors
a. Oral phosphodiesterase type 5 (PDE5) inhibitors
b. Intra-urethral alprostadil
c. Intracavernous vasoactive drug injection
d. Vacuum constriction devices
e. Penile prosthesis implantation

Front 27

What is a drawback of injectable testosterone?

Back 27

The chief drawback to injectable testosterone preparations is their tendency not to produce an even response between doses
-painful IM injection

Front 28

What are contraindications to androgen therapy?

Back 28

: men with prostate cancer or obstruction of the bladder neck caused by prostatic hypertrophy

Front 29

What are adverse effects of oral androgen therapy?

Back 29

Oral testosterone preparations may be associated with idiosyncratic hepatotoxicity even in low doses
-less effective then IM or transdermal testosterone

Front 30

What are adverse effects of transdermal testosterone?

Back 30

skin irritation, contact dermatitis, and itching.

Front 31

What is a drawback of testosterone pellets?

Back 31

One of the biggest disadvantages is that in the face of complications the pellets would have to be removed.

Front 32

What is the first line tx for ED?

Back 32

PDE-5 inhibitor unless contraindicated

Front 33

What are the adverse effects of PDE-5?

Back 33

-usually mild to moderate in intensity, self-limited in duration, and more common with higher doses. They include:
• headache
• flushing (especially facial flushing)
• dyspepsia
• nasal congestion (“stuffy nose)
• abnormal vision ("blue" vision) is usually transient
• hypotension - not common; cardiovascular assessment should be done before therapy
• acute hearing loss (sometimes with tinnitus and dizziness) is reported rarely, but the cause and effect relationship is not established

Front 34

What are contraindications of PDE-5?

Back 34

contraindicated in men taking long-acting or short-acting nitrate drugs because they potentiate the hypotensive effects of organic nitrates.
- could lead to the development of myocardial ischemia, and MI or stroke

Front 35

What is the big warning for men with viagra/nitrate?

Back 35

Men must be warned of the danger of taking sildenafil (Viagra®) 24 hours before or after taking a nitrate preparation.
-The time interval for tadalafil (Cialis®) may be up to 48 hours.
-A time interval for vardenafil (Levitra®) is not reported but may be considered to be 24 hours as with sildenafil.

Front 36

What is the dosing for sildenafil?

Back 36

50 mg taken one hour before sexual activity, but taking it in the range of 0.5-4 hours prior to planned sexual activity is acceptable.

Front 37

What is the duration of action for sildenafil?

Back 37

> or equal to 4 hours.

Front 38

What is the frequency of administration for sildenafil?

Back 38

-The maximal recommended frequency is once per day. --On the basis of effectiveness and side effects, the dose may be increased to 100 mg or decreased to 25 mg

Front 39

What is the dosing for Vardenafil?

Back 39

10 mg taken one hour before sexual activity.
-Doses may be increased to 20 mg or reduced to 5 mg based on efficacy and adverse effects noted.
-if pt is on a CYP3A4 inhibitor, doses may change

Front 40

What is the duration of action for Vardenafil?

Back 40

< 5hours

Front 41

What is the dosing for Tadalafil?

Back 41

10 mg taken before planned sexual activity. It may be taken without regard to food. The dose may be increased to 20 mg or reduced to 5 mg based on efficacy and tolerability.

Front 42

What is the duration of action for tadalafil?

Back 42

36 hours

Front 43

Which PDE 5 inhibitor can be taken daily regardless of sexual activity?

Back 43

Tadalafil
• A daily dose of 2.5 mg daily is also approved and may be taken without regard to planned sexual activity, and this dose may be increased to 5 mg daily if needed.

Front 44

When is tx with transurethral alprostadil best?

Back 44

ED associated with neurogenic, vasculogenic, psychogenic or mixed etiologies

Front 45

What is a disadvantage of of alprostadil?

Back 45

results are inconsistently achieved. Effectiveness is increased when also using Actis®, an adjustable penile-constriction device.

Front 46

What are the advantages of alprostadil?

Back 46

local application, minimal systemic effects, and the rarity of drug interactions.

Front 47

What are common side effects of alprostadil?

Back 47

include penile pain and urethral pain or burning

Front 48

Which intracavernous drug is approved for use in the US?

Back 48

Alprostadil
-It results in an erection in more than 70% of men. It has a relatively low incidence of priapism and fibrosis, the two most common adverse effects associated with intracavernous injection therapy for ED.

Front 49

What are adverse effects of intracavernous alprostadil?

Back 49

-Most commonly penile pain in about a third of patients. Other adverse effects, each occurring in 3-4% of patients, include:
- hematoma
-fibrosis
-priapism.
Priapism occurs most commonly with this therapy relative to all other ED therapies, and it preventable through careful dose adjustment.

Front 50

How can you prevent fibrosis with intracavernous alprostadil?

Back 50

-To prevent fibrosis, men should be instructed to compress the injection site for 5 minutes (up to 10 minutes in men who are anticoagulated).

Front 51

What are major disadvantages of papaverine?

Back 51

-priapism (in up to 35%)
- corporal fibrosis (in up to 33% of cases).

Front 52

What are disadvantages of phentolamine?

Back 52

hypotension and reflex tachycardia.
-usually used in combo with papaverine to achieve full effects

Front 53

What is trimix?

Back 53

The most effective intracavernous therapy used in the U.S. is a three drug mixture of papaverine, phentolamine, and alprostadil=trimix
The rate of response is as high as 90%. This combination is not approved by the FDA but is commonly used in the U.S.
- Combinations of alprostadil with either phentolamine or papaverine are referred to as bimix.
- Bimix and trimix are available from compounding pharmacies.

Front 54

What is vacuum constriction?

Back 54

vacuum is applied to the penis for a few minutes, causing tumescence and rigidity, which is sustained using a constricting ring at the base of the penis.

Front 55

What are surgical treatments for ED?

Back 55

• Semi-rigid or inflatable prostheses may be implanted. These devices produce an unnatural erection and there is a risk of an infection.
• Vascular surgery is curative, particularly for young men with congenital or traumatic erectile dysfunction.

Front 56

What are possible functions of the prostate gland?

Back 56

neutralizing the acidity of the fluid from the vas deferens and associated with vaginal secretions
b. possibly aiding in successful fertilization of the ovum since acidity appears to inhibit sperm motility
c. nourishing the sperm

Front 57

What is the etiology of BPH?

Back 57

-two major factors necessary for the onset of BPH are the presence of the testes and aging.
-The prostate appears to become more sensitive to androgens as the gland enlarges and as plasma levels of testosterone decline.

Front 58

What are symptoms of BPH?

Back 58

a. difficulty in initiating a urinary stream
b. a hesitant, interrupted, weak urine stream
c. urgency (sensation of needing to urinate)
d. incontinence – leaking or dribbling
e. more frequent urination, especially at night (nocturia)
f. sensation of incomplete emptying of the bladder
g. acute urinary retention –
• alcohol
• cold temperatures
• a long period of immobility
h. urinary tract infections – more common with prolonged urinary retention
i. bladder or kidney damage – more likely with prolonged urinary retention
j. formation of bladder stones

Front 59

What may trigger acute urinary retention?

Back 59

may be triggered by:
• taking over-the-counter decongestants such as phenylephrine or pseudoephedrine which stimulate alpha-receptors, causing contraction of the smooth muscle of the bladder's sphincter

Front 60

WHat is the relationship between cancer and prostatic hyperplasia?

Back 60

Prostatic hyperplasia does not predispose to the development of prostatic cancer.

Front 61

Questions to ask to determine severity of BPH

Back 61

1. Over the past month, how often have you had a sensation of not emptying your bladder completely after you finished urinating?
2. Over the past month, how often have you had to urinate again less than 2 hours after you finished urinating?
3. Over the past month, how often have you found you stopped and started again several times when you urinated?
4. Over the past month, how often have you found it difficult to postpone urination?
5. Over the past month, how often have you had a weak urinary stream?
6. Over the past month, how often have you had to push or strain to begin urination?
7. Over the past month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning? (Note: Unlike the other questions above, the number given by the patient is the “score.” Using the scoring below makes no sense when answering this question.)

Front 62

Scoring for BPH symptoms assessment

Back 62

1. not at all 0
2. less than 1 time in 5 1
3. less than half the time 2
4. about half the time 3
5. more than half the time 4
6. almost always 5

Front 63

Disease classification based on score for BPH sxs assessment

Back 63

Total Score Disease Classification
0-7 points mild disease
8-19 points moderate disease
20-35 points severe disease

Front 64

When is the sxys scoring system recommended to be used by the AUA?

Back 64

1. for initial assessment of each patient presenting with symptoms of prostatic hyperplasia
2. as the primary determinant of treatment response
3. to assess for disease progression in the follow-up period

Front 65

Treatment options for BPH (general) (7)

Back 65

1. watchful waiting
2. alpha-blocker drug therapy
3. 5-alpha-reductase inhibitor therapy
4. Combination therapy of alpha-blocker w/ 5-alpha-reductase inhibitor
5. Balloon dilation
6. Surgery
7. Complementary and alternative medicines

Front 66

FDA approved alpha blockers for tx of BPH

Back 66

1. Terazosin
2. Doxazosin
3. Tamsulosin
4. Alfuzosin
5. Silodosin

Front 67

Dosing regimen for Doxazosin (non-selective alpha blocker)

Back 67

Starting dose: 1 mg daily
Maintenance: 1-8 mg daily

Front 68

Dosing regimen for Tamsulosin (selective alpha blocker)

Back 68

Starting dose: .4 mg QD
Maintenance: .4-.8 mg daily

Front 69

Adverse effects of alpha blockers

Back 69

2 most common: dizziness and orthostatic hypotension
-may be more pronounced w/ first few doses of doxazosin and terzosin (non-selective alpha blockers)
-Referred to as the "first-dose" effect
-If pt is already on HTN drug, may result in greater likelihood of "first-dose" effect
-Selective alpha-blockers may have a lower incidence
-Try to avoid by starting low and slowly titrating up

Another side effect: lower volume of ejaculate, more common w/ selective alpha blockers

Front 70

Drug interactions with alpha blockers

Back 70

Use carefully with sildenafil and other PDE-5 inhibitors bc of potential for very low reduction in BP w/ orthostatic hypotension
-Stabilize pt for one week before using a PDE-5 inhibitor

Front 71

Contraindications for Alpha blockers

Back 71

Cataract surgery- avoid until surgery is completed
-pts on tamulosin (and likely others) may develop floppy iris syndrome which may lead to retinal detachment, lens problems or endopthalmitis

Front 72

How long does it take before the benefits of alpha blockers can be adequately assessed?

Back 72

2-6 weeks

Front 73

FDA approved 5-alpha-reductase ihibitors

Back 73

Finasteride and dutasteride

Front 74

Dosing regimen for finasteride

Back 74

5 mg daily with or without meals

Front 75

Dosing regimen for dutasteride

Back 75

.5 mg daily w/ or without mels

Front 76

How long before the full expression of effects of 5-alpha-reductase inhibitors is seen?

Back 76

6-12 mo

Front 77

Adverse effects of 5-alpha-reductase inhibitors

Back 77

-generally well tolerated
-most commonly reported adverse effects:
erectile dysfunction
decreased volume of ejaculate
decreased libido (in approximately 2-3% of those treated)
gynecomastia.
-generally resolve with continued treatment.
*These agents should not be handled by pregnant women because of potential adverse effects on male fetuses if systemic absorption occurs.

Front 78

Role of 5-alpha-reductase inhibitors in Prevention of Prostate Cancer

Back 78

-recommended for those at increased risk (over 50 y/o, who can tolerate 5-alpha-reductase inhibitors, african american pts, and those w/ fam hx)
-Lower the overall risk of prostate cancer
-Specifically: lower the risk of less aggressive CA, but increase risk of more aggressive CA.
*important to reinforce digital rectal exams and PSA checks in men on these meds

Front 79

FDA approved Phosphodiesterase-5 inhibitors for tx of BPH

Back 79

Tadalafil (Cialis)
Currently, only tadalafil has an indication for the use in patients with BPH.
*Tadalafil modestly improves urinary frequency, urgency, and straining, but NOT urine flow rate.

Front 80

When should tadalafil be considered?

Back 80

In those who do not get adequate relief from an alpha-blocker alone or for daily use in men with both erectile dysfunction and milder BPH symptoms.
*However, at this point, alpha-blocker monotherapy should still be considered first line.

Front 81

Dosing regimen for tadalafil

Back 81

-When adding tadalafil to alpha-blocker therapy, initial dose is 2.5 mg daily to reduce the risk of hypotension.
-may be titrated to 5 mg daily as appropriate.

Front 82

Adverse Effect of tadalafil

Back 82

Hypotension?

Front 83

Role of Saw Palmetto in tx of BPH

Back 83

Saw palmetto is an herbal supplement heavily promoted to the general public for treatment of urinary symptoms related to prostatic enlargement; however, it is not approved by the FDA for any use. Recent studies have not shown saw palmetto to be more effective than placebo, even at higher doses. In general, there is a lack of published data.

Front 84

Role of Beta-Sitosterol in tx of BPH

Back 84

Beta-sitosterol is a plant sterol ester found in fruits, vegetables, nuts, and seeds, and it is has been used in the management of BPH. It is likely safe, but its effectiveness is not proven

Front 85

role of pygeum in tx of BPH

Back 85

Pygeum is P. africanum bark extract sometimes suggested as an herbal therapy to treat BPH; however, pygeum does not appear to reduce the size of the prostate gland or reverse the process of BPH.

Front 86

Definition of acute prostatitis

Back 86

an acute infectious disease characterized by sudden onset of fever, tenderness, urinary symptoms (frequency, urgency, dysuria, nocturia, and retention) and constitutional symptoms (chills, malaise, myalgia, and perineal pain).

Front 87

Definition of chronic prostatitis

Back 87

presents with few symptoms related to the prostate but rather symptoms of urinating difficulty (frequency, urgency, dysuria), low back pain, perineal pressure, suprapubic discomfort, or a combination of these. It represents a recurring infection with the same organism(s) that results from incomplete eradication of bacteria from the prostate gland.

Front 88

Most common bacterial cause of acute and chronic bacterial prostatitis

Back 88

Acute: Gram negative enteric organisms are most common in acute bacterial prostatitis
**Escherichia coli (E. coli) occurring in 75% of cases.
Klebsiella pneumonia and Proteus mirabilis are also observed.
-Gonococcal and staphylococcal infections are much less frequent in acute bacterial prostatitis.

Chronic: E. coli is the most common cause

Front 89

Abx used to treat acute bacterial prostatitis

Back 89

1. Oral trimethoprim-sulfamethoxazole (1 double strength tablet twice daily)
2. Fluoroquinolone such ciprofloxacin (500mg twice daily).
*IV is rarely necessary for total treatment, but IV tx followed by oral tx with trimethoprim-sulfamethoxazole or a fluoroquinolone is appropriate.

Front 90

Abx used to treat chronic bacterial prostatitis

Back 90

Chronic bacterial prostatitis is more difficult to treat because it is often harder to achieve effective penetration of antimicrobials into the prostate tissue and sustain therapeutic concentrations.
1. The flouroquinolones may be best.
2. Trimethoprim-sulfamethoxazole is also effective and may be considered.

Front 91

Duration of tx for acute and chronic prostatitis

Back 91

Acute= 4 wks
Chronic= 4-6 wks & up to 12 weeks in some cases

Front 92

2 abx that may be used for long-term suppressive tx for pts w/ recurrent prostatitis

Back 92

1. 3 time weekly ciprofloxacin 500mg
2. Trimethropim-sulfamethoxazole regular strength tablet daily.
-If therapy fails with these regimens, chronic suppressive therapy may be used or surgery considered.

Front 93

What are the injectable forms of testosterone available?

Back 93

testosterone cypionate and testosterone enanthate

Front 94

What labs should be done to monitor long term testosterone therapy?

Back 94

a. testosterone levels – injectable and patch therapy dosing should be adjusted after assessing a serum testosterone level after approximately one to two months of therapy. The usual normal range for serum testosterone is 400-930 ng/dL.
b. hematocrit – testosterone may increase this value
c. serum lipid values – testosterone may elevate total and LDL cholesterol values
d. liver function tests – some testosterone produce may cause liver damage
e. prostate-specific antigen (PSA) and digital rectal examination (DRE) – some testosterone products may aggravate existing prostate disease