Chapter 66
Drugs for Erectile Dysfunction and
Benign Prostatic Hyperplasia
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Erectile Dysfunction
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ED, also known as impotence
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Persistent inability to achieve or sustain an
erection suitable for satisfactory sexual
performance
Affects up to 30 million men
ED commonly associated with chronic
illnesses
Risk for ED increases with advancing age
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Treatment for ED
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Drugs
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Oral agents: PDE5 inhibitors
• Sildenafil, vardenafil, and tadalafil
Nonoral agents
• Papaverine plus phentolamine, and alprostadil
Psychotherapy
Surgical implantation of penile prosthesis
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Sildenafil (Viagra)
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Phosphodiesterase type 5 (PDE5) inhibitor I
First oral agent for ED: introduced in 1998
Generally well tolerated
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ED effects discovered by accident
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Can be dangerous if used concurrently with certain
vasodilators (alpha-adrenergic blockers and nitrates)
Originally developed as cardiac medicine
Only enhances normal erectile response in the
presence of stimuli
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No significant impact on men who do not have ED
Not approved for women
Approved in 2005 as Revatio to treat pulmonary arterial
hypertension
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Sildenafil (Viagra)
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Adverse effects
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Hypotension
Priapism
Headache, dyspepsia, flushing, nasal congestion,
diarrhea, rash, dizziness, mild transient visual
disturbances, intensification of obstructive sleep
apnea
Rare side effects
• Nonarteritic ischemic optic neuropathy
• Sudden hearing loss
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Sildenafil (Viagra)
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Absorption slowed by high-fat meals
Drug interactions
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Nitrates
• Could cause life-threatening hypotension
• 24 hours in between these medications for safety
Alpha blockers
• Can cause symptomatic postural hypotension
Inhibitors of cytochrome P450 (CYP3A4)
• Can suppress metabolism of sildenafil
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Sildenafil (Viagra)
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Drug should be used with caution by men
with the following conditions:
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MI, stroke, and life-threatening dysrhythmia within
the last 6 months
Resting hypotension (BP below 90/50 mm Hg)
Resting hypertension (BP above 170/110 mm Hg)
Heart failure
Unstable angina
Sildenafil should not be used at all by men
taking nitroglycerin or any other drug in the
nitrate family
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Vardenafil (Levitra)
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PDE5 inhibitor II
Relaxes arterial and trabecular smooth
muscle in the penis
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Adverse effects
• Headache and flushing
• Rhinitis and dyspepsia
• Can prolong QT interval
• Can lower blood pressure
• Can also be associated with sudden hearing loss and
vision loss from nonarteritic ischemic optic neuropathy
(NAION)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Vardenafil (Levitra)
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Drug interactions
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Nitrates
• Could cause life-threatening hypotension
• 24 hours in between these medications for safety
Alpha blockers
• Can cause symptomatic postural hypotension
Inhibitors of cytochrome P450 (CYP3A4)
• Can suppress metabolism of vardenafil
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Tadalafil (Cialis)
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PDE5 inhibitor II
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Relaxes penile and arterial and trabecular smooth
muscle
Effects last up to 36 hours (longest of the three
PDE5 inhibitors)
Also now approved for daily dosing if activity
anticipated twice weekly
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Tadalafil (Cialis)
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Adverse effects
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Headache, dyspepsia, back pain, myalgia, limb
pain, flushing, nasal congestion
Can also be associated with sudden hearing loss
and vision loss from NAION
Drug interactions


Nitrates
Alpha blockers (except tamsulosin [Flomax])
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Other Drugs for ED Treatment

Papaverine (smooth muscle relaxant) plus
phentolamine (alpha-adrenergic blocking
agent)
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Increased arterial flow and decreased venous
outflow in the penis
Used to counteract impotence
Administration
• Injected directly into the corpus cavernosum
Adverse effects
• Priapism
• Painless fibrotic nodules in the corpus cavernosum
• Orthostatic hypotension with dizziness
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Other Drugs for ED Treatment
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Alprostadil (prostaglandin E1)
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Administration
• Injected directly into the corpus cavernosum
• Increased arterial flow and decreased venous outflow in
the penis
• Should not be used more than 3 times per week or once
in 24 hours
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Adverse effects
• Burning sensations, prolonged erection, priapism, and
penile fibrosis
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Transurethral—alprostadil pellets (Muse)
• Do not use more than twice in 24 hours
• No priapism or penile fibrosis
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Benign Prostatic Hyperplasia
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Nonmalignant prostate enlargement
Caused by excessive growth of epithelial
(glandular) cells and smooth muscle cells
Signs and symptoms
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Urinary hesitancy
Urinary urgency
Increased frequency of urination
Dysuria
Nocturia
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Benign Prostatic Hyperplasia
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Signs and symptoms
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Straining to void
Postvoid dribbling
Decreased force and caliber of the urinary stream
Sensation of incomplete bladder emptying
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Benign Prostatic Hyperplasia
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Treatment modalities
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Surgery
Watchful waiting
Drug therapy
5-Alpha-reductase inhibitors (mechanical
obstruction)
• Finasteride
• Dutasteride
Alpha1-adrenergic antagonists (dynamic
obstruction)
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Finasteride (Proscar)
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Inhibits 5-alpha-reductase
Most effective in patients with a very large
prostate (mechanical obstruction)
Also sold at lower dosages as Propecia for
male pattern baldness
Adverse effects
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Decreases ejaculate volume and libido
 Gynecomastia
 Decreases levels of prostate-specific antigen
(PSA)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Dutasteride (Avodart)
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Inhibits 5-alpha-reductase
Similar to finasteride but with three
differences:
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Reduction in circulating DHT is more complete
Harmful to a developing male fetus
Extremely long half-life (5 weeks)
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Alpha1-Adrenergic Antagonists
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Four are approved for the treatment of BPH:
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Terazosin (Hytrin)
Doxazosin (Cardura)
Tamsulosin (Flomax)
Alfuzosin (Uroxatral)
Blockade of alpha1 receptors relaxes smooth
muscle in the bladder neck (trigone and
sphincter)
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Alpha1-Adrenergic Antagonists
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Impact on blood pressure
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Tamsulosin (Flomax) and alfuzosin (Uroxatral)
• Selective for alpha1 receptors in the prostate
Terazosin (Hytrin) and doxazosin (Cardura)
• Also block alpha receptors in the blood vessels
• Promote vasodilation and can lower blood pressure
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Alpha1-Adrenergic Antagonists
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Adverse effects
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Tamsulosin (Flomax) and alfuzosin (Uroxatral)
• Less likely to cause the effects of terazosin and
doxazosin
• Tamsulosin can cause abnormal ejaculation

Terazosin (Hytrin) and doxazosin (Cardura)
• Hypotension, fainting, dizziness, somnolence, and nasal
congestion
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These drugs do not decrease PSA levels
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Alpha1-Adrenergic Antagonists
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Drug interactions
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Exercise caution with other blood pressure–
lowering medications
Organic nitrates, antihypertensive drugs, PDE5
inhibitors used for ED
Inhibitors of CYP3A4
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Other Drugs for BPH
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Saw palmetto
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Used widely
Effectiveness not supported
Tolterodine (Detrol)
PDE5 inhibitors
Botulinum toxin
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