Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 66

Drugs for Erectile Dysfunction and Benign Prostatic Hyperplasia

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Erectile Dysfunction ED, also known as impotence

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

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Treatment for ED Drugs

Oral agents: PDE5 inhibitors• Sildenafil, vardenafil, and tadalafil

Nonoral agents• Papaverine plus phentolamine, and alprostadil

Psychotherapy Surgical implantation of penile prosthesis

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Sildenafil (Viagra) Phosphodiesterase type 5 (PDE5) inhibitor I First oral agent for ED: introduced in 1998 Generally well tolerated

Can be dangerous if used concurrently with certain vasodilators (alpha-adrenergic blockers and nitrates)

ED effects discovered by accident Originally developed as cardiac medicine

Only enhances normal erectile response in the presence of stimuli No significant impact on men who do not have ED Not approved for women Approved in 2005 as Revatio to treat pulmonary arterial

hypertension

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Sildenafil (Viagra) Adverse effects

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) Absorption slowed by high-fat meals Drug interactions

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

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Sildenafil (Viagra) Drug should be used with caution by men

with the following conditions: 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) PDE5 inhibitor II Relaxes arterial and trabecular smooth

muscle in the penis 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)

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Vardenafil (Levitra) Drug interactions

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

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Tadalafil (Cialis) PDE5 inhibitor II

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

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Tadalafil (Cialis) Adverse effects

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])

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Other Drugs for ED Treatment Papaverine (smooth muscle relaxant) plus

phentolamine (alpha-adrenergic blocking agent) 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

Alprostadil (prostaglandin E1) 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 Adverse effects

• Burning sensations, prolonged erection, priapism, and penile fibrosis

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 Nonmalignant prostate enlargement Caused by excessive growth of epithelial

(glandular) cells and smooth muscle cells Signs and symptoms

Urinary hesitancy Urinary urgency Increased frequency of urination Dysuria Nocturia

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Benign Prostatic Hyperplasia Signs and symptoms

Straining to void Postvoid dribbling Decreased force and caliber of the urinary stream Sensation of incomplete bladder emptying

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Benign Prostatic Hyperplasia Treatment modalities

Surgery Watchful waiting Drug therapy 5-Alpha-reductase inhibitors (mechanical

obstruction)• Finasteride• Dutasteride

Alpha1-adrenergic antagonists (dynamic obstruction)

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Finasteride (Proscar) 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

Decreases ejaculate volume and libido Gynecomastia Decreases levels of prostate-specific antigen

(PSA)

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Dutasteride (Avodart) Inhibits 5-alpha-reductase Similar to finasteride but with three

differences: 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

Four are approved for the treatment of BPH: 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

Impact on blood pressure 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

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Alpha1-Adrenergic Antagonists

Adverse effects 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

These drugs do not decrease PSA levels

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Alpha1-Adrenergic Antagonists

Drug interactions Exercise caution with other blood pressure–

lowering medications Organic nitrates, antihypertensive drugs, PDE5

inhibitors used for ED Inhibitors of CYP3A4

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Other Drugs for BPH Saw palmetto

Used widely Effectiveness not supported

Tolterodine (Detrol) PDE5 inhibitors Botulinum toxin