Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 66 Drugs for Erectile...
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Transcript of Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 66 Drugs for Erectile...
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 66
Drugs for Erectile Dysfunction and Benign Prostatic Hyperplasia
2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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])
12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Benign Prostatic Hyperplasia
Signs and symptoms Straining to void Postvoid dribbling Decreased force and caliber of the urinary stream Sensation of incomplete bladder emptying
16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Benign Prostatic Hyperplasia
Treatment modalities Surgery Watchful waiting Drug therapy 5-Alpha-reductase inhibitors (mechanical
obstruction)• Finasteride• Dutasteride
Alpha1-adrenergic antagonists (dynamic obstruction)
17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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)
20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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
23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Other Drugs for BPH
Saw palmetto Used widely Effectiveness not supported
Tolterodine (Detrol) PDE5 inhibitors Botulinum toxin