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 Sildenafil, vardenafil, and tadalafil  Nonoral agents Papaverine plus phentolamine, and alprostadil 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 Nonarteritic ischemic optic neuropathy Sudden hearing loss 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 Could cause life-threatening hypotension 24 hours in between these medications for safety 24 hours in between these medications for safety  Alpha blockers Can cause symptomatic postural hypotension Can cause symptomatic postural hypotension  Inhibitors of cytochrome P450 (CYP3A4) Can suppress metabolism of sildenafil 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 Headache and flushing Rhinitis and dyspepsia Rhinitis and dyspepsia Can prolong QT interval Can prolong QT interval Can lower blood pressure Can lower blood pressure Can also be associated with sudden hearing loss and vision loss from nonarteritic ischemic optic neuropathy (NAION) 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 Could cause life-threatening hypotension 24 hours in between these medications for safety 24 hours in between these medications for safety  Alpha blockers Can cause symptomatic postural hypotension Can cause symptomatic postural hypotension  Inhibitors of cytochrome P450 (CYP3A4) Can suppress metabolism of vardenafil 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 Injected directly into the corpus cavernosum  Adverse effects Priapism Priapism Painless fibrotic nodules in the corpus cavernosum Painless fibrotic nodules in the corpus cavernosum Orthostatic hypotension with dizziness Orthostatic hypotension with dizziness

13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Other Drugs for ED Treatment  Alprostadil (prostaglandin E 1 )  Administration Injected directly into the corpus cavernosum Injected directly into the corpus cavernosum Increased arterial flow and decreased venous outflow in the penis 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 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 Burning sensations, prolonged erection, priapism, and penile fibrosis  Transurethral—alprostadil pellets (Muse) Do not use more than twice in 24 hours Do not use more than twice in 24 hours No priapism or penile fibrosis 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 Finasteride Dutasteride Dutasteride  Alpha 1 -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. Alpha 1 -Adrenergic Antagonists  Four are approved for the treatment of BPH:  Terazosin (Hytrin)  Doxazosin (Cardura)  Tamsulosin (Flomax)  Alfuzosin (Uroxatral)  Blockade of alpha 1 receptors relaxes smooth muscle in the bladder neck (trigone and sphincter)

20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Alpha 1 -Adrenergic Antagonists  Impact on blood pressure  Tamsulosin (Flomax) and alfuzosin (Uroxatral) Selective for alpha 1 receptors in the prostate Selective for alpha 1 receptors in the prostate  Terazosin (Hytrin) and doxazosin (Cardura) Also block alpha receptors in the blood vessels Also block alpha receptors in the blood vessels Promote vasodilation and can lower blood pressure Promote vasodilation and can lower blood pressure

21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Alpha 1 -Adrenergic Antagonists  Adverse effects  Tamsulosin (Flomax) and alfuzosin (Uroxatral) Less likely to cause the effects of terazosin and doxazosin Less likely to cause the effects of terazosin and doxazosin Tamsulosin can cause abnormal ejaculation Tamsulosin can cause abnormal ejaculation  Terazosin (Hytrin) and doxazosin (Cardura) Hypotension, fainting, dizziness, somnolence, and nasal congestion Hypotension, fainting, dizziness, somnolence, and nasal congestion  These drugs do not decrease PSA levels

22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Alpha 1 -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