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Chapter 66

Chapter 66. Drugs for Erectile Dysfunction and Benign Prostatic Hyperplasia. Erectile Dysfunction. ED, a lso known as impotence Persistent inability to achieve or sustain an erection suitable for satisfactory sexual performance Affects up to 30 million men

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Chapter 66

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  1. Chapter 66 Drugs for Erectile Dysfunction and Benign Prostatic Hyperplasia

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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

  10. 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

  11. 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])

  12. 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

  13. 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

  14. 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

  15. Benign Prostatic Hyperplasia • Signs and symptoms • Straining to void • Postvoid dribbling • Decreased force and caliber of the urinary stream • Sensation of incomplete bladder emptying

  16. Benign Prostatic Hyperplasia • Treatment modalities • Surgery • Watchful waiting • Drug therapy • 5-Alpha-reductase inhibitors (mechanical obstruction) • Finasteride • Dutasteride • Alpha1-adrenergic antagonists (dynamic obstruction)

  17. 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)

  18. 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)

  19. 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)

  20. 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

  21. 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

  22. 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

  23. Other Drugs for BPH • Saw palmetto • Used widely • Effectiveness not supported • Tolterodine (Detrol) • PDE5 inhibitors • Botulinum toxin

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