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

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 2

Treatment for ED Drugs Psychotherapy Oral agents: PDE5 inhibitors Sildenafil, vardenafil, and tadalafil Nonoral agents Papaverine plus phentolamine, and alprostadil Psychotherapy Surgical implantation of penile prosthesis 3

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 4

Sildenafil (Viagra) Adverse effects Hypotension- small reduction in BP, much greater if other vasodilators are on board 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 5

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 6

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 7

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 8

Tadalafil (Cialis) Adverse effects Drug interactions 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]) 9

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 10

Benign Prostatic Hyperplasia Signs and symptoms Straining to void Postvoid dribbling Decreased force and caliber of the urinary stream Sensation of incomplete bladder emptying 11

Benign Prostatic Hyperplasia Treatment modalities Surgery Watchful waiting Drug therapy 5-Alpha-reductase inhibitors (mechanical obstruction) Finasteride Dutasteride Alpha1-adrenergic antagonists (dynamic obstruction) 12

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) 13

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) 14

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 15

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 16

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 17