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

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 2

3. 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

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 4

5. 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

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 6

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 7

8. 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

9. 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

10. 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

11. 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

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

13. 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

14. 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

15. 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

16. 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

17. 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