556 - Pharmacotherapy Ii - Exam Ii - Erectile Dysfunction

Front 1

What are four common etiologies of erectile dysfunction?

Back 1

Vascular, Neurologic, Hormonal, or Phychogenic. [Of these, the first three, considered “organic” account for 80% of reported ED cases, while psychogenic causes constitute the remaining 20%.]

Front 2

List five patient populations at high risk of erectile dysfunction.

Back 2

1) Patients who have had a radical prostatectomy, 2) Patients who have had cancer treatment, 3) Patients with spinal cord injuries, 4) Low testosterone, & 5) Patients taking medications having ED as an adverse drug reaction.

Front 3

List eleven classes of drugs reported to cause erectile dysfunction.

Back 3

1) Diuretics, 2) Antihypertensive Agents, 3) Cardiac or Cholesterol Drugs, 4) Antidepressants, 5) H2-Receptor Antagonists, 6) Hormones, 7) Chemotherapeutic Agents, 8) Recreational Drugs, 9) Anticholinergic Agents, 10) Antipsychotics, & 11) Anti-Androgens

Front 4

What class of drugs are considered first line therapy for the treatment of erectile dysfunction?

Back 4

Phosphodiesterase-5 (PDE-5) Inhibitors

Front 5

According to Professor Dopp, what are the important aspects to remember regarding the mechanism of action for the Phosphodiesterase-5 Inhibitors?

Back 5

It inhibits an enzyme that break downs cGMP allowing cGMP to accumulate and facilitate smooth muscle relaxation, amplifying the signal for patients who have a low nitric oxide signal, whether that issue arises from vascular origins or nerve problems or other reasons.

Front 6

Which PDE-5 Inhibitors have significantly decreased absorption when taken with food and which are relatively unaffected?

Back 6

Sildenafil and vardenafil have significantly decreased absorption (dosing should be separated from food by 2 hrs). Absorption of tadalafil and avanafil are relatively unaffected by food.

Front 7

What enzyme is responsible for hepatic metabolism of the PDE-5 inhibitors?

Back 7

CYP3A4

Front 8

What is the half-life of sildenafil? What is its duration of action?

Back 8

Half-life: 3.7 hrs; Duration of Action: 4 to 5 hrs

Front 9

What is the half-life of vardenafil? What is its duration of action?

Back 9

Half-life: 3.3 to 3.9 hrs; Duration of Action: 4 to 5 hrs

Front 10

What is the half-life of tadalafil? What is its duration of action?

Back 10

Half-life: 17.5 hrs; Duration of Action: Up to 36 hrs

Front 11

What is the half-life of avanafil? What is its duration of action?

Back 11

Half-life: 5 hrs; Duration of Action: Up to 6 hrs

Front 12

What is the Tmax of sildenafil, of vardenafil, of tadalafil, and of avanafil?

Back 12

Sildenafil = 50 min, Vardenafil = 1 hr, Tadalafil = 2 hrs, & Avanafil = 30 to 45 min

Front 13

Which PDE-5 inhibitors are reported to have adverse drug events associated with inhibition of the type 1A, 1B, & 1C isozymes of phosphodiesterase? How do the relative selectivities of the PDE-5 inhibitors differentiate the likelihood of these adverse effects among these agents?

Back 13

Sildenafil and vardenafil may cause vasodilation, tachycardia, and flushing. Tadalafil and avanafil have a much higher relative selectivity for the type 5 isozyme vs. type 1 isozymes, so they are less likely to cause such effects.

Front 14

Which PDE-5 inhibitors are reported to have adverse drug events associated with inhibition of the type 6 isozyme of phosphodiesterase? How do the relative selectivities of the PDE-5 inhibitors differentiate the likelihood of these adverse effects among these agents?

Back 14

Sildenafil and vardenafil may cause visual disturbances (patients report seeing blue). Avanafil has a higher relative selectivity for the type 5 isozyme vs. type 6, so it is less likely to cause such effects, and the selectivity of tadalafil for type 5 vs. type 6 is higher still, so tadalafil is the least likely to cause visual disturbances.

Front 15

Which PDE-5 inhibitors are reported to have adverse drug events associated with inhibition of type 11 isozymes of phosphodiesterase? How do the relative selectivities of the PDE-5 inhibitors differentiate the likelihood of these adverse effects among these agents?

Back 15

Tadalafil may cause back pain and - absent from lecture notes - alterations in sperm quality. Sildenafil, vardenafil, and especially avanafil have higher relative selectivity for type 5 vs. type 11 isozymes, so they are less likely to have such effects.

Front 16

Which of the PDE-5 inhibitors has the longest duration of action?

Back 16

Tadalafil [May even be taken a day or two before sexual activity.]

Front 17

Which of the PDE-5 inhibitors takes the longest time to take effect?

Back 17

Tadalafil

Front 18

Which PDE-5 inhibitors should be taken on an empty stomach?

Back 18

Sildenafil & Vardenafil

Front 19

What percentage of patients are reported to successfully achieve erection with PDE-5 inhibitors? Is the effect dose-related?

Back 19

70%. And yes, the effect is dose-related.

Front 20

For a patient who does not respond to the first dose, how many subsequent doses should be attempted before a given PDE-5 inhibitor is declared a treatment failure?

Back 20

The drug should be tried at least four times before treatment failure is declared.

Front 21

Describe dosing for sildenafil (Viagra).

Back 21

25 to 100 mg,1 hr before desired effect.

Front 22

What dosage adjustments are required for sildenafil?

Back 22

Limit the dose to 25 mg/day in patients who have severe renal dysfunction or hepatic impairment.

Front 23

Describe dosing for vardenafil (Levitra).

Back 23

2.5 to 20 mg (usually 10 mg), once daily, 1 hr before desired effect.

Front 24

What dosage adjustments are required for vardenafil?

Back 24

Reduce dose with concomitant CYP3A4 inhibitors or in patients who have moderate-severe liver dysfunction.

Front 25

Describe dosing for tadalafil (Cialis).

Back 25

2.5 to 20 mg (usually 10 mg), once daily.

Front 26

What dosage adjustments are required for tadalafil?

Back 26

Reduce dose with concomitant CYP3A4 inhibitors or in patients who have moderate-severe liver dysfunction.

Front 27

Describe dosing for avanafil (Stendra).

Back 27

50 to 200 mg (usually 100 mg)

Front 28

What dosage adjustments are required for avanafil?

Back 28

Reduce dose to 50 mg when using with moderate CYP3A4 inhibitors (erythromycin, diltiazem, fluconazole, verapamil, etc.)

Front 29

Daily administration of a PDE-5 inhibitor may work better than prn use for some patients. Describe four types of patients for whom prn use may not be as effective.

Back 29

1) Diabetic patients, 2) Patients having neurological damage, 3) Patients having severe vascular disease, & 4) Patients have prostate cancer who have undergone radical prostatectomy

Front 30

Which of the PDE-5 inhibitors is the only one currently approved for daily use (2013)?

Back 30

Tadalafil

Front 31

List some common adverse drug events generally associated with PDE-5 inhibitors. (7)

Back 31

Headache, Flushing, Dizziness, Dyspepsia, Nasal Congestion, Altered Vision, Back Pain

Front 32

With what drugs is the concurrent use of PDE-5 inhibitors contraindicated?

Back 32

Nitrates (nitroglycerin, isosorbide dinitrate, etc.), Nicorandil, & Alpha-Blockers (doxazosin & terazosin)

Front 33

What conditions contraindicate use of PDE-5 inhibitors? (3)

Back 33

1) Unstable Coronary Artery Disease, 2) Retinitis Pigmentosa, & 3) Nonarteritic Anterior Ischemic Optic Neuropathy

Front 34

Why are PDE-5 inhibitors contraindicated for use in patients taking alpha-blockers such as doxazosin or terazosin?

Back 34

DPE-5 inhibitors cause some systemic vasodilation. This activates the baroreflex, prompting a sympathetic response to offset the vasodilation. However, if someone is taking an alpha-blocker, it precludes use of their sympathetic nervous system, and norepinephrine, to maintain vascular tone.

Front 35

Generally speaking, what are the guidelines for the treatment of ED in men who have coronary artery disease?

Back 35

Generally speaking, low risk patients may be treated for ED, but those in unstable condition should not. When in doubt, the patient should be evaluated by a cardiologist first.

Front 36

What is the normal range for serum testosterone?

Back 36

300 to 1100 ng/dL