Viagra

1. Viagra Can we turn man into machine?

2. Research Question: • Is Viagra safe and effective for the treatment of erectile dysfunction (ED)?

3. Preview • I. Erectile Dysfunction Review • II. Pre-Viagra Treatments • III. Viagra Background • IV. Viagra Data • V. Review of SE’s and Contraindications • VI. Future Directions • VII. Conclusions

4. Erectile Dysfunction Review • Definition: ED = Impotence = The inability to achieve and maintain a firm erection adequate for sexual intercourse. • For Dx. must be present >6mo. and during at least 50% of attempts. • Prevalence: • 10% across all ages • 52% between ages 50 and 70. • Co-Morbidity: Depression, anxiety, low self esteem.

5. Mechanism of Erection • Add Time Picture

6. Types of Erectile Dysfunction • Psychogenic: >50% of all ED • Neurogenic: Damage/Disease of CNS-PNS • Hormonal: DM, Hypogonadism. . . • Arterial: Insufficiency, Hardening of A’s • Cavernosal: Non-compliant trabeculae • Drug induced: Laundry list in handout.

7. Pre-Viagra Treatments • Oral: Yohimbine, largely inneffective, safe • Injections: Papaverine, Alprostadil • Vacuum: • Surgical Prosthesis Pump: • Failure may mean surgery • Risks of surgery / anesthesia • As so vividly demonstrated, “treatments are invasive and may be ineffective leaving ED as a major clinical problem.”

8. Background on Viagra • Imagine!?! • An oral therapy which would only act in the presence of sexual stimulation. • Developed as an antihypertensive phosphodiesterase (PDE) inhibitor. • The Theory • The Irony • The Money

9. Viagra Mechanism of Action • Add Picture from Computer

10. Viagra Mechanism of Action • Add Time Picture

11. Facts on Viagra • T1/2 = 4 hours • Bioavailability = 40% • Vd = 105L ~ Tissue Deposition • Max • Metabolism = Hepatic p450 system. Start @ 25mg if Hepatic impairment • Geriatrics = 40% Increased {plasma} if > 65 y.o. Start dosing @ 25mg. • Excretion: 80% fecal, 13% urine. Start @25mg if severe renal insufficiency • Effect on Blood Pressure = Mild decrease (Ave. 10mmHg). • Interactions = p450 inhibitors potentiate (Cimetidine, EES, Ketoconazole, Itraconazole • Rifampin stimulates p450 and antagonizes

12. Viagra Study #1: • M. Boolell, S. Gepi-Attee, J.C. Gingell, M.J. Allen, Sildenafil, a novel effective oral therapy for male erectile dysfunction, Brittish Journal of Urology, 78, 257-261, 1996

13. Viagra Data: Study #1 • 12 pts. 36 - 53y.o. w/ Dx. of ED w/o organic cause. • Double blind placebo controlled crossover • 3 Day wash • 2 Phases: • 1 - Placebo, 10, 25, or 50mg Sildenafil -- 30min -- visual/sexual stim -- Rigiscan • 2 - Placebo or 25mg ~2h. prior to sexual activity--Diary maintained - erections graded - 6 mo.

14. Viagra Data: Study #1

15. Viagra Data: Study #1

16. Viagra Data: Study #1

17. Viagra Data: Study #2 • Goldstein I. et. al., Oral Sildenafil in the Treatment of Erectile Dysfunction, New England Journal of Medicine, 338, 20, pp. 1397-1404, May, 1998.

18. Viagra Data: Study #2 • Objective: Assessment of efficacy and safety • 861 pts. >17 y.o. (Mean = 58) w/ Dx. of ED. 6mo. Study • Included Organic (70%), Psychogenic (11%) or Mixed ED (18%). • International Index of Erectile Function (IIEF) • Standard 15Q questionaire used for clinical assessment of ED. • Patients also kept a diary of erectile function (successful attempts, Number of attempts and grading of erections).

19. Viagra Study #2 • Table 2 on overhead - Responses to two questions. • Question #3: “When you attempted sexual intercourse, how often were you able to penetrate your partner?” • Question #4: “During sexual intercourse, how often were you able to maintain your erection after you had penetrated your partner?”

20. Viagra Data: Study #2

21. Viagra Data: Study #2

22. Viagra Data: Study #2

23. Viagra Data: Study #2

24. Viagra Data: Study #2

25. Viagra Side Effects • Cumulative Data Viagra Placebo • Headache 16% 4% • Flushing 10% 1% • Dyspepsia 7% 2% • Nasal Congestion 4% 2% • Urinary Tract Infection 3% 2% • *Visual Changes 3% 0% • Diarrhea 3% 1% • Dizziness 2% 1% • Rash 2% 1% • * Changes in color hue or brightness.

26. Viagra Contraindication • Contraindicated with Nitrates • Potentiates the hypotensive effects leading to an uncontrolled drop in blood pressure. • Includes: NTG, SNP, Isosorbide di / mononitrate, erythatyl tetranitrate, Pentaerythritol tetranitrate.

27. Future Directions • Longer Trials on larger more diverse population. (Which we are going to get). • Thus far, 21 trials similar to those presented • Only up to 6mo. duration. • Used in ~3,500 patients • Benefits in all studies including ED from DM, SC injury, Radical Prostatectomy, TURP, Psychogenic, Drug induced. And in patients w/ CAD, HTN, MDD, s/p CABG.

28. Conclusions • Yes, Viagra appears safe and efficacious to date. • Safe, Effective, Long term studies needed, we’ll see it in a large population. • Don’t forget scenarios such as Phen-Phen • Data may be slightly inflated. • Remember the contraindication. • Start at 25mg if o/ 65y.o., hepatic dysfunction or severe renal insufficiency • It will not work for everyone. Many misconceptions. • Keep current.

29. Humor