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Phosphodiesterase Inhibitor

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Phosphodiesterase Inhibitor, Phosphodiesterase 5 Inhibitor, PDE5 Inhibitor, Avanafil, Stendra

  • Preparations
  1. All agents are very expensive (except generic Sildenafil which costs $1/pill)
  2. Sildenafil (Viagra)
  3. Vardenafil (Levitra, Staxyn)
  4. Tadalafil (Cialis)
  5. Avanafil (Stendra)
    1. Released in 2014 with similar activity as Viagra (onset in 30 minutes and duration for 5 hours)
    2. Similar Drug Interactions as for Vardenafil (Levitra, Staxyn)
  • Indications
  1. Psychogenic Impotence
  2. Neurogenic Impotence
  3. Vasculogenic Impotence
  • Contraindications
  1. Absolute Contraindications
    1. Men using nitrates (causes profound Hypotension)
    2. Men using alpha blockers (e.g. Hytrin for BPH)
  2. Relative Contraindications
    1. Active coronary ischemia in men not on nitrates
    2. Congestive Heart Failure
      1. Borderline low Blood Pressure
      2. Bordrline low volume status
    3. Multidrug antihypertensive regimen
    4. Taking Cytochrome P450-3A4 (CYP3A4) inhibitor
  3. Areas where PDE5 agents may be used safely
    1. Safe in stable coronary disease (no nitrates)
      1. Debusk (2004) Am J Cardiol 93:147-53 [PubMed]
  • Mechanism
  1. Phosphodiesterase Type 5 Inhibitor
    1. Phosphodiesterase Type 5 causes Erection to subside
  2. Blocks Phosphodiesterase Type 5
    1. Results in enhanced Erection if man is aroused
    2. Unlike Alprostadil, will not cause Erection
  3. Enhances vasodilating effect of Nitrous Oxide
    1. Normally released during sexual stimulation
  • Efficacy
  1. Benefits those with organic and psychological Impotence
  2. Initial studies showed improved Erections in 70%
  3. Over Placebo, 3.6 times more likely to improve Erection
    1. Burls (2001) Br J Gen Pract 51:1004-12 [PubMed]
  • Drug Interactions
  1. Decreased effect (or delayed affect) after a fatty meal (esp. Sildenafil, Verdenafil)
  2. Inhibit breakdown of Viagra via Cytochrome P3A4
    1. Cimetidine (Tagamet)
    2. Ketoconazole (Nizoral)
    3. Itraconazole (Sporonox)
    4. Mibefradil (Posicor)
    5. Protease Inhibitors (Ritonavir, Indinavir, Saquinavir, Atazanavir)
    6. Macrolides (Clarithromycin, Erythromycin)
  3. Profound Vasodilitation and Hypotension (Avoid)
    1. Nitroglycerin and other Nitrates
    2. Alpha-blockers (Flomax or Tamsulosin may be used instead)
      1. Uroxatral
      2. Doxazosin
      3. Terazosin
      4. Prazosin
  • Adverse Effects
  • Viagra (but most apply to the PDE5 Class as a whole)
  1. Hypotensive effect for men on Nitrates (Avoid)
  2. Vision effects
    1. Temporary color vision disturbance (6%)
      1. Blue colors may appear to be green
    2. Blurred vision or Vision Loss
      1. Higher risk if atherosclerosis
      2. Rare occurence, but can be permanent
      3. Appears to occur with Levitra and Cialis as well
  3. Mild Headache (21%)
  4. Facial Flushing (27%)
  5. Indigestion or Dyspepsia (11%)
  6. Myalgias
  7. Does not cause Priapism
  8. Sensorineural Hearing Loss
    1. Sudden onset and permanent Hearing Loss
    2. McGwin (2010) Arch Otolaryngol Head Neck Surg 136(5):488-49 [PubMed]