PDE-5 Inhibitors (Sildenafil, Vardenafil, Tadalafil)

Summary

PDE-5 inhibitors are a group of drugs ending in the common suffix “-afil”, including Sildenafil, Vardenafil, and Tadalafil. These drugs work by inhibiting the phosphodiesterase-5 enzyme, increasing levels of cyclic GMP and causing vasodilation through nitric oxide. This vasodilation induced by PDE-5 inhibitors is useful for the treatment of erectile dysfunction and pulmonary hypertension. However, systemic vasodilation may also lead to the side effect of life-threatening hypotension, especially when taken with nitrates.

Key Points

• PDE-5 inhibitors
  • Drug Names
    • - “fil” suffix (Sildenafil, Vardenafil, Tadalafil)
  • Mechanism
    • Inhibit phosphodiesterase inhibitors-5 (PDE-5) →  increased cyclic GMP
      • PDE5 inhibitors reduce degradation of cGMP, which enhances vasodilation of nitric oxide (NO)
  • Indications
    • Erectile dysfunction 
      • Increase vasodilatory effects increase blood flow to penis causing erections
    • Pulmonary hypertension
      • Increase vasodilatory effects reduce vascular resistance in lung, improving symptoms
    • Benign Prostatic Hyperplasia
      • Tadalafil used in this context to improve urine output
  • Adverse Effects
    • Causes Hypotension
      • Systemic vasodilation by NO reduces systemic vascular resistance, which can cause a precipitous drop in blood pressure
      • Absolute contraindication with nitrates
        • Nitrates are converted into NO to function, which acts synergistically with PDE5 inhibitors to cause life-threatening hypotension
    • Causes Cyanopia (blue-tinted vision)
    • Causes Headache, flushing, dyspepsia also seen