PDE-5 Inhibitors (Sildenafil, Vardenafil, Tadalafil)



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