• Clinical science

Phosphodiesterase inhibitors

Summary

Phosphodiesterase inhibitors (PDE inhibitors) are a class of drugs that inhibit phosphodiesterase enzymes (PDE enzymes). PDE enzymes normally break off phosphate groups and decrease cAMP or cGMP in target cells. PDE inhibitors are classified according to which enzyme(s) they act upon as nonspecific, PDE5, PDE4, and PDE3 inhibitors. PDE5 inhibitors cause pulmonary vasodilation and penile smooth muscle relaxation, and are used for pulmonary hypertension and erectile dysfunction. PDE4 inhibitors enable bronchial dilation in severe COPD. PDE3 inhibitors have positive inotropic, vasodilator, and antiplatelet effects, which are used in acute heart failure and in peripheral vascular disease. PDE3 inhibitors are not recommended for long-term use in patients with heart failure because of their strong cardiostimulatory effects. Nitrates or alpha-blockers are strongly contraindicated in patients taking PDE5 inhibitors because of the risk of life-threatening hypotension.

Pharmacodynamics

Phosphodiesterase (PDE) inhibitors are a heterogenic class of drugs that target various isoforms of PDE enzymes. Normally, the PDE decreases cAMP or cGMP in target cells by catalyzing the hydrolysis of these second messengers. By inhibiting this step, PDE inhibitors actually increase cAMP and/or cGMP concentrations. They are classified according to their target isoforms as nonspecific, PDE5, PDE4, and PDE3 inhibitors, each of which has a different clinical use.

Phosphodiesterase inhibitors

Types Active ingredient Indications Mechanism of Action Desired effect

Nonspecific phosphodiesterase inhibitors

(inhibitors of PDE3, 4, and 5)

  • Inhibition of proinflammatory mediators
  • Deceleration of fibrotic changes in the lung
  • Relaxation of the bronchial musculature bronchodilation

Phosphodiesterase type 5 inhibitor

(PDE5 inhibitor)

  • PDE5 inhibition → ↓ breakdown of cGMPcGMP smooth muscle relaxation in reaction to nitrous oxide activation → pulmonary vasodilation, penile smooth muscle relaxation, and increased blood flow
  • Inhibition of proinflammatory mediators
  • Deceleration of fibrotic changes in the lung
  • Relaxation of the bronchial musculature

Phosphodiesterase type 4 inhibitor

(PDE4 inhibitor)

Phosphodiesterase type 3 inhibitor

(PDE3 inhibitor)

  • Intermittent vascular claudication
  • Antiplatelet (antianginal, TIA/stroke prevention)
  • Coronary stent restenosis prophylaxis

Sildenafil, tadalafil, avanafil, and vadenafil are the first-line therapy for filling the corpus cavernosum.

References:[1][2][3]

Adverse effects

References:[1][4][5][7]

We list the most important adverse effects. The selection is not exhaustive.

Contraindications

Because of their vasodilatory and arrhythmogenic effects, PDE inhibitors have a number of contraindications:

Patients being treated with PDE5s should not receive nitrates in unstable angina pectoris, acute coronary syndrome, or myocardial infarction because this could result in a life-threatening decrease in blood pressure!

References:[1][4][9][8]

We list the most important contraindications. The selection is not exhaustive.