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Phosphodiesterase inhibitors

Last updated: April 10, 2021

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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.

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)

  • Sildenafil
  • Tadalafil
  • Avanafil
  • Vardenafil
  • Inhibition of proinflammatory mediators
  • Deceleration of fibrotic changes in the lung
  • Relaxation of the bronchial musculature

Phosphodiesterase type 4 inhibitor

(PDE4 inhibitor)

  • Roflumilast

Phosphodiesterase type 3 inhibitor

(PDE3 inhibitor)

  • Milrinone
  • Amrinone
  • Enoximone
  • Cilostazol
  • Dipyridamole

SildenaFIL, tadalaFIL, avanaFIL, and vadenaFIL: FIrst-Line therapy for FILling the corpus cavernosum

References:[1][2][3]

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

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

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][8][9]

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

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  9. FDA Announces Revisions to Labels for Cialis, Levitra and Viagra Potential risk of sudden hearing loss with ED drugs to be displayed more prominently.