- Clinical science
Phosphodiesterase inhibitors (PDE inhibitors) are a class of drugs that inhibit phosphodiesterase enzymes (PDEs). PDEs 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.
|Active ingredient||Indications||Mechanism of Action||Desired effect|
Nonspecific phosphodiesterase inhibitors
(inhibitors of PDE3, -4 and -5)
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- Nonspecific phosphodiesterase inhibitors
- Phosphodiesterase type 5 inhibitors.
Phosphodiesterase type 4 inhibitors
- GI upset (nausea, abdominal pain)
- Weight loss
- Mental disorders: sleep disturbances, anxiety, depression
- Phosphodiesterase type 3 inhibitors
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:
Phosphodiesterase type 5 inhibitors
Nitrates: Use of PDE5 inhibitors with nitrates can result in life-threatening hypotension.
- Both nitrates (e.g., sublingual nitroglycerin) and PDE-5-inhibitors (e.g., vardenafil) function by increasing cGMP concentration → cGMP leads to activation of myosin-light-chain phosphatase (MLCP) → dephosphorylates light chains of myosin → smooth muscle cell relaxation in blood vessels → vasodilation
- Alpha-blockers: Use of PDE5 inhibitors with alpha-blockers can also result in hypotension
- Nitrates: Use of PDE5 inhibitors with nitrates can result in life-threatening hypotension.
Phosphodiesterase type 3 inhibitors
- Severe obstructive cardiomyopathy or ventricular aneurysm
Patients being treated with PDE5s should not receive nitrates in unstable angina pectoris, acute coronary syndrome, and myocardial infarction because of the risk of a life-threatening decrease in blood pressure!
We list the most important contraindications. The selection is not exhaustive.