Phosphodiesterase inhibitors

Theophylline

Aminophylline

Nonspecific phosphodiesterase inhibitors

(inhibitors of PDE3, 4, and 5)

• COPD (severe and refractory cases)

• Asthma

• Nonspecific PDE inhibition → ↓ hydrolysis of cAMP → ↑ cAMP levels

• Adenosine receptor blockade

• Inhibition of proinflammatory mediators

• Deceleration of fibrotic changes in the lung

• Relaxation of the bronchial musculature → bronchodilation

• Headaches, cutaneous flushing

• Lightheadedness

• Sildenafil: visual deficits (blue-tinted vision, or cyanopia) due to PDE-6 inhibition in the retina [6]

• Runny nose, nasal congestion

• Exanthema

• Dyspepsia

• Rarely: myocardial infarction, stroke, hearing loss, optic neuropathy

• GI upset (nausea, abdominal pain)

• Weight loss

• Mental disorders: sleep disturbances, anxiety, depression

• Tachycardia, ventricular arrhythmias (most common and severe side effect, so not recommended for chronic use)

• Headaches, nausea

• Hypotension

• Gastrointestinal upset

• Facial flushing

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

• Theophylline

  • Damaged cardiac muscle (e.g., following myocardial infarction)

  • Significant risk of drug interactions (e.g., ciprofloxacin, cimetidine)