PDE4 inhibitors
Oral anti-inflammatories that block phosphodiesterase 4 in immune cells; roflumilast reduces exacerbations of severe COPD with chronic bronchitis.
What they are
Phosphodiesterase 4 is the main enzyme that breaks down cyclic AMP in neutrophils, macrophages, T cells and epithelial cells. Selective PDE4 inhibitors raise cyclic AMP there and calm inflammation without being bronchodilators. Roflumilast (oral) is used in severe COPD with chronic bronchitis and frequent exacerbations; apremilast (psoriasis, psoriatic arthritis) and topical crisaborole and roflumilast (skin) belong to the same family. Gastrointestinal effects, weight loss, insomnia and mood changes limit their use.
Mechanism of action
By blocking PDE4, these drugs keep cyclic AMP high inside inflammatory cells. Protein kinase A then reduces the release of cytokines such as TNF-alpha, the recruitment of neutrophils and the production of mucus-related mediators. The effect is slow and anti-inflammatory; airway muscle tone hardly changes. PDE4 in the brain's vomiting centre explains nausea.
Target: Phosphodiesterase 4 (PDE4B and PDE4D)
Drugs in this class
- RoflumilastAn oral PDE4 inhibitor that reduces flare-ups of severe COPD with chronic bronchitis; it is not a bronchodilator.Phosphodiesterase 4 (PDE4B, PDE4D)
- ApremilastAn oral PDE4 inhibitor that calms immune cells, used in psoriatic arthritis, plaque psoriasis and the mouth ulcers of…Phosphodiesterase 4 (cAMP-specific)
Others in the class
- Apremilast
- Crisaborole (topical)
Test yourself
Think of the answer, then tap the question to see it.
Which second messenger rises in inflammatory cells when PDE4 is blocked?
Cyclic AMP.
Which COPD patients are candidates for roflumilast?
Severe COPD with chronic bronchitis and frequent exacerbations despite bronchodilators.
What should be watched in weight and mood during roflumilast treatment?
Weight loss and new or worse depression, insomnia or suicidal thoughts.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - ROFLUMILAST tablet (DailyMed (U.S. National Library of Medicine), 2026); Roflumilast: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2016).
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Representative model, for educational purposes only.