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# PDE4 inhibitors

Oral anti-inflammatories that block phosphodiesterase 4 in immune cells; roflumilast reduces exacerbations of severe COPD with chronic bronchitis.

Updated Nov 1, 2026

## 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)

## Key points

- Roflumilast is not a bronchodilator and never treats acute bronchospasm.
- Indication: severe COPD with chronic bronchitis and a history of exacerbations, added to bronchodilators.
- Adverse effects: diarrhoea, nausea, weight loss, insomnia, headache; psychiatric events including suicidality.
- Contraindicated in moderate to severe liver impairment; strong CYP inducers make it ineffective.

## Drugs in this class

- [**Roflumilast** An oral PDE4 inhibitor that reduces flare-ups of severe COPD with chronic bronchitis; it is not a bronchodilator. Phosphodiesterase 4 (PDE4B, PDE4D)](https://durgical.com/en/pharmacology/roflumilast/)
- [**Apremilast** An oral PDE4 inhibitor that calms immune cells, used in psoriatic arthritis, plaque psoriasis and the mouth ulcers of… Phosphodiesterase 4 (cAMP-specific)](https://durgical.com/en/pharmacology/apremilast/)

## 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.

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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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aaa81c1b-f63d-4e61-8bfa-9d42d92043c7) (DailyMed (U.S. National Library of Medicine), 2026); [Roflumilast: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a611034.html) (MedlinePlus (U.S. National Library of Medicine), 2016).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/pde4-inhibitors/