Daliresp and Phosphodiesterase-4 Inhibitors for COPD

Indications, Benefits and Side Effects of Treatment

Understanding photphodiesterase-4-inhibitors like Daliresp. Istockphoto.com/Stock Photo©endopack

Definition:  Phosphodiesterase-4-Inhibitors (PDE4)

Phosphodiesterase-4-inhibitors (PDE4) such as Daliresp (roflumilast) are a new category of drug for chronic obstructive pulmonary disease (COPD) and other lung diseases.  These drugs work to suppress inflammation in the airways for people who are resistant to standard treatment.  Daliresp (roflumilast) is the only PDE4 inhibitor currently approved in the United States.

How Phosphodiesterase-4-Inhibitors Work

Medications such as Daliresp work by blocking the effects of phosphodiesterase 4, and enzyme that works to  break down a molecule called cyclic adenosine monophosphate (cAMP.)  The resultant increase in cAMP (because it's not broken down by phosphodiesterase 4) acts to decrease inflammation in the lungs among other things.

A hallmark of COPD is chronic inflammation, and people with COPD and asthma often have an overproduction of PDE4 contributing to this inflammation.

By decreasing inflammation, medications such as Daliresp may decrease the mucus overproduction characteristic of COPD, and decrease airway remodeling.

What Do PDE4 Inhibitors Do?

By increasing cAMP levels and decreasing inflammation, PDE4 inhibitors can decrease the number of COPD exacerbations and improve the function of the lungs.  Through increasing cAMP they may also cause some bronchodilation.

  It's important to note that these drugs do not repair the lungs, they work instead to decrease inflammation and prevent further damage and exacerbation of symptoms.

Conditions Where Daliresp (Roflumilast) May Be Used

Conditions for which Daliresp may be used include:

  • COPD
  • Asthma
  • Psoriasis
  • Psoriatic arthritis

    When are They Used?

    PDE4 inhibitors such as Daliresp are used to improve lung function in people with stable COPD who are resistant to standard treatment.

    With COPD they appear to be of most benefit to people with chronic bronchitis who have frequent exacerbations of their disease.

    Since these drugs work on chronic inflammation, the aren't used for acute attacks of COPD or asthma, but rather for chronic maintenance of the disease.

    Unlike inhaled bronchodilators, Daliresp is a once daily, oral medication that has been found to improve lung function in patients treated with salmeterol and Spiriva (tiotropium.)

    The effect of PDE4 inhibitors appears to be additive with corticosteroids.

    Side Effects

    The main side effects of PDE4 inhibitors include diarrhea, nausea, and headaches.  It may cause weight loss, so weight should be monitored during treatment, and has caused psychological symptoms for some people.

    Interactions

    Due to its metabolism by cytochrome P-450, PDE4 inhibitors may interfere (increase or decrease) other medications also metabolized in this way, for example, medications such as erythromycin, cimetidine, birth control pills, some seizure medications, and more.

    Also Known As: PDE4, selective phosphodiesterase-4 inhibitors

    Sources:

    Ferguson, G., and B. Make. Management of stable chronic pulmonary obstructive disease. UpToDate. Updated 01/21/16.

    Mulhall, A., Droege, C., Ernst, N., Panos, R., and M. Zafar. Phosphodiesterase 4 inhibitors for the treatment of chronic obstructive pulmonary disease: a review of current and developing drugs. Expert Opinion on Investigational Drugs. 2015. 24(12):1597-611.

    Reid, D., and N. Pham. Rofluimilast: a novel treatment for chronic obstructive pulmonary disease. Annals of Pharmacotherapy. 2012. 46(4):521-9.

    U.S. National Library of Medicine. MedlinePlus. Roflumilast. Updated 08/15/12. https://www.nlm.nih.gov/medlineplus/druginfo/meds/a611034.html

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