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Phosphodiesterase-4 inhibitors (PDE4 inhibitors) and theophylline aren't considered first-line treatments for COPD, but they may be chosen when other drugs do not offer the relief you need. What should patients be aware of?

Bronchodilators and steroids will be the medications your doctor is most likely to recommend first when it comes to COPD treatment. Two other kinds of medications, phosphodiesterase-4 inhibitors (PDE4 inhibitors for short) and theophylline, are used less often. What should COPD patients know about these drugs if their doctor has just prescribed them? 

What are PDE4 inhibitors, and what should COPD patients know about them?

PDE4 (phosphodiesterase-4) inhibitors do three things — they reduce inflammation, modify the immune system, and actually also have bronchodilatory effects, meaning they open the airways. "Deployed" in the treatment of various inflammatory conditions ranging from ulcerative colitis to psoriatic arthritis, they are prescribed to people with COPD less often.

Though PDE4 inhibitors meet some of the same needs as corticosteroids, their mechanism of action is different — they fight inflammation by inhibiting the action of an inflammatory enzyme called PDE4, hence their name. They can be very helpful for COPD patients who don't tolerate steroids very well, as a maintenance therapy to ease symptoms and reduce the frequency of flare-ups. PDE4 inhibitors are not, however, useful for acute symptoms and cannot act as a "rescue medication". 

At the moment, only one PDE4 inhibitor is approved for the treatment of chronic obstructive pulmonary disease. Daliresp (roflumilast) is taken orally once a day, and patients who take it will also almost always be prescribed an additional bronchodilator. 

The side effects of this medication often subside over time, but can include:

  • Involuntary weight loss
  • Insomnia
  • Gastrointestinal problems such as diarrhea and nausea
  • Headache and dizziness
  • Back pain

Rarer but more serious side effects of PDE4 inhibitors that should cause patients to seek immediate medical attention include depression, anxiety, and suicidality. 

What is theophylline, and what should COPD patients know about it?

Theophylline is a kind of methylxanthine. It acts as a bronchodilator, alleviating shortness of breath, wheezing, and chest tightness, but unlike the inhalers you're probably used to, theophylline is taken orally as a pill, capsule, or syrup. Though it has been around for a long time, theophylline is now considered a third-line treatment for COPD. More recently developed bronchodilators tend to be more effective and better tolerated. 

Theophylline can be considered when other medications have not offered adequate symptom relief, however, as it will bring down inflammation in the lungs and relax the bands of muscles surrounding your lungs. Research has confirmed that this effectively relieves many of the typical symptoms of chronic obstructive pulmonary disease, like shortness of breath and excess air being trapped in the longs. The medication may also have an anti-inflammatory effect. 

People who are prescribed theophylline should be aware that the drug can lead to severe side effects, which is exactly why its popularity in the treatment of COPD has declined. 

Stomach pain, diarrhea, headache, profuse sweating, and insomnia are among the more common side effects of theophylline, but the dru can also lead to more dangerous adverse effects such as:

  • An irregular heartbeat or rapid heartbeat
  • Seizures
  • Vomiting
  • Skin rashes

Even more concerning is the fact that theophylline can cause toxicity when too much is taken, and even after a longer period of using prescribed doses. This is why people with COPD who are taking theophylline should be carefully monitored by their doctors. Because theophylline can also interact with other drugs, including diuretics, beta blockers, contraceptive pills, antibiotics, and steroids, it is extremely important to make sure your doctor knows what other medications you are using. Using caffeine while on this drug is a bad idea, too. 

Should PDE4 inhibitors be chosen over theophylline for COPD patients?

Theophylline and PDE4 inhibitors are both effective in the management of COPD symptoms. Theophylline, however, is not the easiest drug to be on. Not only do patients require careful monitoring to prevent toxicity, which can cause seizures, arrhythmia, and other cardiovascular complications (especially in smokers and older people), the drug also interacts very badly with a number of medications — including ones often prescribed to COPD patients, such as steroids and B2 agonists. 

PDE4 inhibitors are, on the whole, a safer choice. Research has shown that they lead to increased lung function in people suffering from chronic obstructive pulmonary disease, while easing symptoms like dyspnea effectively. In patients with moderate to severe stage COPD, PDE4 inhibitors have consistently been proven to lead to better FEV1, FVC, and PEFR ouctomes. They reduce patients' need for rescue inhalers, make it easier to exercise, and lower the frequenncy of COPD flare-ups. They are also far less likely to cause serious side effects and do not generally interact with other medications. 

In conclusion 

Theophylline and PDE4 inhibitors are both medications that are considered third-line options in the treatment of chronic obstructive pulmonary disease, chosen when other drugs have not worked well enough and alternatives have been exhausted. Out of the two, PDE4 inhibitors are more user-friendly, leading to fewer side effects and with a lower potential for drug interactions.

  • Vignola, A. M. (2004). PDE4 inhibitors in COPD—a more selective approach to treatment. Respiratory Medicine, 98(6), 495–503.
  • Photo courtesy of SteadyHealth

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