How Do Phosphodiesterase-4 Enzyme Inhibitors Work?

Phosphodiesterase-4 enzyme (PDE-4) inhibitors are medications used to treat chronic obstructive pulmonary disease (COPD). COPD is a progressive condition with chronic inflammation that damages the lungs and causes breathing difficulties.

Phosphodiesterase-4 enzyme inhibitors are a novel class of drugs and the first non-steroidal anti-inflammatory drug used in the treatment of COPD. PDE-4 inhibitors prevent inflammation, infection, and resultant damage to the air sacs (alveoli) in the lungs. PDE-4 inhibitors also reduce pulmonary hypertension and excessive mucus secretion.

PDE-4 inhibitors work by selectively inhibiting the activity of subtype 4 in the family of phosphodiesterase enzymes. Phosphodiesterase enzymes are a group of enzymes that regulate the intracellular levels of signaling molecules known as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), by breaking them down.

Phosphodiesterase-4 enzyme inhibitors prevent PDE-4 from breaking down cAMP, increasing its concentration in the lung tissue. An increase in cAMP levels results in several anti-inflammatory effects that include:

• Inhibition of reactive oxygen species (ROS) production in the lung and bronchial tissue and neutrophils, a type of immune cells. ROS are signaling molecules that play a crucial role in inflammation.
• Inhibition of smooth muscle cell proliferation in the pulmonary artery, which prevents the narrowing of the pulmonary artery and reduces pulmonary hypertension.
• Inhibition of fibroblast formation that causes stiffening and scarring of the lungs.
• Inhibition of mucus production.

Phosphodiesterase-4 enzyme inhibitors are oral tablets used to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.

Side effects of phosphodiesterase-4 enzyme inhibitors may include the following:

• Diarrhea
• Weight loss
• Nausea
• Headache
• Back pain
• Insomnia
• Decreased appetite
• Dizziness
• Anxiety
• Depression
• Abdominal pain
• Dyspepsia (indigestion)
• Gastritis
• Vomiting
• Rhinitis (inflammation of the nasal passage)
• Sinusitis (inflammation of the sinuses)
• Muscle spasms
• Tremor
• Urinary tract infection
• Suicidality
• Hypersensitivity reactions include:
  • Rash
  • Urticaria (hives)
  • Angioedema (swelling in the tissue under the skin or mucous membranes)
  • Gynecomastia (abnormal enlargement of breast tissue in males)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of the only FDA-approved phosphodiesterase-4 enzyme inhibitor drug are:

• Daliresp
• roflumilast