How Do Nonselective Phosphodiesterase Enzyme Inhibitors Work?

Nonselective phosphodiesterase enzyme (PDE) inhibitors are medications used to treat respiratory problems such as bronchospasm and neonatal apnea, and congestive heart failure. Nonselective PDE inhibitors work by inhibiting the activity of a group of enzymes known as phosphodiesterase enzymes.

Phosphodiesterase enzymes are a family 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. Signaling molecules cAMP and cGMP are responsible for activating diverse cellular functions.

Nonselective phosphodiesterase inhibitors prevent PDE from breaking down cAMP, increasing its intracellular concentration. An increase in the levels of cAMP results in bronchial smooth muscle relaxation and bronchodilation, dilation of pulmonary blood vessels, strengthened heart contractions, and improved cardiac output.

Caffeine, one of the nonselective phosphodiesterase enzyme inhibitors, stimulates the respiratory center in the brain and improves the respiratory drive and oxygen inflow.

Nonselective phosphodiesterase enzyme inhibitors may be administered as:

• Oral tablets, capsules, lozenges, solutions, or elixir
• Intravenous (IV) injections or infusions, intramuscular (IM) injections

Nonselective phosphodiesterase enzyme inhibitors are used for the treatment of the following conditions:

FDA-approved:

• Bronchospasm
• Acute bronchospasm
• Neonatal apnea (cessation of breathing in newborn)
• Congestive heart failure (inadequate pumping of the heart)
• Fatigue and drowsiness
• Respiratory failure

Off-label:

• As a stimulant diuretic

Side effects of nonselective phosphodiesterase enzyme inhibitors may include the following:

• Central nervous system excitement
• Headache
• Insomnia
• Irritability
• Restlessness
• Tremor
• Skeletal muscle tremors
• Seizure
• Seizures that are resistant to anticonvulsants
• Tinnitus (ringing in the ears)
• Diarrhea
• Nausea
• Vomiting
• Increase in stomach acid secretion
• Abdominal pain
• Anorexia (loss of appetite)
• Transient diuresis (increased urination)
• Exfoliative dermatitis
• Chest pain
• Tachycardia (rapid heartbeat)
• Palpitations
• Arrhythmia (irregular heartbeat)
• Acute myocardial infarction (heart attack)
• Hypotension (low blood pressure)
• Hypercalcemia (high calcium levels in the blood), with concomitant hyperthyroid disease
• Thrombocytopenia (low platelet count in the blood)
• Difficulty urinating in elderly males with prostatism
• Urinary retention
• Fever
• Injection site pain
• Hepatotoxicity (liver toxicity), rare
• Withdrawal symptoms from caffeine discontinuation include:
  • Anxiety
  • Depression
  • Fatigue
  • Headache
  • Muscle tension
  • Nausea
  • Runny nose

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 nonselective phosphodiesterase enzyme inhibitor drugs include:

• aminophylline
• amrinone
• Cafcit
• caffeine
• Elixophyllin
• inamrinone
• NoDoz
• ReCharge
• Theo 24
• Theochron
• theophylline
• Vivarin