Pharm 101: Theophylline

Class

Methylxanthine

Pharmacodynamics

• Theophylline is a methylxanthine. It’s exact mechanism of action is not established but there are several propositions:
  • Inhibition of PDE enzyme family, thereby increasing intracellular cAMP and cGMP. This causes stimulation of cardiac function and relaxation of smooth muscle
  • Inhibition of cell surface receptors for adenosine. Adenosine causes airway smooth muscle contraction and release of histamine from airway mast cells
• Multiple organ system effects, including;
• Central nervous system:
  • Mild cortical arousal with increased alertness and deferral of fatigue
  • Tremor
  • Anxiety
• Cardiovascular:
  • Positive chronotropic and inotropic effects
  • Decreases blood viscosity
• Gastrointestinal:
  • Secretion of gastric acid and digestive enzymes
• Renal:
  • Weak diuretic effect
  • Increased glomerular filtration rate, reduced tubular Na absorption
• Smooth muscle:
  • Bronchodilation
  • Tolerance does not develop
• Skeletal muscle:
  • Improved contractility

Pharmacokinetics

• Bioavailability 96%
• Volume of distribution 0.5L/kg
• Narrow therapeutic window. Therapeutic and toxic effects are related to its blood level. Improvement in pulmonary function is seen at blood levels of 5-20mg/L

Clinical uses

• Previously used in the treatment of asthma, the toxicity and need for blood concentration monitoring has made theophylline almost obsolete in asthma treatment
  • Acute asthma: bronchodilator effect relieves airflow obstruction
  • Chronic asthma: reduces severity of symptoms

Adverse effects

• Adverse effects include sinus tachycardia, tremor and vomiting
• Toxic effects are related to its blood level:
  • > 20mg/L: vomiting, abdominal discomfort, headache
  • > 40mg/L: seizures or arrhythmias
  • Hypotension, hypokalaemia and hyperglycaemia can occur due to beta-2 adrenergic activation (cause unknown)
• Theophylline is an adenosine receptor blocker and reduces the effectiveness of adenosine used in the treatment of SVT

Further Reading

• Long N. Theophylline toxicity