Respiratory: Pharmacology - Methylxanthines

Question 1

Clinical uses of methylxanthines

Answer 1

Acute asthma
Neonatal apnoea

Question 2

Pharmacokinetics of theophylline

Answer 2

Absorption: 100% bioavailability, peak serum level 30-120mins
Metabolism: t1/2 = 4-8hrs
Distribution: VD 0.5L/kg, 60% protein-bound
Elimination: 85-90% hepatic (remainder renal)

Question 3

Describe the three molecular mechanisms of action of theophylline

Answer 3

1. PDE inhibition: increased cAMP -> increased smooth muscle relaxation
2. Adenosine receptor inhibition: inhibits smooth muscle contraction and histamine release from mast cells
3. Histone deacetylation: reduced inflammatory gene transcription

Question 4

Describe how theophylline is clinically useful in asthma

Answer 4

Causes direct bronchodilation, reduced histamine release from mast cells, and reverses fatigue of diaphragm through improved skeletal muscle contractility

Question 5

Describe the CNS, CVS, GIT and renal effects of theophylline

Answer 5

CNS: increased alertness; in overdose causes medullary stimulation, seizures and death
CVS: positive inotropy and chronotropy, in overdose can cause tachycardia and arrhythmia
GIT: secretagogue
Renal: weak diuretic

Question 6

What is the toxic level of theophylline?

Answer 6

> 20mcg/ml

Question 7

What metabolic disturbances are seen in theophylline toxicity?

Answer 7

Hypercalcaemia
Hypokalaemia
Hypophosphataemia
Hypoglycaemia
Acidosis