Theophyllines

Question 1

What is the mechanism of action?

Answer 1

1. Competitive nonselective phosphodiesterase inhibitor, which raises intracellular cAMP, activates PKA, inhibits TNF-alpha and inhibits leukotriene synthesis, and reduces inflammation and innate immunity.
2. Nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors almost equally, which explains many of its cardiac effects
   Theophylline has been shown to inhibit TGF-beta-mediated conversion of pulmonary fibroblasts into myofibroblasts in COPD and asthma via cAMP-PKA pathway and suppresses COL1 mRNA, which codes for the protein collagen.[14]

Question 2

What are the indications?

Answer 2

Reversible airways obstruction, severe acute asthma; see also Management of chronic asthma and Management of acute asthma.

Question 3

What are the contraindications?

Answer 3

Cardiac arrhythmias or other cardiac disease; hypertension; hyperthyroidism; peptic ulcer; epilepsy; elderly; fever; hypokalaemia risk

Question 4

What are the side effects?

Answer 4

Nausea, vomiting, gastric irritation, diarrhoea, palpitation, tachycardia, arrhythmias, headache, CNS stimulation, insomnia, convulsions

Theophylline may have an additive effect when used in conjunction with small doses of beta2 agonists; the combination may increase the risk of side-effects, including hypokalaemia

Question 5

What are the possible interactions?

Answer 5

Calcium channel blockers - plasma concentration of theophylline possibly increased by calcium-channel blockers (enhanced effect)

Cimetidine - metabolism of theophylline inhibited by cimetidine (increased plasma concentration)

Ciprofloxacin - plasma concentration of theophylline increased by ciprofloxacin

Deferasirox - plasma concentration of theophylline increased by deferasirox (consider reducing dose of theophylline )

Erythromycin - plasma concentration of theophylline increased by erythromycin (also theophylline may reduce absorption of oral erythromycin)

Fluconazole - plasma concentration of theophylline possibly increased by fluconazole

Fluvoxamine - plasma concentration of theophylline increased by fluvoxamine (concomitant use should usually be avoided, but where not possible halve theophylline dose and monitor plasma- theophylline concentration)

Fosphenytoin - plasma concentration of both drugs reduced when theophylline given with fosphenytoin

Shit loads more

Question 6

How is it metabolised/eliminated?

Answer 6

Theophylline is metabolised in the liver. The plasma-theophylline concentration is increased in heart failure, hepatic impairment, viral infections, in the elderly, and by drugs that inhibit its metabolism. The plasma-theophylline concentration is decreased in smokers, by alcohol consumption, and by drugs that induce its metabolism. Differences in the half-life of theophylline are important because the toxic dose is close to the therapeutic dose.

Question 7

Patient information?

Answer 7

Theophylline helps relieve symptoms such as cough, wheeze and shortness of breath.
Theophylline works by opening up the air passages in your lungs so that air can flow into your lungs more freely. This makes breathing easier and helps relieve symptoms such as coughing, wheezing and shortness of breath.