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Time Completed: 01:07:02

Final Score 54%

98
82

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Pharmacology

Respiratory

Question 16 of 180

What is the mechanism of action of theophylline:

Answer:

Theophylline may have an additive bronchodilation effect when used in conjunction with small doses of beta-2 agonists. Theophylline is a xanthine which inhibits phosphodiesterase resulting in increased tissue concentrations of cyclic adenosine monophosphate (cAMP).

Theophylline

Theophylline may have an additive bronchodilation effect when used in conjunction with small doses of beta-2 agonists. Theophylline is a xanthine which inhibits phosphodiesterase resulting in increased tissue concentrations of cyclic adenosine monophosphate (cAMP).

Theophylline is metabolised in the liver, and has a narrow therapeutic index. The plasma theophylline concentration is increased in heart failure, hepatic impairment, in viral infections, in fever and in the elderly. A reduction in dosage may be necessary to avoid toxic accumulation. The plasma theophylline concentration is decreased in smokers, and by alcohol consumption.

Indications

It is used as a bronchodilator in asthma and stable COPD. It is not generally effective in exacerbations of chronic obstructive pulmonary disease, but is used rarely for severe or life-threatening acute asthma given by injection as aminophylline, a mixture of theophylline with ethylenediamine, which is 20 times more soluble than theophylline alone.

Contraindications

Theophylline should not be prescribed to:

  • People with porphyria
  • People with hypersensitivity to xanthines
  • Children concomitantly receiving ephedrine
  • Infants under 6 months of age

Cautions

Theophylline should be used with caution in people with:

  • Cardiac arrhythmias or other cardiac disease
  • Hepatic impairment
  • Epilepsy
  • Hypertension
  • Hyperthyroidism
  • Peptic ulcer
  • Risk of hypokalaemia

Interactions

Hypokalaemia may be potentiated by concomitant therapy with beta-2 agonists, corticosteroids and diuretics.

Excretion of lithium may be potentiated by concomitant therapy with theophylline.

There is an increased risk of convulsions when theophylline is given with quinolones.

Examples of enzyme-inhibiting drugs (raise plasma theophylline level) Examples of enzyme-inducing drugs (lower plasma theophylline level)
  • Erythromycin
  • Clarithromycin
  • Ciprofloxacin
  • Fluconazole
  • Verapamil
  • Allopurinol
  • Cimetidine
  • Primidone
  • Phenobarbital
  • Carbamazepine
  • Phenytoin
  • Ritonavir
  • Rifampicin
  • St John's Wort

Side Effects

Side effects include:

  • Tachycardia, palpitations and arrhythmias
  • CNS stimulation, tremor, headache, insomnia and convulsions
  • Gastric irritation, nausea, vomiting and diarrhoea
  • Hypokalaemia (potentially serious hypokalaemia may result from beta-2 agonist therapy; this effect may be potentiated in severe asthma by concomitant treatment with theophylline and its derivatives, corticosteroids, and diuretics, and by hypoxia)

Monitoring Requirements

In most individuals, a plasma-theophylline concentration of 10 – 20 mg/litre (55 – 110 micromol/litre) is required for satisfactory bronchodilation, although a lower plasma-theophylline concentration of 5 – 15 mg/litre may be effective. Adverse effects can occur within the range 10 – 20 mg/litre and both the frequency and severity increase at concentrations above 20 mg/litre.

Plasma-theophylline concentration is measured 5 days after starting oral treatment and at least 3 days after any dose adjustment.

Overdose

Theophylline in overdose can cause vomiting (which may be severe and intractable), agitation, restlessness, dilated pupils, sinus tachycardia, and hyperglycaemia. More serious effects are haematemesis, convulsions, and supraventricular and ventricular arrhythmias. Severe hypokalaemia may develop rapidly.

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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