Pharmacology
Respiratory
Regarding theophylline, which of the following statements is INCORRECT:
Answer:
Theophylline is not recognised as a cause of tendon damage or rupture, unlike ciprofloxacin. The remaining statements listed are correct.Theophylline
Pharmacology / Respiratory
Last Updated: 28th March 2019
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) |
|---|---|
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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 |
