Theophylline Flashcards
Does smoking affect theophylline concentration
- Dose adjustment may be needed if pt has started or stopped smoking during treatment
- Smoking can INCREASE theophylline clearance, thus will need to increase dose
Where in the body is theophylline metabolised
Liver
3 conditions in which plasma-theophylline concentration increased
Heart failure
Hepatic impairment
Viral infections
When does plasma-theophylline concentration decrease
Smoking
Alcohol consumption
Why are differences in half life of theophylline important
Because it has a NTI - toxic dose is close to therapeutic dose
Indications: uniphyllin continus
Chronic asthma
Reversible airway obstruction
Severe acute asthma
Theophylline - cautions
- Cardiac arrhythmias or other cardiac disease
- Elderly (increased plasma theophylline concentration) (in adults)
- Epilepsy
- Fever
- Hypertension
- Peptic ulcer
- Risk of hypokalaemia
- Thyroid disorder
Explain why theophylline should be used with caution in elderly
○ Prescription potentially inappropriate (STOPP criteria) as monotherapy for COPD
○ Safer and more effective alternatives available
○ Risk of adverse effects due to narrow therapeutic index
SE that can result from B2-agonist therapy
- Potentially serious hypokalaemia can result
- Particular caution with severe asthma - this effect may be potentiated by concomitant treatment with theophylline and its derivatives, CCs, diuretics, hypoxia
What needs to be monitored in severe asthma and why
- Monitor plasma-potassium concentration
- Potentially serious hypokalaemia can result from B2-agonist therapy
- Particular caution with severe asthma - this effect may be potentiated by concomitant treatment with theophylline and its derivatives, CCs, diuretics, hypoxia
Signs of overdose
○ Vomiting (may be severe and intractable)
○ Agitation
○ Restlessness
○ Dilated pupils
○ Sinus tachycardia
○ Hyperglycaemia
○ Severe hypokalaemia may develop rapidly
A patient presents with pinpoint pupils and hypoglycaemia. Could they be suffering from theophylline overdose?
No
Features of overdose include DILATED pupils and HYPERglycaemia
More serious effects of theophylline overdose
○ Haematemesis
○ Convulsions
○ Supraventricular and ventricular arrythmias
How is toxicity often delayed?
Usually prescribed as MR formulations, therefore toxicity can be delayed
Treatment of theophylline poisoning (not treating the symptoms that come with it)
Repeat doses of activated charcoal to eliminate theophylline, even if it has been more than 1 hour since ingestion, and especially if a MR preparation has been taken
Treating the symptoms of theophylline poisoning
- vomiting
Ondansetron may be effective for severe vomiting resistant to other antiemetics
Unlicensed use
Treating the symptoms of theophylline poisoning
- hypokalaemia
- Corrected by IV infusion of potassium chloride
- May be so severe that it requires 60mmol/hour - high doses need ECG monitoring
What might need to be monitored when correcting hypokalaemia from theophylline poisoning
- Correcting hypokalaemia: give IV potassium chloride, for severe hypokalaemia it may need such high doses of up to 60mmol/hour
- High doses need ECG monitoring
Treating the symptoms of theophylline poisoning
- convulsions
Control with IV lorazepam or diazepam
Treating the symptoms of theophylline poisoning
- agitation
May require sedation with diazepam
Treating the symptoms of theophylline poisoning
- use of SABA
If the patient doesn’t suffer from asthma, SABA can be administered IV to reverse severe tachycardia, hypokalaemia and hyperglycaemia
Use in pregnancy
- Neonatal irritability and apnoea reported
- Can be taken as normal during pregnancy as it is important that there is good asthma control
Use in breastfeeding
- Present in milk - irritability in infant reported, MR preparation preferable
Can be taken as normal during BF
Use in hepatic impairment
- Caution - risk of increased exposure
- Consider dose reduction
Monitoring requirements
Therapeutic drug monitoring of plasma-theophylline concentration
What plasma-theophylline concentration is required for satisfactory bronchodilation in most individuals?
- 10-20mg/litre (55-110micromol/litre)
- However, lower concentrations of 5-15mg/litre may be effective
At what concentrations can adverse effects occur?
- Within the range 10-20mg/litre (which is also the plasma-theophylline concentration required for satisfactory bronchodilation in most individuals)
- Both the frequency and severity increase at concentrations above 20mg/litre
When should plasma-theophylline concentrations be taken
5 days after starting oral treatment
At least 3 days after any dose adjustments
Blood sample usually taken 4-6hours after dose of MR preparation (sampling times may vary, consult local guidelines)
A prescription comes in for oral theophylline but no brand is stated. What should you do?
- Rate of absorption from MR preps can vary between brands
- Contact prescriber and agree the brand to be dispensed
Important considerations on prescribing theophylline for patients who have been discharged from hospital
Patients discharged from hospital need to be maintained on the brand on which they were stabilised on as an in-patient
Beta blockers
Predicted to increase risk of bronchospasm when given with theophylline
Severe interaction - AVOID
Amiodarone
○ Theophylline predicted to cause hypokalaemia (potentially increasing risk of torsade de pointes) when given with amiodarone
○ Severe interaction
No recommendation made
Citalopram, escitalopram
○ Theophylline predicted to cause hypokalaemia (potentially increasing risk of torsade de pointes) when given with amiodarone
○ Severe interaction
Use of COC with theophylline
○ Predicted to increase exposure to theophylline
○ Monitor and adjust dose
Moderate
Erythromycin
○ Decreases clearance of theophylline; theophylline potentially decreases clearance of erythromycin
○ Adjust dose
○ Severe interaction
○ Also predicted to cause hypokalaemia (potentially increasing risk of torsade de pointes) when given with erythromycin
○ Severe interaction
○ No recommendation made
