Xanthines (High risk)

Question 1

What are the indications for aminophylline and theophylline?

Answer 1

For the treatment and prophylaxis of bronchospasm associated with asthma, chronic obstructive pulmonary disease and chronic bronchitis.

Question 2

What is the difference between aminophylline and theophylline?

Answer 2

1) Aminophylline is a mixture of theophylline and ethylenediamine which is 20x more soluble than theophylline alone
↳ Ethylenediamine - confers greater solubility in water

Question 3

To avoid excessive dosage in obese patients, how should the dose of aminophylline be calculated?

Answer 3

On the basis of ideal body weight for body height

Question 4

Some conditions can result in an increase in plasma theophylline concentration. List these conditions (4)

Answer 4

1) Heart failure
2) Hepatic impairment - (metabolised by the liver)
3) Viral infections
4) In elderly

Question 5

What can increase clearance of theophylline (3)

Answer 5

The following will decrease plasma theophylline concentrations . so it may be necessary to increase dosage to ensure a therapeutic effect:

1) Smokers- Dose adjustment might be necessary if started or stopped smoking
2) Alcohol consumption
3) St John’s Wort

Question 6

What are the general side-effects of theophylline? (5)

Answer 6

1) Arrhythmias, Palpitations
2) Headache
3) Nausea
4) Seizure (when given IV)
5) Hypokalaemia

Question 7

Why should theophylline be given with caution alongside beta2-agonist therapy?

Answer 7

Potentially serious hypokalaemia can occur

Question 8

Why should plasma-potassium concentrations be monitored in severe asthma? (4)

Answer 8

Because hypokalaemia may be potentiated by concomitant treatment with:

1) Theophylline and its derivatives
2) Corticosteroids
3) Diuretics
4) Hypoxia

Question 9

Why might the signs and symptoms of toxicity be delayed in those who have taken an overdose of theophylline?

Answer 9

Often prescribed as modified-release formulations and toxicity can therefore be delayed

Question 10

What are the presenting symptoms of theophylline toxicity? (6)

Answer 10

1) Vomiting
2) Agitation
3) Restlessness
4) Dilated pupils
5) Sinus tachycardia
6) Hyperglycaemia

Question 11

List some of the more serious presenting symptoms of theophylline toxicity (4)

Answer 11

1) Haematemesis
2) Convulsions
3) Supraventricular and ventricular arrhythmias
4) Severe hypokalaemia may develop rapidly

Question 12

Can theophylline be taken in pregnancy and breastfeeding?

Answer 12

1) Pregnancy: can be taken as normal as well controlled asthma is important. Neonatal irritability and apnoea have been reported
2) Breastfeeding: can be taken as normal. M/R preparations preferred

Question 13

Can theophylline be taken in hepatic impairment?

Answer 13

Yes - Reduce dose

Question 14

What should be monitored in patients taking theophylline?

Answer 14

1) Serum potassium

2) Plasma theophylline concentration

Question 15

What should always be measured if a loading dose of IV aminophylline is given to patients who are already taking theophylline and why?

Answer 15

1) Essential to measure plasma theophylline concentration, because serious side effects such as convulsions and arrhythmias can occur
2) Toxic dose of theophylline is close to therapeutic dose

Question 16

What is the therapeutic range for theophylline?

Answer 16

A plasma-theophylline concentration of 10-20mg/L is required for satisfactory bronchodialation (5-15mg/L may also work)

Question 17

Between what range of plasma-theophylline concentration can adverse effects occur?

Answer 17

10-20mg/l (target range) - adverse effects can occur

Above 20mg/L - frequency and severity of symptoms can increase

Question 18

When should plasma-theophylline concentrations be measured following oral administration and dose adjustments?

Answer 18

1) Measured 5 days after starting oral treatment ( Blood sample should usually be taken 4-6h after an oral or MR dose)
2) At least 3 days after a dose adjustment

Question 19

When should plasma-theophylline concentrations be measured following IV administration?

Answer 19

Blood sample usually taken after 4-6h

Question 20

1) When is an IV dose of aminophylline administered?

2) Which patients should not receive a loading dose of IV aminophylline?

Answer 20

1) For the treatment of severe and life-threatening acute asthma
2) Those already taking oral theophylline or aminophylline

Question 21

1) Why should theophylline and aminophylline always be prescribed by brand?
2) What should be done if the brand is not specified on a prescription?

Answer 21

1) Rate of absorption from M/R preparations can vary between brands
2) The pharmacist has to contact the prescriber and agree the brand to be dispensed
↳ if discharged from hospital, maintain same brand they were stabilised on as an in-patient

Question 22

Which patients are prescribed phyllocontin continus forte (aminophylline) tablets?

Answer 22

Patients where theophylline half-life is shorter:

1) Smokers
2) Alcoholics
3) On St John’s Wort

Question 23

Some drugs increase the clearance of theophylline and so it may be necessary to increase dosage to ensure therapeutic effect. List some of the drugs that increase theophylline clearance (6)

Answer 23

Inducers:

1) Barbiturates (phenobarbital, primidone)
2) Carbamazepine
3) Phenytoin
4) Lithium
5) Rifampicin
6) Ritonavir

Question 24

List some of the drugs that reduce theophylline clearance and therefore increase its plasma concentration, increasing risk of toxicity (7)

Answer 24

Inhibitors - increase risk of toxicity

1) Carbimazole
2) Cimetidine
3) Macrolides (azithromycin, clarithromycin)
4) Ciprofloxacin (quinolone)
5) Diltiazem
6) Propranolol
7) Oral contraceptives