XANTHINES

Question 1

Examples

Answer 1

Theophylline
Aminophylline

Narrow TI

Question 2

How do the Xanthines work?

Answer 2

• Phosphodiesterase inhibitor
• They inhibit leukotriene synthesis and therefore cause bronchodilation and inflammation

Question 3

What is the difference between Theophylline and Aminophylline?

Answer 3

• Theophylline is pure form of drug
• Aminophylline is a mixture of Theophylline with Ethylenediamine
• Aminophylline is 20 times more soluble than Theophylline on its own

Question 4

What formulation is
Aminophylline available as?

Answer 4

• Injection
• MR Tablet (Phyllocontin continus)

Question 5

What formulation is
Theophylline available as?

Answer 5

1. MR Tablet
   - Nuelin SA
   - Uniphylline continus
2. MR Capsules
   - Slo-phyllin
   NOTE: Theophylline is only MR oral preparation. If it is to be given as an injection, it would be given as Aminophylline

Question 6

What is the therapeutic range of Theophylline?

Answer 6

-10-20mg/L
- Side effects can still occur during this range
- Frequency and severity of side effects increase when over 20mg/L

Question 7

SE of theophylline < 20mg/L

Answer 7

• DNV
• Headache
• Tremor

Question 8

SE of theophylline > 20mg/L

Overdose

Answer 8

• Severe vomiting
• Insomnia
• Agitation/Restlessness
• Dilated pupils
• sinus tachycardia/ arrythmias
• hyperglycaemia
• convulsions
• Severe hypokalaemia

Question 9

Theophylline concentration is decreased in

Answer 9

• smokers
• alcohol consumption
• enzyme inducers (carbamazepine, rifampicin, phenytoin)

smoking is an enzyme inducer

Question 10

Theophylline concentration is increased in

Answer 10

• heart failure
• hepatic impairment
• viral infection
• enzyme inhibitors (macrolides, cimetidine, cipro)

Question 11

Interactions

Answer 11

Hypokalaemia
- CS
- SABA/LABA
- diuretics
- inducers
- lithium

Question 12

Monitoring

Answer 12

1. Plasma-theophylline concentration
   - Aiming for 10-20mg
2. Plasma-Potassium
   - Especially if concomitant administration with drugs that increase the risk of HYPOkalaemia

Question 13

Check drug plasma levels

Answer 13

o Sample should be taken 4-6 hours after an oral dose
o 5 days after starting treatment
o At least 3 days after dose adjustment

Question 14

Brands

Answer 14

• Brands do not have the same bioavailability
  o Maintain the same brand
  o Prescribe by brand

Question 15

Theophylline and
Disulfiram

Answer 15

Disulfiram can increase the concentration of Theophylline leading to toxicity

Question 16

Aminophylline dosage and obesity

Answer 16

• This only applies to aminophylline
• If a patient is OBESE, then use IDEAL BODY WEIGHT to avoid excessive dosage

Question 17

Can Theophylline be taken in pregnancy and breastfeeding?

Answer 17

• Can be taken as normal in pregnancy & breastfeeding
• It is important that asthma is controlled in pregnancy