Theophylline

Question 1

Therapeutic Index

Answer 1

10-20mg/L

NARROW

Question 2

Plasma protein binding

Answer 2

40%

LOW

Question 3

Describe the metabolism

Answer 3

90% metabolised in liver via CYP450

Question 4

Describe elimination

Answer 4

90% metabolised
10% via kidney unchanged (urine)
FIRST ORDER KINETICS
VARIABLE rates

Question 5

What factors affect clearance?

Answer 5

age, illness, thyroid function, smoking, diet, drugs

Question 6

INTERACTIONS

Answer 6

SSRIs, quinolone antibiotics, allopurinol, erythromycin, cimetidine

SMOKING

Question 7

Which BTS step introduces theophylline - in which form?

Answer 7

STEP 3: SR theophillyne

STEP 4 as an add-on

Question 8

Theophylline structure

Answer 8

PURINE derivative

similar to caffeine

Question 9

Indications

Answer 9

chronic asthma
severe asthma
COPD

Question 10

Define SUSTAINED RELEASE TABS

Answer 10

modified tabs to release drug at a predetermined rate -> achieve constant drug serum conc

Question 11

Advantages of SR tabs

Answer 11

Avoid toxicity
Prolonged half life & efficacy
Control of drug plasma levels
ONE DAILY DOSE - enhances patient compliance
Relieve morning symptoms of asthma

Question 12

Compare distribution or oral & IV theophylline

Answer 12

ORAL: follows one compartment model (simple)
IV: follows PK of a 2 compartment model

Question 13

Effects of theophylline

Answer 13

reduces inflammation

enhances effects of B2-agonists & corticosteroids

Question 14

Mechanism

Answer 14

AFFECTS MANY PATHWAYS & MEDIATORS

Question 15

Side effects

Answer 15

NON-SPECIFIC

Question 16

Discuss interactions with SMOKING

Answer 16

Shortens half life

CYP1A2 induction from smoke chemicals:&raquo_space; metabolism & clearance