Lecture 15 - concentration time profiles

Question 1

when is theophylline used in copd?

Answer 1

add on therapy used in severe acute asthma and for acute exacebations of copd

Question 2

how does theophylline affect phsophodietrase?

Answer 2

inhibits phosphodietrase

PDE3 inhibitor releases the airway smooth muscles at high concentrations and PDE4 inhibition reduces the mediator release from alveolar macrophages

Question 3

what effect does theophylline have on proinflammtory transcription factor?

Answer 3

Inhibits proinflammatory transcription factor nuclear factor-kB (high concs)

Question 4

what effect does theophylline have on apoptosis?

Answer 4

increases apoptosis of inflammatory neutrophils and T cells

Question 5

what effect does thephyllcien have on glisten deacetylase 2 activity

Answer 5

restores histone deacetylase 2 activity (HDAC2) in copd, asthma and reverse corticosteroid resistance in COPD (low concentrations)

Question 6

what effect does theophylline have on adenosine receptors?

Answer 6

theophylline antagonises the adenosine receptor A, A2a, A2b receptors (therapeutic concentrations)
- adenosine causes bronchoconstriction via histamine and leukotrienes release

adenosine receptor blockage may be responsible for severe toxicity

Question 7

Describe the range of concentration and what effect they have when theophylline is used as a weak bronchodilator

Answer 7

little effect < 10mg/l
increases with concentration 10-25mg/l
no additional benefit >25mg/l

Question 8

describe how theophylline has anti-inflammatory activity in asthma.

Answer 8

reduces eosinophil response to allergens, reduces neutrophils influx, CD4+, CD8+ neutrophils in the airways.

Question 9

descried how theophylline has anti-inflammatory activity in COPD

Answer 9

reduces the proportion of neutrophil in the sputum

Question 10

at what concentration does theophylline have therapeutic anti-inflammatory activity ?

Answer 10

5-10 mg/L

Question 11

at what therapeutic contraption does theophylline have steroid sparing effects?

Answer 11

1-5 mg/l

Question 12

describe how copd has steroid sparing effect in COPD

Answer 12

increases the sensitivity of COPD to the anti-inflammatory effects of inhaled corticosteroids

Question 13

what are the toxicity adverse effects of theophylline > 20mg/L concentration?

Answer 13

nausea, vomiting, headaches, tachycardia and diuresis

Question 14

what are the toxicity adverse effects of theophylline at aa concentration above > 40 Mg/L

Answer 14

seizures (may cause rhabdomylosis), cardiac arrhythmias (hypokalaemia), may occur in lower concentrations in chronic overdose

Question 15

what do the different target contraption for theophylline achieve?

Answer 15

10-20 mg/L traditional bronchodilator

5-10 mg/L nit-inflammatory and steroid sparing

Question 16

how is thephyllcien cleared ?

Answer 16

90-95% of theophylline is cleared by hepatic metabolism by CYP1A2

Question 17

what is the clearance of theophylline increased by?

Answer 17

smoking (induction of CYP1A2), cystic fibrosis and enzyme inducers: carbamazepine, rifampicin and phenytoin

Question 18

what is the clearance of theophylline decreased by?

Answer 18

heart failure, acute viral illness, severe chronic obstructive pulmonary disease, cirrhosis and enzyme inhibitors: clarithromycin, erythromycin, ciprofloxacin, fluvoxamine, diltiziam etc

Question 19

what are other drug interaction with theophylline?

Answer 19

Hypokalaemia: diuretics, beta2 agonists
Seizures: quinolone antibiotics, ketamine

Question 20

what is aminophylline?

Answer 20

stable mixture of theophylline and ethylene diamine - improves solubility

Question 21

how is theophylline used?

Answer 21

Theophylline (and aminophylline) formulations are used orally

Question 22

how can aminophylline also be used

Answer 22

Only aminophylline is used intravenously