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3.24 > Lecture 15: Concentration-time profiles and therapeutic drug monitoring of theophylline > Flashcards

Lecture 15: Concentration-time profiles and therapeutic drug monitoring of theophylline Flashcards

1
Q

What is the oral dose of theophylline for?

A

Add on therapy for persistent symptoms of COPD

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2
Q

What is the IV dose of theophylline given as?

A

Aminophylline

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3
Q

What is aminophylline used for?

A

Severe acute asthma and for acute exacerbations of COPD

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4
Q

What are the advanatges of theophylline?

A

Cheap and widely available

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5
Q

What was theophylline originally developed as?

A

A diuretic

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6
Q

What are the pharmacological properties of theophylline?

A
  • Inhibits PDE
  • Antagonises adenosine receptors
  • Inhibits proinflammatory transcription factor nuclear factor-kB
  • Restores histone deacetylase 2
  • Increases apoptosis of inflammatory neutrophils and T cells
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7
Q

What is the result of PDE3 inhibition?

A
  • Relaxes airway smooth muscle
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8
Q

What is the result of PDE4 inhibition?

A

Reduces mediator release from alveolar macrophages

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9
Q

What may be responsible for severe toxicity?

A

Adenosine A1 receptor blockage

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10
Q

What causes bronchoconstriction via histamine and leucotriene release?

A

Adenosine

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11
Q

What concentration of theophylline hasa little effect on bronchodilation?

A

<10 mg/L

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12
Q

What concentrations of theophylline have an increased effect on bronchodilation?

A

10-25 mg/L

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13
Q

What concentrations of theophylline have no additional benefit on bronchodilation?

A

> 25 mg/L

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14
Q

What effect does theophylline have on COPD patients and at what concentration?

A

reduces proportion of neutrophils in sputum
at 5-10 mg/L

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15
Q

What effect does theophylline have on asthma patients?

A

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

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16
Q

What is the steroid sparing effect of theophylline and at what dose?

A

increases sensitivity of COPD to the anti-inflammatory effects of inhaled corticosteroids at 1-5mg/ L

17
Q

At what concentrations dose theophylline become toxic?

18
Q

What are the effects of theophylline at concnetrations >20 mg/L?

A
  • nausea
  • vomiting
  • headache
  • tachycardia
  • tremor
  • diuresis
19
Q

What are the effects of theophylline at concentrations >40 mg/L?

A
  • seizures (may cause rhabdomyolysis)
  • cardiac arrhythmias
  • (hypokalaemia) may occur at lower concentrations in chronic overdose
20
Q

What are the target concentration of theophylline for bronchodilation?

A

10-20 mg/L

21
Q

What are the target concentration of theophylline for anti-inflammatory and steroid sparing effect?

22
Q

What is the bioavailability of theophylline?

23
Q

Why are modified release oral formulations of theophylline used?

A

to reduce need for multiple daily doses

24
Q

What is the distribution of theophylline?

25
How is theophylline cleared?
By hepatic metabolism - by CYP1A2
26
What increases the clearance of theophylline?
- Smoking (including passive) - Cystic fibrosis - Enzyme inducers
27
What decreases the clearance of theophylline?
- Heart failure - Acute viral illness - Cirrhosis - Severe COPD - Enzyme Inhibitors
28
What drugs increase the clearance of theophylline?
- Rifampicin - Carbamazepine - Phenytoin - St johns wart
29
What drugs decrease the clearance of theophylline?
- clarithromycin - erythromycin - ciprofloxacin - fluvoxamine - diltiazem
30
What drugs interact with theophylline to cause hypokalaemis?
- Diuretics - Beta 2 agonist
31
What drugs interact with theophylline to cause seizures?
- Ketamine - Quinolone antibiotics
32
What is aminophylline?
Stable mixture of two molecules of theophylline and one molecule of ethylene diamine
33
What is the purpose of the salt in aminophylline?
Improves solubility - makes it easier to be given IV
34
What is the intravenous form of theophylline?
Aminophylline
35
What is intravenous aminophylline indicated for?
Severe acute asthma
36
What is the dose of IV aminophylline for severe acute asthma?
5mg/kg by slow IV injection followed bt 500-700 micrograms/kg/h by IV infusion
37
Why does the loading dose of aminophylline need to be given slowly?
To avoid severe risk of toxicity particularly arrhythmias
38
How is a loading dose calculated?
Loading dose (IV) (mg) = Target concentration (mg/L) x V (L)/s

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