Xanthine derivatives

Question 1

Theophylline

Answer 1

Direct central nervous system stimulators
- promotes bronchodilation,
- stimulate vagal center causing bradycardia

Question 2

thophylline in large doses

Answer 2

causes positive inotropic effect in myocardium and positive chronotropic effect on the SA node, resulting in:
* Bronchial smooth muscle relaxation
* CNS stimulant
* Cardiovascular effects
* Increased gastric acid production
* Stimulate skeletal muscle
* Increased renal blood flow and glomerular filtration rate

Question 3

Theophylline absorption/distribution

Answer 3

• Absorbed rapidly and completely from gastrointestinal (GI) tract
• Distributed widely
  
  • Volume of distribution altered in:
• premature neonates
• elderly patients
• cirrhosis
• pregnant women (third trimester),
• critically ill patients
  (all due to altered protein-binding)

Question 4

Theophylline metabolism/excretion

Answer 4

Metabolized extensively in liver via CYP 450 into caffeine
* Disease states and CYP inducers can influence metabolism of theophylline
* Eliminated renally

Question 5

Theophylline: Precautions and contraindications

Answer 5

Monitor patients with hypertension, ischemic heart disease, coronary
insufficiency, congestive heart failure, or a history of stroke and cardiac arrhythmias
- Prolonged clearance and half-life in neonate and the elderly
* Pregnancy category C

Question 6

Monitor for theophylline

Answer 6

toxicity: peaks/troughs
* Narrow therapeutic window
* Goal serum theophylline levels are 10–20 mcg/ml

Question 7

Theophylline ADR

Answer 7

CNS effects
GI effects (reflux/heartburn)
cardiac
- Some patients have seizures at 15 mcg/mL or greater
* Toxicity occurs with levels greater than 20 mcg/mL

Question 8

Drug and food interactions

Answer 8

• Smoking tobacco increases clearance
• Benzos are antagonized by theophylline
• Beta agonists may cause additive toxicity
• Reduced lithium levels
• Low-carbohydrate/high-protein diet increases clearance
• Charcoal-broiled foods accelerate the hepatic metabolism of theophylline
  (CYP 1A2)
  Many drug interactions due to metabolism via CYP 450 isoenzyme CYP1A2, CYP 3A3/4 & CYP 2E1

Question 9

Theophylline Clinical use

Answer 9

Second- or third-line drug for asthma and COPD

Question 10

Theophylline: Rational drug selection

Answer 10

Cost and convenience
* Immediate release
* Use at beginning of therapy to determine daily dose
* Timed release
* Taken daily at the same time
* Once stabilized on immediate release, transition to extended release once the total 24-hour dose has been determined

Question 11

Theophylline monitoring

Answer 11

• Signs of toxicity.
• Draw frequent levels when dose is being titrated.
• After at steady state, draw levels every 6–12 months.
• Draw levels whenever any new drug is added or deleted from
  regimen

Question 12

Theophylline Pt edu

Answer 12

Take med exactly as prescribed.
* Discuss signs and symptoms of toxicity.
* Avoid large amounts of caffeine-containing beverages.
* Explain theophylline elimination is influenced by diet.