PK

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Author:
ch.tyrrell
ID:
151489
Filename:
PK
Updated:
2012-05-01 17:03:09
Tags:
Theophylline 14
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Description:
Theophylline
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  1. What is theophylline used to treat?
    • Asthma
    • COPD (chronic bronchitis, ephysema)
    • Premature apnea
  2. What is the MOA of theophylline?
    • Bronchodilation: antagonism of adenosine receptors, inhibition of phosphodiesterase (increase cAMP)
    • Anti-inflammatory
    • Enhances contractile ability of the diaphragm (helps break up mucus in the lungs and gets mucus moving)
  3. What is aminophylline?
    derivative of theophylline
  4. How is theophylline dosed?
    • Use ABW for dosing unless the patient is obese, then use IBW
    • For every 1 mg/kg of theophylline, blood concentrations will rise ~2 mg/L
  5. What is the LD of theophylline?
    • LD is optional for patients who have had previous doses in the past 24 hours
    • Must use IV or rapid-release oral products
    • 4-6 mg/kg
    • 2-3 mg/kg (for patients who have received theophylline in the past 24 hours)
  6. What is the maintenance dose for theophylline?
    • Oral: 10 mg/kg/day (max 900mg daily)
    • decreased to 5 mg/kg/day in patients w/ heart failure or liver dysfunction (max 400mg daily)
    • SR = split dose in half
    • IR = split into 4 doses

    IV continuous infusion: 0.5 mg/kg/hr
  7. What is the therapeutic range for theophylline?
    • Adults: 5-15 mg/L
    • serum concentrations up to 20mg/L may be acceptable in some patients

    Neonates: 6-13 mg/L
  8. What are the AE (within therapeutic range) of theophylline?
    • nausea
    • vomiting
    • dyspepsia
    • insomnia
    • nervousness
    • headache
    • tachycardia
  9. What AE can be experienced with theophylline serum concentrations of 20-30 mg/L?
    tachyarrhythmias
  10. What AE can be experienced with theophylline serum concentrations > 40 mg/L?
    • Life threatening arrhythmias
    • ventricular tachycardia, fibrillations, or PVCs
    • seizures
  11. What is the absorption of theophylline?
    • F=90-100%
    • S = 1 for theophylline
    • S = 0.8 for aminophylline
    • Accelerated absorption and potentially toxic concentration of theophylline may occur if once-daily formulations are administered with food
    • Absorption greatly increased when taken with food
    • Take 1 hour before or 2 hours after eating
  12. What is the distribution of theophylline?
    • Vd = 0.4 - 0.6 L/kg
    • Remains stable regardless of concomitant disease states
    • 40% bound to plasma proteins (limited effect of clearance)
  13. What is the metabolism of theophylline?
    • >90% hepatic metabolism
    • CYP450: 1A2, 2E1, 3A4
    • Leads to hydroxylation, demethylation, or methylation of theophylline
    • Half-life is variable and depends on clearance factors
  14. How is theophylline excreted?
    • 10% unchanged in the urine
    • Dosage adjustment not necessary in patients with renal impairment
    • Removed by hemodialysis (dosing should occur after dialysis)
  15. What is the half-life of theophylline?
    • rages from 5-24 hours
    • longer in neonates and premature neonates
    • accelerated in children 1-9 years
    • may be prolonged in patients > 65 years
  16. What drugs will increase the clearance of theophylline?
    Inducers of 1A2 and 3A4: smoking, phenytoin, carbamazepine, phenobarbital, rifampin

    Hyperthyroidism

    Diet:charbroiled foods, low carbohydrates, high protein
  17. What drugs decrease the clearance of theophylline?
    • Inhibitors of 1A2 and 3A4:
    • ciprofloxacin, azoles, clarithromycin, erythromycin, telitrhomycin, protease inhibitors, verapamil, oral contraceptives,

    Others: cirrhosis, acute hepatitis, heart failure, hypothyroidism, diet (low protein, high carbs)

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