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Theophylline PK

Theophylline PK - Final Exam

What are the 3 major determinants of theophylline dosing interval? - Rate of product ABSORPTION - The patient's rate of ELIMINATION - Amount & acceptability of [SERUM] FLUX in relation to DZ-ctrl ~ (Regimen ADHERENCE can be considered a possible 4th)
What dosage formulation of theophylline is preferred? ORAL, slow-released formulations
2 reasons there might be a lack of bioavailability info accessible - Decreased use & amount of available products
Primary 2 reasons generic substitutions are NOT recommended - Varying ABSORPTION characteristics - NARROW therapeutic range (aka LOW therapeutic index)
Selected product should have __________ & ___________ bioavailability. KNOWN & CONSISTENT bioavailability
It's much more important to consider the drug _______ than _______. ( Manufacturer or Distributor? ) Manufacturer!
How would you convert the dose of IV theophylline to PO theophylline? Calculate total daily dose admin by IV & divide by frequency for PO admin (depndent on product/formulation)
When would you start giving oral theophylline after conversion from IV? Best = start giving oral theophylline when the IV stops - Slow released formulations can be overlapped ~1-2hours - Rapid release formulations must AVOID overlapping! (but they are rarely used anyways)
What is the relationship between dose/[serum] & the airway bronchodilation fx? Bronchodilation is PROPORTIONAL to the LOG [serum] between 5-20mcg/mL
Which dosage change would elicit a larger airway response? 1. A change from 5-->10 or 2. A change from 11-->16 1. A change from 5-->10 (since the dose is associated with the log [serum]
How is [serum] flux related to the therapeutic & SE response? Flux parallels the therapeutic & SE response (we want the dose with the greatest amount of fx while minimizing flux as much as possible)
What would the initial dose be for (a) a <1yo child & (b) adults & children >1yo assuming there are no risk factors that might reduce clearance? Child <1yo: Dose (in mg/kg/day) = 0.2 (age in weeks) + 5 Adult & child >1yo: 10mg/kg/day with a max dose of 300mg
What would the 2nd & 3rd titration steps be for a normal adult assuming there are no SE? 2nd: 13mg/kg/day (max of 450mg/day) 3rd: 16mg/kg/day (max of 600mg/day) * Note: dose is titrated in 3-DAY intervals! *
What would the IV loading dose (note: rarely done) be for a patient who currently has no theophylline on board? This dose would be infused over a time period of ______________. Infuse 5mg/kg over 30-60minutes (to avoid CV-irritability)
If a patient already has theophylline on board what would be the TARGET LEVEL you would aim to achieve when beginning the IV LD? If a patient was not at that level, what dose & rate would you initiate? Target theophylline level = 12 mcg/mL - If not at target, infuse 1mg/kg for each 2mcg/mL increase needed over 30-60min
When would you check theophylline levels after starting an IV loading dose? Check theophylline levels ONE HOUR after the infusion is completed
Generally, the optimal [serum] range associated with the reduction of asthma Sx is: 10-20 mcg/mL
What [serum] levels are generally associated with adverse fx? >20 mcg/mL
How would a patient present if experiencing theophylline-associated SE? Typically this pt would have GI & CNS related SE: GI = N/V/D, reflux --- CNS = nausea, nervous, jittery, insomnia
Transient theophylline SE are related to: Dose absorption (particularly, the peak levels (fx would be similar to having too much caffeine)
When would you monitor levels after starting an initial dose? How would this change if the pt was experiencing SE? - Monitor @ end of dosing scheme aka once maintenance dose is achieved or Css - If pt has SE, REDUCE the dose & check the level to direct next steps
When would you check blood levels to assess maintenance therapy? What was assessed to come up with that time? Measure blood levels 3-DAYS after continuous maintenance tx - This value should represent the Css (assuming no doses were missed or added
The PEAK occurs _____________ after a rapid releasing product & The PLATEAU (pseudo-peak) occurs _____________ after a SR product IR Peak = 2 hours SR Plateau = 4 hours
How often would you monitor a patient for routine care in: - Children (during rapid growing years) - Adults - Children (during rapid growing years) --> q6mo - Adults --> annually
Name 3 other situations that may indicate checking levels during routine care - Complaints are similar to the SE-profile - Poor DZ-control - If any factors that can modify CL are introduced (ie. new drugs/DDI or conditions)
Theophylline is metabolized by: Primarily CYP1A2 (with a little help from 3A4)
What physiologic conditions can effect theophylline levels/metabolism? CHF (bc hepatic Q changes), hepatic failure, fever (requires lower theophylline doses)
How would renal impairment effect theophylline CL? Little-no fx from renal impairment (surprising since urinary excr is the primary elimination for most metabolites bc of water solubility)
Elimination is... * Dose-dependent * Saturable (zero-order) - use caution when changing doses close to therapeutic range
Created by: myassen



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