15. TDM, CPK & LIVER Flashcards
(26 cards)
Define “clinical pharmacokinetics”
The application of PK concepts and principles in humans in order to design dosage regimens that produced the optimal therapeutic response with the least chances for ADEs
What are the two goals of clinical pharmacokinetics?
Optimize therapeutic response & Minimize the risk of adverse effects
Describe therapeutic drug monitoring (TDM)
Individualizing dosage by targeting a certain concentration in biological fluids in order to be within a therapeutic range
What is the “Therapeutic Window” of a drug?
The range between the minimum effective concentration & the minimum toxic concentration
What does a narrow therapeutic window indicate?
The drug may need to be monitored to minimize the risk for toxic effects
What is the “Therapeutic Range”?
The range of drug concentrations that is likely to produce a clinical response and unlikely to produce a toxic response
What is a common trait among drugs that are candidates for TDM?
A narrow therapeutic range
What is important to consider before initiating TDM for a drug?
Whether there is a suitable, timely, and accessible assay to measure the drug concentrations / monitor the effects
Explain a potential impact of cirrohosis
Alterations in QH
Explain a potential impact of damaged hepatocytes
Reduced intrinsic clearance
Explain a potential impact of increased bilirubin
may displace drugs from albumin binding sites
List potential ways to assess liver function
- ALT, AST, Alkaline Phosphatase
- Bilirubin
- Albumin
- INR/Prothrombin time
- Child-Pugh scores
- Marker substances: Antipyrine, ICG, MEGX, galactose
What does decreased albumin levels indicate about liver function?
the liver function is low
What does increased INR/Prothrombin time indicate about liver function?
the liver function is low
What variable indicates what percent of the drug is metabolized by the liver?
fm
What fm indicates that a drug is primarily metabolized by the liver?
fm > 0.6
How should the dose of a drug (fm > 0.6) be adjusted for a moderate Child-Pugh score?
~ 25% reduction in initial dialy dose
How should the dose of a drug (fm > 0.6) be adjusted for a severe Child-Pugh score?
~50% reduction
Consider a drug, fm = 0.95, typical dose = 2000 mg/d (500 mg q6h), in a patient with cirrhosis
Child-Pugh = 10 (severe disease)
What are potential dosage adjustments that can be made?
50 % reduction in total daily dose (TDD) = 1000 mg/day
500 mg q12h
250 mg q6h
What drugs are not likely to be impacted by impaired liver function based on fm?
fm < 20%
Explain how oral bioavailability is impacted by liver impairment
oral bioavailability may be INCREASED due to reductions in hepatic first-pass metabolism
Explain how protein binding is impacted by liver impairment
protein binding may be impacted due to reduced production of albumin
T/F:
All liver diseases impact drugs the same
FALSE !!
Describe why making dosing recommendations in patients with hepatic impairment is difficult
- assessment of hepatic function is difficult
- many drugs do not have specific recommendations
