Fundamentals Flashcards
What is the purpose of Pharmacokinetic models?
Predicting a drug’s behavior, and concentration within complex processes
How does Compartment modeling help understand the behavior of drugs?
A compartment is composed of tissues
that behave similarly -> similar pharmacokinetics
What is the One-compartmental model?
All body tissues are considered part of the compartment
-It is assumed after a bolus dose, distribution is instantaneous within the compartment
ASSUMPTION NOT REALITY just used to make it mathematically work
What is the most commonly used Compartment model?
One-compartmental model is most frequently used in clinical practice
What types of drugs are explained with the one-compartment model?
Drugs that don’t distribute into extravascular tissues
-Polar molecules -> distribute more into the fluid compartment
-small Vd (<1L/kg) aminoglycosides
What are the factors affecting the one-compartment Model?
Fluid changes, renal failure, prematurity (babies contain 80% water)
Which drugs are more likely susceptible to fluid shifts?
-polar drugs
-small Vd
f.e. gentamycin Vd = 0.3L/kg
Where are most drugs bound to in the blood?
-Most drugs bind to Albumin
(some bind to alpha acid 1 Glycoprotein - basic drugs)
What does k stand for in Pharmacokinetics?
Eliminate rate constant
What is a Two compartment model?
consists of a central compartment and a peripheral compartment
- Distribution into the blood and highly perfused organs (central compartment - heart, liver, kidney, blood, lungs)
- Distribution more slowly into peripheral tissues
(fat, muscle, bone, cerebrospinal fluids)
What types of drugs are described with the Two-compartment model
f.e. fat-soluble drugs
-nonpolar molecules, many carbons and rings f.e. steroids
They do not like to stay in the blood
From which compartment are drugs eliminated?
Central compartment, the drugs need to move back from the peripheral compartment into the central compartment (the blood) to be eliminated
How is the Two-compartment model displayed in a Log-linear graph compared to the one-compartment model?
Two lines:
Alpha Phase of Distribution
beta Phase Elimination
in one-compartment model: one straight line
What happens during the alpha and beta Phase?
Alpha Phase of Distribution from central into peripheral tissues
Beta Phase Elimination: Elimination of drug from central compartment to outside of the body
C = A e ^-alphat + B e ^-ßt
Which drug has the most rapid distribution from the central compartment into the peripheral compartment?
A alpha = 0.050 hr ^-1
B: alpha = 0.50 hr^-1
C: alpha = 0.5 hr^-1
Distribution from the central to the peripheral compartment is described by the slope Alpha (in hr inverse -> fraction (percentage) removed per hour)
Answer C = 0.5 per hour
What would the graph look like for a very fat-soluble drug like Propofol?
Alpha would be very steep, bc the fat-soluble drug will tend to leave the blood (central) much faster into fat-soluble tissues (peripheral)