Pharmacokinetics Module Flashcards
What is absorption, and how is it influenced
The movement of drug from the site of administration into the blood
Influenced by concentration gradient, drug size, lipid solubility/ionization/pH, and Pgp
P-glycoprotein
ATP dependent transmembrane drug efflux pump
Expression may be induced or inhibited, which can increase or decrease the concentration of drug in the blood
Expressed on apical membrane of enterocytes (pumps drug back into intestinal lumen)
Decreases drug absorption
What is distribution, and how is it influenced
Drug reversibly leaves the bloodstream and moves between body compartments to receptors
Same influences as absorption PLUS blood flow, protein binding, Pgp
What is the ultimate goal of metabolism
Make the drug more polar for excretion in urine
Where does most excretion occur?
Urine and bile
MTC
Minimum toxic concentration
Over this, can get significant side effects
MEC
Minimum effective concentration
Below which a therapeutic effect won’t occur
Apparent volume of distribution
A proportionality constant that relates the amount of drug in the body to the concentration
Vd = amount of drug in the body / drug concentration in the plasma
The magnitude indicates the extent of drug distribution in the body, but not the specific location
What does a
1. Large Vd (> 42 L)
2. Small Vd (< 42 L)
mean?
- Drug distributes outside blood and body fluids into tissues and/or fat
- Drug has limited distribution, typically restricted to blood or physiological fluids
Steady state
Rate of drug administration = rate of drug elimination
Can occur at any concentration
Want it to fall in the therapeutic range
The concentration is influenced by drug dose and the dosing interval
How many half lives does it take to ready steady state
5
2 ways to get to steady state
Passive approach (give small, repeated doses and let the drug reach SS on its own) Give a loading dose followed by maintenance doses
Loading dose
A large dose of drug that is used to quickly raise the plasma concentration to a therapeutic (target) level
Maintenance dose
Smaller, repeated doses that are administered to maintain the desired plasma concentration
Replaces the amount of drug that is eliminated between doses
First order kinetics
Elimination processes are not saturated at therapeutic [drug]
A constant fraction of the drug is eliminated per unit time (you can calculate a half life)
Proportional relationship between dose and concentration
Applies to MOST drugs at therapeutic concentrations
