Intro to Pharmacokinetics Flashcards
ADME process
Absorption
Distribution
Metabolism
Excretion
Absoption
The movement of drugs from the site of administration into the blood
By passive diffusion in most cases
(IV admin doesnt have an absorption step)
3 factors that influence absorption
Concentration gradient
Size
Lipid solubility/pH
How does charge affect lipid solubility/permeability
Uncharged drug is hydrophobic (can pass membranes)
Charged drug is hydrophilic (cannot diffuse)
What 2 factors control the relative proportion of weak acids and bases in their protonated/unprotonated forms?
pH of the environment
pKa of the drug
Bioavailability
The fraction of drug that reaches systemic circulation unchanged
Distribution
The process by which the drug reversibly leaves the bloodstream
Drug moves between body compartments
Drug reaches the site of action
5 influencing factors for distribution
Concentration gradient Drug size Lipid solubility/pH Blood flow Protein binding
Effect of blood flow on distribution
Drug is delivered to tissues in relation to perfusion
1st to brain, heart, liver, kidneys
2nd to muscle and skin
3rd to fat
What is the effect of drugs binding to protein
Drug cannot distribute to target receptors, so protein bound drug is pharmacologically inactive
Causes a decrease in free drug concentration and therapeutic effect
Where does most drug metabolism occur?
The liver (some in gut, lung and plasma)
End goal of metabolism
Make the drug more polar to increase renal excretion
2 processes of metabolism
Phase 1 oxidation/reduction/hydrolysis
Phase 2 conjugation
Phase 1 metabolism
Cytochrome P450 enzymes
A family of related enzymes that add or uncover polar chemical groups to increase water solubility
Small polar groups
Inducers vs inhibitors
Inducers increase the rate of enzyme activity (if P450 is induced, you get a subtherapeutic effect)
Inhibitors decrease the rate of enzyme activity (you get a potentially toxic effect
