Pharmacokinetics Flashcards
In its most basic form, what is pharmacokinetics the study of?
What the body does to drugs
What are the four major parts of pharmacokinetics?
ADME Absorption Distribution Metabolism Elimination
How do we measure the amount of drug that is actually available in the blood stream? What calculation would you do to calculate it?
Bio availability= serum concentration/ drug dose *100
What would the bioavailability be of an IV drug?
100%
What factors affect bioavailability of a drug?
Drug formulation and administration
Vomiting, malabsorption
Age
Food eaten at same time as drug
What are the major body compartments that a drug could go into?
Extracellular space- includes plasma+ interstitium
Intracellular space
What determines how far a drug is distributed in the body?
Regional blood flow Lipid solubility Disease Specific receptor sites in tissues Protein binding Drug interactions Active transport
How do we measure how far a drug is distributed in the body (hypothetically)
Why is this “apparent” and not true?
Volume of distribution
Vd= dose/ drug concentration at time 0 in plasma. Eg 100mg gentamicin given. Peak plasma concentration 5mg/L, Vd= 20 litres.
Volume of distribution is apparent because it could theoretically work out to be more than the body’s volume itself eg 200l
Why does the degree of protein binding matter?
Highly bound protein drugs displace those which are less tightly bound meaning that the concentration of the less tightly bound drug in the plasma suddenly increases.
Where can first pass metabolism occur?
Liver, gut lumen or gut wall
Where does phase I and phase II metabolism occur?
In the liver
What is the significance of CYP450 enzymes?
They are part of phase I metabolism and break down drugs, being primarily oxidative. They can be induced and inhibited by certain drugs meaning that the metabolism of the drug in question is either sped up or slowed down, so that either concentration in plasma decreases or increases (sometimes into toxic range)
What is a prodrug?
A chemical which has no clinically useful function until it is metabolised by the liver where it has active metabolites which are clinically useful.
Where are most drugs eliminated?
Via the kidney or bile
What affects elimination?
GFR
Passive tubular reabsorption
Active tubular secretion
What is 1st order kinetics?
Rate of elimination is proportional to drug level. I.e a constant fraction of a drug is eliminated per unit time, so half life can be defined.
What is zero order kinetics?
Rate of elimination is a constant. Normally occurs once all of the active sites of the metabolism enzymes are saturated, then concentration in plasma rises rapidly (often into toxic range)
Why do we sometimes need to give a loading dose?
If we need to reach therapeutic dose quickly and the drug has a long half life.
It normally takes 4-5 half lives to reach a steady state
Therefore with a drug with a long half life this is going to take a while
Therefore we need to give a higher concentration of drug to bring them up to steady state. This is called the loading dose.
What is half life proportional to?
What is it inversely proportional to?
It is proportional to Vd and inversely proportional to clearance.
In what situations would be need to measure the concentration of a drug in plasma?
Monitoring of therapeutic effect If it had known toxic effects If the drug had zero order kinetics If the drug had a long half life Narrow therapeutic window Great risk of drug drug interaction
How do we calculate the loading dose?
= volume of distribution* concentration of drug required at steady state
