Lecture 2 Flashcards
What does ADME stand for in pharmacokinetics?
Absorption Distribution Metabolism Elimination
What is volume of distribution?
how well a drug is distributed throughout the body based on the concentration of drug in the blood
Would a drug with high lipid solubility and tissue have a high or low Vd
High volume of distribution e.g. amitriptyline (anti-depressant)
Would a drug with low lipid solubility and tissue binding have a high or low Vd?
Low volume of distribution e.g. warfarin (anti-coagulant)
What is clearance?
Virtual volume of blood cleared of drug per unit time
What is total body clearance the sum of?
Sum of all clearances occurring simultaneously by different organs in the body
What is creatine?
A breakdown product of creatine phosphate in muscles
Why do we measure creatine clearance?
Creatinine clearance is a marker for renal function and reflects drug clearance efficiency.
What are the two ways of measuring clearance?
- single blood sample
- renal clearance= urine collection over 24 hours
How does creatine clearance change with age?
Decreases with age
Define first order elimination
amount of drug eliminated per unit time is proportional to concentration, constant % of drug eliminated per unit time
What is the elimination rate? (Kel)
Proportion of drug eliminated per unit time
What does the elimination rate tell us?
Provides a calculation of the time needed to eliminate a proportion of drug
What is the time constant? (1/Kel)
Time taken for the concentration to fall to 1/e~ 37%
Define half-life
The time required for the amount of drug in the body to decrease by 50%
Can the same drug with two different starting doses have the same half life?
Yes
What do we use the half life to determine?
The dosing interval- the set dosing interval is one half life
What is AUC a measure of?
A measure of amount of drug absorbed
Why would you use a loading dose?
For acute conditions e.g. status asthmaticus, quickens therapeutic effect of drugs with long, slow half lives
Why would you use a continuous infusion?
- maintains an effective constant plasma drug concentration through equilibrium - prevents toxicity that might occur if the drug is presented too quickly
Define zero order kinetics
- constant amount of drug is eliminated per unit time - rate of elimination is independent of plasma drug concentration
What does half life depend on?
Starting concentration
Why must dose adjustments be made for neonates?
- reduced body volume - higher proportion of body is water - less plasma albumin - low renal function - low metabolism
Why must dose adjustments be made for the elderly?
- high proportion of fat - less plasma albumin - reduced renal function - low metabolism
What is the purpose of therapeutic drug monitoring?
- measure concentration of drug in the body - determine most effective dose or avoid toxicity
Examples of drugs that are therapeutically monitored
- cardiac drugs e.g. dioxin - antibiotics e.g. aminoglycosides - antiepileptics e.g. phenytoin - psychiatric drugs e.g lithium
Would we measure peak or trough drug concentration to make sure a drug reaches a certain level?
Peak
Would we measure peak or trough drug concentration to make sure a the drug remains effective?
Trough
Why do we use urine samples?
- do not need blood sample - useful for drugs which are fully/partially eliminated in the urine
Why do we not measure drug concentration in urine?
Urine volume is variable and differences affect the total drug concentration depending on (de)hydration
