Module 6 Flashcards
What is the underlying principle of clinical pharmacokinetics?
A relationship exists between the effects of a drug and the concentration of drug in the body.
What are the most important parameters determining drug disposition in humans?
Clearance, volume of distribution, elimination half-life, bioavailability
Ideally, drug concentrations would be measured from _______, however this is not feasible (generally, and thus drug concentrations are usually measured in ________.
the site of action
plasma
Why is the plasma a good site to measure drug concentrations?
1 - Relatively non-invasive
2 - Good correlation between plasma concentration and therapeutic/toxic effects (generally)
How is plasma obtained?
Phlebotomy (take blood from pt) –> centrifuge blood sample –> obtain plasma
What is measure in terms of drug concentration, in plasma.
Total drug concentration (since free drug concentration is difficult)
Describe the oral administration plasma concentration vs. time curve.
A >> E Cmax - A = E A << E A - absorption E - elimination
What are the different characteristics of plasma concentration time curves?
MEC - minimum effective concentration
Duration
Toxic concentration
Therapeutic range
The minimum concentration required to have a therapeutic effect.
MEC - minimum effective concentration
Length of time the drug is above the MEC.
Duration
Above which, toxic side effects will occur.
Toxic concentration
Range at which the plasma drug concentration is between the toxic concentration and the MEC.
Therapeutic range
The ________ of the therapeutic range is an index for how ________ a drug can be used.
width
safely
Drugs with a narrow therapeutic range often undergo ________ _________ to ensure that drug concentrations are within the target range.
Therapeutic monitoring
Describe therapeutic monitoring.
Typically performed on troughed blood samples
= Take a blood sample just prior to patient’s next dose
What is another word for therapeutic range?
Therapeutic window
Why do oral drugs have a lag time before they reach the MEC?
They have to be absorbed first, and rise in plasma concentration to have therapeutic effects
Using IV administration, there is no drug ________.
absorption
Describe the different phases of the IV plasma drug concentration time curve.
I >> E Steady state - I = E I << E = infusion stopped I - infusion rate E - elimination rate
The elimination of a drug given by IV bolus follows what type of kinetics?
First order - the rate of elimination is dependent on the blood concentration
When patients take repeated dosing of drugs, ___________ occurs.
accumulation
Repeated dosing of drugs results in ________ in the body until a ________ is reached. This is called the _______ _______.
accumulation
plateau
steady state
When drugs are repeatedly administered orally or as an IV bolus, drug concentrations fluctuate. The high level is called the ______, and the low level is called the _________. The goal of drug therapy is for the fluctuations at steady state to be within the ________ _______.
peak
trough
therapeutic range
Steady state is reached in repeated dosing when?
When the peak and trough concentrations are the same between doses.
What are the ways to reduce fluctuations in plasma drug concentrations?
Use continuous IV infusion
Use depot preparations
Change the dosing interval
Describe a depot preparation.
Depot preparations release drug at a slow and constant rate - minimizes peaks and troughs
Describe how changing the dosing interval can reduce peaks and troughs.
Giving the same daily dose, but split up throughout the day reduces the size of peaks and troughs
Describes the efficiency of irreversible drug elimination from the body.
clearance
Volume of blood cleared per unit time.
Clearance
What are the units of clearance?
mL/min
L/hr
Sum of clearance from all routes.
Total clearance (note clearance can also be described based on specific routes of elimination - e.g. renal clearance)
Why is total drug clearance important?
Because it determines the dosage rate required to maintain a certain blood concentration of a drug.
What is the relationship between drug concentration and clearance?
Dosing rate = plasma concentration * Clearance
Time it takes for the plasma concentration to decrease by 50%.
Half-life
How is half-life related to Vd and Cl?
T1/2 = ln2Vd/Cl ln2 = 0.693
When the SAME dose of a drug is administered repeatedly, it takes approximately ___ half-lives to reach steady state.
5
If the dose of the drug remains constant, the time to reach steady state is independent of the ______ of the dose
size/concentration
If a drug has a long half-life, it will take a long time for a patient to reach steady state. What can be done to circumvent this?
Loading doses
How is the loading dose calculated? What is the assumption of this equation?
Loading dose = target plasma concentration * Vd
This assumes 100% bioavailability
The time it takes for plasma concentration to decline from steady state is dependent on a drug’s ________, but not on its _______.
half-life
dose
It takes ___ half-lives for most of a drug (97%) to be eliminated from the body.
It takes ____ half-lives to eliminate every molecule of a drug from the body.
5
9
________ reactions will persist, even when drug concentrations are very low.
allergic
