Basic Pharmacokinetics Flashcards
What are the X2 rate of reaction orders of drug kinetics?
Zero order kinetics
First order kinetics
What is the principle of zero order drug kinetics?
What is the formula given for this?
The drug is eliminated at a constant rate irrespective of the concentration of the drug at that particular time and is only dependant on the elimination rate constant (K).
ΔA / Δt = -K
A = drug concentration t= time
What is the principle of first order drug kinetics?
What is the formula given for this?
The rate of elimination of the drug is dependant on the elimination rate constant AND the concentration of drug at that particular time.
ΔA / Δt = -KA
A = drug concentration t= time
What symbol denotes the elimination rate constant?
What type of measurement is it and what are it’s units?
K
It is a rate measurement with the units (min^1)
What type of kinetics do most drugs follow?
Name a drug that is an exception?
Most follow first order kinetics
Alcohol and phenytoin (an anti-seizure medication) follow zero order
What does the concentration-time graph look like for zero order vs first order kinetics?
Which axis is which?
Zero order = a straight line
First order = curve from top left to bottom right
Y-axis = drug concentration X-axis = time
What are the options for drug compartments and how many phases of decline do each type show?
X1 compartment = shows X1 phase of decline (monophasic or monoexponential)
X2 compartment = shows X2 phases of decline (biphasic)
What is meant by the half life of a drug?
The time it takes for the plasma concentration of the drug to decrease by half.
What formula tells you the concentration of a drug at a specific time?
A = A0 exp (-Kt)
A = concentration of drug (what you are trying to find) A0 = initial concentration of drug at t=0 exp = exponent K = elimination rate constant t = time (current)
What happens to the concentration-time curve for a first order kinetic drug if you plot the ln (natural log) of the concentration instead?
It becomes linear ( \ )
What does the gradient of the ln(concentration)-time graph represent?
The elimination rate constant (K)
What can the y-intercept of the ln(concentration)-time graph be used to calculate?
The concentration of drug at time zero.
CAREFUL! It will give you the ln[A] value; e^value will = [A]
Which formula links the half like of a drug (t1/2) and the elimination rate constant (K)?
t1/2= 0.693 / K
NB: 0.693 = ln2
What are the X4 letters of the X4 phases of pharmacokinetics and what do they stand for?
A = absolution D = distribution M = metabolism E = excretion
What is the absorption phase?
The process where the drug moves from the site of administration to the site of action.
In the distribution phase, what does Vd stand for and what is it?
Vd = volume of distribution
This is the total amount of drug dosed / the plasma concentration of the drug at t=0
How would you calculate the Vd?
Take a sample at t=0 to work out the concentration of drug in the plasma and then divide the drug doses by the sample concentration.
MAKE sure to check for units!
What are the X2 phases of metabolism?
Phase 1 and phase 2!!!
What process is phase 1 metabolism and what does it do?
Oxidation -adding an oxygen to make it more water soluble/easier to excrete
What process is phase 2 metabolism?
Conjugation = binding a conjugate group to make it more water soluble/easier to excrete
In the excretion phase, what does Cl stand for and what is its formulas?
Cl = clearance = volume of plasma cleared of the drug per unit time
Cl(total)= Cl(hepatic)+ Cl(renal) + Cl(metabolic)
OR
Cl(total)= K x Vd
Is a drug considered ‘cleared’ as soon as it enters the metabolic phase as well as the excretion phase?
Yes
What does Eh stand for in terms of hepatic clearance and how is it calculated?
Eh = extraction ratio
It is calculated by the concentration of drug going into the liver - the concentration of drug leaving. It is given as a number between 0-1.
How do you calculate the Cl(hepatic)?
Is this process the same for Cl(renal) (kidneys)?
Cl = Q x Eh
Calculate the Eh (extraction ratio)
Work out blood flow for that organ (Q) (1.4L/min)
Multiply them.
The process is the same for the kidneys but Q (blood flow) = 1.1L/min
What does F stand for and what does it mean?
F = bioavailability = fraction of unchanged drug which reaches the systemic circulation
What is F for IV dosing?
F = 100%
What formula for F (bioavailability) links it to the extraction ratio?
F = 1 - Eh
What is an alternative formula for F?
F = AUC(oral) / AUC(IV)
AUC = area under curve
Name the key equations for this topic.
T1/2 = 0.693 x K
Vd = A (dose of A given) / A0 (concentration of A at time = 0)
Cl(total) = K x Vd Cl(total) = dose / AUC
F = 1 - Eh F = AUC(oral) / AUC(IV)
