Pharmacokinetics Flashcards
Definition of pharmacokinetics
What the body does to the drug
Definition of pharmacodynamics
What the drug does to the body
Definition of PK/PD
The relationship between pharmacokinetics and pharmacodynamics
Definition of half life
How quickly half the drug is removed from the body
Definition of bioavailability (F)
How much of the drug enters the systematic circulation
Definition of clearance (Cl)
Volume of plasma from which a substance is completely removed/unit of time
Definition of volume of distribution (Vd)
Amount of drug in the body to the conc of the drug measured in a biological fluid
Definition of zero order kinetics
Drug is cleared at a constant rate, regardless of the concentration
Definition of first order kinectics
Drug is cleared at a rate which is dependent on the conc in the body so generally doesnt accumulate in the blood
Definition of extra hepatic clearance
Drug is cleared by other organs as well as the liver, eg, kidneys
Definition of therapeutic window
A range of doses that produces a therapeutic response without any significant adverse effects
Definition of safety window
Same as the therapeutic window
What is the difference between pharmacokinetics and pharmacodynamics
Pharmacokinetics, what the body does to the drug
Pharmacodynamics, what the drug does to the body
What are the 5 drug properties and what do they mean
Dose, how much to take
Half life, how quickly half the drug is removed from the system
F (bioavailability), amount of drug that enters the systematic circulation
Cl (clearance), Volume of plasma from which a substance is totally removed/unit of time
Vd (volume of distribution), Amount of drug in the body to the conc of drug measured in a biological fluid
Describe zero order kinetics
What are the potential dangers
What are 2 examples of zero order kinetic drugs
Drug is cleared at a constant rate, regardless of the conc
Can accumulate and occur in overdose
Phenytoin, alcohol as their elimination process is saturated
Describe first order kinetics
What are the positives
Drug is cleared at a rate which is dependent on the conc in the body
Generally does not accumulate in the blood
Describe how drugs equilibrate in a 1 compartment system
Singly kinetically homogenous entity
Drug achieves instantaneous distribution and equilibration
Monophonic decline
Describe how drugs equilibrate in a 2 compartment system (central and peripheral)
Distribution takes time to equilibrate between 2 systems
Biphasic decline
What is a half life
The time taken for the plasma conc of a drug to fall by half
How to calculate the elimination rate constant (k) for a first order reaction
dA/dt = -kA
A=Ao exp(-kt)
A=amount of drug
Ao=initial amount of drug
k=elimination rate constant
t= time
Plot Ln[A] against time to get a linear line
K=gradient
Ao=e^y intercept
What is the relationship between half life and k
t1/2 = In2/k
What is absorption?
What is the absorption rate constant
What affects the rate of absorption in each route
Process by which a drug moves into the site of action
Absorption rate constant is 1st order
Oral absorption : aqueous solution => lipid diffusion => permeation
Can be solubility (dissolution rate) and pH (pKa) dependent
Solubility can be pH dependent
-GI tract starts acidic but becomes more alkali
How would you calculate the volume of distribution
How is the plasma conc linked to the amount of drug
Vd (L) =total amount of drug dosed/plasma conc of drug
Plasma conc, not necessarily the same as the amount of drug, drugs can attach to the sides => Vd increases as a result
What does metabolism aim to do
Give 2 examples
Modify the drug so it is more soluble
Via oxidation
-Propanolol => 4-hydroxypropanolol
Via conjugations so the whole new molecule is soluble
-Chloramphenicol => chloramphenicol-O-glucaronide
What is excretion and what limit its rate
What are the properties of clearance
What are the equations for clearance
The clearance of a drug (volume of plasma cleared of a drug per unit time)
Can be limited by organ blood flow
Can include saturable processes
Products can be metabolized at the same time
Clearance is additive
Cl total = Cl hepatic + Cl renal + Cl metabolic
Cl (L/h)= k x Vd
Cl = dose/AUC
Cl=Q x Eh
How is hepatic clearance calculated
What does it mean when Eh = 1
Extraction ratio (Eh) = difference between amount of drug that enters and leaves the liver/amount of drug that enters the liver
Eh=1, drug is completely cleared by the liver so non enters the systemic circulation
What is the rate of human blood flow in the liver (Q)
How does the flow relate to the clearance
1.4L/min
Faster flow => faster clearance
How does hepatic blood flow and extraction ratio relate to clearance
What is the max hepatic clearance
Cl = Q x Eh
1.4L/min
How does clearance relate to bioavailability
What happens if total clearance is greater than Q?
All GI blood passes into hepatic portal system before it enters the systemic circulation
Maximal oral bioavailability (F) = 1 -Eh
The higher the hepatic clearance, the lower the bioavailability
If total clearance > Q the there is extra hepatic clearance
What organs can take part in extra hepatic clearance
Kidneys and other organs
All organs that can take part can have a different extraction ratio => difference amounts of clearance
What is the renal blood flow in a human
1.1L/min
How does the route of dosage affect the bioavailability
What is bioavailability limited by
Fraction of unchanged drug reaching the systemic circulation
IV = 100%
PO = can vary due to
-Limited absorption
-Limited by gut, hepatic metabolism/excretion
How to calculate bioavailability
F= Area under curve for oral dosing/area under curve for IV dosing
What is the minimum effective conc
The smallest dose needed to produce a therapeutic effect
What controls the PK/PD relationship
The action of a drug controls it
As you increase the amount of drug up to a certain point, the effect does not change due to the sigmoid curve in pharmacodynamics
