Pharmacokinetics

Question 1

Definition of pharmacokinetics

Answer 1

What the body does to the drug

Question 2

Definition of pharmacodynamics

Answer 2

What the drug does to the body

Question 3

Definition of PK/PD

Answer 3

The relationship between pharmacokinetics and pharmacodynamics

Question 4

Definition of half life

Answer 4

How quickly half the drug is removed from the body

Question 5

Definition of bioavailability (F)

Answer 5

How much of the drug enters the systematic circulation

Question 6

Definition of clearance (Cl)

Answer 6

Volume of plasma from which a substance is completely removed/unit of time

Question 7

Definition of volume of distribution (Vd)

Answer 7

Amount of drug in the body to the conc of the drug measured in a biological fluid

Question 8

Definition of zero order kinetics

Answer 8

Drug is cleared at a constant rate, regardless of the concentration

Question 9

Definition of first order kinectics

Answer 9

Drug is cleared at a rate which is dependent on the conc in the body so generally doesnt accumulate in the blood

Question 10

Definition of extra hepatic clearance

Answer 10

Drug is cleared by other organs as well as the liver, eg, kidneys

Question 11

Definition of therapeutic window

Answer 11

A range of doses that produces a therapeutic response without any significant adverse effects

Question 12

Definition of safety window

Answer 12

Same as the therapeutic window

Question 13

What is the difference between pharmacokinetics and pharmacodynamics

Answer 13

Pharmacokinetics, what the body does to the drug

Pharmacodynamics, what the drug does to the body

Question 14

What are the 5 drug properties and what do they mean

Answer 14

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

Question 15

Describe zero order kinetics
What are the potential dangers
What are 2 examples of zero order kinetic drugs

Answer 15

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

Question 16

Describe first order kinetics

What are the positives

Answer 16

Drug is cleared at a rate which is dependent on the conc in the body
Generally does not accumulate in the blood

Question 17

Describe how drugs equilibrate in a 1 compartment system

Answer 17

Singly kinetically homogenous entity
Drug achieves instantaneous distribution and equilibration
Monophonic decline

Question 18

Describe how drugs equilibrate in a 2 compartment system (central and peripheral)

Answer 18

Distribution takes time to equilibrate between 2 systems

Biphasic decline

Question 19

What is a half life

Answer 19

The time taken for the plasma conc of a drug to fall by half

Question 20

How to calculate the elimination rate constant (k) for a first order reaction

Answer 20

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

Question 21

What is the relationship between half life and k

Answer 21

t1/2 = In2/k

Question 22

What is absorption?
What is the absorption rate constant
What affects the rate of absorption in each route

Answer 22

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

Question 23

How would you calculate the volume of distribution

How is the plasma conc linked to the amount of drug

Answer 23

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

Question 24

What does metabolism aim to do

Give 2 examples

Answer 24

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

Question 25

What is excretion and what limit its rate
What are the properties of clearance

What are the equations for clearance

Answer 25

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

Question 26

How is hepatic clearance calculated

What does it mean when Eh = 1

Answer 26

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

Question 27

What is the rate of human blood flow in the liver (Q)

How does the flow relate to the clearance

Answer 27

1.4L/min

Faster flow => faster clearance

Question 28

How does hepatic blood flow and extraction ratio relate to clearance

What is the max hepatic clearance

Answer 28

Cl = Q x Eh

1.4L/min

Question 29

How does clearance relate to bioavailability

What happens if total clearance is greater than Q?

Answer 29

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

Question 30

What organs can take part in extra hepatic clearance

Answer 30

Kidneys and other organs

All organs that can take part can have a different extraction ratio => difference amounts of clearance

Question 31

What is the renal blood flow in a human

Answer 31

1.1L/min

Question 32

How does the route of dosage affect the bioavailability

What is bioavailability limited by

Answer 32

Fraction of unchanged drug reaching the systemic circulation

IV = 100%
PO = can vary due to
-Limited absorption
-Limited by gut, hepatic metabolism/excretion

Question 33

How to calculate bioavailability

Answer 33

F= Area under curve for oral dosing/area under curve for IV dosing

Question 34

What is the minimum effective conc

Answer 34

The smallest dose needed to produce a therapeutic effect

Question 35

What controls the PK/PD relationship

Answer 35

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