eLFH - Pharmacokinetics

Question 1

Euler’s number ‘e’ description

Answer 1

Mathematical constant that describes the process where a variable increases or decreases at a rate that is proportional to its own magnitude

Question 2

e value

Answer 2

2.718

Question 3

Tear away function definition

Answer 3

Exponentially increasing functions

Question 4

Example of tear away function

Answer 4

Bacterial growth

Question 5

Examples of exponentially decreasing functions

Answer 5

Radioactive decay

Elimination of drug from body

Denitrogenation when pre-oxygenating

Water emptying from cylinder of water with tap at bottom

Question 6

Asymptote

Answer 6

With exponentially decreasing functions, end state never quite reaches zero, but the curve gets ever closer to the x axis

This end state is called an asymptote

Question 7

Use of logarithms in exponential graphs

Answer 7

Using logarithms converts curve to straight line graph when same log base as exponential is used

i.e. Natural logarithms are required for natural exponential processes as they relate to ‘e’

Question 8

Natural logarithm definition

Answer 8

Logarithm with base of ‘e’ (2.718)

Question 9

Exponential function vs Rectangular hyperbolic function

Answer 9

Both asymptote the x axis, but rectangular hyperbolic function also asymptotes y axis, whereas exponential function doesn’t

Exponential function models naturally occurring processes
Rectangular hyperbola is a section of a cone

Question 10

Three constants that can be used to describe the exponential decay function

Answer 10

Rate constant (k)

Time constant (tau)

Half life (t1/2)

Question 11

Rate constant (k) definition

Answer 11

Describes relationship between rate of decrease and the magnitude of the variable

I.e. k is ratio of the slope of the graph to its height

Question 12

Units of rate constant ‘k’

Answer 12

In exponential processes that occur over time, units of k are always sec^-1

Question 13

Time constant (tau) definition - 3 ways to describe it

Answer 13

1) Time required for a process to complete if it continued at its initial rate of fall (i.e. tangent to the graph at time = 0)

2) Time taken for the magnitude of the variable to fall to 37% of its initial value

3) Time to fall to 1/e of its original value

Question 14

Half life definition

Answer 14

Time required for the magnitude of the variable to fall to one half of its original value

Half life must always be shorter than time constant by definition

Question 15

Relationship between the three constants

Answer 15

Only need to know one of the constants to describe the shape of the graph

tau = 1 / k
k = 1 / tau
t1/2 = tau x 0.693

Question 16

How much of process is complete after 3 time constants

Answer 16

94.9%

After 1 tau = 63% complete
After 2 tau = 63% + (63% of remaining 37%) = 86.3%
After 3 tau = 86.3% + (63% of remaining 13.7% = 94.9%

Question 17

Single compartment model

Answer 17

Drug administered to the body becomes evenly distributed throughout a single hypothetical compartment which is the volume of distribution

Single compartment model is too simple to accurately model the kinetics of most drugs

Question 18

Volume of distribution

Answer 18

Volume of theoretical compartments that a drug is distributed into

Used by TCI models

E.g. 100 mg of propofol in Vd of 20L equates to 5 microgram/ml

Question 19

Example of drugs which follow a three compartment model

Answer 19

Propofol

Fentanyl

Question 20

Three compartment model

Answer 20

Central compartment - Initial volume of distribution that is very small representing initial dispersal in the plasma

Shallow peripheral compartment - second compartment with perfusion rich organs including brain

Deep peripheral compartment - third and largest compartment with mostly fat redistribution of drug

Question 21

Volume of distribution at a steady state (Vdss)

Answer 21

When drug is redistributed throughout all body tissues - Vdss is very large

Vdss = sum of all compartments
= 16 + 32 + 202
= 250 L in this example

Question 22

3 definitions of clearance

Answer 22

1) Proportion of the compartment volume that flows in unit time

2) Mass of drug eliminated per unit time per unit drug concentration

3) At steady state, the dose rate (flow rate) divided by the steady state blood concentration

Question 23

Conceptual way to think about clearance

Answer 23

Virtual flow of the volume of distribution

When a drug is cleared from the body by passage in the blood through an organ (e.g. liver or kidney) the volume that is completely cleared is the clearance

Question 24

Drug clearance equations (3 of them)

Answer 24

Clearance = Drug infusion rate / Blood concentration
(in the steady state for this first equation)

or

Cl = k x Vd

or

Cl = Vd / tau

Question 25

Units of clearance

Answer 25

L/min

or

L/kg/min