pharmacokinetics in practice

Question 1

define first order kinetics

Answer 1

rate of elimination is proportional to the plasma drug concentration

(processes involved in elimination do not become saturate)

Question 2

what happens in first order kinetics

Answer 2

A drug given IV is rapidly distributed to the tissues

By taking repeat plasma samples, the fall in the plasma concentration with time can be measured

Often, the decline is exponential – a constant fraction of the drug is eliminated per unit of time

Question 3

define zero order kinetics

Answer 3

rate of elimiation is not proportional to the plasma drug concentration

(metabolism processes become saturated)

Question 4

what happens in zero order kinetics

Answer 4

If an enzyme system that removes a drug is saturated the rate of removal of the drug is constant and unaffected by an increase in concentration

Question 5

define half life

Answer 5

the time taken for a concentration to reduce by one half

The units of the rate constant are hard to use practically so we use half life (t1/2)

Question 6

what does half life refer to in practice

Answer 6

normally for the elimination rate from the plasma as this is easy to measure

Question 7

what is Cmax

Answer 7

maximum plasma concetration

Question 8

what is tmax

Answer 8

time taken to reach Cmax

Question 9

what is clearance CL

Answer 9

the volume of blood or plasma cleared of drug per unit time by all eliminating organs

Question 10

what does half life depend on

Answer 10

clearance of drug from body by all eliminating organs (hepatic, renal, faeces, breath)

volume of distribution - a drug with large Vd will be cleared more slowly than a drug with a small Vd

Question 11

what does half life not depend on

Answer 11

drug dose or drug formulation

Question 12

when is half life relevant in clinical practice

Answer 12

• drug dosing (short half life needs more dosing)
• organ dysfunction (increases half life)
• adverse drug reactions or management of toxicity
• short half life increases risk of discontinuation/withdrawal symptoms

Question 13

define bioavailability

Answer 13

Fraction of the administered drug that reaches the systemic circulation unaltered (F)

Question 14

what is bioavailability of IV drugs

Answer 14

IV drugs has F=1 as 100% of drug reaches circulation

Question 15

what is bioavailablity of oral drugs

Answer 15

Oral drugs may have F<1 if they are incompletely absorbed or undergo first pass metabolism

Question 16

what is bioavailablity determined from

Answer 16

by measuring plasma concentration after oral and IV doses

Question 17

define distribution

Answer 17

Rate and extent of movement of a drug into tissues from blood

Question 18

what does distribution of water soluble drugs depend on

Answer 18

rate of passage across membranes

Question 19

what does distribution of lipid soluble drugs depend on

Answer 19

on blood flow to tissues that accumulate the drug

Question 20

define apparent volume of distribution Vd

Answer 20

the total amount of drug in body (dose)/ plasma concentration

Question 21

describe relationshp between rate of elimiation and volume of distribution

Answer 21

The rate of elimination is inversely proportional to Vd

K is the rate constant of elimination
K = CL/Vd
If clearance was zero – drug would not be removed and the plasma concentration would remain at equilibrium indefinitely

Question 22

define steady state

Answer 22

A balance between drug input and elimination (Css)

Question 23

impact of slow elimination on steady state

Answer 23

A drug with slow elimination will take a long time to reach steady state, and it will accumulate high plasma concentrations before elimination rate rises to match drug infusion
Css = rate of infusion/ CL

Question 24

what route is most long term drug adminstration

Answer 24

oral route

Question 25

describe oral administration

Answer 25

Doses are intermittent so will have peaks and troughs

Rate of absorption will affect the profile; rapid = exaggerated peaks, slow = flatter peaks

Question 26

define genomics

Answer 26

the study of the genomes of indivudals and organisms that examines both the coding and non codin regions.

the study of genomics in humans focuses on areas of the genome associated with health and disease

Question 27

define pharmacogenomics

Answer 27

the use of genetic and genomic information to tailor pharmaceutical treatment to an individual

Question 28

how do we currently prescribe

Answer 28

1. patient diagnosed
2. standard treatment at standard dose initaied
3. genetic variation leads to poor response/side effects
4. drug choice or dose is altered
5. patient receives optimal treatment
6. patients genome used to identify most appropriate dose and treatment

Question 29

what is the pharmacogenetic approach to prescribing

Answer 29

1. patient diagnosed
   2.patients genome used to identify most appropriate dose and treatment