Pharmacokinetics & Drug Metabolism

Question 1

What is the journey of a drug through the body?

Answer 1

A ADME V(R)

Administration
Absorption
Distribution
Metabolism
Excretion
Voided (removal)

Question 2

What are the positives and negatives of IV administration of drugs?

Answer 2

Positive - Very rapid onset of action. If we want systemic exposure very quickly IV is the way to go.
Negative - Invasive and requires training

Question 3

Why is intraperitoneal administration of drugs not very common?

Answer 3

This is because the peritoneal cavity has a very rich blood supply so you can get a drug through that blood supply

Question 4

Define systemic, local, enteral and parenteral

Answer 4

Systemic - where the entire organism is exposed to the drug
Local - restricted to one area
Enteral - via the GI tract
Parenteral - everything but the GI tract

Enteral and parenteral are routes of administration

Question 5

Which route of administration is easiest to achieve?

Answer 5

Enteral - parenteral requires more skill

Question 6

List the routes of administration

Answer 6

Dermal, subcutanous, intravenous, intramuscular, inhalation, ingestion, intraperitoneal

Question 7

In terms of an enteral route of administration describe the movement of a drug when ingested

Answer 7

The drug enters the GI tract where it is absorbed and taken to the liver via the hepatic portal system. From the liver it then enters the systemic circulation

Question 8

How do drug molecules move around the body?

Answer 8

Bulk Flow Transfer - bloodstream

Diffusion Transfer - short distances molecule by molecule

Question 9

What kind of environment do drugs have to traverse?

Answer 9

Aqueous and Lipid environments

Question 10

What are compartments and barriers?

Answer 10

Compartments - Aqueous e.g Blood, lymph, extra-cellular fluid, intra-cellular fluid
Barrier - Lipid e.g Cell membanes

Question 11

In what state do drugs exist in?

Answer 11

Most drugs are either weak acids or weak bases. Therefore they exist in their non-ionised (non-polar) and ionised (polar) forms - the ratio of ionised to non-ionised forms depends on the pH and pKa of the molecules

Question 12

What is the pKa of a drug?

Answer 12

The H+ concentration/pH at which 50% of the drug exists in its ionised polar form.

IMPORTANT to understanding pH partition hypothesis

Question 13

Explain the pH partition hypothesis

Answer 13

See Notes

Question 14

What does the ratio of ionised to non-ionised forms of a drug depend on?

Answer 14

It depends on the pH of the environment and the pKa of the drug

Question 15

What is ion trapping?

Answer 15

Once the drug goes to the liver and into the systemic circulation, any ionised drug becomes trapped in an aqueous environment. Lipid barrier that prevents absorption

Question 16

What is the pH of the stomach and the pKa of Asprin? What does that mean in terms of the pH partition hypothesis?

Answer 16

pH 1
pKa 3.4
See notes

Question 17

What are the factor influencing drug distribution?

Answer 17

Regional blood flow
Extracellular binding (PPB)
Capillary permeability
Localisation in tissues

Question 18

What percentage of acidic drugs tend to be bound to plasma proteins?

Answer 18

50-80% - bound to albumin (can bind to ionised and non-ionised forms of the drug)

Question 19

What type of environment is fat?

Answer 19

Lipophilic environment because it isn’t highly perfused - drugs that are lipophilic will localise in fatty tissue (brain + testes)

Question 20

What are the two major routes of excretion?

Answer 20

Kidney - responsible for the elimination of most drugs (most drugs are made water soluble)
Liver - some drugs are concentrated in the bile and secreted into the intestines

Question 21

What kind of drugs are excreted by the liver?

Answer 21

Large molecular weight drugs

Question 22

What is the main method of the excretion of drugs from the kidneys?

Answer 22

Secretion not ultrafiltration

Question 23

What happens at the glomerulus, proximal tubule, proximal and distal tubules?

Answer 23

Glomerulus - Drug-protein complexes are NOT filtered
Proximal tubule - Active secretion of acid and bases
Proximal and distal tubule - Lipid soluble drugs are reabsorbed

Question 24

Why are lipid soluble drugs reabsorbed?

Answer 24

Urine is an aqueous environment - How does lipid material change pH. Lipid soluble means it will be reabsorbed

Question 25

Why might IV sodium bicarbonate increase asprin excretion?

Answer 25

CHECK notes - ask question to lecturer

Question 26

Describe the excretion by the liver

Answer 26

See notes

Question 27

What leads to drug persistence?

Answer 27

Enterohepatic cycling and biliary excretion

Question 28

What pharmacokinetic characteristics can be used to predict time-course of drug action?

Answer 28

Bio availability (linked to absorption)
Apparent volume of distribution (linked to distribution)
Biological half-life (linked to metabolism/excretion)
Clearance (linked to excretion)

Question 29

Define:
Bio availability
Apparent volume of distribution
Biological half-life
Clearance

Answer 29

See notes

Question 30

Define first order kinetics

Answer 30

The rate of elimination of a drug where the amount of drug decreases at a rate that is proportional to the concentration of drug remaining in the body

Question 31

Draw a graph and label the axis for first order kinetics

Answer 31

See diagram

Question 32

How do you calculate volume distribution?

Answer 32

The dose divided by the initial concentration of drug in the plasma