4.1 Principles of pharmacology

Question 1

What is pharmacokinetic variability?

Answer 1

The variability of a drug between the dose and the serum drug concentration.
The change in plasma concentration of the drug over time.
Effectively what the body does to the drug.

Question 2

What is pharmacodynamic variability?

Answer 2

The relationship between drug dose and response.
Effectively what the drug does to the body.

Question 3

What is PK and PD?

Answer 3

PK = pharmacokinetics
PD = phramacodynamics

Question 4

What does [drug]se mean?

Answer 4

Square brackets = concentration
se = plasma
Dot above drug refers to how drug concentration changes in body with time.

Question 5

What factors influence pharmacokinetic variability?

Answer 5

• Age
• Disease (e.g. affecting liver, kindeys, CV system)
• Genetics
• Other xenobiotics (chemical substances affecting the body)

Question 6

What factors influence pharmacodynamic variability?

Answer 6

• Age
• Disease
• Genetics
• Other xenobiotics

Question 7

What is the host response divided into?

Answer 7

• Beneficial
• Harmful

Question 8

What is meant by the term therapeutics?

Answer 8

Process of optimising beneficial effects of a drug whilst minimising harmful effects.

Question 9

Why is pharmacokinetics important?

Answer 9

• Determines the drug concentration at the site of action (including on target and off target effects)
• Determines dose and dose-interval selection (time between doses)
• Determines if dose adjustment or dose-interval adjustment is needed (e.g. extremes of age, liver/kidney impairment, other xenobiotics)

Question 10

Pharmacokinetics is the net effect of which 4 simultaneous reaction types?

Answer 10

ADME
- Absoprtion
- Distribution
- Metabolism
- Elimination

Question 11

Drugs normally follow which 2 types of kinetics?

Answer 11

• Zero order kinetics
• First order kinetics

Question 12

What is meant by the term zero order kinetics?

Answer 12

• Where the amount of a drug changes at a constant rate.
• Rate of reaction is independent of drug concentration.
• Linear relationship between rate of change of drug concentration and time (straight diagonal line).

Question 13

What is meant by the term first order kinetics?

Answer 13

• Most drugs follow first order kinetics.
• Amount of drug changes at a rate that is proportional to the amount of drug in the body.
• The change in drug concentration over time is dependent on the initial drug concentration, heavy involvement of physiological mechanisms.

Question 14

What is meant by the term “velocity of reaction”?

Answer 14

The velocity of the reaction = rate of reaction

Question 15

Give examples of drugs that exhibit zero order kinetics.

Answer 15

• Alcohol
• Aspirin

Question 16

What is a non-linear pharamacokinetic model?

Answer 16

Non-linear relationship between dose and plasma concentration.
The drug has a narrow therapeutic index.
Small dosage increases in some patients may produce large rises in plasam concentrations with acute toxic side effects.
Narrow margin between therapeutic dose and toxicity.
E.g. phenytoin

Question 17

Define absorption in pharamcokinetics.

Answer 17

The passage of a drug from the site of administration to the plasma e.g. orally.

Question 18

What are the 2 key parameters in absorption?

Answer 18

Cmax and Tmax

Question 19

What is Cmax?

Answer 19

Maximum concentration of the drug in plasma.
Depends on dose and bioavailability.
Affected by ability to cross anatomical barriers and metabolism.

Question 20

What is Tmax?

Answer 20

The time of Cmax.
Affected by guy motility and splanchnic blood flow.

Question 21

What does AUC stand for?

Answer 21

Area under the curve.

Question 22

How can drugs cross anatomical barriers?

Answer 22

• Diffusion through lipids
• Using transporter molecules
• Through aquaporin channels
• Pinocytosis

Question 23

Which key factors influence the extent to which drugs can diffuse through lipids?

Answer 23

• Size of molecules
• Charge

pH of environment affects molecular polarity

Question 24

Define distribution in pharmacokinetics.

Answer 24

The extent to which a drug can enter a different anatomical compartment.

Question 25

What is volume of distribution (Vd)?

Answer 25

Relates the total amount of drug in the body to plasma concentration. Therefore determines loading dose.

Question 26

What is loading dose?

Answer 26

The appropriate drug concentration when it is first administered.

Question 27

Which 3 factors affect volume of distribution?

Answer 27

• Lipid/water solubility
• Plasma protein binding
• Carrier mediated transport (organic anion/cation transporters and P-glycoprotein transporters)

Question 28

What does Cp mean?

Answer 28

Plasma concentration.

Question 29

What is the main site of drug metabolism?

Answer 29

The liver

Question 30

Describe phase 1 metabolism.

Answer 30

Carabolic reactions which introduce active functional groups to the molecule, making it more reactive in preparation for phase 2.

Question 31

Describe phase 2 metabolism.

Answer 31

Conjugation of larger, water-soluble molecules to the functional group, this reduces the volume of distribution of the drug and increases renal clearance.

Question 32

What is the risk of bioactivation?

Answer 32

Risk of bioactivation: a relatively non-toxic drug can undergo phase 1 reactions and become toxic e.g. paracetamol.

Question 33

What is elimination in pharmacokinetics?

Answer 33

Loss of the drug from the body.

Question 34

What does Cl mean?

Answer 34

Clearance (Cl): determines relationship between dose rate and steady rate concentration.

Question 35

What are the 4 routes of drug elimination?

Answer 35

• Renal (ultrafiltration, tubular secretion or passive diffusion)
• Enterohepatic circulation (drug secreted into bile, released into intestines)
• Exhalation
• Sweat and stool (minor)

Question 36

What is half life?

Answer 36

Half life (t 1/2): time taken for the concentration of drug to fall by half.

Question 37

How many half-lives does it take to reach the steady state of a drug for drugs that undergo first order kinetics?

Answer 37

5 half-lives to reach steady state

Question 38

What happens to the peak:trough ratio as dose increases, and as dose-interval decreases?

Answer 38

Dose increase = peak:trough increase
Dose-interval decrease = peak:trough decrease

Question 39

Name the key structures that drugs act on.

Answer 39

• Receptors
• Ion channels, transporters and pumps
• Enzymes
• Genome
• Direct chemical and physical reactions

Question 40

What are the 2 ways of studying the interaction between a drug and its receptors?

Answer 40

• Studying affinity between drug and molecular target: use affinity constant. Produces Scatchard plot.
• Studying drug-receptor efficacy: to see if drug is actually having any effect on its target. Uses inhibitory constant (IC50) or excitatory constant (EC50).

Question 41

What are the 4 types of drug when looking at drug concentration and effect in pharmacodynamics?

Answer 41

• Full agonist
• Partial agonist
• Antagonist
• Inverse agonist (eliminate normal cell function and reverse cell development)

Question 42

Summarise the key 3 points regarding pharmacokinetics.

Answer 42

• Determines drug concentration at site of action
• Determines dose and dose interval selection
• May need to adjust dose and dose-interval in certain cases

Question 43

Summarise the key 3 points regarding pharmacodynamics.

Answer 43

• Determines type of response
• Determines potency
• Determines specificity