ICPP 14 - Pharmacodynamics 1

Question 1

What is meant by pharmacodynamics & pharmacokinetics?

Answer 1

Pharmacodynamics = What a drug does to the body
Pharmacokinetics = What the body does to a drug

Question 2

How do endogenous and exogenous ligands exert an effect?

Answer 2

By binding to a target (usually a protein), which is most commonly a GPCR (33% of all drugs)

Question 3

What factor is critical in determining drug action?

What concept is used to measure this?

Answer 3

• The concentration of drug molecules around receptors

- Molarity - A 1M solution contains the molecular weight of the substance in grams (per litre)

Question 4

Give M, mM, uM, nM & pM in their standard forms

Answer 4

mM = 10^-3
uM = 10^-6
nM = 10^-9 
pM = 10^-12

A difference of 1000 between each.

Question 5

What is meant by the term “affinity”?

What does a stronger affinity mean?

Answer 5

Affinity is how well a ligand/molecule binds to its receptor. Therefore binding is governed by affinity

Higher affinity = Stronger binding.

Question 6

What common method measures binding?

Answer 6

Radioligand binding assays - use fluorescently labelled ligand to measure binding.

Question 7

What is Bmax and Kd?

What does a low/high Kd indicate?

Answer 7

Bmax = Maximum binding capacity (all receptors bound)
Kd = Concentration of drug at which 50% of receptors are bound 

Low Kd = High affinity
High Kd = Low affinity

Question 8

When plotting a receptor bound v drug concentration graph, how do we make the curve sigmoidal?

Answer 8

Use log units for concentration of the drug - therefore easier to deremine Bmax & Kd.

Question 9

What do antagonists lack in terms of pharmacodynamics that agonists have?

Answer 9

Both have an affinity for binding to the receptor, however antagonists lack intrinsic efficacy (an ability of a drug to produce a biological effect/stabilise the receptor in its active state).

Question 10

What is the difference between intrinsic efficacy and clinical efficacy?

Answer 10

Clinical efficacy is used as an indication of how well the treatment works, not the ability of a certain drug to produce a certain response.

Question 11

What is Emax and EC50?
What does EC50 determine?
What graph can we extrapolate these values from?

Answer 11

• Emax = The maximum possible response that a drug can elicit
• EC50 = Effective concentration 50, the concentration of drug that produces 50% of the maximum possible response.
• A dose/response curve or a Log dose/response curve

Question 12

What is the difference between concentration and dose?

Answer 12

Concentration = Known concentration of drug at site of action

Dose = Concentration at site of action is unknown, dose is just the amount given to the patient in mg it mg/kg.