Quantitative pharmacology

Question 1

What is a drug?

Answer 1

A chemical compound that when applied to a biological system alters its function in a specific manner.

Question 2

What is affinity?

Answer 2

Strength of interaction between drug and receptor.

Determined by chemical forces involved (hydrogen, VdWs) of drug with the receptor binding site, at minimal free energy.

Question 3

What determines the probability that a drug will bind to its binding site?

Answer 3

The affinity of drug for site

The concentration of the drug

Question 4

What is the efficacy

Answer 4

Ability of drug to conformationally change receptor and trigger response

Question 5

Are efficacy and affinity related, give one example?

Answer 5

No. For evidence: the antagonist has high affinity and zero efficacy

Question 6

What is potency and what effects potency?

Answer 6

Effectiveness of a drug (how much needed to produce an effect of given intensity)

Affected by affinity and efficacy

Question 7

What is an agonist?

Answer 7

A drug than combines with the receptor to produce a response

Question 8

What is an antagonist?

Answer 8

A drug that combines with the receptor without producing a response

Question 9

What does the law of mass action state?

Answer 9

The rate of a chemical reaction is proportional to the concentrations of the reacting substances.

Question 10

What is occupancy and why is it an important parameter to use?

Answer 10

Proportion of receptors that are bound to ligand, including the receptors that are membrane bound (concentration of receptor+ligand discludes membrane bound receptors).

Question 11

What is the Hill-Langmuir equation?

Answer 11

Proportion of AR (ligand receptor complexes) = [A]/[A] + Ka (equilibrium dissociation constant)

Question 12

What is the Ka?

Answer 12

Concentration of the drug at which 50% of the receptors are occupied

Question 13

How does affinity affect Ka?

Answer 13

The higher the affinity the lower the Ka, as less drug is required to reach the same occupancy

Question 14

What does Ka equal (equation)?

Answer 14

Ka=K^-1/K^+1

Question 15

What does Hill-Langmuir resemble? Why is it not the same?

Answer 15

Michaelis-Menten. No Vmax as maximum occupancy is 1

Question 16

What does proportion of receptors occupied at equilibrium depend on?

Answer 16

Equilibrium constant (i.e. affinity constant and dissociation constant)

Ligand concentration

Question 17

What happens when Ka=[A]?

Answer 17

Par = 0.5 so gives concentration required to occupy 50%

Question 18

What is size of response achieved at equilibrium a function of?

Answer 18

Receptor occupancy and drug efficacy

Question 19

What is the relationship between agonist conc and receptor occupancy in non log and log form?

Answer 19

Non log: parabola, flattens out as you increase agonist

Log: sigmoidal

Question 20

When are 50% of receptors occupied?

Answer 20

Ka=1

Question 21

What is Ec50 and what determines it?

Answer 21

Effective drug concentration needed to produce 50% of maximal response.

Determined by affinity and efficacy

Question 22

Why does Ka>Ec50 normally?

Answer 22

Spare receptors if drug response lasts longer than receptor drug interaction.

Number of receptors larger than the number needed to produce a full response.

Question 23

What does the agonist dose response curve look like?

Answer 23

Sigmoidal through origin

Question 24

How do full agonists affect the dose response curve?

Answer 24

Can have different affinities and therefore different Ka values.

The curve is shifted left or right in this instant.

Left for higher affinity and right for lower affinity.

Question 25

How do partial agonists affect the dose response curve?

Answer 25

Partial agonists are described as having different efficacies to a full agonists (decreased efficacy).

Therefore the curve moves up and down (different max response).

Question 26

How do antagonists affect the dose response curve?

Answer 26

No efficacy so no response at all

Question 27

What is the equipotent molar ratio?

Answer 27

Used to establish relative amount of given drug needed to generate same size response as other drug in same tissue

Question 28

Describe dose response curve in the presence of a (reversible) competitive antagonist

Answer 28

Curve still reaches maximum level but moves mainly parallel and right (harder to ellicit response, more agonist needed to produce given response)

EC50 increases until it gets closer and closer to Kd

Question 29

What is the dose ratio?

Answer 29

Ratio by which agonist concentration has to increase to overcome competition by antagonist concentration.

Question 30

Curve for irreversible competitive antagonist and EC50?

Answer 30

Reduces maximum response (fewer receptors available), effect of antagonist increases with exposure time.

EC50 doesn’t increase much unless spare receptors present

Question 31

What is the effect of non competitive inhibitors on the dose response curve?

Answer 31

To the right and less steep than for competitive irreversible (further to the right), decreased maximal response.

May increase EC50

Question 32

How do you calculate dose ratio?

Answer 32

Dose Ratio = agonist concentration in the presence of an antagonist / agonist concentration (dose)
in the absence of antagonist

Question 33

What is an inverse agonist?

Answer 33

Binds to a receptor and produces a pharmacological response that is opposite to that of the corresponding agonist.

Question 34

What is the difference between an antagonist and inverse agonist?

Answer 34

Antagonist - prevent ligand binding, prevent agonist effects

Inverse agonist - opposite response to agonist

Question 35

Is Ka/ equilibrium dissociation constant affected by the presence of antagonists?

Answer 35

No

Question 36

What gives the concentration of free drug required for half-maximal binding of a given
receptor?

Answer 36

Kd