PHARM - Drug Targets and Action - Week 2

Question 1

Define volume of distribution, and what it is not an indication of?

Answer 1

Indication of extent of distribution, but not location.

Question 2

What is a composite of colume of distribution and clearance?

Answer 2

Half life, the time to stady state and dose interval

Question 3

What four factors affect the concentration of of a drug in blood.

Answer 3

Absorption
Distribution
Metabolism
Excretion

Question 4

Define pharmacokinetics.

Answer 4

Effects of the body on a drug

Question 5

Define pharmacodynamics.

Answer 5

Effects of a drug on the body

Question 6

Define an agonist.

Answer 6

A molecule that fits into a receptor to activate it.

Question 7

Define an antagonist.

Answer 7

A molecule thats fits into a receptor to block its action.

Question 8

Define an ion channel blocker.

Answer 8

A molecule that prevents permeation through the channel by blocking it.

Question 9

Define an ion channel modulator.

Answer 9

A molecule that increases or decreases an ion channel’s permeation.

Question 10

Define an enzyme inhibitor.

Answer 10

A molecule that fits into an enzyme to inhibit its normal reaction.

Question 11

Define an enzyme false substrate.

Answer 11

A molecule that fits into an enzyme to result in an abnormal metabolite.

Question 12

Define a prodrug.

Answer 12

A drug that once catalysed by a specific enzyme, will result in an active drug as the product/metabolite.

Question 13

Outline the interaction between a false substrate and a transporter channel.

Answer 13

It results in the accumulation of an abnormal compound.

Question 14

Define affinity.

Answer 14

A quantifiable measure of the molecular attraction to a receptor.

Question 15

Describe the equation for the law of mass action.

Answer 15

[D] + [R] –(k+1)–> [DR] and

[D] + [R]

Question 16

Define Kd, and what it represents.

Answer 16

It is the dissociation constant, the concentration at which 50% of receptors are bound.

Question 17

What does a low Kd represent in terms of affinity?

Answer 17

A low Kd indicates a high affinity for the receptor.

Question 18

What is the main factor that affects the effect of a drug?

Answer 18

The dose

Question 19

How do receptors make drugs powerful and potent?

Answer 19

The amplification mechanisms through 2nd messengers.

Question 20

Describe the following processes in both their mechanisms and in terms of how quickly they signal (in order from quickest to slowest):
Kinase-linked receptors
G protein-coupled receptors
Nuclear receptors
Ligand-gated ion channels

Answer 20

Ligand-gated ion channels - millisecond timescale
-Involves the movement of ions across a channel, leading to hyper- or depolarisation.

G protein-coupled receptors - second timescale
-Involves the amplification of a signal through signal trunsduction and second messengers.

Kinase-linked receptors - hour timescale
-Involves the phosphorylation of a protein factor, which will eventually result in gene transcription and protein synthesis.

Nucleus receptors - hour timescale
-Involves the drug entering the nucleus via a nuclear pore, and inducing gene transcription.

Question 21

Consider a concentration-response curve. Describe its shape, and define the axes, what 50% on the y-axis represents, what the upper and lower limits of the graph mean.

Answer 21

It is a sigmoidal curve, with response as the y-axis, and Log concentration as the x-axis.
pEC50 represents the 50% mark on the response axis.
The upper limit represents Emax, and the drug is an agonist.
The lower limit of the graph represents an antagonistic drug.

Question 22

Define the following:
Emax
EC50

Answer 22

Emax is a measure of the efficacy of a drug, and is represented by the upper limit of a concentration-response curve.

EC50 is a measure of the potency of a drug, how much drug is needed, and is represented by the 50% mark on the response axis of a concentration-response curve.

Question 23

Can antagonists elicit a response in the body?

Answer 23

Yes, the effect is observed when an agonist is present.

Question 24

Do antagonists have efficacy in vitro? What about in vivo, and what is this called?

Answer 24

They do not in vitro, but in vivo they do, and this is called clinical efficacy.

Question 25

Describe how both an agonist and antagonist interact with a receptor, and what kind of efficacy applies to both.

Answer 25

Both drugs will bind the receptor, but only agonists will elicit a cellular response.
Agonists have intrinsic efficacy, while antagonists have clinical efficacy.

Question 26

Consider an antagonist’s clinical efficacy. Is a bigger response generally always better? Explain.

Answer 26

No, you need to optimise the benefit (clinical efficacy), while minimising the risk (clinical toxicity).

Question 27

True or false

All drugs have more than one action.

Answer 27

True

Question 28

Describe the minimum effective, and maximum tolerated dose, and where the therapeutic window fits in.
Bearing your response in mind, how does this fit into a situation where a drug has two different therapeutic and toxic mechanisms? Name a consequence of this.

Answer 28

The minimum effective dose is the dose at which an effect first begins.
The maximum tolerated dose maximum dose delivered that does not cause death.
Between these two doses is the therapeutic window.
As all drugs have more than one action, unwanted side effects will constrain the usable dose of a drug.

Question 29

What factors of a drug does pharmacodynamics deal with (4)?

Answer 29

Where it goes - affinity and selectivity

How much is needed - its potency and efficacy

Question 30

What factors of a drug does pharmacokinetics deal with (6)?

Answer 30

How much is needed - its potency and efficacy
How often it is needed (dictated by)
-Absorption
-Distribution
-Metabolism
-Excretion

Question 31

Consider an antagonist’s clinical efficacy. Is a bigger response generally always better? Explain.

Answer 31

No, you need to optimise the benefit (clinical efficacy), while minimising the risk (clinical toxicity).

Question 32

True or false

All drugs have more than one action.

Answer 32

True

Question 33

In a sick patient, what 3 factors will the drug action depend on?

Answer 33

Target distribution/function
-pathophysiology

Organ system response
-reflexes

Idiosyncrasy
-genetics