Drug target sites

Question 1

What do drugs do?

Answer 1

Produce specific effects

Question 2

What are the target sites drugs act on?

Answer 2

Receptors

Question 3

What are agonists?

Answer 3

A drug which acts on a receptor and produces a response (increase/decrease activity of the cell)

Question 4

What is an antagonist?

Answer 4

A drug which prevents the response of an agonist

Question 5

What are drug receptor controls?

Answer 5

Selectivity of drug effect
Magnitude (size) of response
Mechanisms to mimic/prevent physiological function

Question 6

What is a dose?

Answer 6

Amount of drug

Question 7

What is concentration?

Answer 7

Amount of drug per unit volume

Question 8

What are the common units of a dose?

Answer 8

Micrograms (ug, 10-6 grams)

Nanomoles (nmoles, 10-9 moles)

Question 9

What are the common units of concentration?

Answer 9

Micromolar (uM, 10-6 moles per litre)

Nanomolar (nM, 10-9 moles per litre)

Question 10

How does an agonist bind to its receptor?

Answer 10

With weak bonds

E.g. electrostatic forces, van der waals bonds and hydrogen bonds

Question 11

What are the reactions between an agonist and receptor to produce an effect?

Answer 11

Agonist + Receptor ←→ Agonist-Receptor
[A] + [R] ←→ [AR]
[AR]→Effect

Question 12

What are drug-receptor interactions?

Answer 12

‘Stereo-selective’

Question 13

How are ligand/receptor interactions defined?

Answer 13

In 3 dimensions

Question 14

What does the ligand/receptor interaction mean?

Answer 14

Display selectivity for one stereo-isomer of a ligand over another

Question 15

What is the magnitude of response?

Answer 15

[AR] = [A]

[RT] Kd + [A]

Question 16

What does [A] stand for?

Answer 16

Agonist concentration

Question 17

What does [AR] stand for?

Answer 17

Agonist-receptor concentration

Question 18

What does [Rt] stand for?

Answer 18

Total receptor concentration

Question 19

What does Kd stand for?

Answer 19

Dissociation sonstant

Question 20

What type of response is the magnitude of response?

Answer 20

Hyperbolic

Question 21

What are dose-response curves?

Answer 21

Hyperbolic

Complex relationship between dose and response

Question 22

What are log dose-response curves?

Answer 22

Sigmoid shape

Simple relationship between log dose and response, i.e. log-linear (between 20% and 80% maximum response)

Question 23

What information can be revealed from a log dose-response curve?

Answer 23

Threshold dose
Maximum dose
Effective dose range
Half-maximal effective dose
ED50

Question 24

What is the potency of a log dose-response curve?

Answer 24

Related to affinity of drug for receptor
Determines dose required for effect
ED50 is a useful index of potency

Question 25

What is the efficacy of a log dose-response curve?

Answer 25

An index of maximum response a drug can induce, i.t. its effectiveness

Question 26

What is the efficacy of full agonists?

Answer 26

Have high efficacy (1.0)

Produce the maximum response possible at a given receptor

Question 27

What is the efficacy of partial agonists?

Answer 27

Have low efficacy (<1.0)

Fail to produce the maximum response possible at a given receptor

Question 28

How do antagonists block agonists?

Answer 28

Act on the same receptor site as the agonist
Act at a different site in the pathway leading to a response
Activate an opposing physiological mechanism
Interact chemically with the agonist

Question 29

What are competitive antagonists?

Answer 29

Antagonists which act on the same receptor site as the agonist

Question 30

What do competitive antagonists do?

Answer 30

Have affinity for receptor

Compete with agonist molecules for the receptor

Question 31

Why is there no effect when an antagonist binds to a receptor?

Answer 31

Antagonist has no efficacy at the receptor

The antagonist/receptor complex cannot activate transduction mechanisms and therefore there is no effect

Question 32

What are the two type of competitive antagonists?

Answer 32

Reversible (Surmountable)

Irreversible (Insurmountable)

Question 33

What kind of bonds does a competitive reversible antagonist make with the receptor?

Answer 33

Weak bonds

Question 34

What can happen when agonist concentration is increased when a competitive reversible antagonist is attached to the receptor?

Answer 34

The chance of agonist molecules interacting with the receptor is increased
The effect of the antagonist can be reversed
The antagonist is competitive and reversible

Question 35

In the presence of a competitive reversible antagonist the agonist log-dose response curve changes how?

Answer 35

Is shifted to the right
Is parallel to the curve for the agonist acting alone
Has an unchanged maximum response

Question 36

What happens if the concentration of the agonist increases the reversible competitive antagonist?

Answer 36

The agonist overcomes the effect of the antagonist

Question 37

What kind of bonds does a competitive irreversible antagonist create with the receptor?

Answer 37

Covalent bonds

Question 38

What happens if an antagonist creates covalent bonds with the receptor?

Answer 38

The antagonist binds irreversibly to the receptor
Increasing the concentration of the Agonist cannot reverse the binding of the antagonist
The antagonist is competitive and irreversible

Question 39

In the presence of a competitive irreversible antagonist, what does the log-dose response curve look like?

Answer 39

Is not parallel to the log dose-response curve for the agonist acting alone
Has a depressed maximum response

Question 40

What can happen when agonist concentration is increased when a competitive irreversible antagonist is attached to the receptor?

Answer 40

Does not overcome the depression of the maximum response produced by a competitive irreversible antagonist

Question 41

What kind of agonist log-dose response curve do some competitive irreversible antagonists produce?

Answer 41

Parallel shift before producing a depression in the maximum response