2. Drug-receptor interactions. Dose-response relations, therapeutic concepts

Question 1

At what threshold would the effect of a drug be seen?

Answer 1

When sufficient numbers of receptors are occupied we may see effect

Question 2

The fraction of receptors in each state are dependent on…

Answer 2

Dissociation constant K_d

• Concentration of ligand at which 50% of available receptors are occupied*
• Lower K_d indicates a tighter drug-receptor interaction (high affinity)*

Question 3

Pharmacodynamics of a drug

Answer 3

Relationship between dose of drug and organism’s response to that drug

Question 4

Graded dose-response curve

Answer 4

Demonstrates effect of a drug as a function of its dose

Question 5

Max drug-receptor binding occurs when…

Answer 5

[LR] (cc of ligand-receptor complexes)

=

[Ro] (cc of receptors)

or [LR]/[Ro]=1

Question 6

EC₅₀

Answer 6

Potency of drug (cc at which drug elicits 50% of its max effect)

Question 7

Emax

Answer 7

Efficacy (max response produced by a drug)

Question 8

Potency & efficacy relationship

Answer 8

Not intrinsically related, a drug can be extremely potent but have little efficacy & vice versa

Question 9

Quantal dose-response relationship

Answer 9

Describes cc of a drug that produces a given effect in a population

• Goal is to generalise a result to a population rather than examine grade of effect of different drug doses on a single individual

Question 10

ED₅₀

Answer 10

Dose that produces therapeutic response in 50% of population

Question 11

TD₅₀

Answer 11

Toxic dose in 50% of the population

Question 12

LD₅₀

Answer 12

Death in 50% of the population

Question 13

Agonist

Answer 13

Drugs that bind to its receptor and favour active receptor conformation

• More potent drugs are those that have a higher affinity for their receptors
• More efficacious drugs are those drugs that cause a higher proportion of receptors to be activated

Question 14

Partial agonist

Answer 14

Binds to a receptor at its active site but produces only a partial response

Question 15

Because partial and full agonists bind to the same site on a receptor…

Answer 15

A partial agonist can reduce response produced by a full agonist

(Competetive agonist)

Question 16

Inverse agonist

Answer 16

• The receptor must have a basal level activity in the absence of any ligand
• Decreases activity below basal level

Question 17

Antagonist

Answer 17

Drug that prevents activation of receptor by the agonist

• Can bind to active/allosteric site of receptor for agonist
• Reversible/irreversible

Question 18

Competetive antagonist

Answer 18

Reduces the potency of the agonist

Question 19

Non-competitive antagonist

Answer 19

Reduces efficacy of agonist

Question 20

Chemical non-receptor antagonist

Answer 20

Inactivate an agonist before it has the opportunity to act, by chemical neutralisation

Question 21

Physiological non-receptor antagonist

Answer 21

Cause a physiological effect opposite to that induced by an agonist, by blocking or activating a receptor

Question 22

Therapeutic window

Answer 22

Range of doses of a drug that elicits a therapeutic response, without unacceptable adverse effects in a population

• Can be quantified by therapeutic index

Question 23

Therapeutic index =

Answer 23

[LD₅₀]/[ED₅₀]

• Provides a single number that quantifies the relatively safety margin
• Large TI = Large/wide therapeutic window, TI = 10
• Small TI = Small/narrow therapeutic window, TI = 5

Question 24

What is shown?

Answer 24

Continuous dose-response curve

Question 25

What is shown?

Answer 25

Quantal dose-response curves

Effects on the population

Question 26

Affinity

Answer 26

The degree to which a drug tends to combine with a receptor

Question 27

Efficacy

Answer 27

The desire to produce a successful result

Question 28

Answer 28

Full agonist: Heroin and others

Question 29

Answer 29

Partial agonist - Buprenorphine

Question 30

Title the figure

Answer 30

Occupancy model

Question 31

Title the figure

Answer 31

Two-state model

Question 32

Answer 32

Full agonist

Question 33

Answer 33

Partial agonist

Question 34

Answer 34

Neutral antagonist

Question 35

Answer 35

Inverse agonist

Question 36

Give an example of inverse agonists

Answer 36

Antihistamines

Question 37

Answer 37

Full agonist

Question 38

Answer 38

Partial Agonist

Question 39

Answer 39

Partial agonist

Question 40

Examples of competitive antagonists

Answer 40

• Morphine
• Benzodiazepines
• MACh

Question 41

Give example of noncompetitive antagonists

Answer 41

• Ketamine (on NDMA receptors)

Question 42

When looking at a dose-response curve, a drug is not safe if…

Answer 42

The LD₅₀ crosses with the ED₅₀

Question 43

Compare:

1. Which is more potent, butorphanol or morphine?
2. Which is more effective, butorphanol or morphine?

Answer 43

1. Butorphanol
2. Morphine

Question 44

Full agonist: Efficacy + affinity

Answer 44

High efficacy + affinity

Question 45

Full antagonist: Efficacy + affinity

Answer 45

High affinity; no efficacy

Question 46

Partial agonist: Efficacy + affinity

Answer 46

High affinity; partial activation of receptor

Question 47

Inverse agonist: Example

Answer 47

Antihistamine

Reverses the function of the agonist