P1: How do drugs work?

Question 1

What is a drug?

Answer 1

A substance that affects the body and elicits a change in physiology

Question 2

What is the receptor theory for drug action?

Answer 2

• Drugs act by binding to targets and inducing a response

- Drugs do not work until they bind to their receptors

Question 3

Define agonist

Answer 3

• Agents that elicit a positive response

- Eg. mimic NTs

Question 4

Define antagonist

Answer 4

• Agents that act as inhibitors

- Prevent activity of endogenous hormones, enzymes and neurones

Question 5

Define partial agonist

Answer 5

• Agents that elicit a positive response, but not to the complete extent possible
• Used for controlling

Question 6

Define the law of mass action

Answer 6

The rate of a chemical reaction is directly proportional to the product of the activities or concentrations of the reactants

(ROR = Conc of reactants)

Question 7

What is Kd? (2)

Answer 7

This is the dissociation constant, which is the concentration of a drug which, at equilibrium, occupies 50% of the available receptors.

It measures the likelihood that a Drug and Receptor will dissociate, higher Kd = lower binding.

Question 8

What is Ka?

Answer 8

Affinity constant
indicates the readiness of the drug binding to a receptor
The higher the affinity, stronger the binding

Question 9

Higher Kd means _____ affinity

Answer 9

Lower

Question 10

Higher Ka means _____ affinity

Answer 10

Higher

Question 11

Define potency

Answer 11

Dose of a drug necessary to have an effect

Question 12

What does a low dosage say about the potency of a drug

Answer 12

Lower dosage = Higher potency

Question 13

Define Efficacy

Answer 13

The effectiveness of a drug

Question 14

What is Emax

Answer 14

Maximum effect achievable

Question 15

What are the 3 major types of receptor antagonism?

Answer 15

• Reversible competitive
• Irreversible competitive
• Allosteric

Question 16

Describe reversible competitive antagonisms affect on the Emax and log,dose(agonist) response curve

Answer 16

Emax not depressed

Parallel shift to the right in the dose response curve (EC50 rises)

Question 17

Describe the mechanism of irreversible competitive antagonism

Answer 17

Binds covalently to the receptor active sites, therefore:

• decrease total number of available receptors
• decreases maximum response achievable (Emax)

Question 18

Where do allosteric antagonists bind?

Answer 18

Binds to a separate site on the receptor from the ligand

Question 19

How do allosteric antagonists work?

Answer 19

• Alters conformation of receptor

- Limiting agonist binding

Question 20

What does pA2 rank?

Answer 20

Antagonist potency

Question 21

What is the EC50

Answer 21

This is the dose of a drug needed for a half maximal response, it is a measure of potency.

Question 22

What can a Scatchard Plot be used for with drugs

Answer 22

These can detect drugs that can have 2 or more binding sites with different affinities

Question 23

What is the therapeutic window

Answer 23

This is the gap in doses between therapeutic and toxic effects

Question 24

What is an inverse agonist and name an example

Answer 24

Elicits the opposite response to the endogenous ligand e.g. naloxone for heroin overdose

Question 25

How is the dissociation constant (Kd) related to the affinity constant (Ka)

Answer 25

1/Kd = Ka | Affinity constant is inversely proportional to the dissociation constant

Question 26

What is the shape of a dose response curve with Dose(agonist) on the x-axis and Response on the y-axis

Answer 26

Rectangular hyperbola

Question 27

What is the shape of a dose response curve with Log[Dose(agonist)] on the x-axis and Response on the y-axis

Answer 27

Sigmoidal curve

Question 28

Give an example of a reversible, competitive antagonist

Answer 28

Tolazoline on alpha-adrenceptors

Question 29

How does irreversible competitive antagonism affect a Log Dose [Agonist]/Response curve

Answer 29

Non parallel shift and depressed Emax Occasionally parallel shifts and no depression of the maximum - spare receptors

Question 30

Give an example of an irreversible competitive antagonist

Answer 30

Phenoxybenzamine on alpha-adrenoceptors

Question 31

How does allosteric antagonism affect a Log[Dose]/Response

Answer 31

No change in EC50, Reduced Emax

Question 32

Gives an example of a reversible and irreversible allosteric antagonist

Answer 32

Reversible - Memantine on NMDA receptors | Irreversible - aspirin on cyclo-oxygenase 1

Question 33

What kind of drug are schild plots valid for

Answer 33

competitive antagonists

Question 34

What is the x - intercept in a schild plot

Answer 34

an estimate of the antagonist equilibrium dissociation constant, pA2.