Fundamental Principles of Pharmacology II

Question 1

Definition of Emax

Answer 1

Max effect that a drug can produce

Question 2

Definition of EC50

Answer 2

Conc of a drug that produces 50% of the max response (umol, nmol, pmol)

Question 3

Definition of transduction

Answer 3

A molecule binds to extracellular binding site that induces a response on the cytosidic side

Question 4

Definition of affinity (Kd)

Answer 4

Molar con of a drug required to occupy 50% of the receptors at equilibrium
The higher the affinity, the lower the Kd

Question 5

Definition of efficacy

Answer 5

Drug binds to the receptor and activates the receptor

Usually an agonist

Question 6

Definition of partial agonist

Answer 6

Low efficacy, less effective

Question 7

Definition of full agonist

Answer 7

High efficacy, very effective at producing a biological response

Question 8

Definition of antagonist

Answer 8

Act to inhibit the effects of a NT/drug

Has affinity but doesnt activate it (no efficacy)

Question 9

Definition of competitive antagonists

Answer 9

Compete with agnostic for same site on receptor but doesnt activate it

Question 10

Definition of non competitive antagonist

Answer 10

Act as a different site on the receptor or another molecule closely associated with it

Question 11

Definition of dose ratio

Answer 11

Ratio of the conc of agonist producing the same response in the presence and absence of the antagonist

Question 12

Definition of pA2 (affinity of an antagonist)

Answer 12

-ve log of the molar conc of antagonist that necessitates that you double the agonist con to produce the same response

Question 13

Describe the relationship between the drug conc and the response

What are the key 3 features of this relationship

What determines the max response

Answer 13

Drug conc response curve gives rectangular hyperbola

Log drug conc response curve gives a symmetrical sigmoid

At the lowest conc, no response
In the linear segment, linear relationship between drug conc and response
At the highest conc, increasing [drug] does not increase response

Max response determined by tissues or drug

Question 14

What is Max and EC50 and the importance of both these values

Answer 14

Emax, max effect that a drug can produce
EC50, conc of drug that produces 50% of max response

Indicates the position of the curve on the conc axis
Used to quantify drug potency

Question 15

Describe receptors and their functions and properties

Answer 15

Protein macromolecules, normally inserted across lipid bilayer of cell

2 functions

• Recognition/detection
• Trasnduction

Selectively bind to certain chemicals (hormones, NT)

Question 16

Describe how drugs are classified and why specificity is important

Answer 16

Classified by the drugs they bind to
Drugs designed to bind specifically to a type of receptor
Leads to fewer side effects

Question 17

Describe the relationship between drugs, receptors and binding
Describe what happens to the drug after it has bound to the receptor

Answer 17

D+R <=> DR
Binding is reversible in most drugs
Drug is not altered by the receptor, not like enzymes

Question 18

Describe what affinity (KD) is and what it involves

Answer 18

Molar conc of drug required to occupy 50% of the receptors at equilbrium

Increased affinity, decreased Kd as fewer drug molecules needed to bind to the receptor
Receptors are continually bombarded by chemicals. Only those with affinity will bind

Drugs with a lower Kd stay bound for a long time, have a slow dissociation rate

Question 19

What is the difference between affinity and efficacy

Answer 19

Affinity, whether drug binds to receptor
Efficacy, whether drug activates receptor (normally agonist)

After binding, agonists produce a conformational change in receptor structure

Question 20

Describe how agonists work

Answer 20

A+R<=affinity=>AR<=efficacy=>AR*=>response

Activation of receptor => biological response
Efficacy, the ability of a drug to activate the receptor

Question 21

What are the 2 types of agonist

Answer 21

Partial

Full

Question 22

Describe partial agonists and their graph

Answer 22

Low efficacy, less effective
Often fail to produce a full response despite occupying all receptors

Sigmoid curve does not reach 100 % response but is very far to the R

Question 23

Describe full agonists and their graph

Answer 23

High efficacy, v effective at producing a response
Often produce max response whilst only activating some receptors

Sigmoid curve reaches 100% response but is very far to the L

Question 24

What are the 2 types of antagonists

Answer 24

Competitive

Non competitive

Question 25

Describe how competitive antagonists work

Answer 25

Compete with agonist for same site at the receptor molecule
No efficacy
Can be reversible/ irreversible

Question 26

Describe how non competitive antagonists work

Answer 26

Act at a different site on the receptor or another molecule slowly associated with it

Question 27

Describe how reversible competitive antagonists work

What are 3 examples

Answer 27

Inhibit effect of NT/hormone
Effects overcome by increasing [agonist]
-Propanolol, Mepyramine, Pancuronium

Question 28

What is the parallel shift to the right

Answer 28

Reversible competitive antagonists produce a parallel shift to the R

log [agonist] on x axis
Response on y axis

As the conc of agonist increases, the response increases as more antagonist is being outcompeted

However, if you increase the conc of antagonist, the curve shifts to the R so you need a greater conc of agonist to overcome the inhibition

Question 29

How would you calculate antagonist affinity

Answer 29

Extent of shift measured with dose ratio
Dose ratio, ratio of [agonist] producing the same response in the presence and absence of antagonist

Size of shift = measure of affinity of antagonist for receptor

Question 30

What is the pA2 of an antagonist

Answer 30

Affinity of an antagonist quantified with pA2

-log of molar conc of antagonist that necessitates that you double [agonist] to produce same response

Question 31

Describe the sigmoid curves produced by irreversible competitive antagonists

Answer 31

Shift is not parallel so block is not surmountable

As log [agnost] increases, response decreases, curve shifts to the R and gets shorter