Fundamental principles of pharmacology 2

Question 1

Describe the concentration response curve

Answer 1

-Concentration below which drug does nothing
-Linear relationship between 20% and 80%
-Concentration above which you won’t get a higher response

Question 2

What is the Emax?

Answer 2

-Maximum effect (response) that a drug can produce

Question 3

What is the EC50?

Answer 3

-Concentration of a drug that produces 50% of the maximum response
-Used to quantify potency of drug

Question 4

What is a receptor and what does it do?

Answer 4

-Protein macromolecules usually inserted across the lipid bilayer

Function:
-Recognition/detection of extracellular molecules
-Transduction - bind and change cell activity

Question 5

Why are receptors about which molecules they bind?

Answer 5

-Very specific so are classified according to the drugs they bind to
-Specificity helps reduce side effects of drugs, less likely to bind wrong receptors

Question 6

Affinity and KD definition

Answer 6

Affinity - Molar concentration of a drug required to occupy 50% of the receptors at equilibrium
-This concentration is the KD
-Drugs with high affinity have a low KD

Question 7

What is the KD called?

Answer 7

KD is the equilibrium dissociation constant

Question 8

What is KD a measure of?

Answer 8

-How tightly the receptor holds onto the drug once they come together
-Drugs with high affinity (low KD) stay bound for a relatively long time - have a slow dissociation rate (K-1 very small)

Question 9

What are drugs that have affinity and efficacy called?

Answer 9

Agonists
-They bind and change the shape of the receptor - a conformational change
-This leads to a response in a cell or tissue
-All neurotransmitters and hormones are agonists

Question 10

Full agonists vs Partial agonists

Answer 10

Full agonists:
-High efficacy are very effective at activating receptors/producing a biological response

Partial agonists:
-Low efficacy and less effective at activating receptors/producing a biological response

Question 11

Is the EC50 for an agonist the same as its KD?

Answer 11

NO
-The KD (available receptors) tells you about affinity, not efficacy
-The EC50 (response) is a measure of affinity and efficacy

Question 12

What are antagonists?

Answer 12

-Competitive antagonists compete with the agonist for the same site on the receptor but don’t activate it (have affinity but zero efficacy)
-Can be reversible or irreversible
-Non-competitive antagonists act at a different site on the receptor or another molecule closely associated with it

Question 13

How to reverse reversible competitive antagonists?

Answer 13

-Inhibitory effects overcome by increasing the concentration of the agonist
-The blockade is surmountable

Question 14

What is the dose ratio?

Answer 14

-The extent of the shift in position of the agonist curve produced by the antagonist can be measured by the dose ratio
i.e. the ratio of the concentration of agonist producing the same response in the presence and absence of the antagonist

Question 15

What is the pA2?

Answer 15

-The negative logarithm of the molar concentration of antagonist that necessitates that you double the agonist concentration to produce the same response (i.e. produces a dose ratio of 2)
-Affinity of antagonist for receptor quantified using pA2

Question 16

Worked example

Answer 16

-The bigger the pA2, the less antagonist you need to produce a dose ratio of 2, the higher the affinity of the antagonist (bigger is better)

Question 17

Reversible competitive antagonist graph

Answer 17

-Produces shift to the right
-More antagonist, more shift

Question 18

Irreversible competitive antagonist graph

Answer 18

-Shift is not parallel
-Inhibition they produce is not overcome by increasing agonist concentration
-It is not surmountable