Lecture 31 - Drugs Acting Through Receptors 1

Question 1

What are the elements of drug - receptor interactions?

Answer 1

Ligand
Receptor
Biochemistry
Response

Question 2

Drugs won’t work without …

Answer 2

binding

Question 3

What is the ‘magic bullet’ concept?

Answer 3

This is an aspiration in pharmacology that is never reached, whereby a drug is specific for a single receptor

Question 4

What determines binding of a drug to a receptor?

Answer 4

Shape

Forces

Question 5

Describe the strength and range of ion-ion forces

Answer 5

Strong

Act over large distances

Question 6

Describe the strength and range of hydrophobic forces

Answer 6

Weak
Act over short distances

However, there are usually many of these bonds, which can summate to form strong interactions.

Question 7

What happens to binding when the concentration of the ligand changes?

Answer 7

Higher ligand conc.: more binding

Question 8

What is drug affinity?

Answer 8

A measure of how stable the drug-receptor complex is

Question 9

What is ‘mass action’

Answer 9

The rate of chemical reaction is proportional to the concentration of the reactants

Question 10

What do ‘A’ and ‘R’ represent?

Answer 10

A: agonist
R: receptor

Question 11

What is the forward rate of reaction?

Answer 11

(A) x (R) x forward rate constant

Question 12

How is the forward rate constant represented?

Answer 12

k+1

Question 13

How is the backward rate constant represented?

Answer 13

k-1

Question 14

What is the backward rate of reaction?

Answer 14

(AR) x backward rate of reaction

Question 15

What happens to the rates of reaction at equilibrium?

Answer 15

Forward rate = backward rate

Question 16

What is the equilibrium dissociation constant?

Answer 16

Ka

Question 17

When are half of the ligands bound to the receptor?

Answer 17

Ka = (A)

Question 18

What is the measure of affinity?

Answer 18

Ka

pKa

Question 19

At t=0, why is the forward rate of reaction really high?

Answer 19

Because there are no drug-receptor complexes, all the drug is binding to the receptors at this time

Question 20

Which parameters affect that rate at which the receptor is occupied?

Answer 20

• (A)
• k-1
• Affinity

Question 21

A … drug will form complexes at lower concentrations

Answer 21

Higher affinity

Question 22

High pKa represents …

Explain

Answer 22

low affinity

Low affinity drugs require more of the drug to have half of the receptors occupied

Question 23

Why do we need to get real?

Answer 23

Because occupancy does not always mean response

Question 24

What is a way that we can measure drug response?

What is this?

Answer 24

EC50

This is the concentration of the drug required to give 50% of the maximal effect on the tissue

Question 25

Describe the features of steroid hormones binding to their receptors.

Answer 25

Very strong binding via hydrophobic forces

Though these bonds are weak on their own, there are many of the bonds, so they summate to have a great effect.

Question 26

Why are high affinity drugs favourable?

Answer 26

Increased specificity
–> fewer off target effects

Required dose is lowered

Question 27

What does a low EC50 mean?

Answer 27

A potent drug

Question 28

What does a low pEC50 mean?

Answer 28

High potency drug