pharmacodynamics: receptor theory

Question 1

What is binding governed by ?

Answer 1

affinity

stronger binding= increased affinity

Question 2

What is activation governed by?

Answer 2

intrinsic efficacy

Question 3

What do agonists show?

Answer 3

intrinsic efficacy
efficacy
affinity

Question 4

What do antagonists show?

Answer 4

affinity only

Question 5

What is clinical efficacy?

Answer 5

measure of how well treatment achieves its aims

Question 6

How can you measure binding of ligand?

Answer 6

radioligands

bound vs unbound and different concentrations

Question 7

What is Kd?

Answer 7

measure of affinity
lower kd greater affinity
the concentration of ligand required to occupy 50% of the available receptors

Question 8

Name a high affinity antagonist used to treat heroin overdose ?

Answer 8

naloxene

Question 9

What is EC50?

Answer 9

effective concentration giving 50% of the maximal reponse

measure of agonist potency

Question 10

What is Bmax?

Answer 10

the binding capacity gives info about number of receptors

Question 11

What is Emax?

Answer 11

maximal response

Question 12

What is potency reliant on?

Answer 12

affinity
intrinsic efficacy
cell/ tissue specific components such as receptor number

Question 13

What makes salbutamol selective for beta 2

Answer 13

route of administration

selective efficacy

Question 14

What makes salmeterol selective for beta 2

Answer 14

affinity for beta 2

Question 15

Why may maximal response require less than 100% binding occupancy?

Answer 15

spare receptors

reponse often controlled or limited by other factors

Question 16

What do spare receptors increase?

Answer 16

sensitivity and potency

allow response at low concentration of agonist

Question 17

What happens to receptor number at low activity?

Answer 17

increase

up regulation

Question 18

what happens to receptor number at high activity?

Answer 18

decrease

down regulation

Question 19

What are partial agonists?

Answer 19

have lower intrinsic efficacy

work in absence or low levels of endogenous ligand but can also act as antagonist if high levels of full agonist

Question 20

Explain how buprenorphine works to inhibit heroin effect?

Answer 20

higher affinity so blocks receptor for heroin but only a partial agonist so reduced response

Question 21

What is reversible competitive antagonism? give an example?

Answer 21

relies on dynamic equilibrium between ligand and receptor
increase antagonist to increase inhibition
inhibition surmountable if increase agonist concentration
naloxene and example

Question 22

What is IC50?

Answer 22

concentration of antagonist giving 50% inhibition

Question 23

What is IC50 influenced by?

Answer 23

antagonist and agonist concentration

Question 24

What is irreversible competitive antagonism? give an example

Answer 24

antagonist binds but dissociates slowly or not at all
non-surmountable
at higher concentrations can reduce maximal response
phenoxybenzamide is an example inhibit alpha1 adrenoreceptors in chromaffin cell tumour that causes hypertension through excess adrenaline production

Question 25

What is non-competitive antagonism? given an example

Answer 25

bind allosteric site
similar effect to irreversible competitive antagonism need further experiments to distinguish
maraviroic blocks chemokine receptor 5 used by HIV to enter cell