Receptor theory VI

Question 1

What are the 5 classes in which antagonists can be divided into?

Answer 1

1) Chemical
2) Pharmacokinetic
3) Physiological
4) Non-competitive
5) Competitive by receptor block

Question 2

What is chemical antagonism?

Answer 2

• Drugs which bind up the agonist in a solution
• Chemically alter the agonist
• Effects of the active drugs are lost

Question 3

What is an example of chemical antagonism?

Answer 3

Inactivation of heavy metals - toxicity reduced by the addition of a chelating agent

• Dimercaprol

Question 4

What is pharmacokinetic antagonism and how do they work?

Answer 4

Drugs which reduce the concentration of the agonist by:

1) Affecting to absorption of the agonist
2) Increasing metabolism of the agonist - reducing the effects

Question 5

What do you have to be careful with when treating patients with pharmacokinetic antagonists?

Answer 5

• May stimulate the metabolism of drugs that are treating the patient (eg. Warfarin)
• Reducing the effects

Question 6

What is physiological antagonism?

Answer 6

Antagonist has opposing actions to the agonist

Eg. noradrenaline raises arterial blood pressure and histamine lowers ABP

Question 7

What is non-competitive antagonism?

Answer 7

• Antagonist acts in some way to disrupt receptor signalling
• Blocks a step in the process between receptor activation and response
• Doesn’t compete for the receptor site

Question 8

What is competitive antagonism?

Answer 8

Competitive antagonist competes with the agonist for the occupancy of the receptor

Question 9

What is reversible competitive antagonism?

Answer 9

If raise concentration of agonist high enough - increase in probability that the receptor will bind to the agonist instead of the antagonist

Question 10

What is irreversible competitive antagonism?

Answer 10

Cannot overcome the antagonist binding with the receptor, even when increase the concentration very high

Question 11

With reversible competitive antagonism, what happens when the concentration of the antagonist is increased?

Answer 11

• Parallel rightward shift of the agonist response curve
• Higher concentration of agonist is needed to achieve the same response
• Maximum stays the same

Question 12

What is schild analysis used for?

Answer 12

Used to calculate the affinity of an ANTAGONIST using a conc-response curve

Question 13

What is the dose ratio?

Answer 13

How much more times agonist is needed in the presence of an antagonist

[concentration in presence of antagonist] / [concentration in absence of antagonist]

• Using the EC50s

Question 14

Describe a schild plot

Answer 14

• Linear plot (+ve direction)
• log10 (antagonist) on the X axis
• log (DR -1) on the Y axis
• PA2 is minus the x intercept

PA2 = -1 x log(Kd)

Question 15

What is the schild equation?

Answer 15

DR = (concentration of antagonist/ Kd) + 1
SO

DR - 1 = concentration of the antagonist/Kd

Question 16

What is pA2?

Answer 16

• Constant which describes antagonist affinity
• Molar concentration of the antagonist which gives a dose ratio of 2 (requires DOUBLE the concentration of agonist to over come binding)
• Larger the pA2, the lower the Kd and the higher the affinity

Question 17

Describe irreversible competitive antagonism

Answer 17

• Agonist reach the maximum response at the start of the experiment - due to binding with spare receptors
• Antagonist lowers the receptor reserve
• When there are no more spare receptors - maximum cannot be reaches
• Maximum response which can be achieved decreases with time
• Time dependant

Question 18

What causes desensitisation?

Answer 18

Repeatedly adding and agonist, or treating with an agonist for a long time

Question 19

What can limit desensitisation?

Answer 19

Treating with an antagonist

Question 20

What are the consequences of desensitisation?

Answer 20

• Cell switches off signal
• Breaks down receptors
• Loss of receptor reserve
• Conc-response curve shift

Question 21

How does a partial agonist act in the presence of a full agonist?

What happens when these drugs are given together?

Answer 21

As a competitive antagonist

When given together - effect is LOWER than if they were given on their own

Question 22

If 2 full agonists are given together, what happens and why?

Answer 22

Below maximum concentrations - their response will act ADDITIVELY

As maximum response is governed by the downstream signalling and machinery of the cell - meaning that the agonists converge on the SAME downstream pathway

Question 23

What is the maximum response of a agonist determined . by?

Answer 23

Downstream signalling and machinery of the cell

Question 24

What happens when PA2 increase?

Answer 24

Kd decrease (inverse relationship - log??)
Antagonist affinity increase