Lecture 5 (Receptor Theory Antagonists)

Question 1

What are the 5 classes of Antagonist? (5)

Answer 1

(1) chemical antagonism
(2) pharmacokinetic antagonism
(3) physiological antagonism
(4) non-competitive antagonism
(5) competitive antagonism

Question 2

How does chemical antagonism work?

Answer 2

Substances combine in solution so that the effects of the active drug is lost, i.e.the agonist is chemically altered by the antagonism

Question 3

How does pharmacokinetic antagonism work?

Answer 3

Reduction in amount of drug absorbed, metabolised or excreted by another

Question 4

What do drugs that affect pharmacokinetics also affect?

Answer 4

Concentration

Question 5

Pharmacokinetics refers to processes which control concentrations of drugs in body, what are these? (3)

Answer 5

absorption, metabolism, excretion

Question 6

How can you use pharmacokinetic antagonism to reduce drug concentration?

Answer 6

If we stimulate, we increase activity for enzymes responsible for breakdown of drugs, we therefore lower concentration of drugs

Question 7

How can pharmacokinetic drugs affect drug concentration? (5)

Answer 7

Drugs that alter protein binding and filtration, alter urine flow or pH, or inhibit tubular secretion

Question 8

What is physiological antagonism?

Answer 8

The interaction of two drugs with opposing actions in the body

e.g. noradrenaline raises arterial blood pressure by acting on the heart and peripheral blood vessels, while histamine lowers arterial pressure by causing vasodilation

Question 9

What is non-competitive antagonism?

Answer 9

Blocks some step in the process between receptor activation and response i.e. it does not compete with the agonist for the receptor site and so is termed non-competitive

Question 10

How does non-competitive antagonism work? (2)

Answer 10

Drugs that belong to this class stop agonist from having signalling function by competing indirectly by inhibiting function of a signalling molecule

Or could bind somewhere different on receptor to stop it form working

Question 11

What is a competitive antagonist?

Answer 11

A competitive antagonist as a drug that bind to receptor to form complex, complex is not able to stimulate any downstream signalling

A competitive antagonist goes into same binding site of receptor as agonist, when it gets there it stabilises structure in such a way so that activity is not induced

Question 12

What is competitive antagonism dictated by?

Answer 12

Dictated by the balance of the forward and reverse reaction at equilibrium

Question 13

What are the two types of competitive antagonist? (2)

Answer 13

Reversible

Irreversible

Question 13

How can we overcome effects of competitive antagonist?

Answer 13

Increased agonist concentration

Question 14

What happens to response concentration curve when competitive antagonist concentration is increased?

Answer 14

Shifts right
(gradient and maximum stay same)

Question 15

What happens to EC50 when increased concentration of antagonist is added?

Answer 15

Increases

Question 16

How can we quantify shits of response concentration curves when adding competitive antagonists?

Answer 16

Use Dose ratio

Question 17

How do we calculate Dose ratio?

Answer 17

Dose Ratio (DR) = conc of agonist in presence of antagonist/ conc of agonist in absence of antagonist

Question 18

How do we calculate the affinity of competitive antagonist for receptor?

Answer 18

Perform schild analysis using dose ratio

Question 19

What is dose ratio proportionate to in terms of Kd?

Answer 19

Dose Ratio (DR) = = Xb(conc of antagonist) / Kd (antagonist affinity constant) +1

Question 20

What is on the axises for Schild’s analysis?

Answer 20

Y = Log value of (dose ratio) -1
X = Log value of concentration of antagonist

Question 21

How do we find pA2 from Schild’s analysis?

Answer 21

Where this line crosses X axis we can get constant which is measure of affinity
Known as pA2 value

Question 22

How do you calculate Kd from pA2?

Answer 22

Kd = 10^(-1 x pA2)

Question 23

What dose dose ratio of 2 mean?

Answer 23

Dose ratio of 2 means you need twice as much of agonist to produce response in concentration of that antagonist

Question 24

What is a partial agonist?

Answer 24

Like an agonist but can’t produce 100% max response

Question 24

What does a partial agonist do in relation to a concentration (log) response curve?

Answer 24

Shifts right (like a competitive antagonist)
-Difference is that partial agonist can induce a signal

Question 25

How can you counteract partial agonnist?

Answer 25

If you increase concentration of agonist enough, you can always achieve maximum response

Question 26

How can competitive antagonists (reversible) be reversed?

Answer 26

Washing the tissue

Question 27

Why are some competitive antagonists irreversable?

Answer 27

Irreversible as once it bonds to receptor, there is chemical reaction between protein and drug that form a bond, permanently connected, only way to get rid is to make completely new receptor

Question 28

How can concentration response curve shit right without a change in maximum in the presence of irreversible competitive antagonists?

Answer 28

Spare receptors are present so can still achieve maximum response until they run out

Question 29

What efficacy do competitive antagonists have?

Answer 29

Zero

Question 30

What does the line on the plot of dose-ratio (compared to antagonist) for competitive antgaonist mean? And what shape is it?

Answer 30

It’s linear and the slope of the line is proportional to the affinity of the antagonist for its receptor