2. Drug-receptor Interaction - Antagonists (2)

Question 1

What is an antagonist drug?

Answer 1

Any drug which reduces the response to another drug

Question 2

What are the different types of antagonist drugs?

Answer 2

Competitive antagonist 
Non-competitive antagonist
Physiological antagonists
Pharmacokinetic antagonists
Chemical antagonists

Question 3

What are the two types of competitive antagonists?

Answer 3

Competitive reversible

Competitive irreversible

Question 4

What do competitive antagonist do?

Answer 4

Compete with chemical mediator or agonist drug for binding to similar or overlapping binding site on the same receptor but without initiating a cellular response

Question 5

What is the intrinsic efficacy of competitive agonists?

Answer 5

0

Question 6

What is an example of a competitive antagonist?

Answer 6

atenolol- beta blocker

Question 7

What does atenolol do?

Answer 7

Competes with agonist for binding site but cant cause shape change needed to initiate a signal transduction

Muscle will not contract

Will attenuate the binding and action of noradrenaline and adrenaline on heart

noradrenaline-induced increase in cardiac work and oxygen demand is blunted by atenolol

Question 8

How do you classify competitive antagonists?

Answer 8

Classified by how long they remain associated with receptor

Question 9

What is the effect of a competitive reversible antagonist on the agonist log conc response relationship?

Answer 9

Rightward shift for agonist in presence of antagonist

Parallel shift without reduction in max response to agonist look at slide 7

Question 10

What are irreversible competitive antagonists?

Answer 10

Often covalent bonds

effects of the antagonist cannot be reversed unless new receptor proteins are made

Question 11

What is the effect of competitive irreversible antagonists

on agonist log concentration-response curve

Answer 11

Progressive reduction in max response to agonist without a rightward parallel shift in agonist log conc response curve

Question 12

What is a non-competitive antagonist?

Answer 12

Affects action of agonist at some point in chain leading to response but does not compete with agonist for binding to same site on receptor

Question 13

What does binding to an allosteric site cause?

Answer 13

Conformational change - alters agonist binding elsewhere/intiation of signal transduction

Question 14

How else does a non-competitive antagonist work?

Answer 14

Involves interferenec with a component of signal transduction pathway downstream from receptor

Question 15

What does a physiological antagonist do?

Answer 15

Has an opposite effect to the agonist but achieves its results by acting as an agonist on separate cells or tissues or on different population of receptors in the same cell

Question 16

Examples of functional agonists

Answer 16

Noradrenaline

Acetylcholine

Question 17

What is a pharmacokinetic antagonist?

Answer 17

One drug decreases the conc of another drug by interfering with its absorption, distribution, metabolism or excretion

Question 18

What does the antibiotic rifapicin do?

Answer 18

induces expression of liver enzymes which metabolise anti-coagulant drug warfarin

Question 19

How is the division of the receptor families based upon?

Answer 19

which chemical mediator receptor responds to

Question 20

What is the division of family members based upon?

Answer 20

Comparing potency of endogenous mediators at receptors for that mediators in different tissues
Selective stimulation by agonist drugs
Selective blockade by competitive antagonist drugs

Question 21

What is the division of family members based upon?

Answer 21

Comparing potency of endogenous mediators at receptors for that mediators in different tissues
Selective stimulation by agonist drugs
Selective blockade by competitive antagonist drugs

Question 22

What is the molecular biological approach to receptor classification based on?

Answer 22

Molecular structure of receptor protein
- amino acid sequence 
-2yr and 3yr structure 
-location of antagonist binding sites 
Signal transduction mechanism
-ion flux
-enzyme activity 
-gene expression

Question 23

What are the 4 superfamilies of receptors?

Answer 23

1. Ligand-gated ion channels
2. G-protein-coupled receptors
3. kinase-linked receptors
4. Nuclear receptors

Question 24

What are the simlarites within superfamily 2 (G-protein coupled receptors)?

Answer 24

Possess basic molecular structure and functional properties of that superfamily

DIFFERENCES
Encoded by different genes and differ in region of receptor that forms agonist binding site
Each family responds to a specific agonist mediator

Question 25

What are the similarities and differences between members of the same receptor family?

Answer 25

possess basic molecular structure and functional properties of that family

DIFFERENCES
each encoded by a different gene and differ in region of receptor that forms binding site
Individual family members differ in affinity for chemical mediator associated with the family and in preferences for agonist and antagonist drugs

Question 26

How are receptors classified?

Answer 26

Sequencing of human genome reveals a finite no. of genes encoding receptors proteins
Each protein can be assigned to one of 4 superfamilies
Distinct tissue distribution profile for each receptor

Question 27

How many adrenoreceptors are there?

Answer 27

9