Receptor basic, agonists antagonistic

Question 1

What are the effects of adrenaline?

Answer 1

-Many effects on the body including increasing heart rate and contraction

Question 2

What is bisoprolol and and what is it prescribed for?

Answer 2

-Synthetic drug
-Prescribed to reduce heart rate and contraction

Question 3

What is the bisoprolol used to treat?

Answer 3

-Used to treat cardiovascular conditions such as angina and heart failure when we want to reduce the effort of the heart

Question 4

What does bisoprolol reduce the effect of?

Answer 4

-Bisoprolol reduces the effect of adrenaline

Question 5

What does adrenaline do to the heart?

Answer 5

-Increase heart rate and contraction strength

Question 6

What does adrenaline do to the lungs?

Answer 6

-Dilates airways

Question 7

What does adrenaline do to the liver?

Answer 7

-Increases breakdown of glycogen, increasing plasma glucose

Question 8

What is the importance of enantiomers for adrenaline

Answer 8

-The (+) enantiomer of adrenaline has about 100 fold greater biological than (-) adrenaline

Question 9

Potency of adrenaline?

Answer 9

-Very high. Adrenaline acts at very low concentrations (bc they act act receptors)
e.g. 10-9M - 10-15M ranges can produce significant increases in heart rate

Question 10

What are receptors?

Answer 10

-Target molecules with endogenous substances or ‘given’ drugs bind to produce a cellular response

Question 11

What receptors in the heart does adrenaline stimulate?

Answer 11

-Adrenaline is a physiological hormone, which stimulates the beta-adrenoceptors

Question 12

Where does bisoprolol act in the heart?

Answer 12

Bisoprolol is a synthetic drug which acts at beta adrenoceptors to prevent the action of adrenaline

Question 13

What are the general properties of receptors?

Answer 13

-Expressed in different tissues
-High selective targets: Only specific drug structures bind to receptors
-Amplify signals: Small number of drug/receptor interactions initiate significant biological effects

Question 14

What is the general structure of beta-adrenoceptor?

Answer 14

-Is a large complex protein molecule consisting of transmembrnae domains

Question 15

What do the transmembrane regions contain in beta-adrenoceptor and what does this allow for?

Answer 15

-Transmembrane regions with hydrophilic and lipophilic amino acids
-Allows the folding of membrane hence creates binding sites

Question 16

Where else can beta-adrenoreceptors be found?

Answer 16

-liver
-lungs

Question 17

What are the 4 different types of receptors?

Answer 17

Receptors
-Adrenaline and Bisoprolol act at beta adrenoreceptor
Enzymes
-Ibuprofen acting on cyclooxygenase
Carrier molecules
-Fluoxetine(anti-depressant) acting at serotonin uptake carrier
Ion channels
-Lignocaine (local anaesthetic) acting at Na+ channels

Question 18

What is an agonist

Answer 18

A drug which binds to a receptor to produce a biological cellular response
-e.g. adrenaline is an agonist that increases heart rate

Question 19

What is an antagonist?

Answer 19

A drug which binds to a receptor but does NOT produce a biological cellular response
-e.g. Bisoprolol is an antagonist that blocks adrenaline-mediated increases in heart rate

Question 20

What are drugs classified according to?

Answer 20

Clinical use
- e.g. bisoprolol is used to treat angina hence “anti-anginal drug”
Target receptor
-e.g. bisoprolol binds to beta-adrenoreceptors hence “beta-adrenoreceptor antagonist (beta-blocker)”

Question 21

What are receptors often classified according to?

Answer 21

-Receptors are often classified according to the agonists and antagonists that act upon them e.g. adrenoceptors: These drugs bind to adrenoceptors, but their differential actions define whether an alpha or beta adrenoceptor is involved

Question 22

What receptors do blood vessels express?

Answer 22

Alpha adrenoceptors

Question 23

What is most to least potent on alpha adrenoceptors in blood vessels? What do they do?

Answer 23

Noradrenaline>Adrenaline>Isoprenaline
-Increase constriction

Question 24

What drugs acts as an antagonist on alpha adrenoceptors?

Answer 24

-Alpha adrenoceptors on blood vessels are blocked by prazosin(not bisoprolol)

Question 25

What is most to least potent on alpha adrenoceptors in the heart? What do they do?

Answer 25

Isoprenaline>Adrenaline>Noradrenaline -Increase heart rate

Question 26

What is the occupation of receptor governed by?

Answer 26

-Occupations of receptor is governed by affinity

Question 27

What is activation of receptor goverend by?

Answer 27

-Activation governed by efficacy

Question 28

What is binding of agonist and antagonist assessed by?

Answer 28

Both agonists and antagonists bind to receptors -How well they bind is assessed by equilibrium constant(KA, Kant)

Question 29

How is the quality of action produced by an agonist assessed?

Answer 29

How well they produce an action is assessed by effective concentration producing 50% of maximal response(EC50) - only agonists

Question 30

In what fashion do agonists and antagonists bind to receptors?

Answer 30

Reversibly -Adrenaline and bisoprolol bind to beta adrenoceptor-then dissociate- this is a continuous 'off and on' process

Question 31

What are the types of binding that occur between receptor and agonist/antagonist?

Answer 31

Hydrogen bonding, Ionic bonding, van der waal's forces -Relatively weak therefore reversible binding and good dissociation Covalent binding -Stable strong bonds therefore irreversible binding and poor dissociation hence "conformational change"

Question 32

What governs the reversible binding of agonist to receptor? What is this dependant on?

Answer 32

-Rate of reversible binding of agonist to receptor is governed by law of mass action -Dependent on concentration of the reactants involved

Question 33

What does the law of mass predict?

Answer 33

1. Low concentration of A and lots of Rfree results in a low rate of AR interactions 2. Increase the concentration of A and you increase rate of AR interactions-shifts reaction to right 3. Continue increasing concentration of A results in few Rfree, which results in a low rate of AR interaction

Question 34

When is the equilibrium constant (KA or KANT) reached?

Answer 34

When 50% of receptors are free and 50% are bound by drug

Question 35

What is KA or KANT for the drug and what does this mean?

Answer 35

-KA or KANT is the concentration of the drug at equilibrium: -This means that a KA of 50nM means that at this concentration 50% of receptors will be occupied by agonist

Question 36

What does a small KA or KANT value mean?

Answer 36

Smaller KA or KANT means agonist or antagonist has a greater affinity for receptor(binds more) than an agonist or antagonist with a higher KA or KANT

Question 37

What does efficacy measure?

Answer 37

-Efficacy measures biological effect like increase in heart rate by adrenaline

Question 38

What is EC50?

Answer 38

Effective concentration giving 50% biological response

Question 39

Are affinity and efficacy equal? Why?

Answer 39

Affinity and Efficacy of an agonist are not equal -You do not need full occupancy to give a maximum response -The reason why drugs can work at low concentration is because receptors amplify signals, so only a small number of drug-receptor interactions provide biological effects

Question 40

What happens to response against log(agonist) curve in the presence of a competitive antagonist?

Answer 40

-Presence of a competitive antagonist shift agonist curve to the right -Same maximal response

Question 41

What needs to be done to overcome/surmount competitive antagonism?

Answer 41

-Increasing concentration of agonist will out compete or surmount antagonism

Question 42

What happens to response against log(agonist) curve in the presence of a non competitive antagonist?

Answer 42

-reduce slope and depress maximum

Question 43

How does non-competitive antagonism work?

Answer 43

-Antagonist binds to a different site than agonist

Question 44

How does irreversible antagonism work?

Answer 44

-Antagonists binds irreversibly to either agonist or non-agonist binding sites on the receptor through covalent bonds

Question 45

What impact do both non-competitive/irreversible antagonists have?

Answer 45

-Both non competitive/irreversible antagonists reduce number of receptors