L6- Agonists and antagonists

Question 1

What is the equation for the Effect of a drug?

Answer 1

E= (Emax.[D]) / (EC50 + [D])

Emax= max effect
Ec50= conc giving 50% max effect

Question 2

What relationship witll the shape of concentration-effect curves follow?

Answer 2

Hill-Lagmuir like relationship

So rectangular hyperbola on linear scale

Sigmoidal on a log scale.

Question 3

Are Kd and EC50 the same?

Answer 3

No. Almost always different.

Often EC50 is lower than Kd bevause often receptors activate many enzymes

Question 4

What does Kd describe?

Answer 4

Affinity

Question 5

What does EC50 describe?

Answer 5

potency

Question 6

What is pEC50?

Answer 6

-logEC50

Question 7

What does EC90 mean?

Answer 7

The concentration required to give 90% max response

Question 8

What is a receptor?

Answer 8

Binds a ligand and transduces information. (enzyme is not a receptor!)

Question 9

Whats an agonist?

Answer 9

ligand that binds to a receptor AND actiavtes it

Question 10

What are the 4 types of antagonism?

Answer 10

1. Orthosteric (competitive)
2. Allosteric (non-competitive?)
3. Functional
4. Indirect

Question 11

Whats the most common form of antagonism?

Answer 11

Competitive/orthosteric

Agonist binds reverisbly but cannot activate recepotr. Competes for binding site with agonist

Question 12

Describe affects of policarpine and atropine on saliva production?

Answer 12

Policarpine=agonist at muscarinic receptors so increases saliva production

Atropine= antagonist at muscarinic receptors so decreases saliva production

Question 13

What happens when both policoarpine and atropine are added to saliva production?

Answer 13

production goes back to nomal. Because the baseline of saliva is due to a constant, low level PNS releasing ACh. There’s a lot of agonist around with ACh and pilocarpine, if there’s enough agonist it overcomes the anatagonism of atropine

Question 14

What happens to concentration response curve when you add anatgonist?

Answer 14

Curve shifts to right

Max response doesnt change

EC50 increase

Question 15

How can we quantify how much effect th antagonist has on the agonist?

Answer 15

Measure the concentration ratio (CR)

CR= amount we have to increase the agonist conc. to recover control response

Question 16

What’s the Gaddum equation?

Answer 16

E=(emax.[D]) / ([D]+EC50(1+([B]/kb))

Kb= dissociation constant of anatgonist
[B]= antagonist conc.

This equation takes into account the concentration ratio, so shows the effect with the competitive antagonist

Question 17

What is IC50?

Answer 17

The concentration of antagonist needed to give 50% inhibition. This is dependent on the conc of agonist so is not as useful.

Question 18

What is pA2?

Answer 18

the -log[Antagonist] that gives a CR of 2.

Conc of anatgonist that means you have to double conc of agonist to get same effect.

pA2=-logKb if perfect

Question 19

What is selectivity?

Answer 19

Relative potency of a drug in eliciting one effect compared with another.

If it is more potent at one receptor then it is selective for it

Question 20

What is the equation for [RD]/[Rt]?

Answer 20

RD= drug bound

Rt= Bmax

[RD]/[Rt] = [D]/([D] + Kd)