Pharm - Lecture 2

Question 1

What is affinity?

Answer 1

An equilibrium state; the concentration of the drug that occupies 50% of the receptors is equal to the affinity; Affinity = K subD; Aff = k sub12/ k sub1; Aff is NOT EC50

Question 2

What are k sub1 and k sub2?

Answer 2

K sub1 = the rate of approach (of drug to receptor); k sub 2 = the rate of dissociation

Question 3

When affinity increases the numeric value of the constant (K subD) does what?

Answer 3

Decreases

Question 4

Re: k sub1 and k sub2, which tends to remain constant for all drugs?

Answer 4

k sub1

Question 5

As k sub2 decreases we say that…

Answer 5

affinity increases/is high(er)

Question 6

What units is K subD expressed in?

Answer 6

molar units (typically, nM)

Question 7

All binding curves will look like what?

Answer 7

A sigmoidal function

Question 8

Law of mass action

Answer 8

Y = [D]/(K sub D + [D])

Question 9

Affinity refers to the binding behavior of ligands and receptors; efficacy refers to what?

Answer 9

The subsequent biological response/effect

Question 10

Is the relationship between biological response and the # of receptors occupied linear?

Answer 10

No [flesh this out more]

Question 11

What is potency

Answer 11

The concentration of drug at which you get half of the maximum biological response

Question 12

EC50 is what?

Answer 12

EC50 = numeric value of potency

Question 13

What is a high efficacy agonist?

Answer 13

EC50

Question 14

Who proposed that the EC50 = K subD

Answer 14

AJ Clark

Question 15

What AJ clark correct?

Answer 15

No

Question 16

What’s “in between” the EC50 and K subD?

Answer 16

Signal transduction (the strength of the cranking?)

Question 17

What’s another name for a high efficacy agonist?

Answer 17

a super agonist

Question 18

What’s another name for a low efficacy agonist?

Answer 18

a partial agonist

Question 19

What is a low efficacy agonist?

Answer 19

EC50 > K subD; An agonist (a drug) that only approaches/achieves the EC50 at higher concentrations than would be predicted if the relationship between the binding curve and the efficacy curve was 1 to 1 (i.e., equal to K subD)

Question 20

intrinsic efficacy

Answer 20

[UC]

Question 21

clinical efficacy

Answer 21

[UC]

Question 22

what is an antagonist?

Answer 22

A drug that has no INTRINSIC efficacy (but can have high clinical efficacy); but has high affinity; will block the response of exogenous (e.g., other drugs) and endogenous (i.e., neurotransmitters) agonists; their ability to do so is related to dose (i.e., concentration of antagonist)

Question 23

What NT operates at the neuromuscular junction?

Answer 23

acetylcholine; on nicotinic-acetylcholine receptors

Question 24

Where does curare act? How? To what result?

Answer 24

At the NM junction; acts as antagonist to acetylcholine; death by suffocation (turns off the diaphragm)

Question 25

Two difference kinds of antagonists?

Answer 25

Competitive and non-competitive

Question 26

Is curare comp or non-comp?

Answer 26

competitive

Question 27

How do you surmount the action of a competitive antagonist? This behavior represented graphically is called what?

Answer 27

increase the concentration of the agonist; parallel shift to the right (of the DR curve)

Question 28

What’s the difference between comp and non-comp antagonists?

Answer 28

Comp antagonists fight of the same receptor cites; a non-comp antagonist changes the receptor site conformation

Question 29

Non-comp antagonism results in what kind of change to the DR curve?

Answer 29

There is a downward shift; can’t surmount it

Question 30

Most drugs are comp or non-comp antagonists?

Answer 30

Non-comp

Question 31

what is an inverse agonist

Answer 31

negative intrinsic efficacy; for example: suppose have a muscle tissue prep, with agonist the thing contracts, with an antagonist nothing happens (but you need more agonist to get the response you want), with an inverse agonist the thing relaxes below baseline level of activity