Lecture 5 (Drug Receptor Interactions) Flashcards Preview

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Flashcards in Lecture 5 (Drug Receptor Interactions) Deck (34):
1

When we don't know the endogenous ligand for a receptor it is called an ______ ________

orphan receptor

2

binding is _____

specific

3

There is a ____ binding capacity for receptors

finite

*meaning there are only a limited number of receptors
*it is possible for binding to be matured (all the receptors are occupied)

4

receptors are ___ specific

tissue

5

Drugs bind to receptors using the same interactions that drugs form with solvents as discussed in lecture 2 on solubility:

What are these interactions?

-dispersion forces (london forces)
-dipole-dipole bonding
*this one is not as important)
-H-bonding (a special kind of dipole dipole bonding)
-ionic bonding
-ion-dipole bonding

6

For protein interactions - dispersion forces are referred to as ??

hydrophobic interactions

7

What is KD?

(not the delicious cheesy macaroni treat)

dissociation constant bitches

-it tells you what side of the rxn that it favours
(either free drug and free receptor OR drug-receptor complex)

8

Units of KD?

mol/L or M

9

if KD is small = ?

there is more DR (and therefore more biological response)

*also indicates tight binding

10

1/KD = KA = ?

affinity constant

11

units of KA ?

L/mol or M^-1

12

higher the affinity constant = ?

tighter the binding

13

if KD = 1 microM what does this mean?

1 microM [drug] will produce half maximal receptor binding

14

KD = ?

[drug] at which you get half maximal binding

[drug] at which 1/2 Rt (total receptors) is bound to drug

15

efficacy

constant of proportionality which measures the ability of the drug to produce an effect by forming a drug receptor complex

Eobs = alpha [DR]

alpha = efficacy (intrinsic activity)

16

Emax is achieved when ?

Emax = maximal effect

all receptors are mound to the drug

17

What is ED50?

[drug] and 1/2 Emax

concentration of drug which produces half of the maximal effect

18

T or F: KD and ED50 have the same value

true man

19

lower ED50 = ?

more potent

20

potency is ____ of efficacy

independent

21

What is an agonist?

-they bind to receptors and have affinity for the receptor which produce an effect (they have intrinsic activity) or response

22

What is a full agonist?

it binds to the receptor and is capable of producing the same maximal response as the endogenous agonist

23

What is a partial agonist?

it can bind to the receptor but produces a smaller maximal response.

-therefore it has lower intrinsic activity than a full agonist which is capable of eliciting a maximal response

24

What is an antagonist?

an antagonist binds to receptors and has affinity for the receptor but has NO INTRINSIC ACTIVITY
-no efficacy (no response)

25

Describe the spare receptors theory

-it is frequently found that for the same drug KD > ED50

*this means that the maximal effect is still being achieved without binding to all of the receptors

*potential of signal amplification
(see slide 22)

26

Two most important types of antagonists?

competitive
non-competitive

27

Describe competitive antagonists

compete for the same binding site as the drug/agonist/endogenous ligand

If antagonists binds = no response
If drug binds = response

28

Can you overcome a competitive antagonist? If so, how?

Yes you can
-increase amount of agonist

29

What is competitive antagonism characterized by?

An increase in apparent Kd
OR
Decrease in affinity of drug

30

Describe non-competitive antagonists

they don't compete for the same binding site

the Antagonist binds to the Receptor at a different spot than the agonist but even if the drug still binds - it cannot produce a response when the antagonist is present.

Affinity of the drug for the receptor does not change!!!
-it does with competitive antagonists

*reduces maximal efficacy

31

non-competitive antagonism is characterized by?

reduction in the apparent number of receptors

32

with non-competitive antagonists ... KD = ?

stays the same

33

Can non-competitive antagonists be overcome with increasing agonist?

NO WAY MAN
-only competitive antagonism can be overcome this way

34

understand slide 30

kay ma'am