Lecture 15- Pharmacodynamic receptor theory

Question 1

drug targets include

Answer 1

• Mainly GPCR
• Ion channels
• Kinases
• Few nuclear receptors
• Enzymes

Question 3

drugs are

Answer 3

ligands for a receptor

Question 4

how many GOCRs in man

Answer 4

800

• 400 olfactory receptors e.g. sigh and smell
• non-olfactory receptors

Question 5

olfactory receptors are regulated by

Answer 5

light, odorants, hormones, NT and ions

Question 6

what is critical in determining drug action

Answer 6

the concentration of drug moelcule around receptors

Question 7

uM

Answer 7

10^-6M

Question 8

nM

Answer 8

10^-9M

Question 9

pM

Answer 9

10^-12M

Question 10

how many moles in a uM

Answer 10

100,000

Question 11

most drugs bind to receptors in an

Answer 11

irreversible manner

Question 12

drugs either act

Answer 12

as antagonists

as agonists

Question 13

antagonists

Answer 13

block the binding of endogenous agonists

Question 14

agonists

Answer 14

activate the receptor

Question 15

to bind to a receptor (as an antagonist or agonist)

Answer 15

drug must have affinity

higher affinity= stronger binding

Question 16

mode of action: antagonists

Answer 16

• goverened by affinity
• no intrinisc efficacy

Question 17

intrinsic efficacy and antagonists

Answer 17

wont switch the receptor to active state

Question 18

mode of action of agonists

Answer 18

have both affinity and intrinsic efficacy

Question 19

ligands bind tor eceptor due to

Answer 19

affinity

• both antagonists and agonists

Question 20

intrinsic efficacy means that

Answer 20

ligand activates rthe recpetor and causes a response inside the cell

Question 21

pharmacology efficacy

Answer 21

if drug causes blood vessel to dilate

Question 22

clinical efficacy

Answer 22

if the drug actually lowes BP

Question 23

lock and key analogy of antaognists and agonists

Answer 23

both bind due to affinity

Agonists- cause activation of receptor and repsosne inside cell (intrinsic efficacy)

Antagonists- have affinity but do not have intirnsic efficacy (block response of effector)

Question 24

two ways the effect of drug concnenreation can be looked at

Answer 24

1) binding to the receptor
2) functional response

Question 25

how do we measure binding

Answer 25

• Many cells/ many receptors e.g. 10,000- 1000,0000 receptors per cell
  
  • Incubate radioligand and receptors —> binding
  • Low ligand conc= low binding
  • High ligand conc= high ligand binding

Question 26

quantifying binding

Answer 26

using conentration of drug vs proption of bound receptors graph

Question 27

B_max

Answer 27

the maximum binding capacity

• gives info about receptor no.

Question 28

Kd

Answer 28

dissociation constat

• concentration of ligand needed to occupy 50% of available receptors

Question 29

the lower the Kd

Answer 29

the higher the affinity the ligand has for the receptor

Question 30

high affinity (low kd) allows

Answer 30

binding at low conc of ligand

Question 31

to treat morphine or heroin overdose

Answer 31

• Naloxone used to treat overdose :
• High affinity antagonist of u-opioid receptors
• Outcompetes opioid

Question 32

nalaxone

Answer 32

has a higher affinity for the receptor than morphine or heroine (antagonist)

Question 33

[drug] on graph usually presented

Answer 33

in logarithmic and not linear way

Question 34

Log₁₀ of a no.

Answer 34

power by which 10 has to be raised to get that number

e.g. 0.001 or 1mM = 10^-3

Question 35

scale on a logarithmic graph for receptor binding

Answer 35

between -11 and -7 ( ligand concentration at receptors usually <<1M

Question 36

response by a cell requries

Answer 36

drug efficacy - onyl agonists give this

Question 37

conenctration reponse curve

Answer 37

graphs which plot receptor binding usually use the sigmoidal log curve

Question 38

Emax

Answer 38

maximum effect evoked by a ligand (intrinsic activity)

Question 39

EC₅₀

Answer 39

effecitve concetration giving 50% of the maximal response

Question 40

EC₅₀ is a measure of agonist

Answer 40

Potency

depends on both affintiy and intrinsic efficacy

Question 41

concentration is the

Answer 41

known concentration of drug at site of action e.g. in cells and tissue

• usually unknown*
• so we use DOSE*

Question 42

dose

Answer 42

concentrationa t site of action generally unknown

however we can quanitify have much of a drug a patient is getting in mg or mg/kg