Lecture 15- Pharmacodynamic receptor theory Flashcards

1
Q

drug targets include

A
  • Mainly GPCR
  • Ion channels
  • Kinases
  • Few nuclear receptors
  • Enzymes
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2
Q
A
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3
Q

drugs are

A

ligands for a receptor

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4
Q

how many GOCRs in man

A

800

  • 400 olfactory receptors e.g. sigh and smell
  • non-olfactory receptors
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5
Q

olfactory receptors are regulated by

A

light, odorants, hormones, NT and ions

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6
Q

what is critical in determining drug action

A

the concentration of drug moelcule around receptors

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7
Q

uM

A

10-6M

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8
Q

nM

A

10-9M

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9
Q

pM

A

10-12M

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10
Q

how many moles in a uM

A

100,000

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11
Q

most drugs bind to receptors in an

A

irreversible manner

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12
Q

drugs either act

A

as antagonists

as agonists

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13
Q

antagonists

A

block the binding of endogenous agonists

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14
Q

agonists

A

activate the receptor

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15
Q

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

A

drug must have affinity

higher affinity= stronger binding

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16
Q

mode of action: antagonists

A
  • goverened by affinity
  • no intrinisc efficacy
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17
Q

intrinsic efficacy and antagonists

A

wont switch the receptor to active state

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18
Q

mode of action of agonists

A

have both affinity and intrinsic efficacy

19
Q

ligands bind tor eceptor due to

A

affinity

  • both antagonists and agonists
20
Q

intrinsic efficacy means that

A

ligand activates rthe recpetor and causes a response inside the cell

21
Q

pharmacology efficacy

A

if drug causes blood vessel to dilate

22
Q

clinical efficacy

A

if the drug actually lowes BP

23
Q

lock and key analogy of antaognists and agonists

A

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)

24
Q

two ways the effect of drug concnenreation can be looked at

A

1) binding to the receptor
2) functional response

25
Q

how do we measure binding

A
  • 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
26
Q

quantifying binding

A

using conentration of drug vs proption of bound receptors graph

27
Q

Bmax

A

the maximum binding capacity

  • gives info about receptor no.
28
Q

Kd

A

dissociation constat

  • concentration of ligand needed to occupy 50% of available receptors
29
Q

the lower the Kd

A

the higher the affinity the ligand has for the receptor

30
Q

high affinity (low kd) allows

A

binding at low conc of ligand

31
Q

to treat morphine or heroin overdose

A
  • Naloxone used to treat overdose :
  • High affinity antagonist of u-opioid receptors
  • Outcompetes opioid
32
Q

nalaxone

A

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

33
Q

[drug] on graph usually presented

A

in logarithmic and not linear way

34
Q

Log10 of a no.

A

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

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

35
Q

scale on a logarithmic graph for receptor binding

A

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

36
Q

response by a cell requries

A

drug efficacy - onyl agonists give this

37
Q

conenctration reponse curve

A

graphs which plot receptor binding usually use the sigmoidal log curve

38
Q

Emax

A

maximum effect evoked by a ligand (intrinsic activity)

39
Q

EC50

A

effecitve concetration giving 50% of the maximal response

40
Q

EC50 is a measure of agonist

A

Potency

depends on both affintiy and intrinsic efficacy

41
Q

concentration is the

A

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

  • usually unknown*
  • so we use DOSE*
42
Q

dose

A

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

43
Q
A