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Pharm 507 > Receptor Pharm I > Flashcards

Receptor Pharm I Flashcards

1
Q

Target molecules for drugs

A

Receptors, enzymes, ion channels, transporters, proteins

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2
Q

Ligand

A

Endogenous or exogenous substance that binds to specific sites of target protein

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3
Q

Endogenous ligand examples

A

Neurotransmitters, hormones, growth factors, cytokines

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4
Q

Exogenous ligand examples

A

Drugs, toxins

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5
Q

How do exogenous ligands work?

A

Mimic the specific binding of the endogenous ligand

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6
Q

Types of exogenous ligands

A

Agonist - activate receptor and produces cellular response

Antagonist - blocks agonist from activating receptor

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7
Q

How do drugs interact with targets?

A

Receptor/ion channels - bind to same site as endogenous ligand to mimic or block it
Enzymes/transporters - bind the active/ligand binding site and inhibit catalytic/transport of protein

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8
Q

Drug + receptor = ??

A

Drug-receptor complex

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9
Q

Example of epinephrine and GPRC reaction

A

Epi(GPCR) -> AC -> cAMP -> PKA -> increase phosphorylation enzyme -> increased glycogen breakdown

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10
Q

Binding of drug to its receptor is reversible

A

Leads to “free” drug and “free” receptor

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11
Q

What does reversible drug binding lead to?

A

Competition among drugs and with endogenous ligands

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12
Q

Saturation

A 
Occupancy of all receptor sites by drugs
# of receptors is finite
Drug to occupy all receptors, adding more drug does nothing
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13
Q

Binding of drugs to receptors is ______; depends on the relative ______ the drug has for its receptor

A

Selective, affinity

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14
Q

Affinity determines…

A

Probability of a drug binding to a receptor site and duration of receptor occupancy

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15
Q

Structural points of attachment determine…

A

Receptor activation (agonists) or blockage (antagonists)

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16
Q

Selectivity is _____, not ______

A

Selectivity is relative, not absolute

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17
Q

Drug-Receptor Binding Equation

A

R + D RD

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18
Q

Drug-receptor binding obeys what law?

A

Law of mass action

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19
Q

Forward rate of constant for association

A

Kon

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20
Q

Reverse rate constant for dissociation

A

Koff

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21
Q

High affinity = ____ Koff

A

Low Koff

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22
Q

Low affinity = ___ Koff

A

High Koff

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23
Q

What is Koff used to determine?

A

Drug affinity

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24
Q

What is KD?

A

Equilibrium dissociation constant, units of concentration

Amount of drug needed to bind to receptor

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25
Q

What is the dissociation constant equation?

A

KD = (Koff/Kon) = ([R][D])/[RD]

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26
Q

KD definition

A

Concentration of drug that occupies 50% of the receptors

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27
Q

High drug affinity yields ____ KD values

A

Low

28
Q

Low drug affinity yields ____ KD values

A

High

29
Q

Affinity equation

A

Affinity = 1/KD

30
Q

Why is KD used?

A

To determine the amount of drug (concentration) needed to achieve a degree of receptor occupancy

31
Q

Fractional receptor occupancy (FRO)

A

FRO = [D]/(KD + [D]

32
Q

As drug concentration increased, receptor is saturated and FRO approaches __

A

1 (100% receptor occupancy)

33
Q

Drug-receptor complex equation

A

[RD] = ([RT][D]/KD+[D])

34
Q

Drug concentration vs receptor occupancy plot

A

Hyperbolic curve

Never actually reach 0 or 100

35
Q

At KD, 50% of receptors are occupied…

A

1/10th KD yields 9% occupancy, 10x KD yields 91% occupancy

36
Q

Fractional drug effect (E/Emax) is directly related to…

A

FRO

37
Q

A low FRO yields ____, high FRO yields ____

A

Low effect, high effect

38
Q

Binding and effect are NOT 1:1, this is due to…

A

Spare receptors

39
Q

E/Emax proportional to FRO equation

A

(E/Emax) ~ ([D]/(EC50+[D])

40
Q

EC50

A

Effective drug concentration that produces 50% of the response (half max effect)

41
Q

Drug concentration vs effect graph

A

Sigmoidal curve

42
Q

What is used to compare different drugs?

A

EC50

43
Q

What kind of scale is a sigmoidal curve graph?

A

Semi-log

44
Q

ED50

A

Dose required to produce 50% of maximal response

45
Q

EC50 vs KD

A

EC50 substitutes for KD in drug effect equation, related but not identical

46
Q

EC50 is usually < KD; why?

A

Spare receptors

47
Q

What value is used to determine drug potency?

A

EC50

48
Q

Amount of drug required to generate a given fractional effect is analogous to…

A

Affinity

49
Q

EC50 value for high potency drug

A

Low

50
Q

EC50 value for low potency drug

A

High

51
Q

Does EC50 indicate drug efficacy?

A

Nope

52
Q

Drug Efficacy

A

Magnitude of max effect drug is able to produce

53
Q

What determines drug efficacy?

A

How well the drug activates the receptor when bound

54
Q

Potency vs. Efficacy

A

Highly potent drugs can have low efficacy

Low potency drugs can have high efficacy (just need higher dose)

55
Q

Does low efficacy mean the drug is clinically ineffective?

A

No

56
Q

Signal amplification

A

Receptor signaling pathways that lead to intermediate and final responses

57
Q

Outcome of a downstream amplification event

A

100% receptor binding is not required to generate 100% response

58
Q

What direction does EC50 shift in the presence of spare receptors?

A

Left; EC50 < KD

59
Q

Drug response _______ is often higher than its receptor ______.

A

Potency, affinity

60
Q

Define spare receptors

A

More receptors than necessary

61
Q

Direction shift with loss of spare receptors

A

Right

62
Q

What happens with the agonist potency when receptors are lost

A

Decreases

63
Q

Clinical significance of spare receptors

A

Low concentrations of endogenous ligands

Lower drug doses than what’s required for full receptor occupancy

64
Q

Can cells lose some of their receptors but still generate full responses?

A

Yes, to a point

65
Q

What causes receptor loss?

A

Diseases
Chronic agonist administration (down-regulation)
Irreversible antagonists

66
Q

Clinically, what do you when receptors are lost?

A

Increase drug dose to achieve therapeutic effect

Pharm 507 (6 decks)

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