Mechanisms Of Drug/receptor Interactions (Pharm Firsth Block)

Front 1

potency?

Back 1

Affinity only

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Efficacy?

Back 2

Maximal effect

Front 3

Drugs modify receptor activity by? (3 mechanisms?

Back 3

activating the receptor, or by changing the characteristics of the activated state of the receptor.

Front 4

Using labeled receptor studies can yield wht kinds of info?

Back 4

saturable binding implies a specific interaction with a discrete binding site

tissue distribution of receptor may provide clue about its identity and the mechanism of drug action

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agonist

Back 5

favors active site of receptor

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partial agonist?

Back 6

Partial agonists favor the active state, but not as much as a full agonist

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Inverse agonist?

Back 7

Binds inactive state of receptor

Front 8

antagonist?

Back 8

Do not have a preference between active and inactive state of receptor. Simply block agonist binding.

Front 9

Two state model?

Back 9

R and R* equilibrum changed by binding of one or the other

Front 10

Induced fit?

Back 10

Drug binding alters receptor shape, stabilizing the active state of the receptor.

Front 11

Define Chemical antagonism?

Back 11

chelation of drug lowers absorption or effective concentration in bloodstream (dimercaprol vs. Hg2+)

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Pharmacokinetic Antagonism

Back 12

one drug activates metabolism and/or excretion of another drug, or interferes with absorption

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Receptor competition?

Back 13

drugs with different potencies or efficacies compete for the same receptor

Front 14

Physiological antagonism?

Back 14

drugs eliciting opposite responses via different pathways/mechanisms

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Non-competitive antagonist?

Back 15

affects a step of receptor activation by an agonist other than binding

Front 16

What is the Schild equation and what is it used for?

Back 16

Ratios of EC50s (without antag) to EC50 (with antag) as a function of antagonist concentration and dissociation constant of the antagonist.

Front 17

Irreversible Competitive antagonism:
1) change in Km?
2) Change in Vmax

Back 17

1) same
2) decrease

Acts as functional enzyme loss

Front 18

in what case a partial agonist act like an antagonist?

Back 18

Many GCPRs have significant basal activity, and apparent "antagonists" may actually function as inverse agonists

Front 19

fill in 1,2,3,4

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1) agonist
2) inverse agonist
3) agonist
4) inverse agonist

Front 20

Why spare receptors?

Back 20

-at any point in time a given percentage of receptors may be occupied, but over time, all will be activated and may have long lasting effects. Thus having extra ones allows this buildup of long lasting effects.

Front 21

Drugs cause two types of responses. Name them

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Rapid physiological responses

Delayed responses mediated by altered gene expression

Front 22

Mechanism of Desensitization?
B-adrenoreceptors?

Back 22

receptor loss/downregultion

Front 23

Mechanism of Desensitization?
Coumadin, Barbiturates

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enhanced drug metabolism

Front 24

Mechanism of Desensitization?
Amphetamine

Back 24

depletion of a response mediator

Front 25

Mechanism of Desensitization?
MDR

Back 25

increased drug efflux

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Mechanism of Desensitization?
histamin receptors

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physiological adaptation

Front 27

Two phases of desensitization at the NMJ. Describe them.
1)fast
2) slow

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1) change in the functional state of the receptor
2) Decrease in receptor number

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What kind of drug receptor is being described?
16-20 membrane-spanning segments surrounding a central ion channel

Back 28

ligand gated ion channel

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What kind of drug receptor is being described?

Growth factor receptors

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Kinase-linked receptors

Front 30

What kind of drug receptor is being described?

Directly controlgene transcription

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Nuclear Receptors

Front 31

Describe the activation of a GPCR

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Front 32

What is bidirectional control of an enzyme?

Back 32

may be regulated by both excitatory and inhibitory GPCRs

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PIP2 cleavage by _____ yields
1) PLC
2)PLA2

Back 33

1)IP3 and DAG
2) arachidonic acid

Front 34

GPCR responses can differ by these mechanism

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pair to different G-proteins
different agonist can cause different acitve states
different downstream effectors
Receptor Activity Modifying Proteins (RAMPs)

Front 35

In what case can a GPCR bypass the g-protein?

Back 35

ion channel activation

Front 36

The nicotinic Ach receptor is what kind of receptor?

Back 36

Ligand gated ion channel (ionotropic)

Front 37

The Muscarinic Ach receptor is what kind of receptor?

Back 37

GPCR (metabotropic)

Front 38

Toll-like receptors, insulin receptors, growth factor receptors are all examples of what kind of receptor.

Back 38

RTK

Cytokine receptors too but they are not enzymatically active (need a kinase like JAK)

Front 39

These receptors are involved in many chronic disease states (diabetes, cancer, CVD, obesity.

Many are lipid sensors.

Back 39

Nuclear receptors

Front 40

Zinc fingers are founs in what kind of receptor

Back 40

Nuclear

Front 41

Class-1 nuclear receptos
1) dimerization?
2) ligands?

Back 41

1) homodimer
2) Endocrine ligands

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Class 2 nuclear receptor
1) ligands
2) dimerization

Back 42

1) lipids
2) RXR heterodimers

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Class 3 nuclear receptor
1) ligands
2) dimerization
3) 2 examples

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Hybrid calss
1) endocrin
2) RXR hetero
3) Vit D., T3