UNIT 2 Flashcards

(67 cards)

1
Q
  • interacts with a drug
  • initiates the chain of events
A

Receptor

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2
Q

central focus of investigation of drug effects and their mechanisms of action

A

Receptor

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3
Q

The receptor concept, extended to what areas

A

endocrinology, immunology, and molecular biology

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4
Q

Important practical consequences of receptor concept

A
  1. development of drugs
  2. therapeutic decisions in clinical practice.
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5
Q

Receptors largely determine the ___ relations between ___ of drug and ___

A

Quantitative; dose or concentration; pharmacologic effects

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6
Q

T/F

total number of receptors may limit the maximal effect a drug may produce.

A

Th

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7
Q

T/F

Receptors are responsible for selectivity of drug action.

A

T; receptors select the drug action

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8
Q

T/F
The affinity of the drug to its receptor depends on the molecular size, shape, and electrical charge of the drug

A

T

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9
Q

T/F
Change in the chemical structure of a drug will also change its affinity, and toxic/therapeutic effect

A

T

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10
Q

T/F
Receptors mediate the actions of pharmacologic agonists and antagonists.

A

T

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11
Q
  • regulate the function of receptor macromolecules

-they activate the receptor to signal as a DIRECT RESULT of binding to it.

A

Agonists

ie. some drugs and natural ligands (hormones, neurotransmitters)

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12
Q

T/F

Some agonists activate a single kind of receptor to produce all their biologic functions

A

T

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13
Q

T/F

other agonists selectively promote one receptor function more than another.

A

T

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14
Q
  • bind to receptors but do not activate generation of a signal
  • they interfere with the ability of an agonist to activate the receptor.
A

Antagonists = pakielamero

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15
Q
A
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16
Q

T/F
Antagonists are useless

A

F; their blocking action is purposeful

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17
Q
A
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18
Q
  • bind to a different site on the receptor and can produce useful and quite different clinical effects
A

Allosteric modulators

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19
Q

T/F
Most receptors for clinically relevant drugs, and almost all of the receptors are proteins.

A

T

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20
Q

used to identify or purify receptor proteins from tissue extracts

A

Drug binding; was traditionally used

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21
Q

T/F

receptors were discovered after the drugs that bind to them

A

T

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22
Q

natural ligands are presently unknown

A

Orphan receptors

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23
Q
  • best-characterized drug receptors
  • mediate the actions of endogenous chemical signals (hormones, neurotransmitters, autocoids)
A

Regulatory proteins

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24
Q

mediates the effects of many of the most useful therapeutic agents.

A

Regulatory receptors

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25
may be inhibited or, less commonly, activated, by binding a drug.
Enzymes
26
receptor for the antineoplastic drug methotrexate
dihydrofolate reductase
27
receptor for statins
3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase
28
membrane receptor for cardioactive digitalis glycosides
Na+/K+-ATPase *transport
29
membrane receptors for antidepressant drugs
norepinephrine and serotonin transporter proteins *transport
30
membrane receptors for cocaine and a number of other psychostimulants
dopamine transporters *transport
31
receptor for colchicine
tubulin *structural
32
33
three aspects of drug receptor function
1. As determinants of the quantitative relation between the concentration of a drug and the pharmacologic response 2. as regulatory proteins and components of chemical signaling mechanisms that provide targets for important drugs 3. as key determinants of the therapeutic and toxic effects of drugs in patients.
34
plot of the drug effect (ordinate) against the logarithm of the dose or concentration (abscissa)
Dose-response data
35
reduce the effects of agonists (other drugs or endogenous regulatory molecules) that normally activate receptors.
Antagonists
36
reduce receptor activity below basal levels observed in the absence of any agonist at all.
Inverse agonist
37
- Competes with agonist receptor - Binds to the receptor REVERSIBLY without activating the effector system - Antagonist increases the agonist concentration needed for a given degree of response - Concentration-effect curve is shifted to higher doses (ie, horizontally to the right of the dose axis) - Same maximal effect is reached
Competitive antagonist
38
39
tells you how much more agonist you need to achieve the same response when the antagonist is blocking some receptors.
Dose ratio
40
- Effects are overcomed by adding more agonist - Increases the median effective dose (ED50)
Competitive antagonists
41
T/F The Degree of inhibition produced by the competitive antagonist depends on the concentration of antagonist
T; A competitive antagonist's effectiveness depends on its concentration. (eg, propranolol)
42
T/F Clinical response to a competitive antagonist depends on the concentration of agonist that is competing for binding to the receptor
T; eg propanolol
43
- Binds with the receptor via COVALENT bonds - Antagonist’s affinity to the receptor maybe so high - Receptor is not available to bind the agonist - Duration of action depends more on receptor turnover than drug elimination - More dependent on the rate of turnover of receptors (Eg, phenoxybenzamine binding with alpha receptors)
Irreversible antagonist; eg. Phenoxybenzmine
44
- Concentration-effect curve moves downward - No shift of the curve in the dose axis - Emax is not reached - No increase in median effective dose (ED50) unless there are spare receptors (if spare receptors are enough, it may increase ED50 but requires a higher concentration of agonist
Irreversible antagonist
45
T/F Antagonists can function noncompetitively in a different way by binding to a site on the receptor protein separate from the agonist binding site
T; negative allosteric modulators in which their action can be reversed
46
T/F Not all allosteric modulators act as antagonists; some potentiate rather than reduce receptor activity.
T; eg. Benzodiazepines (positive allosteric modulators)
47
- Does not depend on interaction with the agonist’s receptor - interacts directly with the drug being antagonized to remove it or to prevent it from reaching its target
Chemical antagonism (eg. Protamine counteracting the effect of heparin)
48
- Makes use of the regulatory pathway - Effects are less specific and less easy to control
Physiologic antagonism
49
- Binds to a different receptor producing an effect opposite to that produced by the drug it is antagonizing
Physiologic antagonism (eg. Glucocorticoids opposed by insulin, histamine by salbutamol and epinephrine)
50
Lower response, at full receptor occupancy
Partial agonist
51
concentration-effect curves that resemble those observed with full agonists in the presence of an antagonist that irreversibly blocks some of the receptor sites
Partial agonist
52
T/F failure of partial agonists to produce a maximal response is not due to decreased affinity for binding to receptors.
T; partial agonists competitively inhibit the responses produced by full agonists
53
T/F Not all mechanisms of antagonism involve interactions of drugs or endogenous ligands at a single type of receptor, and some types of antagonism do not involve a receptor at all.
T; eg. Protamine
54
ionic binding that makes the other drug unavailable for interactions with proteins involved in blood clotting.
Chemical antagonist
55
specific DNA sequences near the gene whose expression is to be regulated.
Response elements
56
protein that prevents normal folding of several structural domains of the receptor
hsp90; where receptor is bound to in the absence of hormone
57
gene- active hormones cannot be expected to alter a pathologic state within minutes
T; effects are produced after 30 minutes to several hours
58
Receptor molecules that mediates the first steps in signaling by - insulin - epidermal growth factor (EGF) - platelet-derived growth factor (PDGF) - atrial natriuretic peptide (ANP) - transforming growth factor-β (TGF-β) - many other trophic hormones.
Ligand-Regulated Transmembrane Enzymes Including Receptor Tyrosine Kinases
59
These receptors are polypeptides consisting of an extracellular hormone-binding domain and a cytoplasmic enzyme domain * the two domains are connected by a hydrophobic segment of the polypeptide that resides in the lipid bilayer of the plasma membrane.
Ligand-Regulated Transmembrane Enzymes Including Receptor Tyrosine Kinases
60
61
intensity and duration of action of EGF, PDGF, and other agents that act via receptor tyrosine kinases are often limited by a process called
down-regulation
62
often induces accelerated endocytosis of receptors from the cell surface, followed by the degradation of those receptors
Ligand binding
63
It is essential physiologically to limit the strength and duration of the growth factor signal;
Down-regulation process (eg. Genetic mutations)
64
65
- not rapidly degraded - are translocated in endocytic vesicles from the distal axon, where receptors are activated by nerve growth factor released from the innervated tissue, to the cell body.
Internalized nerve growth factor receptors
66
- is transduced to transcription factors regulating the expression of genes controlling cell survival. - effectively opposite to down-regulation, transports a critical survival signal from its site of agonist release to the site of a critical downstream signaling effect and can do so over a remarkably long distance
Growth factor signal
67
respond to a heterogeneous group of peptide ligands - growth hormone -erythropoietin - several kinds of interferon - regulators of growth and differentiation.