Drug Receptors & Pharmacodynamics

Question 1

the component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug’s observed effects.

Answer 1

receptor

Question 2

receptor concept:

Answer 2

1. Receptors largely determine the quantitative relations between dose or concentration of drug and pharmacologic effects.
2. Receptors are responsible for selectivity of drug action.
3. Receptors mediate the actions of pharmacologic agonists and antagonists.

Question 3

They activate the receptor to signal as a direct result of binding to it.

Answer 3

agonists

Question 4

They bind to receptors but do not activate generation of a signal; consequently, they interfere with the ability of an agonist to activate the receptor.

Answer 4

antagonists

Question 5

drugs bind to a different site on the receptor than that bound by endogenous ligands; such drugs can produce useful and quite different clinical effects by acting as so-called ___ ___ of the receptor.

Answer 5

allosteric modulators

Question 6

So-called because their natural ligands are presently unknown; these may prove to be useful targets for future drug development

Answer 6

orphan receptors

Question 7

mediate the actions of endogenous chemical signals such as neurotransmitters, autacoids, and hormones. The best-characterized drug receptors; mediates the effects of many of the most useful therapeutic agents.

Answer 7

regulatory proteins

Question 8

Other classes of proteins have been clearly identified as drug receptors:

Answer 8

Enzymes: HMG-CoA
Transport proteins: Na+/K+-ATPase
Structural proteins: tubulin

Question 9

overall transduction process that links drug occupancy of receptors and pharmacologic response is called?

Answer 9

coupling

Question 10

Increases presence of agonists

Answer 10

receptor reserve or spare receptors

Question 11

Binds to receptors but do not activate them, reduces effects of agonists that normally activates receptors

Answer 11

Receptor antagonists

Question 12

progressively inhibit the agonist response; high antagonist concentrations prevent the response almost completely

Increase concentration of agonist can overcome the competitive antagonist

Answer 12

Competitive antagonist

Question 13

they also reduce receptor activity below basal levels observed in the absence of any agonist at all.

Answer 13

inverse agonist

Question 14

bind to the receptor in an irreversible or nearly irreversible fashion, sometimes by forming a covalent bond with the receptor.

May react not to prevent agonist but shaping the response

Answer 14

noncompetitive antagonist

Question 15

Allosteric Modulators:

Answer 15

Positive Allosteric Modulators: activate

Negative Allosteric Modulators: inhibits

Question 16

___ ___ produce a lower response, at full receptor occupancy

___ ___ maximal response at full occupancy

Answer 16

Partial Agonists

Full Agonists

Question 17

by ionic binding that makes the other drug unavailable for interactions with proteins involved in blood clotting.

Answer 17

chemical antagonist

Question 18

between endogenous regulatory pathways mediated by different receptors.

Answer 18

physiologic antagonism

Question 19

a protein that prevents normal folding of several structural domains of the receptor

Answer 19

hsp90

Question 20

Major Receptors:

Answer 20

Ligand-gated ion channels
G protein-coupled receptors
Enzyme-linked receptors
Intracellular receptors

Question 21

changes in membrane potential or ionic concentration within cell

Answer 21

Ligand-gated ion channels

Question 22

protein phosphorylation

Answer 22

G protein-coupled receptors

Question 23

protein and receptor phosphorylation

Answer 23

Enzyme-linked receptors

Question 24

protein phosphorylation and altered gene expression

Answer 24

Intracellular receptors

Question 25

2 main function of receptor:

Answer 25

Ligand binding

Activation of an effector system

Question 26

Chemicals that buy into receptor

Answer 26

Ligand

Question 27

Tranduce drug-receptor interactions into cellular effects

Answer 27

Effectors

Question 28

Adding phosphate group to another molecule

Answer 28

Phosphorylation

Question 29

Synthesis of complex molecules from simple molecules

Answer 29

De novo complex

Question 30

respond to a heterogeneous group of peptide ligands (growth hormone, erythropoietin, several kinds of interferon, and other regulators of growth and differentiation)

Answer 30

Cytokine receptors

Question 31

separate protein tyrosine kinase, binds noncovalently to the receptor.

Important to cytokine receptors.

Answer 31

Janus-kinase (JAK) family

Question 32

drugs often mimic or block the actions of natural agonists

Natural ligands of such receptors include acetylcholine, serotonin, GABA, and glutamate; all are synaptic transmitters.

Answer 32

ligand-gated ion channels,

Question 33

Is one of the best characterized of all cell-surface receptors for hormones or neurotransmitters

Answer 33

nAChR

Question 34

Do not bind neurotransmitters directly but are controlled by membrane potential; such channels are also important drug targets.

e.g Verapamil

Answer 34

Voltage-gated ion channels

Question 35

Largest receptor family - receptor polypeptide chain “snakes” across the plasma membrane seven times.

Answer 35

G proteins and Second Messengers

Question 36

Well-established Second Messengers:

Answer 36

Cyclic Adenosine Monophosphate (cAMP)
Phosphoinositides
Calcium
Cyclic Guanosine Monophosphate (cGM)

Question 37

Continuous stimulation may cause _____ decreased responsiveness

Answer 37

Desensitization

Question 38

Second Messengers:

Answer 38

cAMP
Calcium ion
Phosphoinositides

Question 39

refers to the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect.

Answer 39

Potency

Question 40

(sometimes referred to simply as efficacy) of a drug is obviously crucial for making clinical decisions when a large response is needed

This parameter reflects the limit of the dose-response relation on the response axis.

Answer 40

maximal efficacy

Question 41

Is the dose at which 50% of individuals exhibit the specified quantal effect.

Answer 41

median effective dose (ED50),

Question 42

the dose required to produce a particular toxic effect in 50% of animals

Answer 42

median toxic dose (TD50)

Question 43

the toxic effect is death of the animal, a ___ ___ ___ may be experimentally defined.

Answer 43

median lethal dose (LD50)

Question 44

One measure, which relates the dose of a drug required to produce a desired effect to that which produces an undesired effect, is the ___ ___

Answer 44

therapeutic index

Question 45

The range between the minimum toxic dose and the minimum therapeutic dose is called the ___ ___ and is of greater practical value in choosing the dose for a patient.

Answer 45

therapeutic window

Question 46

individuals exhibit an unusual or ___ ___ ___, one that is infrequently observed in most patients.

Answer 46

idiosyncratic drug response

Question 47

usually refers to allergic or other immunologic responses to drugs.

Answer 47

hypersensitivity

Question 48

responsiveness usually decreases as a consequence of continued drug administration, producing a state of relative ___ to the drug’s effects.

Answer 48

Tolerance

Question 49

The study of genetic factors determining drug response is called?

Answer 49

pharmacogenetics

Question 50

the use of gene sequencing or expression profile data to tailor therapies specific to an individual patient is called?

Answer 50

personalized or precision medicine