Drug-Receptor Interactions

Question 1

drug

Answer 1

any substance that brings about a change in biologic function (usually an increase or decrease in an existing function, rather than a new function) through it chemical actions

Question 2

endogenous ligands

Answer 2

drugs that originate from inside the body that binds to a receptor in the body

Question 3

xenobiotics

Answer 3

drugs that come from sources outside of the body; substance that is foreign to the body

Question 4

ligand

Answer 4

molecule that binds to a receptor

Question 5

poison

Answer 5

a drug with mainly harmful effects

Question 6

toxin

Answer 6

a poison of biologic origin

Question 7

receptor

Answer 7

a specific molecule in a biological system with which drugs interact to produce changes in the function of a system; most drugs act by binding a receptor

Question 8

receptors must:

Answer 8

1. possess an appropriate steric/chemical configuration to interact with a drug
2. trigger some downstream action

Question 9

target or “target receptor”

Answer 9

the intended receptor for a drug; the receptor that produces therapeutic effects

Question 10

off-target receptor

Answer 10

a receptor that is not involved in the therapeutic response; may produce side-effects

Question 11

specificity/promiscuity

Answer 11

a drug with high specificity interacts exclusively with its target; a drug that binds promiscuously interacts nonspecifically with many types of target

Question 12

acceptor (or “inert receptors”)

Answer 12

an entity that a drug binds to, which produces no change in the function of a system

Question 13

effectors

Answer 13

component of a system that translate the drug-receptor interaction into a change in cellular activity (an effect)

Question 14

equilibrium dissociation constant (Kd)

Answer 14

the drug concentration at which 50% of the total receptors in the system are bound to a drug at a given time

Question 15

Why do drugs differ in terms of their Kd?

Answer 15

because each drug has a different affinity for its receptor

Question 16

Drug potency

Answer 16

the amount (expressed as concentration or dose) of a drug needed to produce a given level of effect

Question 17

EC50 (or ED50)

Answer 17

Potency: the concentration or dose of drug required to produce a half-maximal effect

Question 18

Drug efficacy

Answer 18

the largest degree of effect that a drug (or endogenous ligand) is capable of producing, if administered at the highest tolerated dose

Question 19

Emax

Answer 19

Efficacy: the maximum degree of effect that you can achieve by increasing the drug’s concentration

Question 20

agonist

Answer 20

a drug (or ligand) that binds to a receptor and increases the receptor’s activity (activator)

Question 21

primary agonist

Answer 21

binds at the same site as the endogenous ligand for the receptor and produces the same type of effect

Question 22

allosteric agonist/ allosteric activator

Answer 22

binds at a different site than where the endogenous ligand binds; alone, it produces no effect, but it changes the shape of the receptor so that when a primary agonist binds, the receptors responds with a greater than usual effect

Question 23

full agonist

Answer 23

capable of producing the maximum receptor response

Question 24

partial agonist

Answer 24

cannot elicit a maximum receptor response (by definition, their Emax is always lower vs. a full agonist); can be more or less potent than full agonists

Question 25

antagonist/ inhibitor

Answer 25

a drug or ligand that reduces the effect of a receptor

Question 26

competitive antagonist

Answer 26

binds to the same site as an agonist, but does not activate the receptor; can be overcome by adding more agonist; shifts the concentration-effect curve to the right

Question 27

allosteric antagonist

Answer 27

binds at a site different than where the endogenous ligand binds; it changes the shape of the receptor so that when the endogenous ligand binds, the receptor responds with a lower than usual effect

Question 28

irreversible antagonist

Answer 28

binds covalently/irreversibly to a receptor, either at the site that the endogenous ligand binds, or at an allosteric site

Question 29

physiologic antagonist

Answer 29

acts at a different receptor to produce a physiological effect that opposes the effect of the agonist

Question 30

True or False. Non-competitive inhibitors produce effects that can NOT be overcome by adding more agonist

Answer 30

True.

Question 31

What effect do non-competitive inhibitors have on Emax?

Answer 31

They lower the apparant Emax of the agonist

Question 32

3 non-competitive inhibitors and why they are non-competitive

Answer 32

allosteric, irreversible, and physiologic antagonists are all non-competitive inhibitors because they don’t compete with agonists for the same binding site

Question 33

quantal dose-response curve

Answer 33

generated by administering many different dose sizes to a large number of subjects and recording the percent of subjects who respond to the drug at each dose

Question 34

ED50

Answer 34

the dose that produces a therapeutic effect in 50% of the subjects (the 50% effective dose level)

Question 35

TD50

Answer 35

50% toxic dose level. The dose that produces a toxic effect in 50% of the subjects

Question 36

therapeutic window

Answer 36

refers to the range of doses that produce therapeutic effects, but not toxic effects in most subjects

Question 37

therapeutic index

Answer 37

a way to express the size of the therapeutic window numerically. calculated as TI = TD50 / ED50

Question 38

narrow therapeutic index drugs

Answer 38

those with less than a 2-fold difference between minimum effective and toxic concentrations; requires careful titration of plasma concentrations and patient monitoring