51. Introduction to drug action

Question 1

what are the 4 receptor superfamilies:

Answer 1

ligand-gated ion-channel receptors,
G-protein-coupled receptors, kinase-linked receptors
nuclear receptors.

Question 2

what are the four drug targets

Answer 2

receptors, ion channels, enzymes and transport/channel proteins.

Question 3

what is a ligan

Answer 3

A substance that is bound to a protein.

Question 4

what is affinity

Answer 4

the tendency of a ligand to bind to its receptor

Question 5

what is an agonist

Answer 5

A ligand that binds to a receptor and alters the receptor state resulting in a biological response.

Question 6

what is an antagonist

Answer 6

A drug that reduces the action of another drug, generally an agonist. Many antagonists act at the same receptor macromolecule as the agonist.

Question 7

what is a partial agonist

Answer 7

An agonist that cannot elicit as large an effect (even with 100% receptor occupancy) as can another agonist acting through the same receptors in the same tissue

Question 8

what is efficacy

Answer 8

the tendency for an agonist to activate the receptor state resulting in a biological response

and the maximum response achievable from a drug

Question 9

what is - Drug Potency -

Answer 9

the concentration or amount needed to produce a desired effect (e.g., EC50).

Question 10

describe - Drug selectivity –

Answer 10

the degree to which a drug has affinity for its intended target to the exclusion of other (‘off’) targets.

The greater the selectivity for the intended target, the greater the likelihood that the drug will evoke the intended physiological mode of action and less the likelihood that the drug will evoke an adverse effect by acting at ‘off’ targets.

Question 11

Dose

Answer 11

• a specified quantity of drug administered once or at stated intervals. Doses can be relative to body weight (e.g., mg/kg).

Question 12

From the dose-response curve, we can estimate the …..

Answer 12

ED50 (note, not the EC50!).

Question 13

what is drug specificity

Answer 13

• To be useful, a drug must act selectively for a specific receptor, i.e., it must have a high degree of specificity for the binding site of the receptor.

Question 14

The Relationship Between Ligand Concentration and Receptor Occupancy. What is the equation.

Answer 14

Hill- Langmuir equation

Question 15

what is the EC50

Answer 15

Concentration of agonist that elicits half maximal effect

Question 16

The lower the conc. of the drug the …..the affinity

Answer 16

greater

Question 17

The lower the Ka that ………..the affinity

Answer 17

greater

Question 18

describe competitive antagonism

Answer 18

Binding of agonist and antagonist occur at same (orthosteric) site - competitive

Question 19

competitive antagonism causes a …..shift of agonist conc. response curve with no depression in maximal response

Answer 19

right

Question 20

describe non competitive antagonism

Answer 20

Agonist binds to normal site and antagonist binds to separate (allosteric) site - not competitive

Question 21

If both antagonist and agonist occupy sites simultaneously, can activation occur

Answer 21

no

Question 22

what does an agonist and non competitive antagonist do to the agonist conc. response curve

Answer 22

Depress the slope and maximum response curve, but do not cause a rightwards shift

Question 23

what does an agonist and competitive antagonist do to the agonist conc. response curve

Answer 23

shifts right but no depression of curve and no decrease in maximal

Question 24

the disassociation equilibrium constant is …

Answer 24

Ka

Question 25

the disassociation equilibrium constant Ka is equal to what

Answer 25

the concentration of ligand required to occupy 50% of the receptors

Question 26

higher pEC50 values indicate what

Answer 26

higher potency

Question 27

The lower the IC50, the …….

Answer 27

the greater the affinity!
a lower IC50 means the drug is very potent and binds strongly to its target, showing high affinity. It’s like needing fewer strong magnets to hold something in place tightly

Question 28

the lower the Ki…..

Answer 28

the greater the affinity.

Question 29

what drug is an antagonist at NET and SERT

Answer 29

Amitriptyline

Question 30

A + R <—> AR <—> AR*
which bit of this is governed by efficacy

Answer 30

state 2 the activated receptor AR*

Question 31

A + R <—> AR <—> AR*
which bit of this is governed by affinity

Answer 31

State one the ligand receptor complex AR

Question 32

………..activates muscarinic acetylcholine receptors which then leads to a contraction of the smooth muscle of the ileum

Answer 32

Carbachol

Question 33

Carbachol activates muscarinic acetylcholine receptors which then leads to a contraction of the smooth muscle of the ……

Answer 33

ileum