Drug Target Sites - Receptors

Question 1

Potency

Answer 1

dose required for effect

Question 2

Agonist

Answer 2

drug which acts on a receptor and produces a response (increase or decrease of activity in a cell)

Question 3

Antagonist

Answer 3

A drug which prevents the response to an agonist

Question 4

Drug Receptors Control…

Answer 4

• selectivity of drug effect
• magnitude of response
• mechanisms to mimic/prevent physiological functions

Question 5

Unit of dose: Micrograms

Answer 5

(10-6 grams)

Question 6

Unit of Dose: Nanomoles

Answer 6

(10-9 moles)

Question 7

Unit of concentration: Micromolar

Answer 7

(10-6 moles per litre)

Question 8

Unit of concentration: Nanomolar

Answer 8

(10-9 moles per litre)

Question 9

Drug-Receptor Interaction

Answer 9

An agonist binds to its receptor with weak bonds:
-electrstatic forces
-van der waals
-h bonds
[AR] ====>  Effect

Question 10

Stereo-selective

Answer 10

Ligand/receptor interactions are defined in 3D

-hence display selectivity for one stereo-isomer of a ligand over another

Question 11

[A]

Answer 11

Agonist conc

Question 12

[AR]

Answer 12

Agonist-receptor conc

Question 13

[Rt]

Answer 13

total receptor conc

Question 14

Kd

Answer 14

Dissociation constant

Question 15

Magnitude of response

Answer 15

hyperbolic relationship

Question 16

LOG DOSE - response curves

Answer 16

sigmoid in shape

Question 17

Info from LOG dose response curves:

Answer 17

• threshold dose
• max dose
• effective dose range
• half-maximal effective dose (ED50)

Question 18

POTENCY

Answer 18

related to affinity of drug for receptor

-ED50 usually index of potency

Question 19

EFFICACY

Answer 19

-an index of the max response a drug can induce (effectiveness)

Question 20

FULL AGONISTS

Answer 20

• have high efficacy

- produce maximum response

Question 21

PARTIAL AGONISTS

Answer 21

• have low efficacy (<1.0)

- fail to produce max. response

Question 22

ANTAGONISTS

Answer 22

-block the actions of agonists
-they may:
act on same receptor site as agonist
act at diff. site in the pathway leading to the response
-activate an opposing physiological mechanism
-interact chemically with the agonist

Question 23

COMPETITIVE ANTAGONISTS

Answer 23

• antagonists with act on the same receptor site as the agonist
• have high affinity for the receptor
• have no efficacy at the receptor
• doesnt produce effect

Question 24

REVERSIBLE competitive antagonists

Answer 24

-Surmountable
-weak bonds
-agonist is competitive and reversible
(curve shifts to right, )

Question 25

IRREVERSIBLE competitive antagonists

Answer 25

• Insurmountable
• covalent bonds
• curve has depressed maximum response

Question 26

Receptor reserve

Answer 26

-powerful agonists do not need to occupy all the receptors to produce the max response
(<5%)?
-full agonists occupy a small % of the receptors to produce max response (HIGH EFFICACY)
-partial agonists cannot produce the max response even when they occupy all the receptors (LOW EFFICACY)

Question 27

NON-COMPETITIVE ANTAGONISTS

Answer 27

can:

• act at diff site-activate opposing physiological mechanism
• interact chemically with agonist

Question 28

Inverse Agonism

Answer 28

an inverse agonist is a ligand that binds to the receptor and limits agonism-independent activity

Question 29

Allosteric ligands

Answer 29

• Ligands that bind to the same region of the receptor as the natural hormone/neurotransmitter are termed ‘ORTHOSTERIC’
• There are potentially many other sites on receptors to which synthetic ligands may bind - such ligands are termed ‘ALLOSTERIC’
• these do not produce an effect in isolation but only modulate the effect of an orthosteric ligand

Question 30

Positive allosteric ligands

Answer 30

enhance the funciton of an orthosteric ligand

Question 31

Negative allosteric ligands

Answer 31

reduce the function of an orthosteric ligand