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1

Whats Pharmacokinetics?

Its abbreviated as Pk, it is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism 

2

In pharmacokinetics, what does drug concentration depend on?

Absorption --> distribution --> metabolism --> excretion e.g. urination

3

Whats pharmacodynamics ?

A study of the biochemical and physiological effects of drugs to their target

4

What do drugs bind to ?

They bind to specific targets, when this happens it effects the activity of a target it is "true" receptor

5

When drugs can activate receptors what are they known as?

When drugs activate a receptor they are known as agonists 

6

When drugs inhibit the receptor what are they known as?

When drugs inhibit the receptor they are known as antagonists 

7

When was the concept of receptors introduced?

In the late 19th century bu Paul Ehrlich, he introduced the concept of receptors to explain the selective toxicity of some early chemotherapeutic agents 

8

What did J.N. Langley do experiments with?

 

What did he propose?

He did experiments with neuromuscular junctions 

 

His proposals: 

  • there must be a "receptive substance that transmits the stimulus from the nerve to the muscle" 
  • First example of receptor pharmacology

9

Give an example of an agonist and antagonist

Agonist: Nicotine 

Antagonist: Curare (a skeletal muscle relaxant) 

10

What is a receptor

A macromolecular component of a cell with which a drug interacts to produce its characteristic biological effect 

11

Give 7 properties of receptors

  • Present in low concentrations and show saturable binding 
  • Many drugs have high affinities for their receptors
  • Receptors show selectivity 
  • Drug-receptor interactions are usually fully reversable 
  • Drugs are usually small molecules 
  • Receptors have a binding site with a complementary structure to the drug 
  • Agonists include conformational changes in their receptors 

12

Whats meant by saturable binding?

The binding of a ligand to a single binding site is definable by the concentration of the binding site (Bmax) and the concentration of unbound ligand at which the binding site is 50% occupied (Kd)

13

When receptors are present in low concentrations, how can the binding be measured?

using radioligand binding 

14

If drugs have a high affinity for their receptor, is a higher or lower concentration of the drug required?

If they bind effectively due to high affinity then only a small amount of the drug is needed to bind to receptor

15

Whats the drug and receptor formula and include K values and their directions

16

What is used to measure affinity?

Whats the units?

Affinity is measured by the equilibrium constant KD 

 

KD is measured in units of concentration (M)

17

Whats KD formula?

KD= K-1 / K+1

18

Here are some values of KD

KD = 1x10-3 M

KD= 1x10-6 M

KD= 1x10-9 M

Place them in order of highest affinity for receptor to lowest 

High affinity for receptor 

1x10-9 M

1x10-6 M

1x10-3 M

 

Low affinity for receptor 

 

The higher the Kd value, the weaker the binding and the lower tbe affinity. The opposite occurs when a drug has a low Kd

19

Place the following in order of selectivity for ß-adrenoreceptors: 

  • adrenaline 
  • noradrenaline 
  • Isoprenaline 

ß-adrenoreceptors: isoprenaline > adrenaline > noradrenaline

20

Place the following in order of specificity for α-adrenoreceptors: 

  • isoprenaline 
  • adrenaline 
  • noradrenaline

α-adrenoreceptors: noradrenaline > adrenaline>> isoprenaline

21

What do these two structures show?

22

When its said that drug-receptor interactions are usually fully reversible, what does this mean?

Neither the drug nor the receptor are permanently changed 

Drug + receptor DR

23

Drugs are usually small molecules, whats their mw and also whats the rough mw for receptors in comparison?

Drugs usually have an mw of 200 

receptors tend to have an mw of roughly 250,000

24

Why is a close fit required between a drug and receptor?

Because the drugs are held by only a weak binding force 

25

What forces are found between drugs and receptors?

Van der waals 

Ionic bonds 

Hydrogen bonds 

(when agonists bind to receptor, these bonds are present)

26

Are receptors rigid?

No

27

Do antagonists cause conformational changes?

 No

28

To allow comparison between drugs, their effects need to be quantifies. What 3 ways is this done?

  1. Assume the law of mass action 
  2. Assume that only a negligable amount of the total drug is bound
  3. at equilibrium

29

Whats the definition of law of mass action?

The rate of a reaction is directly proportional to the product of the reactants 

30

Whats the equation for the law of mass action? 

Whats the rate of the forward and the reverse reaction?

Drug (D) + Receptor (R) DR

Rate of forward reaction: K1[D][R]

Rate of reverse reaction: K-1[DR]