Drug And Drug Target Interactions

Question 1

What is a ligand?

Answer 1

Something that binds to a target (mainly protein) to exert an effect

Question 2

What is affinity?

Answer 2

How easily a ligand binds to a receptor

Higher affinity= binds at lower concentrations

Question 3

What is the measure of affinity and what does it mean?

Answer 3

Kd

Is the concentration of drug when half if the receptors are occupied

Lower value= higher infinity

Question 4

How is drug action determined?

Answer 4

By concentration of drug molecules around receotors at the site of action

Question 5

If two drugs have the same molarity what does this mean?

Answer 5

They have the same number of molecules (same concentrations)

Question 6

If the same weight of 2 differnt drugs is given what does this mean?

Answer 6

Could have a different no. Of molecules (different molarity) if have different molecular weight

Different concentrations

Question 7

What is Intrinsic efficacy?

Answer 7

The ability of a ligand to cause a confirmational change to a receptor (active it)

Question 8

What is efficacy?

Answer 8

The measured response to a ligand binding to a receptor (response of whole cell)

Question 9

What is clinical efficacy?

Answer 9

Releates to whole desired outcome eg, lowering bp

Question 10

How do you measure efficacy?

Answer 10

Using response vs drug concentration graphs

Question 11

What is Emax?

Answer 11

The max response you can generate

Question 12

What is EC50?

Answer 12

The concentration of drug needed to give 50% of maximal response

Question 13

What is drug Potency?

Answer 13

EC50

Depends on both affinity and instrinsic efficacy plus cell/ tissue specific elements (cellular response)

Question 14

What is the maximal binding capasity of a cell called?

Answer 14

Bmax

Question 15

What do agonists have?

Answer 15

Affinity
Intrinsic efficacy
Efficacy (if response evoked)

Question 16

What do antagonists have?

Answer 16

Affinity

Question 17

Why is potency not fixed for a ligand- receptor combination?

Answer 17

Due to differnt cell and tissue factors

Eg, no of receptors on that cell

Question 18

What is concentration in terms of drugs?

Answer 18

Known concentration at site of drug action

Question 19

What is dose?

Answer 19

Amount given to patient

Unknown concentration at site of action

Question 20

What is the relationship between agonist potency and affinity?

Answer 20

Simular Kd and EC50 (no spare receptors)

But resonse often limited by other fators. Eg, muscles can only contract so hard (spare receptors) Kd=Emax

Question 21

What are partial agonists?

Answer 21

Have lower intrinsic activity than full as have lower efficacy

Can have greater affinity

Question 22

How can you cause a partial agonist to act like a full one?

Answer 22

By increasing receptor number to get full response

Question 23

Why do we use partial agonists?

Answer 23

To get a more controlled response (dont always need to reach Emax

Work in low levels of endogenous ligand

Act as antagonists if high levels of full agonist by preventing a full response

Question 24

What is an example of a partial agonist?

Answer 24

Treatment of opiod addiction

Use Buprenorphine
Inhibits the action of heroin binds to opiod receptors with a higher affinity
Stops respiratory derpession but still get feeling of receptors activated

Question 25

What is functional antagonism?

Answer 25

Stimulating the oppostite effect of the orgional action

Treatment doesn’t matter on cause

Question 26

What is an example of functional antagonism?

Answer 26

Asthma treatment

Sakbutamol- activates B2 adrenoreceptors causing relaxation of smooth muscle (bronchdilation)

Opposed the origional constriction

Question 27

What is reversible competive antagonism?

Answer 27

Antagonist and agonist both in competition of receptor and the realative concentration of each determines which binds

Question 28

What is IC50?

Answer 28

The concentration of an antagonist needed to give 50% inhibition

Is an indictaion of affinity

Question 29

What does surmountable mean?

Answer 29

That the effect of an antagonist can be over come by incraesing agonist concentration (the transverse can also be true)

Question 30

What influeneces IC50?

Answer 30

Antagonist concentration

Stength of stimulus (agonist)

Question 31

What is an example of competitive antagonism?

Answer 31

Naloxone
High affinity competive inbititor for opiod receptors

Competes against heroin (stops respiratory depression occouring)

Question 32

What is irreversible competitive antagonism?

Answer 32

When the antagonists dissociates very slowly/ not at all from receptor

Due to tight bonds to receptor eg,covalent

Question 33

Why are irreversible competitive antagonists non surmountable?

Answer 33

Their effect cannot be overcome by increasing agonist concentration

Once antagonist bound agonist have no oportunity too

Question 34

What happens at high concentrations of irreversible competitive antagonsits?

Answer 34

The maximal response if surpressed (even increasing the agonist concentration wont achieve it)

Question 35

What is an example of irreversible competitive antagonism?

Answer 35

Phenoxybenzamine

Binds to A1 receptors so prevents vasoconstriction (stops high bp, headaches ect)

Used when pheochromocytoma (adrenal gland turmour that produces ardenaline)
Although high levels of adrenaline they are unable to assert an effect

Question 36

What are non competitive antagonists?

Answer 36

Bind to an allosteric site on the receptor

Question 37

How do non competitive antagonists work?

Answer 37

Reduce the effect of the ligand binding to the orthosteric site by reducing its;

• affinity
• efficacy

Question 38

What is an example of non competitve antagonist?

Answer 38

Maraviroc

Binds to CCR5 receptor and prevents it chaning shape and allowing HIV to be taken into cell