Pharmacodynamics

Question 1

How does a drug exert its effects?

Answer 1

By binding to a target receptor

Question 2

What proportion of targets do G protein-coupled receptors account for?

Answer 2

30%

Question 3

List the order of molarity starting with picomolar.

Answer 3

Picomolar
Nanomolar
Micromolar
Millimolar
Molar

Question 4

Define what a ligand is.

Answer 4

A molecule that binds specifically to a receptor

Question 5

How does an agonist act at a receptor?

Answer 5

An agonist activates a receptor

Question 6

How many moles is 1 micromolar?

Answer 6

10-6 M

Question 7

How do antagonists function?

Answer 7

They block the binding site of endogenous molecules, meaning the receptor cannot be activated

Question 8

Define the term efficacy.

Answer 8

A molecules efficacy is its ability to evoke a response in the cell its acting on

Question 9

Do antagonists have any affinity and/or efficacy?

Answer 9

Antagonists have affinity as they can bind their target, but they have no efficacy, as they do not evoke any response in the cell

Question 10

Do agonists have any affinity and/or efficacy?

Answer 10

Agonists have affinity as they bind their target, and they have efficacy, as their binding evokes a response in the cellular target

Question 11

How can you measure drug-receptor interactions by binding?

Answer 11

By measuring the binding of a radioligand, which you can measure

Question 12

How are high affinity drugs pharmacologically useful?

Answer 12

You will not need a high amount of the drug as its affinity for its target is already high

Question 13

What is Bmax? What is Emax?

Answer 13

Bmax is the number of molecules that lead to maximal binding, while Emax is the number of molecules that lead to a maximal effect

Question 14

What is the difference between concentration and dose?

Answer 14

Concentration is the amount of drug given to a known site of action, while dose is the concentration of drug given to a site of unknown action

Question 15

What is the EC50?

Answer 15

The EC50 is a measure of the effective concentration of a ligand that gives 50% of the maximal response/effect - the EC50 is a measure of potency

Question 16

Other than affinity and intrinsic efficacy, what else might affect a molecules potency (EC50)?

Answer 16

The number of receptors a cell contains

Question 17

What are receptors termed that are bound by their ligand but have no effect on a ligands efficacy within the cell?

Answer 17

Spare receptors

Question 18

Other than affinity and intrinsic efficacy, what else might affect a molecules potency (EC50)?

Answer 18

The number of receptors a cell contains

Question 19

What are receptors termed that are bound by their ligand but have no effect on a ligands efficacy within the cell?

Answer 19

Spare receptors

Question 20

What receptors are the therapeutic target in asthma? What does binding cause?

Answer 20

B2-adrenoreceptors - binding of an agonist causes relaxation

Question 21

Describe the mechanism of action of salbutamol.

Answer 21

Salbutamol acts as a B2 adrenoreceptor agonist - it stimulates a G protein cascade through adenyl cyclase to increase levels of cAMP, activating protein kinase A - this leads to a series of events which leads to bronchodilation, widening the bronchial passages

Question 22

What is the difference between a partial agonist and a full agonist?

Answer 22

A partial agonist has less efficacy than a full agonist

Question 23

What is the role of spare receptors?

Answer 23

They increase sensitivity

Question 24

What happens to spare receptors when a cell is over-stimulated?

Answer 24

The cell will remove receptors from its surface if over-stimulated - the cell is therefore less sensitive as a higher concentration will need to bind in order to bring about a response - this is seen in drug addiction

Question 25

What happens respectively to receptor number in low activity and high activity?

Answer 25

In low activity receptor numbers generally tend to increase (receptors are up-regulated), while in high activity receptor numbers are generally decreased (they are down-regulated)

Question 26

What is down-regulation of receptors (due to over-stimulation) otherwise called in drug addicts?

Answer 26

Tolerance

Question 27

What is withdrawal/abstinence syndrome?

Answer 27

Neonatal abstinence withdrawal syndrome results from the cessation of the administration of drugs by the mother - this may lead to the child experience withdrawal symptoms as if they had been taking the drug themselves

Question 28

List 3 examples where a partial agonist may be relevant?

Answer 28

- due to an absence/low levels of an endogenous ligand - when concentrations/doses of a full agonist are too high (acting as an antagonist) - to induce a more specifically controlled response

Question 29

Give an example of a partial agonist. What receptors are their target?

Answer 29

Opioids are partial agonists - these usually target u-opioid receptors

Question 30

What are the effects of opioids?

Answer 30

Pain relief Euphoria Respiratory depression (leading to death)

Question 31

If a heroin addict injects buprenorphine, why will he/she immediately become ill? What does this say about the affinity of the 2 substances?

Answer 31

Buprenorphine (a partial agonist) will act as an antagonist - this antagonism will lead to withdrawal symptoms and as such the individual will feel ill - buprenorphine has a higher affinity to u-opioid receptors than heroin

Question 32

How can you change a partial agonist into a full agonist?

Answer 32

Increasing the receptor number, meaning more partial agonists will bind and produce greater efficacy (check)

Question 33

List 3 types of antagonism.

Answer 33

- reversible competitive antagonism - irreversible competitive antagonism - non-competitive antagonism

Question 34

How does increasing the concentration of a reversible competitive antagonist affect an agonist concentration-response curve?

Answer 34

It will shift the curve to the right

Question 35

Give an example of a reversible competitive antagonist. Clinically, how may this be useful?

Answer 35

Naloxone - this may be used in respiratory depression after opioid overdose - it's high affinity means it will compete effectively with other opioids

Question 36

What is the IC50?

Answer 36

The concentration of an antagonist needed to give 50% inhibition

Question 37

What is irreversible competitive antagonism?

Answer 37

Where the antagonist dissociates from to target slowly, or not at all

Question 38

Where do non-competitive antagonists bind?

Answer 38

Allosteric sites of the target

Question 39

How does increasing the concentration of a irreversible competitive antagonist affect an agonist concentration-response curve?

Answer 39

Initially it will shift it right, like a reversible competitive antagonist - at higher doses it will also decrease the maximal response (decrease the height of the curve)

Question 40

What is an allosteric site?

Answer 40

A site on a protein other than the active site where molecules bind to either enhance or reduce the effects of an agonist