Pharmacodynamics

Question 1

Do most drugs bind reversibly or irreversibly to receptors?

Answer 1

Reversibly

Question 2

How is drug concentration measured?

Answer 2

Molarity

Question 3

What is intrinsic efficacy?

Answer 3

Ability of a drug to activate a receptor

Question 4

What is efficacy?

Answer 4

Ability of a ligand to cause a response

Question 5

What do agonists and antagonists have in reference to efficacy, affinity and intrinsic efficacy?

Answer 5

Agonists - have affinity, intrinsic efficacy and efficacy

Antagonists - have affinity, NO intrinsic efficacy/efficacy

Question 6

How can drug-receptor interactions and binding affinity be measured? What sort of graph can be plotted?

Answer 6

Using a radioligand - radioactively labelled ligand
Graph plotted of [drug] against proportion of bound receptors
Gives a hyperbolic curve

Question 7

What is Bmax?

Answer 7

Maximum binding capacity (number of receptors)

Question 8

A high Kd = _________ affinity

Answer 8

Low

Question 9

What is Kd?

Answer 9

Ligand concentration that occupies 50% of the available receptors (1/2 Bmax)

Question 10

Drug concentration is usually measured using which type of scale? Therefore graphs with [drug] on one axis usually give which shape curve?

Answer 10

Logarithmic

Sigmoidal

Question 11

How can you measure drug efficacy?

Answer 11

With a concentration-response curve

Question 12

What does a concentration-response curve measure?

Answer 12

% response vs. [drug]

Question 13

What is Emax?

Answer 13

100% drug response (maximal drug response)

Question 14

What is EC50?

Answer 14

Effective [drug] giving 50% of the maximal response

Question 15

What is concentration (of a drug)?

Answer 15

Known concentration of a drug at the site of action

Question 16

What is dose?

Answer 16

Unknown concentration of drug at site of action (what you give to the patient)

Question 17

EC50 gives an indication of _______/________

Answer 17

Efficacy and potency of a drug

Question 18

What is potency?

Answer 18

Generation of a measurable response

Question 19

What is required for a ligand to have potency? (3)

Answer 19

Affinity
Intrinsic efficacy
Things to happen to cause a response

Question 20

Giving drugs for asthma is an example of functional antagonism. What is meant by this?

Answer 20

Drugs for asthma cause relaxation of smooth muscle rather than just preventing contraction of smooth muscle

Question 21

Drugs for asthma act on which receptors?

Answer 21

B2-adrenoceptors

Question 22

Activation of B1-adrenoceptors results in what?

Answer 22

Increased heart rate/force of contraction of the heart

Question 23

What two drugs work on B2-adrenoceptors for the treatment of asthma?

Answer 23

Salbutamol

Salmeterol

Question 24

What selectivity and selective efficacy does salbutamol show to b2-adrenoceptors?

Answer 24

Has poor selectivity for b2-adrenoceptors - so similar affinity

Has good selective efficacy for b2-adrenoceptors - causes a greater response in b2-adrenoceptors)

Question 25

What selectivity and selective efficacy does salmeterol show to b2-adrenoceptors?

Answer 25

Has good selectivity for B2-adrenoceptors No selective efficacy between the receptors

Question 26

How does salmeterol work compared to salbutamol?

Answer 26

Salmeterol is longer lasting

Question 27

Why are there problems in prescribing salmeterol and salbutamol to patients with cardiac problems?

Answer 27

Salmeterol = insoluble Salbutamol = will cause increased heart rate/contraction

Question 28

You would expect a 50% binding to result in 50% response but this is not the case, why? What does this result in?

Answer 28

There is only so much a muscle can contract and so much a gland can secrete It means there will be some spare receptors that do not contribute to a response

Question 29

What are spare receptors?

Answer 29

Receptors that don't contribute to a response

Question 30

If a situation existed where there were spare receptors, what would the binding curve look like compared to the response curve?

Answer 30

Response curve shifted to the left compared to the binding curve

Question 31

Where are spare receptors often found?

Answer 31

When receptors are catalytically active e.g. GPCRs

Question 32

What is the benefit of having spare receptors?

Answer 32

Allows increased sensitivity | E.g. A response at a low [agonist]

Question 33

Changing receptor numbers changes agonist _____

Answer 33

Potency

Question 34

Are receptor numbers fixed?

Answer 34

No

Question 35

What can cause an increase or decrease in receptor numbers? What can this result in, in reference to drugs?

Answer 35

Increase when there is low activity Decreases when there is high activity Drug tolerance/toxicity

Question 36

What is a full agonist? Are there spare receptors found in a full agonist?

Answer 36

Can give a full, maximal response | Has spare receptors

Question 37

What is a partial agonist? Does it have spare receptors?

Answer 37

Does not give a full response - low intrinsic efficacy No spare receptors

Question 38

What is the benefit of using partial agonists as drugs?

Answer 38

They allow a more controlled response

Question 39

How can heroin cause death?

Answer 39

Can result in respiratory depression ---> death

Question 40

What is buprenorphine?

Answer 40

A high affinity partial agonist - used to gradually withdraw use of illicit opioids

Question 41

How can a change in the number of receptors affect the action of a partial agonist?

Answer 41

It could change a partial agonist into a full agonist

Question 42

What is the efficacy of a partial agonist compared to a full agonist?

Answer 42

Partial agonist has a lower efficacy

Question 43

What do antagonists do?

Answer 43

Block the action of agonists - bind and do not cause a response

Question 44

What are 3 types of antagonism?

Answer 44

Reversible competitive antagonism Irreversible competitive antagonism Non-competitive antagonism (allosteric)

Question 45

What is IC50?

Answer 45

The [antagonist] giving 50% inhibition

Question 46

What does IC50 give an indication of?

Answer 46

Antagonist potency

Question 47

What happens in reversible competitive antagonism? How can this inhibition be surmounted?

Answer 47

Antagonist competes with the agonists for binding By increased agonist concentration

Question 48

What result does reversible competitive inhibition have on the % response-concentration curve?

Answer 48

Shift to the right

Question 49

What happens in irreversible competitive antagonism?

Answer 49

Antagonist dissociates from receptor very slowly/not at all | Usually as a result of covalent modification/very high affinity

Question 50

Is irreversible competitive antagonism surmountable by increasing [agonist]?

Answer 50

No

Question 51

What effect does irreversible competitive antagonism have on the % response - concentration curve?

Answer 51

Shifts it to the right and can lower the maximal response at high [antagonist] as there are not enough receptors

Question 52

What is the site where ligands bind called?

Answer 52

The orthosteric site

Question 53

What happens in non-competitive antagonism?

Answer 53

Antagonist binds to allosteric site | Reduce or enhance the effects of the agonist