Drug-Receptor Interactions

Question 1

Drug or ligand which binds to the same site as the endogenous ligand and produces the same signal

Answer 1

Agonist

Question 2

Drug or ligand which binds to a different site than the endogenous agonist without producing a signal itself; it enhances the response of the endogenous agonists

Answer 2

Allosteric agonist

Question 3

Drug which produces a lower response when at full receptor occupancy than do full agonists (these by themselves evoke a response, but in the presence of a full agonist, they act to competitively inhibit full agonist binding to the receptor)

Answer 3

Partial agonist

Question 4

Drug that binds to the receptor or components of the effector system used by the endogenous ligand and inhibits the action of the agonist; these initiate no effect themselves

Answer 4

Antagonist

Question 5

Typical drugs that bind reversibly to the receptor; inhibition can be overcome by increasing the concentration of the agonist, ultimately achieving the same maximal effect

Answer 5

Competitive antagonist

Question 6

Typical drugs that bind irreversible or allosterically to the receptor; this is a drug that prevents the agonist at any concentration from producing a maximum effect on a given receptor

Answer 6

Non-competitive antagonist

Question 7

What is the receptor, signal, and response for an agonist, compared to an agonist?

Answer 7

Receptor: same
Signal: same
Response: same

Question 8

What is the receptor, signal, and response for an allosteric agonist, compared to an agonist?

Answer 8

Receptor: different
Signal: none (by itself)
Response: greater than an agonist (with an agonist)

Question 9

What is the receptor, signal, and response for a partial agonist, compared to an agonist?

Answer 9

Receptor: same
Signal: same
Response: less than an agonist (b/c not full effect

Question 10

What is the receptor, signal, and response for an antagonist, compared to an agonist?

Answer 10

Receptor: same (with some exceptions)
Signal: none (just blocks receptor)
Response: less than an agonist

Question 11

What can look like an antagonist sometimes?

Answer 11

Partial agonist

Question 12

What is it if the line does not reach 100% on the scale?

Answer 12

Partial agonist

Question 13

Besides in potentiation, what does the line on the very left represent?

Answer 13

Control (agonist all by itself)

Question 14

What happens to the max effect during competitive antagonism?

Answer 14

Max effect does NOT decrease; curve just shifts to the right

Question 15

What kind of bonds are present in competitive antagonism?

Answer 15

Weak ionic bonds (H+ bonds)

Question 16

In competitive antagonism, as the antagonist goes up, what do we do to combat it?

Answer 16

Give more agonist as well

Question 17

What happens to the max effect in noncompetitive antagonism?

Answer 17

Max effect decreases b/c it reduced amount of available receptors

Question 18

What’s the difference between competitive antagonism and noncompetitive antagonism?

Answer 18

Competitive antagonism: curve (max effect) doesn’t decrease, shifts only to the right
Noncompetitive antagonism: curve (max effect) decreases; shifts down and to the right like swinging on a door hinge

Question 19

What are the 2 types of noncompetitive antagonism that you can have? Which one is more common?

Answer 19

Irreversible or allosteric

Irreversible is more common

Question 20

What kind of bonds are in noncompetitive antagonism?

Answer 20

Covalent (strong) bonds

Question 21

In irreversible noncompetitive antagonism, what can’t you do?

Answer 21

You can’t give more agonist to maintain the max effect

Question 22

What happens to the curve during potentiation?

Answer 22

The curve shifts to the left

Question 23

What kind of curve is on the left in potentiation?

Answer 23

An allosteric agonist plus an agonist

Question 24

What can the allosteric agonist in potentiation do?

Answer 24

Enhance activity of agonist, which shifts the curve in the opposite direction of allosteric antagonist

Question 25

You do a study to see the effect of beta blockers dosage on a patient's heart rate. The results are below: 10mg dec HR x 10 beats 20mg dec HR x 20 beats 40mg dec HR x 30 beats 80mg dec HR x 30 beats What can you conclude from this?

Answer 25

- As the dose increases, the response increment diminishes until a dose is reached where no further increase in response can be achieved - Give pt 40mg at most, because 80mg is not going to do anything extra for the patient

Question 26

What 2 things do you need to know in order to calculate the effect of the drug?

Answer 26

E(max) and EC(50)

Question 27

What's the equation to find the effects of a drug

Answer 27

E = (Emax x C)/(C + EC50)

Question 28

What's the equation to find the receptor's affinity to bind a drug?

Answer 28

B = (Bmax x C)/(C + Kd) ``` Bmax = total number of receptor sites Kd = concentration of free drug at which 1/2 max binding is observed ```

Question 29

When you see Emax and EC50 on a graph, what is being plotted?

Answer 29

Drug concentration per drug effect

Question 30

When you see Bmax and Kd on a graph, what is being plotted?

Answer 30

Drug concentration per receptor-bound drug

Question 31

If given a response curve and the Emax, how can you calculate EC50?

Answer 31

- Divide Emax by 2 (ex: Emax can change HR by 100 beats/min, so 100/2 = 50) - Find where the curve crosses the y-axis at that number (ex: 50) - Draw line down to x-axis, and this is your EC50 (ex: 5)

Question 32

Will EC50 and Kd always be the same?

Answer 32

They may be identical, but need not be

Question 33

Refers to the concentration required to produce 50% of that drug's maximal response (EC50)

Answer 33

Potency

Question 34

Reflects the upper limit of the dose-response relation on the response axis (max effect = Emax)

Answer 34

Efficacy

Question 35

On a response curve, how can you tell if a drug is more potent than another drug?

Answer 35

The further to the left it is, the more potent it is

Question 36

On a response curve, how can you tell the efficacy of a drug compared to another drug on the same chart?

Answer 36

Look at the height that it goes up to. The higher it goes, the greater the efficacy of the drug

Question 37

Do we care more about efficacy of a drug or the potency of a drug?

Answer 37

Efficacy b/c we want it to fix the issue, not worrying about the dosage of it if it works

Question 38

You have a chart that has some drugs with 100% efficacy and some with 50% efficacy. If you want the response to be in the lower part of the chart, which drugs will you pick to achieve this goal?

Answer 38

You can choose any of them because all drugs can achieve this; most likely, you'll choose based on price

Question 39

For therapeutic purposes, how should potency of a drug be stated?

Answer 39

In dosage units and in terms of a therapeutic endpoint (ex: 50mg for mild sedation; 1mg/kg/min for an increase in HR of 25 beats/min)

Question 40

In the in-class case, raloxifene took the place of estrogen, not hindering it's effects in the process. What type of drug is raloxifene?

Answer 40

Partial agonist

Question 41

If TD50 (same as LD50) 130, and ED50 is 4, what is the toxicity of the drug?

Answer 41

130/4 = 32.5 | This means that you have to take 32.5 pills to get to toxicity when the recommended dose is 1 pill

Question 42

When is the graph relatively safe for a drug when discussing toxicity?

Answer 42

If ED50 and TD50 (or LD50) are relatively far apart

Question 43

How many drugs and receptors are involved with pharmacological antagonism?

Answer 43

2 drugs, 1 receptor

Question 44

How many drugs and receptors are involved with physiologic antagonism?

Answer 44

2 drugs, 2 receptors

Question 45

How many drugs and receptors are involved with chemical antagonism?

Answer 45

2 drugs, no receptors

Question 46

Type of antagonism where drugs may bind to and antagonize action of drug (ex: dimercaprol binds to and chelates lead and other toxic metals)

Answer 46

Chemical antagonism

Question 47

Type of antagonism where the antagonist produces a physiological action that is opposite of agonist and by a separate mechanism (ex: glucocorticoid hormone can increase blood sugar; insulin would oppose this action; these agents act on distinct receptor-effector systems) (like ANS: parasympathetic vs sympathetic)

Answer 47

Physiologic antagonism