2-Pharmacodynamics

Question 1

What is pharmacodynamics?

Answer 1

term used to describe the effects of a drug on the body

Question 2

What is affinity?

Answer 2

the number of bound receptors is directly proportional to the concentration of the drug

Question 3

Give me an equation for affinity for affinity

Answer 3

[LR] is the number of occupied receptors at the concentration of a drug (ligand) [L]
Ro is the maximum concentration of receptors available
Kd is equilibrium concentration constant

Question 4

What exactly is Kd?

Answer 4

the concentration of ligand at which 50% of the available receptors are occupied, inversely proportional to infinity

Question 5

True or False: a small Kd means a large affinity

Answer 5

True.

Small affinity= large Kd
Large affinity= small Kd

Question 6

Graphically, is a drug with a higher affinity for a receptor to the left or right of a drug that has lesser affinity to it’s receptor?

Answer 6

To the left.

The Kd is smaller.

(drug A has a higher affinity for it’s R than B)

Question 7

What is the relation between the body’s response to a drug and the concentration of receptors?

Answer 7

the body’s response is porpotional to the concentration of receptors that are bound by the drug

Question 8

What are Graded Dose-Relationships?

Question 9

What is the drugs Potency(EC50)?

Answer 9

the concentration at which the drug elicits 50% of its maximal response

This enables doctors to determine how much of a drug you need to achieve a certain effect

Question 10

What is the relationship between potency and EC50?

Answer 10

Potency is inversely proportional to EC50.

The higher the EC50, the less potent of a drug, or vice versa.

Is determined in part by affinity for the receptor

Question 11

What is Efficacy(Emax)?

Answer 11

Maximal response produced by the drug.

This enables doctors to decide what the drug does and if it’s appropriate for a given therapy

Question 12

Should you choose a drug based off efficacy or potency?

Answer 12

Efficacy

You want the drug that has the maximum efficacy for the job you want it to do, and then you can look at the potency to see how much drug you need to produce that effect.

Question 13

Which drug is more potent? A or B?

Answer 13

Drug A more potent than B b/c its EC50 is at a lower concentration

Question 14

Which drug has a higher efficacy? A or B?

Answer 14

TRICK QUESTION

Drugs A and B have the same efficacy b/c both elicit the same maximal response

Question 15

What are Quantal dose response curves?

Answer 15

plots the fraction of the population that responds to a given dose of a drug as a function of the drug dose used to find median effective dose (ED50), median toxic dose (TD50), and medial lethal dose (LD50)

Question 16

What is the ED50?

Answer 16

the dose that effectively treats 50% of the population

Question 17

What is the TD50?

Answer 17

that dose of drug that causes a toxic response on 50% of the population

Question 18

What is the TI?

Answer 18

the therapeutic index, or margin of safety

Question 19

What is the TI equation?

Answer 19

TI=TD50/ED50

Question 20

Is a larger or a smaller TI safer?

Answer 20

Larger TI

Remember, TI=TD50/ED50

Larger TI=safer drug, that dose that kills and the dose that treats are further apart
Small TI=dangerous drug, the dose that is toxic is very close to the dose that treats

Question 21

If drug A has an ED50 of 150 mg, and drug B has an ED50 of 10mg, how much less potent is drug A than B?

Answer 21

15x less potent than B

Question 22

What is the LD50?

Answer 22

the dose required to kill half the members of a tested population after a specified test duration

Question 23

Generally, what are the 2 states that a drug receptor can be in?

Answer 23

Active and passive state

Question 24

How are drugs named according to the state of the receptor?

Answer 24

If upon binding the drug favors the active conformation, it’s an agonist.

If the drug prevents agonist-induce activation, its an antagonist

Question 25

In which state does a partial agonist stabilize the receptor?

Answer 25

It stabilizes the receptor equally in the inactive and active conformations, with no specific preference for either form.

Question 26

Does a partial agonist produce the same full effect of a regular agonist?

Answer 26

No. it’s always less because it stabilizes the receptor in the inactive form as well as the active form

Question 27

Why are partial agonists sometimes called “partial antagonists?”

Answer 27

Since partial agonist and full agonist bind to the same receptors, a partial agonist can reduce the response caused by a full agonist

It’s like you want to get people to go out to lunch to Subway. There are a group of people who really want to go to subway (the full agonists) and some are indifferent to Subway or Burger King (partial agonists). If you get a group of 10 people who are full agonists for Subway, 10 people will be going to Subway. However, if you get 6 people who are full agonists and 4 that are indifferent to Subway or Burger King, you’ll probably only end up getting 8 to go to Subway. Youll get a better turnout (response) if you only have the full agonists (those who want to go to subway) than with people who are indifferent (the partial agonists). Sorry if this confuses you. I tried!

Question 28

Why is Pindolol a partial agonist?

Answer 28

It’s a partial agonist for beta-adrenergic cells of the heart.

partially inhibits the beta1 receptors (competes with epinephrine, which is the normal agonist)

Question 29

Burprenorphrine is a partial agonist for which receptors?

Answer 29

high affinity for mu-opioid receptors

used to stop relapse of opioid addiction

Question 30

What are full agonists?

Answer 30

Drugs that stabilize the receptor in the active conformation

Question 31

What is the main mechanism of competitive antagonists?

Answer 31

it binds directly to the active site and prevents the agonists from binding

Question 32

What does competitive antagonists do to the potency of an agonist?

Answer 32

Reduces it.

It will shift the EC50 to the right, thus lowering the potency

Question 33

What does competitive antagonists do to the efficacy of an agonist?

Answer 33

NOTHING

The effects in the human will be the same as the competitive antagonist can be overcome with saturation of agonist.

In the graph, it’s like drug A was the “before exposure to competitive antagonist” and B was “after exposure.” The EC50 shifted right, thus reducing the potency, but the efficacy was unchanged.

Question 34

What is an example of a drug that is a competitive antagonist that binds to the active site of HMG-CoA?

Answer 34

Pravastatin

Question 35

Where does a noncompetitive antagonist bind?

Answer 35

either the active site or an allosteric site.

Question 36

What is significant of the strength of binding of a noncompetitive antagonist?

Answer 36

It’s irreversible

the receptor cannot be activated and cannot be washed out with agonist

Question 37

What is an example of a noncompetitive antagonist to COX? It’s mechanism?

Answer 37

Aspirin

Aspirin irreversibly acetylates cyclo-oxygenase which is needed to make thromboxane A2 in platelets which is needed for platelet aggregation

Question 38

What is the mechanism of action of a chemical antagonist?

Answer 38

It inactivates the agonist by modifying or sequestering it to make it unavailable

Question 39

What does a chemical antagonist not use that other antagonists use?

Answer 39

A receptor!

It just goes in there and kicks the agonist drug in the face

Question 40

What is an example of a chemical antagonist that is basic and binds to the acidic heparin and forms a complex?

Answer 40

Protamine

Think -amine means basic

Question 41

What is the mechanism of action of a physiological antagonist?

Answer 41

It activates or blocks a receptor that mediates a response physiologically opposite to that of the agonist

Question 42

What is an example of a mechanism to treat the symptoms of hyperthyroidism without affecting the thyroid hormone receptors or thyroid hormone at all?

Answer 42

Using beta-adrenergic antagonists binds and counteracts the tachycardic effect of endogenous thyroid hormone, even though thyroid hormone does not use beta-adrenergic receptors to cause tachycardia.

Question 43

What is an inverse agonist?

Answer 43

it binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist

Question 44

What is the concept of “spare receptors?”

Answer 44

it is a concept that allows for maximal response to occur when there is not 100% receptor occupancy by the agonist

Question 45

Again, what is the difference between EC50 and Kd?

Answer 45

**EC50 ** is the concentration that a drug elicits 50% of its max response

Kd is the concentration where 50% of the available receptors are bound

Question 46

In the concept of the spare receptors, is the EC50 more or less than the Kd?

Answer 46

Less

50% of the response from the drug (EC50) is less than 50% if the total # of receptors that are bound (Kd)

essentially, the # of receptors to physiological response is not always a 1:1 ratio. There can be < 50% of the receptors bound but there is already 50% of the response from the drug.

Question 47

What are 2 molecular mechanisms behind the spare receptor concept?

Answer 47

1. Receptor could remain activated after the agonist departs allowing one agonist molecule to activate several receptors
2. Cell signaling pathways could allow for amplification, or a relatively small signal and activation of only a few receptors could cause a maximal response

Question 48

Do you need more or less of a noncompetitive antagonist for the desired effects when talking about spare receptors?

Answer 48

More

The antagonist will bind to the spare receptors and inhibit them, but that won’t matter because the agonist won’t bind to those receptors to elicit it’s response (it’s like it’s being wasted).

You need a higher dose of a noncompetitive antagonist to bind to the receptors that elicit the physiological response.

Question 49

When talking about spare receptors, at low concentrations of the noncompetitive antagonist, what happens to the potency and efficacy?

Answer 49

Potency decreases because it’s proportional to the amount of receptors that must be occupied to produce 50% response (which has now been decreased even though it’s binding to spare receptors)

Efficacy is unchanged because there are receptors there to elicit the same amount of physiological response.

Question 50

When talking about spare receptors, at high concentrations of the noncompetitive antagonist, what happens to the potency and efficacy?

Answer 50

Both efficacy and potency decrease because both the spare receptors and the receptors needed for the response to the agonist are blocked by the antagonist.