Principles Of Drug Action (1) : The Concentration-Response Relationship

Front 1

What does the concentration-response curve look like?

Back 1

Front 2

What does the log drug concentration-response curve look like?

Describe it

Back 2

First part of curve is the concentration which the drug does nothing ( threshold conc)

Middle part = linear

Then reach maximum response

Front 3

What are the three main types of experiment to measure the effect of a drug?

Back 3

In vitro (test tube)

In vivo (living animal)

Ex vivo (in between in vivo and in vitro)

Front 4

How are a drugs effects measured in vitro?

Back 4

Drug effects are studies on a piece of tissue dissected from an animal (or human) and kept alive outside the body

Includes experiments on cells grown in tissue culture

Front 5

What are some examples of responses that might be measured from in vitro experiment?

Back 5

Changes in the tension of muscle

Changes in the activity of an enzyme

Changes in the secretion of hormone or neurotransmitter

Front 6

How are a drugs effects measured in vivo?

Back 6

Drug effects are studied on the living animal

Include clinical trials

Front 7

What are some responses that might be measured from an in vivo experiment?

Back 7

Change in blood pressure

Change in pain threshold

Reduction in allergen-induced bronchoconstriction

Front 8

How are a drugs effects measured ex vivo?

Back 8

A tissue or organ is removed from an animal that has been treated with a drug, and the effects that drug has had on the organ function are tested in vitro.

Front 9

What may an example be of an ex vivo experiment?

Back 9

To see whether long-term treatment with a drug induces liver damage

Front 10

For experiments in vitro, how are drug concentrations expressed?

Back 10

Moles per litre i.e Molar (M)

We are interested in the number of drug molecules

Front 11

Will a 1 Molar solution of drug X contain the same number of drug molecules as a 1 Molar solution of drug Y?

Back 11

Yes.

Front 12

Most clinically useful drugs act at very low concentrations. What kind of concentrations are these?

Back 12

1 x 10 -6M to 1 x10-12M

Front 13

What does a typical in vitro set up look like?

Back 13

Front 14

How may a concentration-response curve be constructed?

Back 14

Front 15

How may a cumulative concentration response curve be created?

What is meant by a cumulative concentration response curve?

Back 15

Don't wash drug off after each addition

Front 16

Why would we use the cumulative approach?

Back 16

In tissues that respond slowly, so we don't have to wash drug out between times.

Front 17

Why is it not possible to use molar concentrations in vivo?

Back 17

Because the volume of solvent (e.g blood) is not known

Front 18

How are drug doses expressed in vivo?

What does this allow for?

Back 18

As a weight of drug per weight of animal

e.g 1mg per kg

Approximate extrapolation of the dose from, for example, a 20g mouse to a 70 kg human

Front 19

What is the Emax?

Back 19

Indicates the maximum response a drug can produce

Increasing the contcentration of the drug produces no greater effect

Front 20

What is the EC 50?

Back 20

The Molar concentration of drug that produces 50 % of the maximum response for that drug

(sometimes use other percentage values e.g EC90 or EC20)

Front 21

What is meant by potency?

A potent drug is effective in small or large amounts?

Back 21

Describes the concentration at which a drug is effective (often quantified using the EC 50)

Small

Front 22

How can the EC 50 be used to measure the potency of a drug?

Back 22

The lower the EC 50, the more potent the drug.

Front 23

Comparing the EC 50 values for two drugs with the same action allows us to calculate what?

Back 23

Their relative potencies, describes by the potency ratio (M)

Front 24

Which drug is more potent, A or B?

Back 24

Drug A

Front 25

Assuming A to be our standard drug, and B to be the test drug, then what is the potency ratio and how is this calculated?

Back 25

M = EC50 (test) / EC50 (standard)

300/15 =20

M=20

Front 26

How can we calculate Log M?

Back 26

Log M = logEC50(test)- logEC50 (standard)

Front 27

What does a potency ratio >1 indicate?

Back 27

The test drug is less potent than the standard

Front 28

If we are developing a new drug, what do we want the potency ratio for it to be?

Back 28

<1

This indicates it is more potent than the standard

Front 29

What is a bioassay?

Back 29

Way of measuring the effects of a drug in a biological system

Front 30

What is a "2 + 2" bioassay?

Back 30

The simplest bioassay for determining the relative potency of 2 drugs

Take 2 concentrations of the standard, then take 2 concentrations of the test drug and compare them

Front 31

What does the "2 + 2" bioassay make use of?

Back 31

The middle portion of the log concentration-response curves are almost linear, and if the two drugs are acting by the same mechanism, then the lines should be parallel.

Front 32

How can 'M' be obtained in a "2 + 2" bioassay?

Back 32

Comparing 2 doses of the standard (S1, S2) with 2 does of the unknown (U1, U2)

Front 33

What do the dotted lines represent?

Back 33

An average

Front 34

What is meant by the therapeutic index?

Back 34

The ratio between the toxic dose of a drug and the dose producing the desired therapeutic effect

Front 35

Do we want the therapeutic index to be high or low?

Back 35

High

The higher the therapeutic index, the less chance of the drug producing toxic side effects

Front 36

Why is the therapeutic index no longer used?

Back 36

We are not interested in the concentration that kills people, more interested in a drug concentration that causes harm

Ethically no longer defensible to obtain LD 50 values in animals

A drug can have different ED 50's depending on the disease being treated

Wide person to person variation in both toxic and beneficial effects of drugs

Front 37

In humans, what is the therapeutic index?

Back 37

TD50 /ED50 where TD 50 is the "toxic" does in 50% of the population