Pharmacodynamics: Dose-response relationship

Question 1

The relationship between the dose (amount) of a drug and the response observed can often be extremely complex, depending on a variety of factors.
These include

Answer 1

absorption
metabolism
elimination of the drug
site of action of the drug in the body
presence of other drugs
disease.

Question 2

At relatively low levels, Increase in response of a drug is __________ proportional to increase in the dose

Answer 2

Directly

Question 3

What happens At higher doses?

Answer 3

With an increase in the dose, the amount of change in response gradually decreases until a dose is reached that produces no further increase in the observed response (i.e., a plateau)

Question 4

The relationship between the concentration of the drug and the observed effect can therefore be graphically represented as a _______________

Answer 4

Hyperbolic curve

Question 5

Drug- relationship effect is therefore defined as Measurement of the relationship between
_______________ & ________________

Answer 5

the quantity/concentration of a substance and its overall effect on an organism.

Question 6

_________________ controls the effect of a drug

Answer 6

The concentration of the drug at the site of action

Question 7

Y axis is known as
X axis is known as

Answer 7

Ordinate

Abscissa

Question 8

to transform the dose-response relationship into a sigmoidal curve, what is plotted?

Answer 8

Ordinate: response

Abscissa: logarithm of the drug concentration

Question 9

This transformation makes it easier to compare different dose-response curves—since the scale of the drug concentration axis is expanded at low concentrations where the effect is rapidly changing, while compressing the scale at higher doses where the effect is changing more slowly

Answer 9

From hyperbolic to sigmoid

This representation is more useful because it expands the dose scale in the region where drug response is changing rapidly and compresses the scale at higher doses where large changes have little effect on response. Note that, in reality, it is ligand concentration (and resulting receptor occupation) that affects response - the term ‘dose-response curve’ assumes that the drug dose and ligand concentration are closely linked.

Question 10

Salient Features of the dose response curve are

Answer 10

Threshold
Slope
E max

Question 11

How does the body take in toxic insults and still remain healthy?

Answer 11

Below the threshold concentration, there are no adverse effects from exposure to chemical.

Cells in the liver and kidney break down chemicals into non toxic substances to be excreted in urine & feces

Question 12

Thresholds based on ________________ are more easily determined, while thresholds for ________________ are more difficult to determine.

Answer 12

Acute responses eg death

Chronic responses eg chemicals that cask use cancer

Question 13

When is slope used

Answer 13

When threshold is difficult to determine, toxicologists look at the slope of the dose-response curve to give them information about the toxicity of a chemical.

Slope is change in response per unit dose

Question 14

sharp increase in the slope of the curve can suggests that? ___________________

A relatively flat slope suggests that?

Answer 14

As dose increases, there’s a higher risk of toxic responses

Increase in dose gives minimal effect

Question 15

A steep curve that begins to climb even at a small dose suggests a chemical of

Answer 15

High potency

Question 16

The potency of a chemical is a measure of

Answer 16

its strength as a poison compared with other chemicals.

Question 17

Characteristics of LDR curve
Log dose response

Answer 17

i. curve is sigmoid,

2 having between 20 and 80 % as straight lines for statistical analysis eg slope

3 Drugs with a similar mechanism of action have parallel curves.

4 Beyond Emax, further increase in drug concentration cannot produce any increase in response.

5. LOG dose is plotted on absicca
6. Response is plotted on y axis

Question 18

Types of drug response relationships

Answer 18

Graded dose-response curve : Intensity of effect
Quantal dose-effect curve : frequency of effect

Question 19

Characteristics of graded curve

Answer 19

Measured in a single biologic unit

Continuous scale (†dose -› Effect)

Relates dose to intensity of effect

Question 20

Characteristics of Quantal curve

Answer 20

Used in Population studies

All-or-none pharmacologic effect

Relates dose to frequency of effect

Question 21

Dose response parameters include

Answer 21

Potency
Efficacy
Relative safety of a drug

Question 22

POTENCY is a measure of drug activity expressed in terms of

A highly potent drug e.g. ________ evokes a given response at a low concentration. A drug of lower potency e.g. ____________ evokes the same response only at higher concentrations.

Answer 22

the amount of drug required to produce an effect of given intensity.

Fentanyl

Meperidine

Question 23

Potency is often measured at?

It is also known as

Answer 23

50% concentration/ dose level

EC50 ie efficacy at 50%

Question 24

Potency is relatively important in clinical use of drugs T/F

Answer 24

False

Potency is relatively unimportant in clinical use of drugs

Question 25

Efficacy is?

Answer 25

The ability of a drug to produce effect

Question 26

Emax is

Answer 26

The maximal effect that can be produced by a drug

Question 27

Efficacy is determined mainly by ___________________ & __________________

Answer 27

the properties of the drug and

its receptor-effector system.

Question 28

True or False

Efficacy is Important clinical measure.

Partial agonist have greater maximal efficacy than full agonists.

Answer 28

True

False: lower maximal efficacy

Question 29

_____________ help in estimating the safety of a drug

Answer 29

Dose response curve

Question 30

Therapeutic Index =

Answer 30

TI = LD50 / ED50

Question 31

LD50 is?

Answer 31

The median lethal dose of a drug

Question 32

Types of antagonism are

Answer 32

Pharmacological
Physiological
Chemical

Question 33

In chemical antagonism,?

Example

Answer 33

caused by combination of agonists with antagonists, with resulting inactivation of the agonists

dimercaprol and mercuric ion

(Dimercaprol is a chelating agent used as an antidote to arsenic, gold, and mercury poisoning, as well as acute lead poisoning)

[Chelating agents are chemical compounds that react with metal ions to form a stable, water-soluble complex. They are also known as chelants, chelators,]

Question 34

Physiological antagonism is caused by agonist and antagonist acting at two independent sites and inducing independent, but opposite effects. E.g.

Answer 34

histamine and adrenaline.

A physiologic antagonist binds to a different receptor molecule, producing an effect opposite to that produced by the drug it antagonizes. Thus, it differs from a pharmacologic antagonist, which interacts with the same receptor as the drug it inhibits. Familiar examples of physiologic antagonists are the antagonism of the bronchoconstrictor action of histamine by epinephrine’s bronchodilator action and glucagon’s antagonism of the cardiac effects of propranolol.

Question 35

Pharmacological antagonism is caused by?

•In the case of pharmacological antagonisms, the terms competitive and non-competitive antagonism are used.

Answer 35

action of the agonist and antagonist at the same site.

Question 36

In Quantal dose effect curve, they are grouped &

Answer 36

Each group is given a different dose

Question 37

In Quantal experiment, you get 5 parameters.
List and explain these

Answer 37

ED 50 : dose that causes a desired effect on 50% of subjects

TD 50: dose required to cause a toxic effect or undesired effect in 50% of population

LD 50: dose required to kill 50% of the population

TI 50 : LD 50/ED50
High TI is safe eg penicillin
Low TI is unsafe eg digoxin

Margin of safety: ration of LD1/ED99