pharmacodynamic

Dr Herni Suprapti MKes

Pharmacodynamics
deals with the effects of drugs on biologic
systems

Pharmacokinetics
deals with actions of the biologic system
on the drug

are

the specific molecules in a biologic

system with which drugs interact to
produce changes in the function of the
system

the

interaction of a drug with its receptor

is the fundamental event that initiates the
action of the drug

RECEPTORS
5

are

molecules that translate the drugreceptor interaction into a change in

cellular activity
examples : enzymes such as adenylyl
cyclase
example

a tyrosine kinase effector is part of the insulin

receptor molecule, and
a sodium-potassium channel is part of the
nicotinic acetylcholine receptor

EFFECTORS
10

the

graph of the response versus the drug

concentration or dose

is

called a graded dose-response curve

(Figure 2-1, panel A)

GRADED DOSE-RESPONSE
RELATIONSHIPS
11

The

efficacy (Emax) and potency (EC50)

parameters are derived from these data

The

smaller the EC5O, the greater the

potency of the drug

GRADED DOSE-RESPONSE
RELATIONSHIPS
12

13

The

concentration of drug required to bind

50% of the receptor sites is denoted the
Kd and is a useful measure of the affinity
of a drug molecule for its binding site on
the receptor molecule

The

smaller the Kd, the greater the affinity

of the drug for its receptor

14

15

When

the minimum dose required to

produce a specified response is
determined in each member of a
population, the quantal dose-response
relationship is defined (Figure 2-2)

QUANTAL DOSE-RESPONSE
RELATIONSHIPS
16

17

The

median effective (ED50), median toxic

(TD50), and median lethal (LD50) doses
are derived from experiments carried out
in this manner

18

Efficacy

often called maximal efficacy is

the maximal effect (Emax) an agonist can
produce if the dose is taken to very high
levels

It

can be measured with a graded doseresponse curve (Figure 2-1) but not with a
quantal doseresponse curve.

EFFICACY
19

Potency

denotes the amount of drug

needed to produce a given effect

In

graded dose-response measurements,

the effect usually chosen is 50% of the
maximal effect and the dose causing this
effect is called the EC50 (Figure 2-1,
panels A and B)

POTENCY
20

Potency

is determined mainly by the affinity of

the receptor for the drug

In

quantal dose-response measurements, ED50,

TD50, and LD50 are typical potency variables
(median effective, toxic, and lethal doses,
respectively, in 50% of the population studied)

Thus,

potency can be determined from either

graded or quantal dose-response curves (eg,
Figures 2-1 and 2-2), but the numbers obtained
are not identical

POTENCY
21

Inert

binding sites are components of

endogenous molecules that bind a drug
without initiating events leading to any of
the drug's effects

In

some compartments of the body (eg,

the plasma), inert binding sites play an
important role in buffering the
concentration of a drug because bound
drug does not contribute directly to the
concentration gradient that drives
diffusion
INERT BINDING SITES
22

An

agonist is a drug capable of fully

activating the effector system when it
binds to the receptor

partial agonist produces less than the

full effect, even when it has saturated the
receptors (Figure 2-4)

In

the presence of a full agonist, a partial

agonist acts as an inhibitor.

AGONISTS & PARTIAL

AGONISTS

23

24

A.

Competitive and Irreversible

Pharmacologic Antagonists

B.

Physiologic Antagonists

C.

Chemical Antagonists

ANTAGONISTS
25

Competitive

antagonists are drugs that

bind to the receptor in a reversible way
without activating the effector system for
that receptor

COMPETITIVE AND IRREVERSIBLE

PHARMACOLOGIC ANTAGONISTS
26

27

The

effects of competitive antagonists can

be overcome by adding more agonist.
Irreversible antagonists cannot be
overcome by adding more agonist
Competitive

antagonists increase the

ED50;
Irreversible antagonists do not (unless
spare receptors are present)

COMPETITIVE AND IRREVERSIBLE

PHARMACOLOGIC ANTAGONISTS
28

physiologic antagonist is a drug that

binds to a different receptor, producing an
effect opposite to that produced by the
drug it is antagonizing

Example

: antagonism of the
bronchoconstrictor action of histamine
(mediated at histamine receptors) by
epinephrine's bronchodilator action
(mediated at beta adrenoceptors)

pharmacologic antagonist, which

interacts with the same receptor as the
drug it is inhibiting

PHYSIOLOGIC ANTAGONISTS

29

30

31

32

is

a drug that interacts directly with the

drug being antagonized to remove it or to
prevent it from reaching its target

example

: dimercaprol, a chelator of lead

and some other toxic metals

example

: pralidoxime, which combines

avidly with the phosphorus in
organophosphate cholinesterase inhibitors

CHEMICAL ANTAGONISTS
33

34

is

the ratio of the TD50 (or LD50) to the

ED50,
determined from quantal doseresponse
curves

represents

an estimate of the safety of a

drug, since a very safe drug might be
expected to have a very large toxic dose
and a much smaller effective dose.

THERAPEUTIC INDEX
35

Example

: the ED50 is approximately 3 mg

and the LD50 is approximately 150 mg.

The

therapeutic index is therefore

approximately 50 (150/3)

THERAPEUTIC INDEX
36

more clinically relevant index of safety

describes

the dosage range between :

the minimum effective therapeutic

concentration or dose, and
the minimum toxic concentration or dose

For

example, if the average minimum

therapeutic plasma concentration of
theophylline is 8 mg/L and toxic effects
are observed at 18 mg/L, the therapeutic
window is 8-18 mg/L.

THERAPEUTIC WINDOW
37

38

39

40

terima kasih

41

Apakah

bedanya efikasi dengan potensi ?

Berikan

contohnya

42