PHARMACOLOGIC PRINCIPLES

CHAPTER 2
Pharmacodynamics
（ drug Acts on bod
y ） 
 Basic Action of Drug
1. Excitation and Inhibition

The intrinsic functions of body are altered by

drugs:
1) Excitation or stimulation ： the functions
are increased by drugs. (heart rate↑, BP↑,
contraction, unstable …)
2) Inhibition ： the functions are decreased by
drugs. (heart rate↓ 、 Bp↓ 、 relaxation, stable
…)
For example, magnesium sulfate (orally)
→80% no absorption
2. Local →intestinal
action and generalosmotic
action
pressure↑→ volume ↑→purgation
： action onaction
1) Local action↘cholagogic the locale
before absorption of administered drugs.

2) General action (absorptive action,

systemic action) ： action of drugs on
For example,
general magnesium
system sulfate (orally) →2
after absorption.
0% absorption→circulation →action site ↗v
asodilation → BP↓
↘central inhibition → sedation Great dose
 3. Selectivity ： Selective action of drugs
on some organs or tissues in general
Digoxin (low concentration in the heart) → inh
action. + +
ibition Na -K pump →positive intropic acti
on → high sensitivity on heart
1) Selective action
* high sensitivity of the organ or tissue on
the drug (high iodine
density →intaked
of receptorbyorthyroid
…… ）
* high concentration of →
gland thehigh
drug in the organ
concentration
or tissue （ active permeation
→action on thyroid
）
2) Extensive action
* low selectivity of the drug itself
* overdose
4. Clinical effect┌therapeutic action
└untoward reaction

1) Therapeutic action
 etiological treatment ： eliminate
cause.
 symptomatic treatment ： remission

2) Untoward reaction* of symptoms.

* side reaction, * toxic effect, * allergy,
* after effect, * dependence
 2)blocking
atropine → Untoward reaction*
M receptor
internal organ↓ treatment of abdominalgia
constipation, distension
① Side reaction
secretion↓ The reactions
sweat gland↓→body without
temperature
↑ relationship to therapeutic purpose of a
drug administrated in normal dose
salivary secretion↓→dry mouthare
occurred in almost patients, because of
the extensive action of the drug. 　　　　
bronchial secretion↓ →
therapeutic purposemedication
preanesthetic
therapeutic side
action reaction
② Toxic effect Pharmacological responses
are too strong and induce injury in the body
when drug administration in overdose or
improper long time.

③ Allergy It can occur in minority of

idiosyncrasy patients without relationship to
pharmacology and dose.
④ After effect Effects remain when
drug blood concentration is reduced
below threshold concentration.

TC

⑤ Dependence New balance induced

following repeated administration of
some drugs.
Physical dependence Addiction induced
following repeat administration. The vital
activity of body depends on drugs, the
serious abstinence syndrome is induced
after discontinue.

psychic dependence Psychic desire and

pleasant feeling are induced following rep
eat. The mental state depends on drugs wi
thout abstinence after discontiune.
 food success drug happy

amuse
sports sex
starvation
thirsty failure go blind abstinence misery

ache disappointed
pain

hometown family drug miss

good friend lover

 Dose-response relationship

Graded • Continuous scale

BP (mmHg)
• Measured in a single biologic unit
• Relates dose to intensity of effect
• Mean ± standard difference (x ± s)
Dose
Quantal • All-or-none pharmacologic effect
有效数 • Population studies (χ
( 2 test)
有效率
• Relates dose to frequency of effect

Dose
 Graded response

rectangular
Ordinate Effects hyperbola
D/E symmetry
S curves
Abscissa arithmetic
(dose)
Straight line
logarithm
E D/E

lgD
D D
 effect
  Emax

Kd logD (C)
D (C)

Threshold maximal minimal

dose dose Toxic dose
↓  ↓ ↙
├─┴┴─────┴─╂─┴───┴── D (C) ↑
common minimal
dose lethal dose
① Threshold dose ： Minimu
m effective dose
② Efficacy (Emax)
： Maxim
③um effect of a drug or the limit of the drug resp
Potency
onse.

： Doses necessary for i

nducing given effect, or a dose (Kd) inducing 5
0% Emax. Dose or Kd↑→ Potency↓

Efficacy is usually more important tha

n potency in selecting drugs for clinical u
④ Slope： Slope at 50% Emax (slope↑→range o
f common dose↓→less safety ）
⑤ Maximal dose : The limit of dose permitted i
n pharmacopeia for some drugs.
⑥ Common dose： The effective dose in most of p
atients.
maximal dose ＞ common dose ＞ threshold d
ose
 E
B
A C

logD (C)
potency ：Ａ＞Ｂ＞Ｃ
efficacy ：
Ｂ＞ C ＞Ａ
threshold dose ：
Ｃ＞Ｂ＞Ａ
slope ：Ａ＝Ｂ＞Ｃ
 Quantal response

An all-or-none response to a drug and relates

to the frequency with which a specific dose of a
drug produces a specific response in a
population.
(e.g., death among the the mice in a pre-
clinical study or effective among the patients in
a clinical trial.
 Quantal response (Qualitative Response)
（ response frequency or rate(%), χ2 test ）
skew
distribution
Cumulative frequency or rate
long tail
(effects) cumulative F or R S curves
probit unit （ p ）
Abscissa arithmetic normal
(dose) distribution
logarithm
symmetry
S curves
F F p
straight line

D lgD lgD
 Quantal response

D (mg) 1 1.2 1.4 1.6 1.8 2 2.2 2.4 2.6 2.4 2.6

F 0 1 3 5 7 12 8 7 4 2 1
0 1 4 9 16 28 36 43 47 49 50

R (%) 0 2 6 10 14 24 16 14 8 4 2
0 4 10 20 34 58 74 88 94 98 100
E

lgD
 Individual variation

There is variation of sensitivity to a

drug among patients or animals.
Supersensitivity or tolerance to a dr
ug can occur in a few patients or anim
als, most of them are middle sensitivit
y.
 toxicity
E effective or death
100%
95%

50%

ED95
5%
dose
ED50 ED95 LD5 LD50

Therapeutic index (TI) ＝ LD50 ／ ED50

Safety index (SI) ＝
Therapeutic index (TI): The index used for
judging drug's safety.

TI ＝ LD50 ／ ED50
ED50 (Median effective dose) ： The dose at w
hich 50% of individuals (experimental animals)
exhibits specified effect.
LD50 （ Median lethal dose ）： The dose
requied to produce death in 50% of anim
als.
 Safety index (SI)

The TI may be misleading if the dose-

responses curves for effectiveness and toxicity
have different slopes (i.e., not parallel).
Therefore, the Safety index (SI) may be more
useful.
SI ＝ LD5/ED95
 Mechanism of action of drugs

1. Alteration of chemical or physical

character of locale administered to:
Osmotic diuretics; antacid.

2. Participate or interference in
metabolism of cells ： Vitamin, ferrous
sulfate 、 sulfa-drugs.
 3. Influence on activity of enzymes ：
Insulin→hexokinase↑→oxygenase of gluc
ose↑→blood sugar↓;
Neostigmine→cholinesterase↓→ACh↑
4. Influence on ion-channel of ：
Antiarrhythmics

5. Influence on release of transmiters or hor

mones ：
Ephedrine→release of noradrenaline↑
　 Iodide→release of thyroxine↓
6. Drug-receptor *
Drug receptor and Pharmacodynamics
1. Drug-receptor concept

Receptor The receptive substances of a cell

or an organism that specifically interacts wit
h their ligands (corresponding drugs, transmi
tter or hormone) and initiates the chain of bi
ochemical and physiological changes.
ligand ： A corresponding drug, transmitter
or hormone binding to a receptor.
 2. Drug-receptor binding Character

1)Saturation for finitude of number of recep

tor→Emax
2) Specific binding
3) Reversible binding: ionic bond, hydrogen
bond, molecular attraction covalend bond.
Therefore, there is competitive binding bet
ween 2 drugs binding to same receptor.
 3. Drug-receptor binding Theory

1) Occupation theory ： The relation between

given drug and the effect is described as: the

magnitude of the effect observed depends on

the amount of occupied receptors by drug.

 In general, the effect (E) is a function of
the the quantity of the drug -receptor
complex (DR), and can be expressed as:
E = α[DR]

Once all receptors are saturated, the

maximum effect (Emax) is achieved. If
the 50% of receptors were Occupied, 5
0% Emax is produced.
 2) Rate theory ：

The effect associates not only with bin

ding rate, but also with dissociation rat
e.
Dissociation rate↑→the effect↑→
Emax↑
3. Parameter of receptor-specific interaction
Affinity (or potency)

The ability of a drug's binding to receptor.

A drug's affinity for binding its receptors det
ermines the concentration of drug required t
o occupy 50% of drug-receptors or elicits 50
% Emax.
The greater concentration required, the w
eaker affinity of a drug;
The smaller concentration required, the gr
eater affinity of a drug.
 pD2: The parameter of agonist's affinity
. The negative logarithm of molarity (mol,
KD) of a drug required to binding 50% rec
eptor or inducing 50% Emax.
Emax Emax

50% KD 50% pD2

c -log c
pD2 = -lg KD
 Intrinsic activity (or afficac
y)
The ability of inducing effect of a dru
g after binding to receptor.
The faster dissociation rate, the great
er intrinsic activity, the greater Emax.
4. Classification of drugs binding to receptor
Classification of drugs

Classification Affinity intrinsic activity

agonist ＋＋ ＋＋
antagonist (blocker) ＋＋ －
partial agonist ＋＋ ＋
 5. Competitive antagonism

1) In the presence of a fixed concentration of a

ntagonist, dose-effect curves of the agonist w
ould be shifted following increasing concentra
tion of agonist:
a. Threshold concentrations are increased;
b. Curves is shifted to the right in equal slope;
c. Emax is unchanged.
 pA2: The parameter of Blocker’s affinity. The
negative logarithm of molarity (mol) of a bloc
ker required to inducing same effect ( or 50%
Emax) in double concentrations of agonist .

E
50% A A+B’ A+B’’
pA2=-log B’

1 2 3 C (agonist)
2) In the presence of a fixed concentration of
partial agonist, dose-effect curves of the
agonist would be altered following increasing
concentration of agonist.

a. Threshold concentrations are decreased;

b. Emax is unchanged;
c. Curves is shifted to the left at low concentration of
agonist (partial agonist would like agonist); Curves i
s shifted to the right at high concentration of agonist
(like antagonist). 
 Agonist + Partial agonist

E A A+P' A+P''

lgC
 6. Noncompetitive antagonism

After administration of a noncompetitive anta

gonist, high concentrations of agonist cannot com
pletely overcome the antagonism and Emax cann
ot be obtained. Dose-effect curves of agonost are
altered:
a. Threshold concentrations are unchanged;
b. Shifted to the right ;
c. Emax is decreased.
Agonist + Noncompetitive antagonism

E
A
A+N’
A+N’’
A+N’’’

KD C
The End of pharmacody
namics