Pharmacology

PART 1
GENERAL PHARMACOLOGIC
PRINCIPLES

YUAN Bing-xiang （袁秉祥）

7275165, ybx@xjtu.edu.cn
 Pharmacology (7 parts)
1. General Principles
2. Peripheral Nervous Pharmacology
3. Central Nervous Pharmacology
4. Cardiovascular Pharmacology
5. Splanchnic Pharmacology
6. Endocrine Pharmacology
7. Chemotherapeutic Pharmacology
 PART 1
GENERAL PHARMACOLOGIC
PRINCIPLES

CHAPTER 1
INTRODUCTION OF PHARMACOLOGY

 
【 CONCEPTION 】
1. Pharmacology is the discipline stud
ding interaction or relationship between
drugs and bodies including animals, hu
man being and pathogen including micr
oorganisms (bacteria, virus) , parasites
and tumor cells….
Drugs is the chemicals beneficially alt
ering biochemical and physiologic state
of body, applied to prevent, diagnose an
d treat diseases.
 2. Two areas of pharmacology
　　　 pharmacodynamics
drugs body
pharmacokinetics
pharmacodynamics
(drugs on body)
┌effects┌beneficial or
┤ │ therapeutic action
│ └untoward reaction
└mechanism of action 　 　　　
pharmacokinetics
(body on drugs)
┌* undergoing of drugs in body:
┤ absorption, distribution, biotrans-
│ formation and excretion
└* drug blood concentration--time curves
(C-T) and the pharmacokinetic para-
meters.
 【 RESEARCH METHOD OF PHARMACOLOGY 】

　 Other medical research methods (ph

ysiology, biochemistry, pathology, clini
cal medicine….) plus special methods o
f pharmacology.
1. Method of preclinic pharmacology:
The experimental object is animals
( healthy animals or ill animals)
┌①clear-headed animals
┤②anesthetic animals
│③normal or abnormal organs, tissues,
│ cells, cell substructures and molecules

└④pharmacokinetics
2. Method of clinic pharmacology:
The experimental object is human bei
ng ( healthy volunteer and patients ） .
 PART 1
GENERAL PHARMACOLOGIC
PRINCIPLES

CHAPTER 2
Pharmacodynamics
 （ drugs Acting on body ） 
。
【 Basic action of drug 】
1. Excitation and Inhibition
The intrinsic functions of body are alte
red by drugs:
1) Excitation or stimulation ： the func-ti
ons are increased by drugs. (heart rate↑, B
P↑, contraction, unstable …)
•
2) Inhibition ： the functions are decrea-
sed by drugs. (heart rate↓ 、 Bp↓ 、 relacti
on, stable …)
2. Local action and general action ：
1) Local action ： action on the loca
le before absorption of administered d
rugs.
2) General action (absorptive action,
systemic action) ： action of drugs on
general system after absorption.
3. Selectivity ： Selective action of drugs on so
me organs or tissues in general action.
1) Selective action
┌high sensitivity of the organ or tissue on
│ the drug
└high concentration of the drug in the organ
or tissue
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
of symptoms.
 2) Untoward reaction*
① Side reaction ： Reactions without re
lationship to therapeutic purpose of a dr
ug administrated in normal dose are occ
urred in almost patients, because of the
extensive action of the drug.
　　　　　
therapeutic purpose
therapeutic action side reaction
 ② Toxic effect ： Pharmacological responses a
re too strong and induce injury in the body wh
en administration in overdose or improper long
time.
③ Allergy: It can occur in minority of idiosync
rasy patients without relationship to pharmacol
ogy and dose.
④ After effect ： Effects remain when drug blo
od concentration is reduced below threshold co
ncentration.
Dependence is new balance induced following re
peated administration of some drugs.
Physical dependence is addiction induced follo
wing repeat administration. The vital activity of
body depends on drugs, abstinence syndrome is
induced after discontiune.
psychic dependence ： Psychic desire and ple
asand feeling are induced following repeat. Men
tal state depends on drugs, without abstinence a
fter discontiune.
 【 Dose-response relationship 】
1. Dose-responses curves or concentration-effect
curves ： Coordinate
┌ordinate┌graded response ： gaugeable data
┥ (effects)└quntal response ： frequency
│ (all-or-none response)
└ abscissa┌ arithmetic ： "long tail S"
(dose) │ curves
　　 　 └ logarithm ： symmetry "S" curv
es
2. Graded response （ mean±standard deviation, ±
S）
effect t test
  Emax

Kd logD (C)
D (C)
threshold maximal minimal
dose dose toxic dose
↓  ↓ ↙
├─┴┴─────┴─╂─┴───┴── D (C)
└ common ┘ ↑
dose minimal lethal dose
① Threshold dose ： Minimum effective dose
② Efficacy (Emax) ： Maxiumum effect of a
drug or the limit of the drug response.
③ Potency ： Doses necessary for inducing gi
ven effect, or a dose (Kd) inducing 50% E
max. Dose or Kd↑→ Potency↓
Efficacy is usually more important than po
tency in selecting drugs for clinical use.
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
patients.
maximal dose ＞ common dose ＞ threshold d
ose
 Ｂ
E potency ：Ａ＞Ｂ＞Ｃ
Ａ Ｃ efficac
y ：Ｂ＞ C ＞Ａ
threshold dose ：Ｃ＞Ｂ＞
Ａ
　　　　　　　　 slope ：Ａ＝Ｂ＞Ｃ
logD (C)
 3. Qualitative Response or Enumeration Data
（ response rate, %, χ2 test ）
An all-or-none response to a drug and relate
s to the frequency with which a specific dose of
a drug produces a specific response in a popul
ation.
(e.g., death among the the mice in a pre-clini
cal study or effective among the patients in a c
linical trial.
 1) Frequency distribution curves ： Ordinate is response freq
uency or ratio (%) of a dose.
E
100%
( frequency
or ratio) 50% normal distribution
skew distribution

log dose dose

dose (mg) 1 1.2 1.4 1.6 1.8 2 2.2 2.4 2.6 2.4 2.6 T
frequency 0 1 3 5 7 12 8 7 4 2 1 50
ratio (%) 0 2 6 10 14 24 16 14 8 4 2 100
 Individual variation: There is variati
on of sensitivity to a drug among patient
s or animals.
Supersensitivity or tolerance to a drug
can occur in a few patients or animals,
most of them are middle sensitivity.
E
%
D
 2)Cumulative frequency curves ： Vertical is accum
ulative response frequency or ratio (%).

E Frequency distribution curves

logD dose
Cumulative frequency curves
logD dose

dose (mg) 1 1.2 1.4 1.6 1.8 2 2.2 2.4 2.6 2.4 2.6
frequency 0 1 3 5 7 12 8 7 4 2 1
ratio (%) 0 2 6 10 14 24 16 14 8 4 2
CF 0 1 4 9 16 28 36 43 47 49 50
CR (%) 0 2 8 18 32 56 72 86 94 98 100
100%
E effective toxicity or death
95%

50%

5%
ED50 ED95 LD5 LD50 dose
 Therapeutic index (TI): The index used for ju
dging drug's safety.
TI ＝ LD50 ／ ED50
ED50 (Median effective dose) ： The dose at wh
ich 50% of individuals (experimental animals) ex
hibits specified effect.
LD50 （ Median lethal dose ）： The dose requ
ied to produce death in 50% of animals.
 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 may
be more useful.
Safety index (SI), SI ＝ LD5/ED95
【 Mechanism of action of
drugs 】
 1. Alteration of chemical or physical character
of locale administered to: Osmotic diuretics; ant
acid.
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→cholin
esterase↓→ACh↑
4. Influence on ion-channel of ： antiarrh
ythmic
5. Influence on release of transmiters or h
ormones ：
Ephedrine→release of noradrenaline↑
　　 Iodide→release of thyroxine↓
【 Drug receptor and pharmacodynamics 】
1. Drug-receptor concept
Receptor ： The receptive substances of a cell
or an organnism that specificly interacts with a
ligand (a corresponding drug, transmiter or ho
rmone) and initiates the chain of biochemical a
nd physiological changes.
ligand ： A corresponding drug, transmiter o
r hormone binding to a receptor.
 2. Drug-receptor binding Character
1) Saturation for finitude of number of r
eceptor→Emax
2) Specific binding
3) Reversible binding: ionic bond, hydro
gen bond, molecular attraction covalend
bond.
Therefore, there is competitive binding
between 2 drugs binding to same recepto
r
3. Drug-receptor binding Theory
1) Occupation theory ： The relation be
tween drug given and effect is describ
ed as: the magnitude of effect observe
d depends on the ammount of occupie
d receptors.
 In general, the effect (E) is a function o
f the the quantity of the drug -receptor c
omplex (DR), and can be expressed as:
E = α[DR]
Once all receptors are saturated, the ma
ximum effect (Emax) is achieved. If the 50
% of receptors were Occupied, 50% Emax i
s produced.
 2) Rate theory ： The effect associate not on
ly with binding rate, but also with dissociation
rate.

Dissociation rate↑→the ffect↑→Emax↑

 3. Parameter of receptor-specific interaction
Affinity (or potency) ： The ability of a drug's bin
ding to receptor. A drug's affinity for binding its rece
ptors detemines the concentration of drug required t
o occupy 50% of drug-receptors or elicits 50% Emax
.
The greater concentration required, the weaker aff
inity of a drug;
The smaller concentration required, the greater af
finity of a drug.
 pD2: The parameter of agonist's affinity. The
negative logarithm of gram -molecular concent
ration (mol) of a drug required to binding 50%
receptor or inducing 50% Emax. Emax
Emax

50% 50%
Kd pD2
c -log c
Intrinsic activity (or afficacy)
The ability of a drug's inducing effect
after binding to receptor.
The faster dissociation rate, the greater
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 ant
agonist, dose-effect curves of the agonist would
be shifted following increasing concentration 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 gram -molecular concent
ration (mol) of a blocker required to inducing s
ame effect ( or 50% Emax) in double concent
rations of agonist .
E A A+B’ A+B’’

pA2=-log B’
50%

1 2 3 log c
 2) In the presence of a fixed concentration of partial
agonist, dose-effect curves of the agonist would be alte
red 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 is
shifted to the right at high concentration of agonist (li
ke antagonist).
E A A+P' A+P''

 logC
6. Noncompetitive antagonism
After administration of a noncompetitive antag
onist, 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. E A
A+B’
A+B’’

log c
The End of pharmacodyna
mics