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Pharmacodynamics
Department of pharmacology
Yang Fangju(杨芳矩）
2010.3

1. Drug action and pharmacological effects
(1) pharmacological action: The action of the
drug does the body. That is original action
between the drug and the cells of the body. The
action of the drug does the body. That is
original action between the drug and the cells of
the body.
 (2)
pharmacological effects:
The functional change of the organs or
tissue in the body that is produced by the
original drug action.
 (3) excitation and exciter
 (4) inhibition and inhibitor
 (5) selectivity of pharmacological effect

drugs are only selective--rather than
specific--in their actions, because they
bind to one or a few types of receptor
more tightly than to others and because
these receptors control discrete processes
that result in distinct effects.
 In drug development and in clinical
medicine, selectivity is usually considered
by separating effects into two categgries:
beneficial or therapeutic effects versus
toxic effects.

It is only because of their selectivity that
drugs are useful in clinical medicine.
Thus, it is important, both in the
management of patients and in the
development and evaluation of new drugs,
to analyze ways in which beneficial and
toxic effects of drugs may be related, in
order to increase selectivity and
usefulness of drug therapy.
Therapeutic Effects and Adverse
Drug Reaction
1. Therapeutic effect
 The action is accord with using drug aim
and propitious to prevention or treatment
disease.
 (1) etiological treatment
 (2) symptomatic treatment
 (3) supplement therapy

2. Adverse Drug Reaction (ADR)
 The action is not accord with using drug aim
and bring ailment or harm to the patients.
(1) side reaction
 This term is used to describe therapeutically
undesirable but unavoidable effects of drugs.
 Characteristics: ① it occurs in the treatment
dose, ② the symptoms are light, ③ it can be
predicated, ④ and it is avoidable or lighten
by combing with other drugs, but
unavoidable when using alone.
(2) toxic reaction:
 These may be arise from a single large
dose or by accumulation after repeated
dose and are usually shown as an
exaggerated form of the pharmacological
actions typical of the drugs.
 Characteristics: ① it occurs in
overdosage, ② the symptoms are severe,
③ it can be predicated, ④ and it is
avoidable.
Toxic effects of drugs may be classified as
pharmacological, pathological change, or
special toxicity (alteration of DNA, such as
carcinogenesis, mutagenesis and teratogenesis).
Toxic effects of drugs may also be classified as
acute and chronic toxic effects.
The acute toxicity mainly affects the
circulation system, CNS, or blood system.
The chronic toxicity mainly induces
pathological change of tissue or special
toxicity of cells.
(3) Allergic Reactions:

These are mediated by an antigen-antibody
reaction and usually involve previous
exposure and sensitization to the drugs.
 Characteristics:
 ① the occurrence of the symptoms is not
concerned with dose,
② the symptoms can be light or serve,
③ it can not be predicated,
 ④ and it is unavoidable in a tiny minority
condition.
(4) Residual (after) Effect:
 the residual biological effects when the
drug concentration in blood is decreased
under the minimum effective
concentration (threshold concentration).
(5) Withdrawal Reaction:
 it is induced after withdrawal drug
administration.
(6) Idiosyncrasy:
 it is used to describe a qualitatively
abnormal reaction to a drug. An example
is the hemolytic anemia that occurs in
some patients after taking the
antimalarial drug primaquine
dose effect relationship
Dose effect relationship:
 the regular variation between the dose
and the effects that the effects increase
following the dose increase in some range.
1.Dose effect curve:
 the curve is obtained from intensity of
effect for the ordinate and dose or
concentration for the abscissa.
(1) Quantitative dose response curve:
 the quantity for the ordinate expresses
the intensity of effects. Such as heart rate,
blood pressure, volume of Na+ excretion .
(2) Qualitative dose response curve:
 A cumulative frequency distribution of individuals
achieving the defined effect as a function of drug
concentration is qualitative dose response curve.
 ( the concentration-percent curve or the quantal
concentration effect curve).
 the effect of a drug is recorded as an “ all or none
event ” ( positive, negative response) for the ordinate
of effects, e.g. death or survival, convulsion or
unconvulsion, anaesthetization or unanaethetization.

This curve resemble the sigmoid shape of the
graded concentration-effect curve.

Both above curves are plotted rectangular
hyperbolic relationship.
 these curves become symmetrical Sshaped(sigmoidal) if a ogarithmic dose axis
is used.
2. Dose effects relationship
 (1) dose: the share of drug administered.
 ① minimal effective dose( minimal effective
concentration), it is also called threshold dose or
concentration.
 ② maximum effective dose
 ③ treatment dose
 ④ median effective dose ( ED50):the dose of drug
that produces 50 percent effectivity in a group of
animals.
 ⑤ median lethal dose(LD50): the dose of drug that
produces 50 percent mortality in a group of animals.
lethal effect
effective
inaction
Lethal dose
ineffective dose
minimal effective
dose
Effective dose
Minimal toxic dose
Minimal fatal dose
Tolerance dose
Toxic dose
Acted intensity
toxic action
(2) Effect
 ① maximal effect( efficacy, Emax)
 The maximal effect can be produced by a
drug. It is determined principally by the
properties of the drug and its receptoreffecter system and is reflected in the
plateau of the concentration-effect curve.
 ② potency
The location of the concentration-effect curve
along the concentration axis is an expression
of the potency of a drug.
Potency refers to the concentration (EC50) or
dose (ED50) of a drug required to produce
50% of that drug's maximal effect.
50
0.l
0.3 1
3
10
30
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戊
100
?
furosemide
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）
150
堵
米
?
??
cyclopenthiazide
volume of Na+ excretion .
mmol

（
200
100 300 1000
dose （ mg ）
The potency and Emax Comparison of Various diuretics
(3) assessment of drug safety
 ① therapeutic index:
 the ratio which is the ratio of the dose
which kills 50 percent of a group of
animals, the median lethal dose(LD50),
and which produces a desired
pharmacological effect in 50 percent of a
group of animals, the median effective
dose(ED50).

Therapeutic index =
 ② margin of safety:
 the ratio of the dose which kills 5 percent of a
group of animals(LD5), and the dose which
produces a desired pharmacological effect in 95
percent in a group animals(ED95).

Margin safety =
LD5
ED9 5
③ reliable safety coefficient:
 the ratio of the dose which kills 1 percent of
a group of animals(LD1), and the dose
which produces a desired pharmacological
effect in 99 percent in a group
animals(ED99).
 reliable safety coefficient = LD1 /ED99
(4) individual variability
The concentration of a drug that produces a special
effect in a single patient is termed the individual
effective concentration.
This is quantal response, since the defined effect is
either present or absent.
 Individual effective concentration usually are
lognormally distributed, which means that a normal
variation curve is the result of plotting the logarithms
of the concentration against the frequency of patients
achieving the defined effect.
mechanisms of drug action







1 enzyme
2 ion channel
3 nucleic acid
4 carrier
5 immunity system
6 gene therapy and gene engineering drug
7 others: receptor action of drugs; physic and chemical
action; complementarity action.
receptors
1.concept of receptors
 Drug receptors are proteins that serve as receptors
for endogenous regulatory
 ligands. Many drugs act on such physiological
receptors and are often particularly selective.
2. interaction theory of drug and receptor
 (1) occupation theory
 (2) rate theory
 (3) two model theory
 3. response dynamics of receptor and
drug
 (1) basic formula of response kinetics of
receptor and drug

A+R
AR
E
 A: drug, R: receptor,
 AR: complex of receptor and drug;
 E: effect
[ A][ R]
 KD =k2/k1 =
① ( KD: ionized constant),
[ AR]
r

[ A][ R]
KD
[AR] =
①
 ∵RT=[ R]+[ AR] ② ,

(RT is total amount of receptor)
 [R]=RT - [AR]
[AR]=RT - [R]

[ A]
K D  [ A]

From ② to ① :

[ A][ RT ]  [ AR] [ A][ RT ]  [ AR]
KD =

[ RT ]  [ R]
[ AR]



KD[AR] =[A]([RT]-[AR])=[A][RT]-[A][AR]
 KD[AR]+[A][AR]=[A][RT]
 [AR](KD+[A])=[A][RT]
 ∴
[ AR]
[ A]

[ RT ]
K D  [ A]

When binding ratio of receptor and drug arrives
100%, the effect arrives 100%.
 ∴
E
[ AR]
[ A]
E max

If:

[ RT ]

K D  [ A]
(r is binding percent of
[ AR]

 rdrugs and receptor)
[ R]
 the binding receptor holds in r of total receptors, the
effect arrives in corresponding
 fraction E/Emax, then r =
E
[ AR]
[ A]


E max
[ RT ] that
K D  [ Aarrives
]
 When r increase far off exceed
KD, r→1,
in Emax.
[ A]
∵ r
,
K D  [ A]

Transposition:
[ A]
K D  [ A] 
r
[ A]
[ A](1  r )
KD 
 [ A] 
r
r


∴
r
[ A] 
KD
1 r
When r→1, K D
[ A](1  1)

0
1

When r=50%, K D
KD
[ A](1  0.5)

 [ A] 1  [ A]
0.5
A
That is drug dose when Emax arrives in the
half (it means 50% of receptors hold).
 PD2: -logKD of KD. That is direct ratio with
affinity of A and R.

3. agonist and antagonist
(1) agonist
 ① affinity: The binding ability of the drug with
receptor.
 ② intrinsic activity: The ability of the drug excites
receptor. It can be expressed asа.
 ③ full agonist: it has intense affinity and intrinsic
activity(а= 1)
 ④ partial agonist: it has intense affinity, but weak
intrinsic activity(а< 1)
 ⑤ inverse agonist or negative antagonist ligand.
(2) antagonist:
 it has intense affinity, but has no intrinsic
activity(а= 0)
 ① competitive antagonist
 affinity of competitive antagonist expresses as
PA2. It is negative logarithmic
 value of mol concentration of competitive
antagonist added in reacted system of agonist
that makes the effect of agonist in 2 times
concentration equal to the effect of agonist in 1
time concentration.
② non-competitive antagonist
 affinity parameter of non-competitive
antagonist expresses as PA2’. It points
negative logarithmic value of mol
concentration of non-competitive
antagonist during it makes Emax of
agonist descend to half.
transmembrane signaling and intracellular
messenger

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1. classification of drug receptors according to
mechanism of transmembrane signaling
(1) G protein-coupled receptor
(2) ligand gate ion channel receptor
(3) Tyrosine kinases receptor
(4) cell nuclear hormone receptor
(5) cytokine receptor
(6) other enzyme receptor
2. intracellular signal transductant
 (1) first messengers: hormones, neurotransmitters,
cytokines(interleukins, growth factor ).
 (2) Second messengers
 ① cAMP
 ② cGMP
 ③ phosphatidylinositol，DG, IP3
 ④ calcium ion, it participates in protein medium,
such as PKC, calomodulin, etc.
3. signal transduced system of receptor and
intracellular