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Pharmacodynamics
Pharmacological effect
How do drugs acts?
drugaction
mechanism of drug action or signal transduction
pharmacological effect
In most circumstance
drug action=pharmacological effect
Type of pharmacological effect
Excitation:
e.g. adrenaline blood pressure increase
Inhibition:
e.g. propranolol heart beat slow down
sedative-hypnotics cause sedation or
facilitate sleep
Selectivity of pharmacological effect
etiological treatment
symptomatic treatment
supplement treatment (therapy)
Adverse drug reaction
Side effect
Toxic reaction
After effect
Withdrawal reaction
Allergic reaction
Idiosyncrasy
A. Side effect: under the dose, lower selectivity of the drug,
usually is non-deleterious
e.g. Atropine
F. Idiosyncratic reaction
Idiosyncratic is defined as genetically determined
abnormal reactivity to a chemical.
e.g. Black males, Hemolytic anemia, by primaquine
because of deficiency of G-6-PD.
III Dose-effect relationship
Learning Objective
100 100
% maximal responses
% maximal responses
50 50
0 0
EC50 C EC50 log C
Fig.2-1 The dose-effect curve of drug action. The EC50 is the concentration at
which a drug reaches to the half-maximal effect. When plotted semi-logarithmically,
the hyperbolic shape of the curve (figure on the left ), is switched into a sigmodial
one (figure on the right). However, it is approximately linear between 20% ~ 80%
of the maximal effect, a range commonly observed for drugs used at therapeutic
doses.
What is graded dose-response curve?
Efficacy
Intensity of effect
pe variability
S lo
Potency
Concentration of drug
Fig.2-2 The log dose-effect relationship. Representative log dose-effect curve,
illustrating its four characterizing variables
What is guantal dose-response curve ?
Slope
ED50
LD50
Fig.2-3 The frequency curve and cumulative frequency curve of a drug action
in a quantal-effect experiment
Maximal Efficacy and potency
2. Potency
The location of the concentration-effect curve
along the concentration axis is an expression
of the potency of a drug.
How to evaluate drugs with dose-effect
curve?
200
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(mmol/ L / day)
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150
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100
hlo
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thi
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50
ch
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0.1 0.3 1 3 10 30 100 300 1000
dose(mg)
1. Therapeutic Index, TI
TI=LD50/ED50
o △ □ o □
(TD50∕ED50) and margin of
△
△ safety(LD5 ~ ED95). For therapeutic
o o △
□
50 △
□ 50 △
index (TI): drug A= C>B, and for
o △
△
□ △
margin of safety: drug A >B>C. When
□
△ o △
(A) o
o
□
□
△ (B) o o □
□ △ drug A reaches Emax , it causes no toxic
logC
100
logC
o o □
reaction. However, in the cases of drug B
□
o or drug C, the dosage of Emax may cause
effect (%)
□
o △
over 50% individual toxic reactions.
△ □
△
50 △
□
In the figure:
△
o □ o for effective dose-response curves;
△
(C) o □
o o □
□ △ △ □ for toxic-response curves; and
logC
△ = o% - □ %.
Evaluation of drug safety
A. Enzymes
a. Digitalis inhibits Na/K ATPase(pump)
b. Antibiotics inhibit crucial enzymes of microorganisms
B. Membrane ion channels
Local anesthetics inhibit voltage-gated Na channels of nerve
C. Structural proteins
Colchicine binds to and diassembles microtubules
D. Nucleic acids
Target of some chemotherapeutic agents used in treatment
of cancer
V Receptor Theory
D+R DR E
[D][R]
KD =
[DR]
[RT]=[R]+[DR]
代入
[D] ( [RT]- [DR] )
KD =
[DR]
E [DR] [D]
= =
E max [RT] KD+ [D]
[D] = 0 E=0
[D]>>> KD E=E max
[DR]
=50%
[RT]
KD = [D]
100 100
% maximal responses
% maximal responses
50 50
0 0
EC50 C EC50 log C
Fig.2-1 The dose-effect curve of drug action. The EC50 is the concentration
at which a drug reaches to the half-maximal effect. When plotted semi-
logarithmically, the hyperbolic shape of the curve (figure on the left ), is
switched into a sigmodial one (figure on the right). However, it is
approximately linear between 20% ~ 80% of the maximal effect, a range
commonly observed for drugs used at therapeutic doses.
KD : the equilibrium dissociation constant
pD2 : pD2 = - ㏒ KD
If pD2 is large, binding affinity is high, and vice versa.
Affinity ( 亲和力 )
Intrinsic Activity ( 内在活 性 )
intrinsic activity: α
E [DR]
=α
E max [RT]
0 ≤ α≤ 1
1. Agonist
full agonist α=1
partial agonist 0< α<1
2. Antagonist α=0
competitive antagonist
noncompetitive antagonist
pA2
pA2’
Fig. 2-5 Comparison of drugs’ affinity and intrinsic activity in dose-
response curves.
For fig. (A): drugs’ affinity: X<Y<Z, and intrinsic activity : X=Y=Z.
For fig. (B): drugs’ affinity: A=B=C, and intrinsic activity : A>B>C.
Fig. 2-6 Dose-response curves for agonist in the presence of increasing
concentrations of competitive (A) and noncompetitive (B) antagonists.
Furthermore, in the cases of (C) and (D), the antagonists display different
intrinsic activities.
B. Rate theory (Paton, 1961)