Dose response relation ship (Drug safety)
DR.maha:
Dose response relation ship : When the response is measured against increasing concentrations of a drug,
There are 2 types of drug response
1- graded response.2-quantal response.
Drug Concentration
ResponseDOSE-EFFECT RELATIONSHIP
Graded drug-response :
In the graded drug-response relationship, the intensity of response is relatively proportional to the effective drug conc.
(dose ® effect)
Quantal responseQuantal response is under law : all or none response .
E.g anesthesia or no anesthesia ( the dose of drug either produce or fails to produce effect ) i.e each individual responding or not responding to a given dose.
Plotting the same data on a semilogarithmic concentration axis usually results in a sigmoid curve, which simplifies the mathematical manipulation of the dose-response data
Drug safety:
Mean the relationship between dose required to produce toxic effect and desired effect.ED50 (Median effective dose)
The dose of a drug required to produce response in 50% of the treated animals.ED50
50% EffectMaximal Effect
Drug Concentration
LD50 (Median lethal dose)The dose of drug required to kill 50% of the animals
Safety of drug
the margin of safety is referred to as the therapeutic index.therapeutic index (Ti): is define as the ratio of the dose required to produce toxic effect to that required to produce desired effect.
therapeutic index= ------------
LD50ED50
10
This index is not sufficient as the assessment of drug safety, because median dose tell nothing a bout the slopes of the drug- response curves for toxic and therapeutic effects.
Drug safety could be better assessed by using the following ratio which is known as certain safety factor(CSF)
Certain safety factor= --------------
ED99
LD1
13
This ratio could also be expressed as a percentage value, and is called Standard Safety Margin.(SSM)
Standard Safety Margin (%) = (---------- - 1)* 100
LD1ED99
The wider the margin between ED99 and LD1, the safer the drug.
ED99 -- LD1Drug A: 100 – 120
Drug B: 100 – 101.
Which drug is more safe ?
% died
No. mice died
%anesthesia
No. mice anesthesia
No. mice
Dose mg/kg
10
1
10
10
20
2
10
20
30
3
10
30
40
4
10
40
50
5
10
50
60
6
10
60
70
7
10
70
80
8
10
80
90
9
10
90
100
10
10
100
0
0
10
110
10
1
10
150
30
3
10
200
40
4
10
400
60
6
10
600
100
10
10
800
Therapeutic index .
Calculate Certain safety factor .Standard Safety Margin (%).
This is safe or not ? Why?