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Drug safety

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

Response
DOSE-EFFECT RELATIONSHIP

Drug safety



Graded drug-response :

In the graded drug-response relationship, the intensity of response is relatively proportional to the effective drug conc.

(­dose ® ­effect)

Quantal response
Quantal 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.


Drug safety


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.


Drug safety

ED50

50% Effect
Maximal 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= ------------

LD50
ED50


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

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This ratio could also be expressed as a percentage value, and is called Standard Safety Margin.(SSM)

Standard Safety Margin (%) = (---------- - 1)* 100

LD1
ED99

The wider the margin between ED99 and LD1, the safer the drug.

ED99 -- LD1
Drug 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?



Drug safety





رفعت المحاضرة من قبل: Ayado Al-Qaissy
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