Measuring Drug Action

 Dose – Response Curves

KA
R + D R:D Response
KD

Response  fraction bound (fb) =

[ R : D] [ R : D] K A[ R ][ D] [ D]
  
[ R]O [ R]  [ R : D] [ R]  K A[ R][ D] K D  [ D]

1.0
Fraction bound

0.5

[D] = KD

0.0
[D]

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 Measuring Drug Action

 Dose – Response Curves

D in system ‘R:D’ Response

100 %
90%
Response

IC50 or EC50 or LD50

50%
IC90 or EC90 or LD90
Inhibition Concentration
Effective Concentration
0% Lethal Dose
Log [antagonist]O
Or Log [agonist]O

Agonist: An agent that facilitates or enhances the normal action of a receptor .

Antagonist: An agent that prevents the normal action of a receptor.

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 Measuring Drug Action

 Dose – Response Curves

Drug 1
100 %

Response ~30 % Drug 2

0%
Log [antagonist]O

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 Measuring Drug Action

 Efficacy and Potency

More
potent
than D 2
D1 D2
100

% Response
D3
Less
efficacious
than D2
0
Log [Drug]
…… Potency corresponds to the strength of a drug, while Efficacy corresponds to the
effectiveness of a drug.
…… e.g., if 1 mg of drug A relieves pain as effectively as 10 mg of drug B, drug A is
twice as potent as drug B
…… the diuretic furosemide eliminates much more salt and water through urine than
does the diuretic chlorothiazide. Thus, furosemide has greater efficacy than
chlorothiazide.

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 Measuring Drug Action

 Efficacy / Potency / Toxicity

Desired Response (%)

100 100

Toxicity (%)
50 50

0 0

Log [Drug]
Blue lines …. Drug 1
Red lines …. Drug 2
Solid lines …. Desired response
Dotted lines …. Toxicity response

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 Measuring Drug Action

 How are these drug-response profiles generated?

e.g., anticoagulants and inhibition of pro-coagulant enzymes

Anticoagulant

S S

T S T S

[A] =0 100 %
Color Development =

Response of Enz:
Activity of Enzyme

Inhibition KI or IC50

[A] = max
0%
Time (s) Log[anticoagulant]
Log [antagonist]O

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 Measuring Drug Action

 How are these drug-response profiles generated?

 Cellular/Pharmacological assays

Cell Viability Assay

Drug

100 %
Mouse Tail Flick Assay
Heat!

Drug

esponse
Heat!

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 Measuring Drug Action

 How are these drug-response profiles generated?

 High Throughput Screening Assays

 Simultaneous …. 96- or 384-well microtiter plates …. robotic analysis

 Chromogenic substrates …. develop color
 Yes or No answer ….. fixed concentration of drug
 Quantitative …. may also give you KI values!!

96-well microtiter plate

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