Some drugs are converted to an active compound which exerts a potent effect which may be positive (pharmacologic) or negative (toxic). The overall effect depends on the rate of production for this active agent versus the rate of its clearance.
precursor ‡ active metabolite ‡ clearance
Activation (input) may involve:
(1) increased or decreased metabolism due to genetic enzyme activity
(2) increased (induced) or decreased (inhibited) metabolism due to acquired change in enzyme activity
Clearing of the active metabolite (output) may involve:
(1) increased or decreased metabolism to an inactive molecule due to genetic enzyme activity
(2) increased (induced) or decreased (inhibited) metabolism to an inactive molecule due to acquired change in enzyme activity
(3) increased or decreased excretion
|
Metabolite |
Increased/Decreased Effect |
|
pharmacologically active |
drug effect |
|
toxic |
toxic effect |
|
Input or Output Activity |
Points |
|
very slow |
1 |
|
slow |
2 |
|
normal |
3 |
|
fast/rapid |
4 |
|
ultrarapid |
5 |
overall effect score =
= (points for input) - (points for output)
Interpretation:
• minimum overall effect score: -4
• maximum overall effect score: +4
|
Overall Effect Score |
Positive or Negative Effect |
|
-4 |
extremely low |
|
-3 |
very low |
|
-2 |
decreased |
|
-1 |
slightly decreased |
|
0 |
normal |
|
1 |
slightly increased |
|
2 |
increased |
|
3 |
very high |
|
4 |
extremely high |
The overall effect will determine how high a dose of the compound is needed to exert an effect. A drug that is metabolized rapidly will need a much higher dose than if it were metabolized slower.
Specialty: Toxicology, Emergency Medicine, Critical Care, Genetics
ICD-10: ,
