Dose Response Curve
DOSE-RESPONSE CURVE (DRC)
- A curve that illustrates the relationship between the dose administered and the observed response.
COMPONENTS:
- Dose-plasma concentration curve
- Plasma-concentration response curve – Usually referred as DRC.
USES:
- Threshold level & relative toxicity of chemicals are estimated to help establish safe levels of chemical exposure.
- Potency and efficacy of a drug can be compared.
- For comparison study of agonism & antagonism actions.
TYPES OF DRC:
- Quantal DRC
- Graded DRC
1. QUANTAL DRC:
- Refers mainly to response that is “All or None” phenomenon.
- Used to calculate Median Effective Dose (ED50) & Median Lethal Dose (LD50).
MEDIAN EFFECTIVE DOSE (ED50):
- Dose producing half of the maximum (50%) response.
- More ED50, lower is the potency.
- Lower ED50, higher is the potency.
MEDIAN LETHAL DOSE (LD50):
- Dose resulting in death of 50% of animals receiving the drug.
- More LD50, safer is the drug.
THERAPEUTIC INDEX (TI):
- Measures margin of safety for a drug.
- Defined as “Gap between minimal therapeutic effect DRC & maximal acceptable adverse effect DRC”.
- Calculated as a ratio of LD50 to ED50.
- TI = LD50 / ED50.
- Higher the TI, safer is a drug.
- Lower the TI, more likely toxic drug.
2. GRADED DRC:
- Enables measurement of drug responses on a continuous scale.
- Relates the intensity of drug response to drug dose used for characterizing drug actions.
- Graded response means slight increase of drug dosage causes slight increase in response.
SHAPE OF GRADED DRC:
- Usually, DRC of drugs is rectangular hyperbola.
- Log DRC – Sigmoid shaped curve.
- DRC for vitamins & essential metals – U-shaped
PARAMETERS DETERMINED BY DRC:
- Potency
- Efficacy
- Slope of curve
- Inhibition type – Competitive/non-competitive inhibitor.
POTENCY:
- Measure of amount of drug required to produce a response.
- Drugs producing same effect at lower drug dose are more potent.
- More the curve is on left side – Higher is drug potency.
EFFICACY:
- Maximum effect produced by a drug.
- Clinically more important than potency.
- More the curve peak – Greater is the efficacy.
SLOPE OF CURVE:
- Steeper DRC means “Response will increase dramatically with slight increase in dose”.
- Also, these drugs have narrow Therapeutic index.
IDENTIFICATION OF INHIBITION TYPE:
Competitive inhibitor:
- Curve shifts to right.
- Have less potency in presence of antagonist.
- Unaffected efficacy.
Non-Competitive inhibitor:
- Curve shifts to left.
- Unaffected potency.
- Efficacy decreases.
- Only on irreversible antagonist type – Both potency & efficacy decrease.
Exam Important
DOSE-RESPONSE CURVE
- Best mode to study response of wide number of drugs in population is DRC.
- ED50 refers to Effective Dose of a drug.
- ED 50 is a measure of Potency.
- Therapeutic index is a measure of the margin of safety of a drug.
- Therapeutic index = Median lethal dose/Median effective dose.
- LD 50/ ED 50
- The maximum effect of a drug is defined by Efficacy.
- Efficacy is more important for choice of a drug.
- In non-competitive inhibition, potency is reduced.
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