Log/Dose Response

Question 1

[6-minute video]: Dose-response Relationship - AMBOSS

Answer 1

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Question 2

What are the two types of log/dose response curves?

Answer 2

(1) Graded dose-response
(2) Quantal dose-response

Question 3

Graded dose-response curve
(a) Definition
(b) Curve shape
(c) Parameters

Answer 3

(a) Definition: This is a type of graph that measures the continuous range of responses to different doses of a drug in a single subject or a homogenous group.

(b) Curve shape: Typically sigmoidal when plotted on a logarithmic scale.

(c) Parameters:
Emax: Maximum effect achievable.
EC50: Dose at which 50% of the maximum effect is observed.

[Diagram]

Further notes:
Example: Measuring the decrease in blood pressure with increasing doses of an antihypertensive drug.

Question 4

Quantal dose-response curve
(a) Definition
(b) Curve shape
(c) Parameters

Answer 4

(a) Definition: This type measures the all-or-none response (e.g., presence or absence of a therapeutic effect) in a population. [Plots the rate of an outcome occurence against drug dose.]

(b) Curve shape: Also sigmoidal but represents the cumulative percentage of subjects responding at each dose.

(c) Parameters:
ED50: Dose at which 50% of the population exhibits the desired effect.
LD50: Dose at which 50% of the population dies.
TD50: Dose at which 50% of the population experiences a toxic effect.

[Diagram]

Further notes:
Example: Determining the dose at which 50% of a population experiences pain relief from an analgesic.

Question 5

Outline some problems with determining TD50.

Answer 5

Toxicity may be difficult to measure experimentally.
Toxicity may develop after years.
Toxicity may be unrelated to dose [anaphylaxis].

Question 6

What is Therapeutic Index?

Answer 6

Therapeutic index (TI) is a measure of a drug’s safety. It is defined as the ratio of the dose that produces toxicity (TD50) to the dose that produces a therapeutic effect (ED50) in 50% of the population. The larger the value, the safer the drug.

Question 7

What is Therapeutic Dose/Window?

Answer 7

This is the range between the minimum toxic dose and minimum therapeutic dose. It defines the dose range over which the drug is effective and relatively non-toxic in most of the population.

Question 8

What are four main parameters that can be defined from a graded dose-response curve?

Answer 8

(1) Potency (EC50): This is the concentration of the drug that produces 50% of the maximum effect. It indicates the drug’s affinity for its receptor; lower EC50 means higher potency.

(2) Efficacy (Emax): The maximum effect that can be achieved with the drug.

(3) Slope: The steepness of the curve, indicating how the response changes with increasing dose.

(4) Threshold dose: The lowest dose at which a measurable effect is observed. It helps in determining the minimum effective dose for therapeutic purposes.

Question 9

List three types of quantitative variations in drug responsiveness.

Answer 9

(1) Hyporeactive or Hyperreactive: intenisty of effect of a given dose of drug is diminished or increased
(2) Tolerance: responsiveness decreases as a consequence of continued drug administration
(3) Tachyphylaxis: responsiveness diminishes rapidly after administration of the drug