15. Dose Response 2

Question 1

Define population.

Answer 1

A group of individuals all exposed to a drug using a standardized dosing regiman.

Question 2

Define response variability.

Answer 2

Observed range in responses in a population administered a standardized dosing regiman.

Question 3

What can we use to describe and quantify drug response variability in populations?

Answer 3

1. histograms of responses
2. means and standard deviations of responses

Question 4

What are parameters are on the x- and y- axis of a histogram?

Answer 4

X-axis –> concentration (mg/L) (given dose)
Y-axis –> percentage of patients responding

Question 5

Explain ED50.

Answer 5

Effective dose at which 50% of the population is responding.

Question 6

Describe a symmetric histogram.

Answer 6

• can be turned into normal distribution standard curve

Question 7

Describe a bimodal histogram.

Answer 7

• there is likely important subpopulations among the overall population
• important to determine the cause of this for patient safety and efficacy of treatment

Question 8

What are the genetic factors that affect individual responses to pharmaceuticals?

Answer 8

Phase 1 drug metabolizing enzyme genetics - drug modification (CYP 450)

Phase 2 drug metabolizing enzyme genetics - drug conjugation (glucouronidation, methylation, etc)

Drug transporter genetics - drug influx and efflux genes

Question 9

What is the difference between EC50 and ED50?

Answer 9

EC50 (median effective concentration) - the concentration required for an individual to experience 50% of the max effect.

ED50 (median effective dose) - the average dose in a population required to obtain a desired (measurable) therapeutic effect.

Question 10

Define LD50.

Answer 10

LD50 (medial lethal dose) - the median dosage of a drug that is fatal in a population

Question 11

Define TD50.

Answer 11

TD50 (median toxic dose) - the average dose of a drug that causes adverse affects in a population.

Question 12

What is a therapeutic window?

Answer 12

The range of dosages which is effective but relatively free of risk of adverse drug reactions.

Question 13

Explain the significance of therapeutic index.

Answer 13

Higher therapeutic index = safer drug

interpretation: a therapeutic index of 4 means that the LD50 occurs at a 4-fold higher dosafe than the ED50.
(taking 4x recommended dose will be lethal to half of patients)