PD

Question 1

Pharmacodynamics definition

Answer 1

a discipline that quantifies the relationship between drug concentration at the site of drug action and the drug’s

Question 2

Pharmacodynamics

Answer 2

Refers to the actions of the drug on the body

Receptor interaction with the drug

Dose-response phenomenon
-efficacy
-toxicity

Mechanisms of therapeutic and toxic effects

Question 3

Importance of PK/PD

Answer 3

Relate temporal patterns of response to drug administration following acute and chronic dosing

Provide a rational basis for drug design, drug selection, and dosage regimen design

Aid in the design protocols to evaluate events in vivo and in subsequent interpretation of the date obtained

Provide a means for rationally initiating and individualizing drug administration in patients

Question 4

Exposure

Answer 4

any dose or drug input to the body or various measures of acute or integrated drug concentrations in plasma or other biological fluid

Question 5

Response/effect

Answer 5

Direct measure of a pharmacological observation

Question 6

Desired

Answer 6

clinical response (QOL, survival, organ survival)

Biomarker (LDL-cholesterol, blood glucose, and BP)

Surrogate endpoint: biomarker that substitutes for a clinically meaningful endpoint

Question 7

Harmful

Answer 7

mortality, hospitalization

ADR

change in biologic/pharmacologic observation from one time to another

Question 8

Drug-receptor interactions

Answer 8

drug + receptor=drug-receptor complex=response

Drugs exert effects through interactions with biomolecules

Drug action is mediated by free drug concentrations

Question 9

Graded response

Answer 9

continuous scale

measured in a single biologic unit

relates dose to intensity of effect

Question 10

Quantal response

Answer 10

all or none

measured in more than one (large numbers added together) individual

relates dose to frequency of effect

Question 11

Efficacy

Answer 11

Efficacy Emax

Maximum effect

Question 12

Potency

Answer 12

EC50

Sensitivity to the drug

Question 13

Therapeutic window

Answer 13

Minimum effective concentration
Therapeutic window
Minimum toxic concentration
Toxicity

Question 14

Therapeutic index

Answer 14

TI=TD50/ED50

Question 15

Response vs. Time

Answer 15

predicts response will decline linearly

one compartment model
linear log-dose relationship

decrease in effect is impact by both K (PK) and m (PD)

Question 16

What happens to the time course of response if k is increased?

Answer 16

effect will go away more quickly and slope will be steeper

Question 17

What happens to the time course of drug effect if k is increased?

Answer 17

E0 is unchanged
m is unchanged
time course changed due to a change in PK

Given dose, Vd, k, and m, you could estimate/predict response at any given time

Question 18

Linear model

Answer 18

E= S x C

Effect= E0 + S x C

Question 19

Emax model

Answer 19

E=Emax x C/ Ec50 + C

Question 20

Sigmoid Emax model

Answer 20

E= Emax x Ch/ Ec50h + Ch

Question 21

Direct effect model

Answer 21

Dose–>Cp–>Cmax: concentrations fall faster

Cp–>Response Rmax

Question 22

Hysteresis loop

Answer 22

counterclockwise

as concentration increases relative to when concentration decreases

Question 23

Reasons for delay in response

Answer 23

delay in drug reaching the effect site/biophase

production of an active metabolite that produces a response similar to parent

up-regulation of receptor response or sensitization

indirect effect

Question 24

Proteresis loop

Answer 24

clockwise

Question 25

Reasons for proteresis

Answer 25

alteration in distribution between venous and arterial concentrations

production of an “active” metabolite opposite of the parent

down-regulation of receptor response or tolerance

indirect effect