Final L1 - PKD 1

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 pharmacologic effect

Question 2

Pharmacodynamics

Answer 2

What the DRUG does to the BODY

Question 3

Importance of PK/PD

Answer 3

-Relate temporal patterns of response (efficacy, harm) to drug admin following acute and chronic dosing
-Provide a rational basis for drug design, drug selection, and dosage regimen design

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

Answer 5

Direct measure of a pharmacologic observation

Question 6

Desired response

Answer 6

Clinical response (quality of life, survival, organ survival, etc)
-Biomarker (LDL-cholesterol, blood glucose, blood pressure, etc.)
-Surrogate endpoint: biomarker that substitutes for a clinically meaningful endpoint

Question 7

Harmful response

Answer 7

Mortality, hospitalization, etc.
-ADRs
-Change in biologic/pharmacologic observation from one time to another

Question 8

Effect

Answer 8

Change in response from one time to another

response and effect will be used interchangeably

Question 9

Exposure vs Effect

Answer 9

Exposure - measure of CMAX
Effect - measure of Rmax

Question 10

Drug effect is mediated by (unbound/bound) drug concentration?

Answer 10

Unbound (free) drug concentration

Question 11

Graded response

Answer 11

Continuous scale
Measured in a single biologic unit (person, animal, etc)
Relates dose (and concentration) to intensity of effect
(EC50, Emax, Kd)

Question 12

Quantal response

Answer 12

All or none effect
Measured in more than one (large numbers of) individual
Relates dose (or concentration) to frequency of effect

Question 13

Units for EMax are

Answer 13

100% (hematocrit units

Question 14

Emax is the

Answer 14

maximal effect (max binding)

Question 15

EC50 units

Answer 15

Concentration; (mg/L)

Question 16

Concentration effect relationship

Answer 16

EMax, EC50 and Kd
Sigmoid shape (S shaped curve)
Looks like non-linear PK

Question 17

Kd

Answer 17

Dissociation constant

Question 18

EC50 is a measure of

Answer 18

Potency - sensitivity to the drug

Question 19

Clinical correlation to heart failure: If an agonist is given, it will shift curve to (right/left) and make it (more/less) potent

Answer 19

Left; less potent
reason why we give naloxone in overdose cases

Question 20

Disease states on ADME: CKD

Answer 20

When a patient has CKD:
-Diuretic is less potent, and causes about 1/2 of the max response
need an increase in dose, or same dose but given more often
Concentration response curve is steep

Question 21

Most drugs, we are trying to achieve concentrations between (%range) of the max effect

Answer 21

20-80%

Question 22

Response vs time

Answer 22

Predicts response will decline linearly
-One compartment model (monoexponential decline)
-Linear log-dose relationship
Decrease in effect is impact by both K (PK) and m (PD)

Question 23

Changes in response profiles: What happens to the time course of response if k is increased

Answer 23

Start at the same point, but curve is shifted more to the left
-Eo is unchanged
-m is unchanged
-Time course changed due to a change in PK
-Declines more quickly
Given Dose, Vd, k and m, you could estimate/predict response at any given time

Question 24

Direct effect model

Answer 24

Peak conc happens at the same time as peak response
CP = Exposure
-Max conc and response happen at roughly the same time
Response is directly related to concentration

Question 25

Disequilibrium in concentration effect relationship

Answer 25

When conc and response do not happen at the same time Max drug conc vs max response - displaced to the right (Takes more time) = delay

Question 26

Hysteresis Loop

Answer 26

**Counterclockwise** -S curve turns into this loop because there is a delay in drug reaching the effect side = takes longer to reach response -Up slope: The effect is **lower** than that of the down slope -Greater effect LATER in therapy as opposed to EARLIER in therapy

Question 27

Potential reasons for delay in response: Increased effect as compared to earlier temporal effect at same CP

Answer 27

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 -Ex, steroids, have to get into system to trigger something else, takes more time = delayed response

Question 28

Proteresis loop

Answer 28

**Clockwise** -Greater effect EARLY in therapy as opposed to later in therapy

Question 29

Potential reasons for Clockwise Proteresis: Decreased effect as compared earlier temporal effect at same Cp

Answer 29

-Alteration in distribution between venous and arterial concentrations -Production of an "active" metabolite opposite of the parent Down-regulation of receptor response or tolerance (desensitization) Indirect effect

Question 30

Biggest example of a tolerance drug

Answer 30

Opioids; keeps up max effect even at later doses