Pharmacodynamics

Question 1

What is PD

Answer 1

what drug does to the body
— influences the beneficial and toxic effects caused by the drug

** need to understand this when developing dosage regimen

Question 2

Reversible Direct MoA

Answer 2

via receptor binding (most common)

• C effect relation

Question 3

Reversible indirect MoA

Answer 3

direct action of the drug may start other effects that ultimately lead to desired effect

generally no C effect relationship

Question 4

Irreversible effects

Answer 4

work via killing cells (damage

— may still be relationship bw conc + effect

Question 5

Types of responses

Answer 5

All or none: once reach threshold conc —- get effect (once pass — all the effect you will get)

Graded: direct + reversible interaction where correlation bw effect + degree of binding

Question 6

What is the Emax model

Answer 6

model that indicates that effect plateaus eventually at a max C

• commonly seen in direct + reversible interaction
• at low C: linear relation bw C + effect but as number of receptors bound increases, nonlinear relation + reach max effect

linear bw 20-80% when plot E vs log C

above 80%: increase in C will have little E

Question 7

What is m

Answer 7

slope of the log C and effect graph

• if steep: difference bw dose that causes therapeutic vs toxic effects is small
  ——— small therapeutic window

Question 8

Counter-Clockwise Hysteresis

Answer 8

Seen in some drugs: impact of T on effect + C

• effect of drug increases with T when at same C (larger effect at later T)

Question 9

Causes of counterclockwise hysteresis

Answer 9

• delay or time lag to reach site of action
• need active metabolite; takes while for conc of these to raise + get effect

Question 10

Clockwise hysteresis

Answer 10

T impacts C and effect

• effect of drug decreases with time even when at same Conc (larger effect earlier on)

Cause: tolerance or tachyphylaxis
—— depletion of endogenous transmitter or receptor for drug to bind to

Question 11

What impacts disappearance of drug over time (if no hysteresis)

Answer 11

• k
• slope of conc-effect relationship (m)
• clear C and e relation (peak C and E close together)

—- effect of drug will decrease faster if drug has short t1/2 or if steep slope

Question 12

Plot of T and effect

Answer 12

linear relationship

slope is dependent on m and k

** no such thing as t1/2 for duration of effect

Question 13

What determines duration of effect

Answer 13

• determined by time when C is above MEC

Question 14

T duration for single IV dose

Answer 14

t dur: time to decline from peak C (Co) to MEC
—- dependent on k (therefore changes to Cl or V will change it)

Question 15

Single IV: impact of increasing dose on t dur

Answer 15

Double dose —-double Co (peak C)
- increases t dur by 1 t1/2

Question 16

Single IV: impact of changing Cl on t dur

Answer 16

decrease CL by 1/2 : no change to Co

— k will decrease by 1/2

t dur will double

Question 17

Single IV: change in V on t dur

Answer 17

Increase V by 2x - decrease k by 1/2 and Co will decrease by 1/2

—- no change to t dur

** doenst’ cause predictable change

Question 18

What can cause a predictable change in t dur

Answer 18

changes in Cl or dose

Question 19

How to ID therapeutic range

Answer 19

TW: range of concentration where we expect to see higher probability to response vs toxicity (low)

• want a good gap bw response + toxicity levels

C for toxicity: should be higher than C needed for therapeutic effects

LL: MEC

UL: when toxicity levels/risks are not acceptable + improvement in response not much/plateaus