15 - Time course of delayed and cummulative effects

Question 1

3 ways to think of the time course of drug effects

Answer 1

immediate
> drug effects are immediately related to the observed drug concentration in plasma (not immediate i.e. has to be absorbed [PK gets drug into blood] and then diffuse to receptors etc)

delayed
> drug effects are delayed in relation to observed drug concentration

cumulative
> drug effects are determined by the cumulative action of the drug

Question 2

PK and PD

Answer 2

PK describes the time course of conc while PD describes how effects change with concentration

Question 3

3 reasons for delay in effect in relation to plasma drug conc?

Answer 3

1. distribution to receptor site (PK)
2. binding and unbinding from receptors (receptor kinetics)
3. turnover of a physiological mediator of the effect (physio-kinetics)

Question 4

Does drug conc at the tissue tell you conc at the receptor

Answer 4

no and so the concentration at the tissue is NOT the concentration that is producing the effect

Question 5

How then do you predict the concentration that is producing the observed effects?

Answer 5

Observes the concentration and the effects. Work out the concentration at the site of action from the shape of the conc effect curve and the time course of effect

Question 6

What is the time course of infusion - conc in plasma and effector compartments dependent on?

Answer 6

NOT INPUT
Dependent on output
i.e. 4 HLs of elimination or 4 equilibration HLs

Question 7

What is the equilibration HL determined by?

Answer 7

1. The volume of the effector compartment (organ size, tissue binding extent)
2. Clearance of the effect compartment (blood flow to washout, diffusion)

i.e. thiopentone in the brain: small volume binding to GABA receptors and large CL (BF). Reaches the brain quickly and is washed out quickly. Short equilibration HL of 1 minute. If allowed to reach equilibrium would see a delay of 4 HLs = 4 minutes

Question 8

Is the time to reach INR steady state affected by the C50?

Answer 8

C50 will affect the effect/INR but NOT the time it takes to reach SS as this is only determined by the half life of the elimination of the clotting factors

Question 9

ACEIs and physiological turnover

Answer 9

Slow effect on BP due to loss of na and plasma volume - sodium turnover takes a week to reach a new ss

Question 10

What drugs improve survival in HF

Answer 10

• digoxin
• ACEIs
• B blockers

Question 11

What drugs provide symptom relief in HF

Answer 11

diuretics - remove excess fluid

Question 12

How do pk and pd affect treatment decisions?

Answer 12

Treatment decisions depend on knowing the time course of exposure and knowing how to adjust the concentration and dose to achieve the concentration that will achieve the desired effect