10 - Time course of delayed drug effects

Question 1

mechanisms that explain delayed effects

-speed of delay

Answer 1

Most drug effects are delayed in relation to plasma conc due to

• distribution to the receptor site (pharmaco-kinetics) -if delay is mintues
• binding to and unbinding from receptors (receptor kinetics - may be slow binding)
• Physiological intermediate

Question 2

Effect compartment - how to work out time course of observed drug effect

Answer 2

The time needed to reach steady state in a PK system receiving constant input is determined by elimination half life from the plasma compartment.

Question 3

Equilibration half life

-what is it, what determines it

Answer 3

Is the effect compartment half life
Volume of effect compartment - organ size, tissue binding
Clearance of effect compartment - blood flow and diffusion

Question 4

Thiopentone

Answer 4

reaches the brain quickly and is washed out rapidly because of high blood flow to hte brain
-rapid washout leads to a short equilibrium half life of about a minute

Question 5

Binding to receptor - example

Answer 5

• Digoxin - dissociates slowely from receptor
• causes delay in drug effect
• rapid perfusion to heart
• potent drug due to slow dissociation rate

Question 6

Physiological intermediate

Answer 6

drug action - vit K activation inhibited
Rapid effect - less coagulation factors
Delayed response - prolonged coagulation time (INR)

Question 7

Cumulative drug response

Answer 7

Frusemide - diuretic

• Effect - quick, reaches plateau then effect reduces at a quicker rate than concentration
• (hill 3 )
• can use 40mg doses instead, still reach close to emax and can enahance effect
• Peak conc can be reached at alsmot 80% of emax