Time Course of Delayed Drug Effects Flashcards
What are the three possibilities for a drug time course?
- Immediate (drug effects are immediately related to drug concentration)
- Delayed (drug effects are delayed related to drug concentration)
- Cumulative (drug effects determined by the cumulative action of the drug)
What are the mechanisms that can explain delayed drug effects?
Distribution to the receptor site (pharmaco-kinetics)
Binding to and unbinding from receptors (receptor-kinetics)
Turnover of a physiological mediator of effect (physio-kinetics)
Explain why distribution to effect site could cause a delay in drug response
It takes time for the drug to perfuse from the blood to a target tissue. This is driven by the central blood volume. (thiopentone in brain)
What is an effect compartment in determining the time course of distribution?
Effect compartment is used to deduce the time course of drug concentration at the site of action. The time needed to reach steady state when receiving constant input is determined by the elimination half life of the plasma compartment
What is equilibration half life?
The effect compartment half life. Determined by the volume of the effect compartment and the clearance of the effect compartment. Eg. Thiopentone has rapid clearance so has an equilibration half life of 1 min
How can binding to a receptor cause a drug delay?
Some drugs (usually potent ones eg. digoxin) dissociate slowly from their receptors which causes a delay
Why does digoxin effect compartment reach its peak before the average tissue concentration?
The heart as rapid perfusion compared with other tissues
Why is the half life of digoxin slow despite rapid perfusion?
Slow unbinding from Na/K ATPase caused delayed onset of effects
What are the actions of warfarin?
Action: inhibition of Vitamin K recycling (VitK reductase)
Rapid effect: decreased synthesis of clotting factors
Delayed response: prolongation of coagulation time
What is INR?
International normalised ratio -time measure
How is the time to reach steady state INR with different warfarin doses different?
It is unchanged by the C50 because the only determinant is the half life of clotting factors
How long does it take warfarin to reach steady state?
2-3 days as half life of prothrombin complex is 14 hours
C50 for synthesis is 1.5 mg/L
What are the two types of drugs used in heart failure?
Dixogin, ACE inhibitors and beta blockers: used to improve survival
Diuretics (Frusemide): provide relief from symptoms
What is the relationship of Frusemide intake and sodium loss?
Sigmoidal curve with an Emax of 180mmhol/h C50=1.5 mg/L Hill coefficient of 3
How does Frusemide intake compare with loss with a large dose (120 mg)?
The loss of effect is quicker than the plasma concentration of Frusemide disappears due to steep concentration effect relationship