Exam 3 Flashcards
What are the two Calcineurin Inhibitors?
Cyclosporine A
Tacrolimus
What are the antimetabolites?
- Mycophenolate Mofetil
- Mycophenolate Sodium
mTor?
Sirolimus
What makes cyclosporine a good canditate for drug monitoring?
What is its most common and serious SE?
- It is large and poorly soluble so that gives it a poor bioavailability
- Nephrotoxicity is the side effect and one of the reasons for TDM
What is cyclosporines Black Box?
Monitoring needs to be done
to avoid toxicity due to high concentrations
What kinetics does cyclosporine follow?
Linear, dose-proportionate PK within the therapeutic range
CsA PK Factors that affect it
What enhances absorption?
Bioavailability is reduced in what?
F increases with inhibition of?
- Food effect, high calorie meals increase absorption
- F is reduced in reduced bile production (liver transplant)
- F is increased with inhibition of p-gp and gut CYP3A4
CsA PK Factors that affect it
Clearance?
- Increased in children
- Reduced in pts with hepatic dysfunction (including immediately after liver transplant)
- Increased with induction of CYP3A4
- Reduced with inhibition of CYP3A4
What is the primary measurement of exposure for Tacrolimus?
Trough levels good correlation with AUC
Time Since Transplant is a factor that alters target levels of exposure and how does this work?
- As time increases risk of rejection decreases
Age can affect target levels of exposure what is the difference in child vs adults?
- Children overall have a lower risk of rejection but each follow a similar trend
The organ being transplanted can affect target levels of exposure how?
- Liver vs Kidney
- Liver shows a lower risk of rejection
Pts can be on other therapies while how does induction affect target levels of exposure?
- Pts that are not on induction therapy typically need a higher target level of exposure
Where you are taking your samples in the body can affect target levels of exposure what is the difference between Blood and Plasma levels?
- Drugs like CsO, Tacrolimus, Sirolimus are highly bound to Erythrocytes which are found in whole blood so your concentration levels if taken from blood will be much higher than if taken from just plasma
CsA What is the best measurement for target levels of exposure?
- 2 hour post dose peak levels (levels taken within 10 minutes either way will give you a 10% variability in target levels and pose the risk of posible overdose for the pt)
- Trough is taken sometimes but is more variable
What levels are measured in Tacrolimus and Sirolimus?
- Trough levels and have the same variability parameters as CsA
What is the wild tpe fully function CYP2D6?
*1
How many whites have deficient CYP2D6?
5-10% of caucasians
What consitutes a PM for CYP2D6 or others?
They must have two “inactive” forms of the alleles
What percentage of the Asain population are PMs?
- 1% but overall CYP2D6 functionality as a whole is lower than whites
What is the effect of a poor metabolizer?
PMs are at increased risk for concentration dependent SEs when given normal dosing but increased effect can occur (tramadol, codiene)
What are the alleles that are non functional for CYP2D6?
3456
What are the wild types or green allel>
1,2
Characteristics of UMs
CYP2D6
- Will have much higher clearance of drug therefore need higher doses
- But on the other end danger of overdose with other drugs (codiene)
