PGx of Transplant Flashcards
life saving transplants
liver, heart, heart-lung, multi-visceral
not life saving; quality of life
kidney, pancreas, face, hands uterus
most common transplant
kidney
characteristics of transplant pt
pre-transplant, long-standing organ failure
surgical intervention and its complications
donor-recipient tx
drug tx: delicate balance
- can get rejection or infection/toxicity
Metabolizes 50% of drugs
CYP3A4 and 3A5
transport protein
MDR1: P-glycoprotein
transport protein
MDR1: P-glycoprotein
adverse effects of transplantation
nephrotoxicity (esp with liver transplant) 50% develop ERSD
HTN - almost 100% of kidney failure pts develop
DM
Hepatotoxicity
Neurotoxicity
Hyperlipidemia
PTLD
MMF, Azathioprine - leukopenia, thrombocytopenia, GI SE
adverse effects of transplantation
nephrotoxicity (esp with liver transplant) 50% develop ERSD
HTN - almost 100% of kidney failure pts develop
DM
Hepatotoxicity
Neurotoxicity
Hyperlipidemia
PTLD
MMF, Azathioprine - leukopenia, thrombocytopenia, GI SE
Types of transplantation
Life saving: liver, heart, heart-lung, multi-visceral
Quality of life: kidney, pancrease (rare), face, hand, uterus
most common solid organ transplant
kidney
characteristics of the transplant patient
- requires the most complex drug therapy
- pt must be able to endure stress of long surgery
- HLA matching for donor-receipient
Drug therapy for transplant patient
risk rejection or infection
too much immunosuppresion = infections or cancer
not enough immunosuppression = organ rejection
current immunosuppressive agents
- calcineurin inhibitor
- corticosteroids -> every pt on these
- antimetabolites
- mTOR inhibitors -> mammalian target of rejection
- Abx products
Why do PGx research
pts take meds for life
identify and reduce SE
genotypes of drug transporters
determine risk factors for complications post-transplant
CYP3A and MDR1
about 50% of all agents metabolized by 3A4/3A5
MDR1: Pgp drug transporter (efflux)
both influence PK
Adverse effects of transplantation
Nephrotoxicity, HTN, DM, hepatotoxicity, neurotoxicity, hyperlipidemia, PTLD, MMF, Azathioprine (leukopenia, thrombocytopenia, GI issues)
ERSD
can happen in liver transplant due to drug toxicity or transplant meds
5-10% of pts develop it
Major immunosuppressants
cyclosporine
tacrolimus
sirolimus
Calcineurin inhibitors
backbone of immunosuppression
- cyclosporine
- tacrolimus
- every pt takes ONE of these meds
PK of calcineurin (CNI) and TOR inhibitors
WIDE inter and intra subject variability
unpredictable PK and PD
DDI’s - b/c metabolized by CYP3A and Pgp, so there is a lot of competition for binding sites and metabolism
Factors affecting CNI/TORI PK
Major: Genetics, age, liver function, meds, food intake, time after transplant
Minor: time of admin (esp for lipophilic drugs), formulation, gender, obesity, hematocrit/lipoprotein
Major metabolic factors for CNI/TORI
CYP3A4 and CYP3A5
Pgp
