Flashcards in Pharmacology Of Immunosuppressant Therpies Deck (11)
Leading causes of ESRD
Type 1 DM (43%)
Chronic glomerulonephritis (12%)
Polycystic kidney disease (3%)
Interstitial nephritis (3%)
What was the first mainstay immunosuppressant drug introduced which increased lifespan of transplants?
Cyclosporine in 1979
- overall 20% increase in graft survival
Cellular events of graft rejection
Afferent phase: recognition of the allograft by the recipient immune system
Central phase: alloantigen-specific activation fo APC/T-cells/B-cells occurs
Efferent phase: cellular and humoral rejection mechanisms occur by lymphocytes, macrophages, CD-8 T-cells, complement and antibodies
Types of HLA
Class 1 = A/B/C
Class 2 = DR/DP/DQ
What are the three major cellular events that occur once a T-cell is activated in allo-rejection?
1) PKC activation: protein phosphorylation occurs, causes Ca2+ release in cells and activated cal model in protien which binds to PKC
2) calcaneurin activation: result sin IL-2 gene being transcribed multiple times
3) NFAT dephosphorylation: results in nuclear production of other cytokines
What are the broad categories of immunosuppressive pharmacotherapy?
- cyclosporine A
- mycophenolate mofetil
- any “mab”
What should you not drink if using cyclosporine A?
Dont drink grapefruit or tropical fruit juice
Dont consume pineapples or papaya
**all of this inactivates metabolism of CSA which increases apparent dose and can lead to bad ADRs**
What are the most common infectious complications post TPX?
- 30-90% of immunocompetent adults are sero+
- very deadly to immunosupression patients
- usually need to give anti-viral therapies as adjuvants (acyclovir, ganciclovir, Foscarnet, etc)
- *will show early onset fever and leukopenia in recent transplant patients who have this
Herpes simplex virus (HSV)
Pneumocystis jirovecii-induced pneumonia (PJP)
What are the most common non infectious complications post-TPX?
Liver disease (HBV/HCV)
What is CytoGam?
Human immunoglobulin containing IgG/IgA/IgM antibodies to CMV
1st line in TPX recipients to present primary CMV disease
- aseptic meningitis* (monito for this)