Pharmacology Of Immunosuppressant Therpies Flashcards
Leading causes of ESRD
Type 1 DM (43%)
HTN (23%)
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?
Calcineurin inhibitors
- cyclosporine A
- Tacrolimus
Antimetabolites
- azathioprine
- mycophenolate mofetil
Antilymphocytes
- ATGAM
- OKT3
- any “mab”
Corticosteroids
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?
Cytomegalovirus (CMV)
- 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?
HTN
Hyperlipidemia
GI ulceration
Liver disease (HBV/HCV)
Lymphoma
What is CytoGam?
Human immunoglobulin containing IgG/IgA/IgM antibodies to CMV
1st line in TPX recipients to present primary CMV disease
ADRs:
- hypersensitivity
- aseptic meningitis* (monito for this)
Why Do we give TPX patients magnesium?
Many medications used for TPX patinets (tacrolimus, cyclosporine, etc) come with side effects that increase magnesium excretion in the renal tubules
Often asymptomatic until its too late (so need to monitor levels <1.6 mEq/L = hypomagneium)
- *also often coexists with hypokalemia or hypocalcemia
