Pharmacology Of Immunosuppressant Therpies Flashcards Preview

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Flashcards in Pharmacology Of Immunosuppressant Therpies Deck (11)
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1

Leading causes of ESRD

Type 1 DM (43%)

HTN (23%)

Chronic glomerulonephritis (12%)

Polycystic kidney disease (3%)

Interstitial nephritis (3%)

2

What was the first mainstay immunosuppressant drug introduced which increased lifespan of transplants?

Cyclosporine in 1979
- overall 20% increase in graft survival

3

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

4

Types of HLA

Class 1 = A/B/C

Class 2 = DR/DP/DQ

5

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

6

What are the broad categories of immunosuppressive pharmacotherapy?

Calcineurin inhibitors
- cyclosporine A
- Tacrolimus

Antimetabolites
- azathioprine
- mycophenolate mofetil

Antilymphocytes
- ATGAM
- OKT3
- any “mab”

Corticosteroids

7

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**

8

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)

9

What are the most common non infectious complications post-TPX?

HTN

Hyperlipidemia

GI ulceration

Liver disease (HBV/HCV)

Lymphoma

10

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)

11

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