Immunosuppressive List for Exam 1 CMOD

Question 1

Cyclophosphamide
Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique) 
Contraindication for Breastfeeding

Answer 1

Class:
Cell Cycle Disruptor

Commercial Name(s):
Cytoxan

MOA:
General - Causes Intrastrand DNA crosslinks
Specific - Supresses Humoral Immunity most

Metabolism:
Not sure

Toxicities (unique):

• Low Sperm Count
• Hemorrhagic bladder infection (via acrolein metabolite)

Contraindication for Breastfeeding - YES, don’t give it

Question 2

Mycophenolate mefetil

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 2

Class:
Cell Cycle

Commercial Name(s):
CellCept

MOA:
INHIBIT INOSINE MONOPHOSPHATE DEHYDROGENASE (used for purine recycling => interrupt DNA synthesis => S phase arrest in T and B cells specifically - Poor Salvage pathway)

Metabolism:
RENAL

Toxicities (unique) :
NEUTROPENIA

Question 3

Prednisone

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 3

Class:
Nuclear Transcription Inhibitor

Commercial Name(s):
Deltasone

MOA:
Inhibit HAT (histone acetyltransferase) directly and by recruting histone deacetylase 2 OR inhibit proper functioning of NFkb (transcription factor for inflammatory cytokines); also cause neutrophilia, eosniopenia, monocytopenia	

Metabolism:
Hepatic

Toxicities (unique) :
Dyslipidemia, Hypercorticism (CUSHING’s syndrome)

Contraindication for Breastfeeding:
NO

Question 4

Cyclosporine

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 4

Class:
Calcineurin Inhibitor

Commercial Name(s):
Sandimmune

MOA:
General - Inhibit transcription of IL2, (Ifg, and IL4) by preventing dephospharylation of NFAT by Calcineurin=> generally prevent activation or proliferation of T cells

Specific - Bind cyclophilin (necessary for calcineurin)

Metabolism:
CYP3A4

Toxicities (unique) :

• RENAL TOXICITY (30%)
• HIRSUITISM or HYPERTRICHOSIS

Contraindication for Breastfeeding:
YES

Question 5

Atgam

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 5

Class:
Polyclonal Ig against T-lymphocytes

Commercial Name(s):
Thymoglobuline, Anithymocyte globulin

MOA:
Binds to many extracellular targets on T-cells

Metabolism:
None really

Toxicities (unique) :
horse/rabbit protein hypersensitivity

Contraindication for Breastfeeding:
NO

Question 6

Belatacept

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 6

Class:
Co-Stimulatory Blocker / Monoclonal Ab

Commercial Name(s):
NULOJIX

MOA:
Prevents CD80/86 co-stimuation from APCs

Metabolism:
None

Toxicities (unique) :
MUST be EBV+ (or risk Progressive Multifocal Leukoencephalopathy or Post-Transplant Lymphoproliferative Disorder)

Contraindication for Breastfeeding:
NO

Question 7

Tacrolimus

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 7

Class:
Calcineurin Inhibitor

Commercial Name(s):
N/a

MOA:
General - Inhibit transcription of IL2, (Ifg, and IL4) by preventing dephospharylation of NFAT by Calcineurin=> generally prevent activation or proliferation of T cells

Specific - Bind FK binding protein 12 (necessary for calcineurin); 100X as potent

Metabolism:
CYP3A4

Toxicities (unique) :

• RENAL (30%)
• Neurotoxicity (headache, Insomnia, Temor)

Contraindication for Breastfeeding:
YES

Question 8

Sirolimus

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 8

Class:
mTOR (aka mammalian target of rapamycin)

Commercial Name(s):
Rapamycin

MOA:
Ultimately inhibit cell PROLIFERATION due to IL-2: Bind to FKBP12 (like tacrolimus) BUT just inhibit activation of mTOR => G1 arrest; SYNERGISTIC with CYCLOSPORINE; prevent B-cell differentiation (low IgM, IgG, IgA); use with coronary stents

Metabolism:
CYP3A4

Toxicities (unique) :

• Hyperlipidemia
• Renal Toxicity
• Hepatotoxicity

Contraindication for Breastfeeding:
NO

Question 9

Azathioprin

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 9

Class:
Cell Cycle

Commercial Name(s):
Imuran 

MOA:
AZA => 6-MP => 6-thio-IMP=>6-thio-GMP=> 6-thio-GTP (Final pdt. Halts S phase when put in DNA) ; Also, blocks CD28 Co-stimulation, and promotes CD45RO memory cell apoptosis

Metabolism:
RENAL

Toxicities (unique) :
- Neutropenia

Contraindication for Breastfeeding:
YES

Question 10

Basiliximab

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 10

Class:
Prevention of Stimulatory binding

Commercial Name(s):
Simulect

MOA:
CD-25 antagonist with prevention of IL-2 binding

Metabolism:
None

Toxicities (unique) :
- Murine Protein Sensitivity

Contraindication for Breastfeeding:
NO

Question 11

Tersirolimus

Answer 11

same as Sirolimus, its just the pro-drug of Sirolimus

Question 12

Methotrexate

• MOA
• Unique Features/Side effects
• Commercial Name

Answer 12

Class:
Cell Cycle

Commercial Name(s):
Trexall

MOA:
Inhibit de novo pyrimidine synthesis (S phase arrest), AICAR accumulates in purine pathway => adenosine accumulates [anticancer: Dihydrofolate reductase inhibitor, Also prevents Pyrimidine Synthesis] (anti-inflammatory by binding receptors on APC surface, downregulate IL12 (diminished TH1 dev., TNFa, macrophage inflammatory protein, nitric oxide; increase IL10 and VEGF, immature dendritic chemotaxis)

Metabolism:
Hepatic?

Toxicities (unique) :
Pulmonary Fibrosis

Contraindication for Breastfeeding:
Yes

Question 13

Muromonab

Class
Commercial Name(s)
MOA
-General
- Specific 
Metabolism
Toxicities (unique)

Answer 13

Class:
mAb

Commercial Name(s):
Orthoclone CD3, OKT3

MOA:
Prevents CD3 activation on TCR binding to MHC

Metabolism:
None

Toxicities (unique) :
Murine protein sensitivity; angioedema; hypovolemia or pulmonary edema with initial doses; seizures

Contraindication for Breastfeeding:
NO