Immuno supressants

Question 1

Tacrolimus

Answer 1

Calcineurin inhibitor (maintenance phase)

• Inhibit transcription of IL-2, IF-g, and IL4 by preventing dephosphorylation of NFAT
• generally prevent activation or proliferation of T cells
• side effects: Renal toxicity, HTN, Neurotoxicity*
• Drug-interactions: CYP3A4 substrate

Question 2

Belatacept

Answer 2

• Monoclonal Ab
• Target CD80/86 (B7)
• prevents co-stim signal => apoptosis
• MUST be Epstein-Barr Virus positive (or => Post-Transplant lymphoproliferative disorder) (black box)

Question 3

Mycophenolate Mofetil

Answer 3

• Cell cycle disruptor (maintenance phase)
• Inhibit inosine monophosphate dehydrogenase (used for purine recycling => interrupt DNA synthesis => S phase arrest in T and B cells selectively)
• Side effects:
  GI* tract problems, neutropenia*, infections and tumors

Question 4

Azathioprine

Answer 4

• Cell cycle disruptors (maintenance phase)
• Many products: Block co-stimulation by CD28=> apoptosis after IL2 stimulation, Fraudulent nucleotide* (S phase arrest)
• SE: Myelosuppressive, co-toxic w/ Allopurinol

Question 5

Muromonab

Answer 5

• Monoclonal Ab
• Target CD3; great for organ transplant
• prevents co-stim signal => apoptosis
• SE: murine protein sensitivity (Angioedema, hypovolemia, seizures)

Question 6

Thymoglobulin (Antithymocyte globulin)

Answer 6

• Polyclonal IgG against human T-lymphocytes
• Many targets; great for organ transplants
• Induction phase

Question 7

Sirolimus

Answer 7

mTOR inhibitor
=> G1 arrest (no cell cycling) prevent B-cell differentiation
- Drug-interactions: CYP3A4 substrate
- SE: Hyperlipidemia, Renal toxicity, Hepatotoxicity* (incl fatal necrosis)

Question 8

Cyclosporine

Answer 8

• Calcineurin inhibitor (maintenance phase)
• Inhibit transcription of IL2, IF-g, and IL4 by preventing dephospharylation of NFAT
• generally prevent activation or proliferation of T cells
• side effects: Hirsutism (hypertrichosis), Gingival Hyperplasia, Renal toxicity, HTN,
• Drug-interactions: CYP3A4 substrate

Question 9

Prednisone

Answer 9

• Nuclear transcription inhibitors: corticosteroids (anti-inflammatory)
• Inhibit histone acetyltransferase (also NFkB function)
• maintenance phase
• side effects: Protein metabolism dysfunction, infection susceptibility (esp TB), dyslipidemia* and assoc issues, neuropathy, impaired wound healing

Question 10

Basiliximab

Answer 10

• CD-25 antagonists (IL-2 receptor)
• inhibit activation by IL2
• Induction phase (NOT lymphocyte depleting)
• Side effects: Infection (including reactivating latent viruses), secondary malignancies

Question 11

Methotrexate

Answer 11

• Cell cycle disruptors (maintenance phase)
• inhibit de novo pyrimidine synthesis
• also ant-inflammatory (bind receptors on APCs)
• SE: GI, pulmonary fibrosis, neuro, hepatotoxicity