Block V- Pulm Immunomodulation Flashcards
Glucocorticoids:
Prednisone
Prednisolone
Indicate = Immunosuppression, graft rejection, GvHD, autoimmune, tx cytokine release syndrome
MOA = Activates the glucocorticoid receptor TF –
Modifies expression of cytokine + immunoregulatory genes = Suppresses active immune responses
SFX = many. Hyperglycemia, HTN, HLD, Obesity, DM, poor wound healing, mania & psychosis, INC infection risk
Misc = dose gradually reduced – should not
be withdrawn abruptly
Azathioprine
Indicate = Immunosuppression, graft rejection, GvHD, autoimmune
MOA = Prodrug. –>6-MP by HGPRT
Inhibits de novo purine synthesis
Incorporated into DNA & causes SSB base mispairing ➔ apoptosis
Inhibits CD28 co-stimulation
SFX = Leukopenia/thrombocytopenia, Hepatotoxicity, INC risk infections/ malignancy
MISC = Interacts with anti-gout drugs (Allopurinol & Febuxostat) Leading to INC [Azathioprine] ➔INC toxicity
Mycophenolate Mofetil
Indicate = Immunosuppression, graft rejection, GvHD, autoimmune
MOA = Prodrug –> mycophenolic acid
Inhibits inosine monophosphate dehydrogenase II (IMPDH2 …selectively expressed in lymphocytes) ➔ Inhibition of purine nucleotide synthesis
- no salvage pathway in lymphocytes
SFX = Leukopenia/anemia, Teratogenic, INC risk infection/ malignancy
RARE- Risk of Progressive multifocal leukoencepalopathy (PML)- Fatal viral disease caused by reactivation of JC virus
MISC = Contraindicated in pregnancy women + men
Calcineurin Inhibitors:
Cyclosporine
Tacrolimus
Indicate = Immunosuppression, graft rejection, GvHD, autoimmune
MOA = Formation of inhibitory complexes –> stop calcium-regulated phosphatase, calcineurin
- Inhibition of calcinurin = inhibition of activation of NFAT TF… involved in regulating IL2 expression
- Potently inhibit the T cell immune response by inhibiting Signal 1
Cyclosporin + Cyclophilin
Tacrolimus + FKBP
SFX = many… Nephrotoxicity*** Hypertension
Neurotoxicity/Tremor. Glucose intolerance (T>C). HLD (C>T). Hypertrichosis (C). Alopecia (T)
INC risk infection/ malignancy
MISC =
Metabolized by CYP3A4 – drug interactions
3A4 inhibitors promote INC drug levels ➔ risk of toxicity
3A4 inducers promote DEC dDrug levels ➔ risk graft rejection
mTor Inhibitors:
Sirolimus
Everolimus
Indicate = Immunosuppression, graft rejection (NOT LIVER OR LUNG), GvHD, autoimmune, prevention of stent restenosis
MOA = Drugs form complex with FBKP –>
INHIBITION OF:
- IL-2 mediated activation of mTor kinase (T cell signal 2)
- IL-2 stimulated protein synthesis, Cell proliferation and survival
SFX = MANY. HLD, Lung disease, DM, Anemia/ Thrombocytopenia/ Leukopenia, DEC wound healing, Teratogenic. INC risk infection/ malignancy
MISC =
Metabolized by CYP3A4 = Many drug interactions
Contraindicated in
- Pregnancy
- Lung transplantation (risk anastomotic dehiscence)
- Liver transplantation (risk hepatic artery thrombosis)
Rabbit anti-thymocyte globulin
Indicate = Induction Immunotherapy
MOA = Rabbit polyclonal antibodies specific for human lymphocytes…. Depletes lymphocytes from blood
SFX = Cytokine release syndrome & Leukopenia
Alemtuzumab
Indicate = Induction Immunotherapy
MOA = Binds to CD52 on T, B, macrophages, NK cells & granulocytes
Depletes cells from blood by Ab-mediated lysis
SFX = Cytokine release syndrome & Leukopenia
Can take > 1 yr for immune system to recover
Basiliximab
Indicate = Induction Immunotherapy
MOA = Antagonist of the IL-2R & Blocks T cell proliferation
IVIG
Immunoglobulin for passive immunization
Indicate = short lived humoral immunity to patients with deficiency in humoral
e.g. hypogammaglobulinemia
MOA = Pooled Ig from healthy individuals –>Provides patient with pooled Ig to provide immunity
to common pathogens
Rho (D)
Immunoglobulin for passive immunization
Indicate = Prevention of HDN in babies to Rh- moms
MOA = Purified Ig to Rh (D) antigen
Given to Rh- mother at 28 weeks & 72 hr post pregnancy to deplete any fetal RBC in maternal blood to prevent the mother from generating an immune response to fetal RBC
Hyperimmune Ig
Immunoglobulin for passive immunization
Indicate = provide rapid specific antibody immunity
to specific viruses and/or toxins
MOA = Purified Ig to specific antigens purified from healthy
Given IV to promote clearance of virus/toxin
Ipilimumab
Immune Checkpoint Inhibitors
Indicate = late stage melanoma & Non-small cell lung cancers
MOA = Antibody for CTLA4 –> Antagonizes the negative regulatory CTLA4 protein responsible for downregulating activated T cells
Enhances T cell responses
SFX = Potential for RARE Autoimmune response (can be fatal)
Misc = CI in pregnancy
Pembrolizumab/
Nivolumab
Immune Checkpoint Inhibitors
Indicate = late stage melanoma & Non-small cell lung cancers
MOA = Antibody specific for the PD1 protein, a negative regulatory receptor expressed on activated T cells –responsible for downregulating T cell responses
The PD1 ligand PD-L1 is expressed on tumor cells = mechanism for tumor cells to avoid the immune response
Antibody drugs block PD1/PD1-L1 interactions –> no inhibitory signal –> enhanced tumor immune responses
SFX = Potential for RARE Autoimmune response (can be fatal)
Misc = CI in pregnancy
