immuno drugs Flashcards
Cyclophosphamide
Cytotoxic and Antiproliferative Agent (T and B)
pro-drug, needs to be activated by cP450
cell cycle-nonspecific (CCNS) alkylating agent (entire cycle)
tx: anti-cancer agent, sev. rheumatologic conditions
suppressive: infections may happen
* SIGNAL 3*: can inactivate cell cycle
cyclophosphamide SEs: short term
GI: Nausea, vomiting, diarrhea; stomatitis; abdominal discomfort or pain.
Dermatologic: Alopecia (frequent).
Azathioprine [ImuranR]
Cytotoxic and Antiproliferative Agent (T*>B cells)
derivative of 6-mercaptopurine (anti-metabolite)
cell cycle specific: only targets S phase
inhibits adenosine deaminase
kidney transplants
RA
SIGNAL 3
Azathioprine [ImuranR] SEs: short and long term
GI: N/V (12%), diarrhea
- Hematologic: leukopenia or thrombocytopenia, macrocytic anemia, severe bone marrow depression. dose-related
- GU: temporary depression in spermatogenesis and reduction in sperm viability and sperm count
Pregnancy category D (fetal harm)*
may cause serious infections
carcinogen

Methotrexate [RheumatrexR]
Cytotoxic and Antiproliferative Agent (T and B)
inhibits dihydrofolic acid reductase (THF)
cell cycle specific
-targets 2nd phase of imm. response
tx for RA, Crohn’s, malignancy
SIGNAL 3
Methotrexate [RheumatrexR] potential for toxicity from high-dose regimens or delayed excretion is reduced by ??? during the final phase of methotrexate plasma elimination
leucovorin calcium
protects normal cells
Methotrexate [RheumatrexR] SEs
GI: N/V/D, stomatitis *hepatotoxicity *nephrotoxicity *obstructive pulmonary disease (COPD) infections
Cyclosporine [SandimmuneR]
T-Cell Suppressant
comes from a fungus
inhibits SIGNAL 1 by inhib. calcineurin phosphatases
inhib. IL-2–>inhib. T cell activation
suppresses CMI, some humoral immunity,
*reversible inhib.
Cyclosporine [SandimmuneR] may be affected by concomitant use of ???
because it requires ?? for metabolism
HIV protease inhibitors
anticonvulsants
azole antifungals
cytochrome P450 3A enzymes
Cyclosporine [SandimmuneR] SEs
nephrotoxicity (mild–>chronic progressive)
(peritubular cap. congesion, interstitial fibrosis w. tubular atrophy)
HTN
*can cross placenta!: terotgen
Cyclosporine [SandimmuneR] uses
organ transplants (take with corticosteroids, azathioprine)
RA
psoriasis
MYCOPHENOLATE MOFETIL [CellceptR]
T-Cell Suppressant
reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH)–>
inhib guanosine nucleotide synthesis
(affects T and B cells)
SIGNAL 3
MYCOPHENOLATE MOFETIL [CellceptR] SEs
GI
severe neutropenia
use in combo with cyclosporine, corticosteroids
Muromonab-CD3 (Orthoclone OKT3R)
T- cell suppressant
murine monoclonal Ab (IgG2a) blocks TCR (CD3) Ag
block calcineuria–>block IL-2–>block cell cycle/clonal expansion
tox: hypersn to murin products
* SIGNAL 1*
Lymphocyte Immune Globulin (AtgamR)
T-cell suppressant
- SIGNAL 1*
tox: may cause hypersn: prepped from horse IgG
risk for systemic infection
use with antimetabolite/cortster.
don’t use in pregnancy
Daclizumab (ZenapaxR)
T-cell suppressant
“humanized” (90%)
binds to the IL-2 receptor (vs. CD3) blocks IL-2
tox: GI
* SIGNAL 3*
RHo Immune Globulin (RhoGamR)
Ab agains Rh Ag
immunosuppressive:
prevents Rh- mother from becoming sensitized to Rh Ag–>prevents hemolytic disease of the newborn (42-96 hrs)
- SIGNAL 1*
- don’t use in Rh+ pts or Rh- who have dev. Rh Abs
Immune Globulin (GammagardR)
IgG and IgM
donor human plasma
agent for replacement thereby
broad spectrum of IgG antibodies against bacterial, viral, parasitic, and mycoplasma antigens
binding to IL-1 α, IL-6, TNF-α, and T-cell receptors–>suppress pathological cytokines and phagos
SIGNAL 1
Immune Globulin (GammagardR) uses
- hypogammaglobulinemia
- HIV-inf. ped pts
- idiopathic thrombocytopenic purpura
- Guillain-Barre’ syndrome
systemic and local
infections in bone marrow transplantation patients
INTERFERON BETA-1b [BetaseronR]
recomb. DNA technology
immunomodulator
trigger signalling cascades
relapsing-remmitting MS
INTERFERON BETA-1b [BetaseronR] SEs
hypersensitivity
depression, suicide, other mental disorders
flu-like symptoms
injection site reactions
INTERFERON GAMMA- 1b [ActimmuneR]
immunomodulator
generation of toxic oxygen metabolites (via NADPH oxidase) within phagocytes–>IC killing of organisms
tox: flu-like
tx for CGD:
enhances killing mech. does not fix pt. mutation
genetic factor of drug reactions
slow vs. rapid acetylators
assoc. illnesses that cause drug reactions
PCP develop drug reactions (skin rash to sulfa drugs)
this accounts for 5-20% of all observed adverse drug reactions
allergic drug reactions
Type 1 hypersensitivity
tx?
Anaphylactic (Immediate)
IgE binds via Fc portion to mast cell/basophil–>crosslink–>mediators released–>histamines, leukotrienes, etc.
prednisone, isoproterenol, epinephrine, theophylline
TYPE II hypersensitivity
tx?
Cytotoxic reactions
IgG and IgM
attach to circulating cells
hemolytic disease of newborn
thrombocytopenia, agranulocytosis, autoimmune hemolytic anemia
remove offending drugs
corticosteroids
Type III hypersensitivity
tx?
Serum Sickness or Arthus Reactions
Ab does not attach to circ. cell but rather BV wall: complex attaches Fc portion–>complement–>inc. vasc. perm–>neutrophils aggregate–>hemorrhagic vasculitic lesion
remove offending drugs
corticosteroids
Type IV hypersensitivity
tx?
CMI (delayed)
Mediated by sensitized T lymphocytes and macrophages
contact dermatitis
corticosteroids
case: abd. pain, arthralgia, low grade fever, glomerulonephritis 2 wks tx with prednisolone elevated WBC, CRP CT: thick duodenal and jejunal walls purpuric lesions (jejunum) *IgA deposition, vasculitis*
HSP
tx with high-dose gluccorts, tapered, then cyclosporine
case
pain redness in one eye, 2 mos
deep violacious episcleral injection, dialed perilimabl vessels and edema
corneal thinning
elev. CRP ESR
test for antineutorphilic cytoplasmic Ab was +
OM, wl, epistaxis, SOB
Urine: granular red cell, nodular parenchemal casts
peripheral ulcerative keratitis in wegener’s granulomatosis
tx with oral corticosteroids, cyclophosphamide
APC presents to T cell via TCR–>signaling pathway–>
produces IL-2–>signalling pathway that activates cell cycle
*cascade blocked by drugs
Cyclophosphamide long term side effects
Hematologic: Leukopenia, thrombocytopenia, anemia.
GU: Amenorrhea, oligospermia, azoospermia, sterility; urinary bladder fibrosis;
hematuria; hemorrhagic ureteritis; renal tubular necrosis.
Azathioprine uses
renal homotransplantation
RA
Crohn’s
SIGNAL 1 DRUGS
Cyclosporine Muromonab-CD3 Lymphocyte Immune Globulin (AtgamR) RHo Immune Globulin (RhoGamR) Immune Globulin (GammagardR)
SIGNAL 3 DRUGS
Cyclophosphamide Azathioprine Methotrexate Mycophenolate mofetil Daclizumab
