1-3: Intro, biologics Flashcards
study of AEs of chemical, biological, or physical agents on living organisms and the environment
toxicology
substances that cause death, injury, or harm
poison
chemical/ physical agent/ substance having the characteristics of producing an undesirable or adverse health effect
toxic
ability of a toxic agent to cause adverse effects in living organisms
toxicity
chemical/ physical agent/ substance that produces AEs on biological organisms (anthropogenic source), may be chemical or physical (ex- pesticides)- typically man made
toxicant
toxic substance (peptides or proteins) that is produced by biological systems such as plants, animals, fungi, or bacteria. Venoms are toxins produced by a bite or sting- typically natural
toxin
anything that can produce an AE (chemical (cocaine), physical (radiation), or biological (venom))
toxic agent
organisms that invade and multiply within another organism and produce their effects by biological activity are not classified as toxic agents but biological agents (ex- COVID)
biological agent
invading organism excretes a chemical that causes the toxicity (ex- tetanus)
biological toxin
T lymphocytes sense foreign peptide fragments presented by
antigen presenting cells- MHC
collection of antibodies from a variety of B cells which are capable of recognizing multiple epitopes on the antigen
polyclonal antibodies
antibody from single B cell which are only capable of recognizing a distinctive epitope
monoclonal antibodies
solid organ transplant prolongs life by
~4yrs in most patients
what is the most common solid organ transplant
kidney graft
describe the graft rejection sequence
organ recipient recognizes graft as foreign → activates B and T cells = differentiate/ divide/ generate immune mediators (ex- cytokines) to upregulate the immune system → host immune system attacks the graft → graft destruction → eventual graft rejection
describe the immune process from when the T cell receptor identifies the antigen bound to the MHC on APC
cosimulatory signal activated (CD 80/86-CD28) = activates intracellular activities = increases IL2 generation = feedback amplification
what is the purpose of induction therapy
enhance initial immunosuppressive effects + delay usage of nephrotoxic agents (Ex- calcineurin inhibitors)
induction therapy is a _______ course, often ________ with maintenance tx
short course
overlapping with maintenance
2 options for induction therapy
depleting agents
immune modulators
describe depleting agents
depletes T lymphocytes
describe immune modulators
inhibits IL2 associated activation of T lymphocytes
High immune risk/ steroid sparing = preferred to use ______ as induction therapy
depleting agents
low/ medium immunological risk = preferred to use ________________ as induction tx
immune modulators
rank the induction agents from low to high risk
no induction < basiliximab < alemtuzumab < antithymocyte globulin
describe 3 cases where there would be lower risk of rejecting transplant
zero HLA mismatch, live donor, caucasian, lower panel reactive antibody, absence of donor specific antibody, blood group compatibility, immediate graft function, short cold ischemia time, first transplant
describe 3 cases where there would be higher risk of rejecting transplant
more HLA mismatches, younger recipient + older donor age, african-american ethnicity, high panel reactive antibody, presence of donor specific antibody, blood group incompatibility, delayed onset of graft function, long cold ischemia time, retransplant
what is antithymocyte globulin
purified gamma globulin from rabbits or horses immunized with human thymocytes
ATG is
equine
rATG is
rabbit
rabbit ATG is ____ immunogenic, ______ potent compared to equine
less immunogenic, more potent
agglutination og ATG on as cellular surface results in
complement induction + cell mediated cytotoxicity to
phagocytosis by macrophages + necrosis/ apoptosis
ant thymocyte globulin binds to
T cell surface receptors
T or F: antithymocyte globulins can affect B cells or other leukocytes
T
antithymocyte globulin can only be adminsitered
IV
ATG distribution
binds to circulating lymphocytes, granulocytes, platelets = poor tissue distribution
ATG elimination
very little urinary excretion, no typical phase 1 or 2 metabolism
PK interactions against ATG
minimal due to lack of renal excretion + conventional phase 1/2 metabolism
how is ATG metabolized
proteolysis in the liver +/- reticuloendothelial systems
endocytosis + pinocytosis and degradation in lysosomes
MOA of serum sickness to ATG
formation and deposition of antibody-ATG complex in tissues = arthralgia + painful joints, ↓ LT graft survival,
common infusion related SEs
chills/ fever/ itching/ erythema
how to tx common ATG infusionr eactions
prophylactic antihistamine, antipyretics (ex- APAP), slow infusion (4-6hrs)
how tto avoid phlebitis from ATG
infuse ATG through central vein
how to tx ATG anaphylaxis
stop ATG inf + admin epi, steroids, do not restart
how to tx ATG hemolysis
transfusion, pharmtx (eg mannitol to ↓ osmotic swelling of RBCs), hold ATG PRN
describe thrombocytopenia as a SE to ATG tx + treatment
transient in kidney transplant pts → platelet count usually return to normal w/out stopping ATG, may req platelet transfusion in resistant cases
how to treat respiratory distress from ATG
possible sign of anaphylaxis → can hold ATG, admin antihistamine, epi, corticosteroids
chest, flank, back pain to ATF infusion is possibly a sx of
anaphylaxis
persistent hypotension from ATG infusion is a possible sx of
anaphylaxis
how to tx persistent hypotension from ATG
possible sx of anaphylaxis → stop ATG inf + admin epi, steroids, do no restart ATG, pressors PRN
monoclonal antibodies ADME
same as ATG
OKT3 (muromonab) is a
depleting agent
alemtuzumab is a
depleting agent
OKT3 MOA
murine monoclonal antibody, binds to CD3 on the T receptor complex on the surface of T lymphocytes, inactivates T cells = eventual phagocytosis
OKT3 indication
solid organ transplants
alemtuzumab indication
off label for solid organ transplant for induction + tx of acute rejection
alemtuzumab MOA
humanized monoclonal antibody agent against CD52 surface antigen (T and B lymphocytes, macrophages, monocytes, eosinophils), binding to CD52 = antibody dependent lysis = T and B cell removal from various tissues = complete lymphocyte depletion
basilizimab indication
induction tx in kidney transplant
allows delayed initiation or low dose calcineurin inhibitor
basiliximab MOA
chimeric monoclonal antibody which binds competitively to the alpha chain on the CD25 protein (IL2 receptor) on activated T lymphocytes = prevents IL2 mediated T cell activation/ proliferation, immunomodulatory, non depleting
belatacept indication
alt to calcineurin inhibitors fro prophylaxis of organ rejection in kidney graft recipients in conjunction wiht basiliximab induction, mycophenolate mofetil, and steroids
first MAB maintenance tx in organ transplant
belatacept MOA
blocks T cell costimulation inhibitor (binds CD80/86 on APC = reduces interactions and activation = T cell apoptosis)
belatacept must be used in conjunction with
basilizimab, mycophenolate mofetil, and steroids
which biologic sees post transplant lymphoproliferative disorder in Epstein- Barr virus seronegative patients
belatacept
belatacept has a modified ____ segment connected to the extracellular domain of human ______ with ___ mutations to enhance bindign to CD80 /86
modified Fc segment
CTLA4
2 mutations
leukopenia is more common with _________ agents
lymphocyte depleting agents
leukopenia would be more expected with
1. OKT3
2. belataceptt
3. mycophenolate mofetil
4. steroids
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there is a higher incidence of cytomegalovirus infection with
depleting agents
rATGs are associated with
1. melanoma
2. nonhodkin’s lymphoma
3. colorectal cancer
4. kidney disease
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