Pharmacology Immunosupressants I Flashcards

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1
Q

T- Cell Activation

A

MHC peptide complex tcr-cd3 (signal 1) + CD 80/86 (B7) costimulatary cd28 (signal 2) = required for activation

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2
Q

Allograft rejection

A

Recipients immune system attacks foreign antigens in allograft

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3
Q

GVHD. ( graft versus host disease)

A

Competent immune cells in allograft ( bone marrow , stem cell) recognize the recipients antigens as foreign

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4
Q

Hyperacute rejection

A

Performed host antibodies against alloantigens bind grafted vascular endothelium and complement is activated —> necrosis. Happens within minutes to hours

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5
Q

Acute rejection

A

Cellular humoral or both . Happens within days to weeks

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6
Q

Chronic rejections

A

Happen gradually over several years.leads to fibrosis and loss of graft function

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7
Q

Positive point of many immunosuppressives

A

They block multiple targets. Which allows for low dose of drugs to be used so less toxicity risk

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8
Q

TherApy for prevention of acute organ rejection

A
  1. Calcineurin inhibitor ( or mTOR inhibitor or CTLA4 inhibitor)
  2. Antimetabolite
  3. glutocorticoid
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9
Q

Established acute allograft rejection

A

T cell mediated:
1. Gluticorticoid, high dose pulse then oral taper
2. RATG ( or alemtuzumab if patient doesn’t tolerate rATG)
Antibody mediated:
1. Gluticorticoid, high dose pulse then oral taper
2. IVIG
Individual cases: plasmapheresis/ritumixab

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10
Q

Exceptions to general therapy approach

A

Lung transplantation- gluticorticoid omitted for several weeks to promote bronchial anastomosis healing

Liver requires less immunosuppression. Only calcineurin inhibitor required to suppress long term

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11
Q

Immunization during immunosuppressant therapy

A

NO LIVE VIRAL IMMUNIZATIONS DURING TREATMENT

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12
Q

RATG (thymoglubin)

A

-purified gamma globulin from serum rabbits immunized w/ human thymocytes
- depleting agent tht causes T cell lysis= depletion of circulating lymphocytes
- bind variety of proteins on human T lymphocyte surface (I.e cd20)
-acts on long lived lymphocytes tht circulate btw blood and lymph
Direct cytotoxicity- complement & cell mediated
Block lymphocyte function- bind surface molecules involved In regulation of cell function

  • destruction/inactivation of T cells Impairs hypersensitivity and immunity = marked cellular immunity suppression
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13
Q

RATG Adverse effects

A

Common- fever, chills , leukopenia, thrombocytopenia
Infusion reactions- flu-like symptoms , cytokines release syndrome, local site reactions
Serum- rash pruritis, fever, hypotension, lymphadenopathy
Infection- bacterial, viral, fungal, protozal
Pregnancy-use effective contraception during and at least 3 months following treatment

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14
Q

Alemtuzumab

A
  • Anti-CD52 monoclonal antibody depleting agent
  • bind cd52 on t/b cells-> indices direct antibody dependent cellular cytotoxicity and complement mediated lysis-> depletion of t & B cells -> reduces host immune response against transplanted organs
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15
Q

Alemtuzumab toxicity

A

Common-nausea, vomiting, diarrhea, insomnia
Infusion- flu like symptoms, cytokines release syndrome, local site reaction.
Autoimmune- hemolytic anemia, thrombocytopenia, antiglomerular basement membrane disease
Infection - malignant neoplasms among bacteria,viral,fungal
Pregnancy- contraception during and 6 months after treatment men and women

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16
Q

Baxiliximab

A

MOA
1. Binds high affinity IL-2Ra on surface of activated T cells
2. Competitively blocks IL-2 binding to activated T cells
3. Prevents T cell activation
4. IL-2R downregulation prevents proliferation
Uses:
Induction therapy with GC and cyclosporine
-renal
-heart,liver,lung
-2 doses
Treatment of acute refractory GVHD

17
Q

Basiliximab toxicity

A

Anaphylaxis , infections/ lymphoproliferative disorder

NO CYTOKINES RELEASE SYNDROME
NO SIGNIFICANT METABOLIC DRUG INTERACTIONS METABOLIC INTERACTION S

18
Q

Glutocosteroids

A

Binding of CS-GR complex to nuclear elements —> trans repression or transactivation of genes.
Induce lipocortin—> inhibits PLA2-> inhibit synthesis of prostaglandins and lipoxygenase products
- inhibit T cell proliferation
- humoral immunity dampened but little effect on it
Inc in : lymphocyte apoptosis, lymphocyte redistribution
Dec in: chemotaxis, il1,il6,il2, T cell proliferation, lysosomal enzyme release of neutrophils and monocytes

19
Q

Glucocorticoids use

A
  1. GVHD prevention and treatment
  2. Prevention and treatment of transplant rejection
    Induction and maintenance of allograft; acute transplant rejection
  3. Management of cytokine release syndrome, infusion reactions
20
Q

Gluticosteroids toxicity

A

Acute effects:
-INCREASE IN plasma cholesterol, salt retention, BP, opportunistic infection
- delayed wound healing
- depressive/ euphoria mood
Delayed effects:
- peptic ulcers /GI bleeding
- reduced growth in children
- cataracts
- osteoporosis, avascular necrosis of bone
CUSHINGS EFFECT:
- moon face, ruddy complexion
-unchallenged fat deposition, Buffalo hump
- weight gain, abdominal obesity
- muscle wasting, weakness of limbs
- thin skin, hirsuitism, acne, bruisability