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TitleImmunopharmacology
TagsImmunology Immune System Antibody Monoclonal Antibody Immunoglobulin G
File Size987.0 KB
Total Pages6
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Page 1

   DR. DR. SALVADOR SALVADOR 

-- 11stst to have lympholytic property to have lympholytic property
-- reduces the size and lymphoid content of the lymph nodes and spleenreduces the size and lymphoid content of the lymph nodes and spleen
--
--
-- immunologic effects are probablyimmunologic effects are probably
--
--

!! idiopathic thrombocytopenic purpura and rheumatoid arthritisidiopathic thrombocytopenic purpura and rheumatoid arthritis

!! first-line immunosuppressive therapy for both solid organ andfirst-line immunosuppressive therapy for both solid organ and
hematopoietic stem cell transplant recipients, with variable resultshematopoietic stem cell transplant recipients, with variable results

!! asthmaasthma

!!  Adrenal suppr Adrenal suppressionession

!! Proximal muscle wastingProximal muscle wasting

!! DiabetesDiabetes

!! GI bleedingGI bleeding

!! Fluid retentionFluid retention

!! Serious viral, bacterial and fungal infectionSerious viral, bacterial and fungal infection

!! CyclosporineCyclosporine

!! TacrolimusTacrolimus

CYCLOSPORINECYCLOSPORINE
-- Cyclosporine is a peptide antibiotic that appears toCyclosporine is a peptide antibiotic that appears to

activationactivation
-- binds tobinds to

-- Cyclosporine and cyclophilin complexCyclosporine and cyclophilin complex "" inhibits calcineurin (necessary for the activation of a T-cell-specific transcription factor called inhibits calcineurin (necessary for the activation of a T-cell-specific transcription factor called
is involved in the synthesis of IL- 2is involved in the synthesis of IL- 2

-- absorbed drug is primarily metabolized by theabsorbed drug is primarily metabolized by the
--

!! graft-versus-host disease after hematopoietic stem cell transplantationgraft-versus-host disease after hematopoietic stem cell transplantation

!! kidney, pancreas, liver, and heart transplantkidney, pancreas, liver, and heart transplant

!! ophthalmic solution: dry eye syndromeophthalmic solution: dry eye syndrome

!! Inhaled cyclosporine: lung transplantationInhaled cyclosporine: lung transplantation

!! autoimmune disorders: uveitis, rheumatoid arthritis, psoriasis, andautoimmune disorders: uveitis, rheumatoid arthritis, psoriasis, and
asthmaasthma

!! nephrotoxicity, hypertension, hyperglycemia, liver dysfunction,nephrotoxicity, hypertension, hyperglycemia, liver dysfunction,
hyperkalemia, altered mental status, seizures, and hirsutismhyperkalemia, altered mental status, seizures, and hirsutism

!! increased incidence of lymphoma and other cancers due to its releaseincreased incidence of lymphoma and other cancers due to its release
ofof

-- (FK 506) is an immunosuppressant macrolide antibiotic produced by(FK 506) is an immunosuppressant macrolide antibiotic produced by

-- binds to thebinds to the blocking calcineurinblocking calcineurin
-- tacrolimus is 10–100 times more potent than cyclosporinetacrolimus is 10–100 times more potent than cyclosporine
--

!! preventing rejection in solid-organ transplant patients even after failurepreventing rejection in solid-organ transplant patients even after failure
of standard rejection therapyof standard rejection therapy

!! considered aconsidered a
graft-versus-graft-versus-host disease.host disease.

!! Tacrolimus ointment:Tacrolimus ointment:

!! nephrotoxicity, neurotoxicity, hyperglycemia, hypertension,nephrotoxicity, neurotoxicity, hyperglycemia, hypertension,
hyperkalemia, and gastrointestinal complaints.hyperkalemia, and gastrointestinal complaints.

 on proliferating myeloid or erythroid stem cells in the bone marrow on proliferating myeloid or erythroid stem cells in the bone marrow

 rather than to direct cytotoxicity rather than to direct cytotoxicity
 than humoral immunity than humoral immunity

and blocks theirand blocks their

w/cw/c

 in the liver in the liver

 (usually in combination with (usually in combination with
) for ) for

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  DR. SALVADOR 

! Sirolimus and its analogs

- immunosuppressant macrolide antibiotic produced by
- , resulting in an active complex that inhibits mTOR
- available only as an

! prophylaxis and as therapy for steroid-refractory acute and chronic
graft-versus-host disease in hematopoietic stem cell transplant
recipients

! profound
hepatotoxicity, diarrhea, hypertriglyceridemia, pneumonitis, and
headache.

! semisynthetic derivative of .

! inhibits

! first-line drug for preventing or reducing
in cardiac transplant recipients

! used as
versus-host diseases in hematopoietic stem cell transplant patients

! Toxicities include gastrointestinal disturbances (nausea and vomiting,
diarrhea, abdominal pain) headache, hypertension, and reversible
myelosuppression (primarily neutropenia).

! sedative drug that was withdrawn from the market in the 1960s because of its

! inhibits

! It inhibits
expression, and enhances cell-mediated immunity via interactions with T cells.

! Thalidomide is currently used in the treatment of
initial diagnosis and for relapsed-refractory disease

! The most important toxicity is

!  Azathioprine

! Cyclophosphamide

! Leflunomide

! Hydroxychloroquine

! Other cytotoxic agents

" prodrug of mercaptopurine and, like mercaptopurine, functions as an

"

"

! maintaining renal allografts and may be of value in transplantation of
other tissues.

! The chief toxic effect of azathioprine and mercaptopurine is bone
marrow suppression,

! Hepatic dysfunction, manifested by very high serum alkaline
phosphatase levels and mild jaundice

and

 drug

 (especially thrombocytopenia),

 isolated from the mold

, including mitogen and mixed lymphocyte responses, probably by .

 of both acute and chronic graft-

.

.

! , , alters adhesion molecule

 at

 much of the active material to 6-thiouric acid prior to excretion in the urine

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  DR. SALVADOR 

" alkylating agent cyclophosphamide is

"

! In smaller doses: autoimmune disorders (including

bleeding syndromes, autoimmune hemolytic anemia, antibody-induced
pure red cell aplasia, and Wegener’s granulomatosis.

! carries considerable risk of pancytopenia and hemorrhagic cystitis

" inhibitor of pyrimidine synthesis

"

! only

!

! elevation of liver enzymes with some risk of liver damage, renal
impairment, and teratogenic effects.

" antimalarial agent with immunosuppressant properties.

" It is thought to
endosomal compartments, thereby decreasing T-cell activation.

! only

" including and

! useful in idiopathic thrombocytopenic purpura refractory to prednisone. !  primarily used as an antineoplastic
agent for lymphoid malignancies, and produces a profound
lymphopenia.

!

-  ALG acts
-  As a result of the destruction or inactivation of T cells , an

!  ALG and ATG are
and play a definite role in the

management of solid organ and bone marrow transplantation

! Local pain and erythema often occur at the injection site (type III
hypersensitivity)

! Complexes of host antibodies with horse ALG may precipitate and
localize in the glomeruli of the kidneys

-

! Treatment of acute renal allograft rejection and steroid-resistant acute
cardiac and hepatic transplant rejection

NONE (as per Katzung)

available

 and in patients with  and

at present

molecules by increasing the pH of lysosomal and

at present

that circulate between the blood and lymph
and occurs while

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  DR. SALVADOR 

-  An approach of intravenous use of polyclonal human immunoglobulin
- immunoglobulin preparation (usually

! safe and effective in Kawasaki’s disease

! systemic lupus erythematosus and refractory idiopathic
thrombocytopenic purpura.

!

! reduction of T helper cells

! increase of regulatory T cells

! decreased spontaneous immunoglobulin production,

! Fc receptor blockade

! increased antibody catabolism, and idiotypic-anti-idiotypic interactions
with “pathologic antibodies.

- The technique is based on the observation that a

higher titer of antibodies against the

! prophylactic treatment to prevent erythroblastosis fetalis ! infrequent and consist of local discomfort at the injection site or, rarely,
a slight temperature elevation

!

normal and malignant B and T lymphocytes, NK cells, monocytes,
macrophages, and a small population of granulocytes

!

!

thrombocytopenia

!

especially on endothelial cells.

!

!

! MOA: decreases in kinase activity, matrix metalloproteinase activity,
and growth factor production, and increased apoptosis

!

!

thrombocytopenia

!

!

!

!

! MOA: It inhibits cell growth, induces apoptosis, decreases vascular
growth factor production, and suppresses internalization of the EGFR

!

!

!

!

Hodgkin’s lymphoma and chronic lymphocytic leukemia and treatment
of rheumatoid arthritis

! recombinant DNA-derived,

receptor

! MOA: blocks the natural ligand from binding and down- regulates the
receptor

!

) is

. Rho(D) immune globulin is a concentrated  containing a
 the red cell.

found on

: lymphopenia, neutropenia, anemia, and

 and inhibits VEGF from binding to its receptor,

treatment of patients with

: lymphopenia, neutropenia, anemia, and

treatment of patients with

: slight risk of hepatitis B virus reactivation

relapsed or refractory low-grade or follicular B-cell non-

of the human epidermal growth factor

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  DR. SALVADOR 

! murine Fab fragment from an anti- carcinoembryonic antigen (CEA)
antibody labeled with
imaging patients with metastatic colorectal carcinoma
(immunoscintigraphy) to determine extent of disease

! murine monoclonal antibody specific for

! ! another

! completely human IgG1 approved for use in patients with

! It is coupled to a

!

!

! MOA: decreases in kinase activity, matrix metalloproteinase activity,
and growth factor production, and increased apoptosis

!

 juvenile idiopath ic arthritis, ankylosing spondylitis and psoriatic
arthritis. It may be used in combination with methotrexate in some
patients with arthritis.

! human IgG monoclonal antibody that also binds to soluble and

membrane-associated TNF-!

!

!

!

human constant (Fc) regions and murine variable regions

! MOA: decreases in kinase activity, matrix metalloproteinase activity,
and growth factor production, and increased apoptosis

!

ankylosing spondylitis, plaque psoriasis, and psoriatic arthritis.

! recombinant fusion protein composed of the extra- cellular domain of
cytotoxic T-lymphocyte-associated antigen
CH2, and CH3 domains of human IgG1

! binds more tightly to

!

! engineered protein consisting of the CD2-binding portion of leukocyte-
function-associated antigen-3 (LFA-3) fused to a human IgG1 Fc region
(hinge, CH2, and CH3).

!

! chimeric mouse-human IgG1 that
on activated lymphocytes.

! MOA: Both agents function as
binding to activated lymphocytes, and are therefore
immunosuppressive.

! humanized IgG4 monoclonal antibody that binds to the !

! expressed on the surfaces of all leukocytes

except neutrophils, and inhibits the !4-mediated adhesion of
leukocytes to their cognate receptor.

!

that is used for . It is coupled to isotopic (111In)

murine monoclonal antibody labeled with isotopic monoclonal antibody and is complexed with

! recombinant humanized Fab fragment that binds to TNF-!.

treatment of patients with

! "

approved for , polyarticular
treatment of patients with

: slight risk of hepatitis B virus reactivation

monoclonal anti- body possessing

Crohn’s disease, ulcerative colitis, rheumatoid arthritis,

 fused to hinge,

treatment of patients with

, blocking IL-2 from
" and !4"7 integrins

treatment of patients with

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