|
return to menu I--return
to menu II
Organ Transplantation:
return to menu I--return
to menu II
- Primary
Renal Disease:
- Two primary types of
glomerular injury-- immune-mediated:
- systemic
lupus erythematosus (renal
aspect)
- acute
glomerulonephritis
- immunosuppressive treatment may
be beneficial -- not definitively
resolved
- underlying
disease may easily damage the
new, transplanted kidney
- e.g.
patients with
anti-basement membrane
antibody® acute graft
rejection (such patients
may require
immunosuppressive
treatment for 6-8
weeks after bilateral nephrectomy, before
donor transplantation)
- Patients
with systemic lupus
erythematosus: poor
candidates for transplant
until systemic disease is
controlled
- Factors which have improved
success rate in renal transplantation:
- prior
blood transfusions
- cyclosporine (improved graft
survival, patients survival,
decreased patient morbidity)
- 80%
of carefully selected
(not related)
transplanted kidneys
survive over two years
- OKT3
(monoclonal anti-T cell
antibody): significant
reduction in acute graft
rejection
return to menu I--return
to menu II
- Bone marrow transplantation in
patients with:
- aplastic anemia,
refractory acute leukemia
- intensive
immunosuppression before
transplantation required
- monoclonal
antibody to leukemia-, lymphoma-,
neuroblastoma-associate antigens
are employed to (cleanup)
patient's own bone marrow:
autologous transplantation
- monoclonal antibody-immunotoxin conjugates:
may allow broader useof
autologous bone marrow treatment
- Patients
who cannot receive either
autologous bone marrow or a grant
from an identical twin require
immunosuppression postengraftment
to reduce graft-versus-host
syndrome {caused by donor
immunocytes in marrow graft}
- cyclosporine or anti-T
cell antisera may be
helpful in altering or
preventing
graft-versus-host
syndrome
return to menu I--return
to menu II
return to menu I--return
to menu II
Autoimmune
disorders
return to menu I--return
to menu II
- Mechanism
of drug action:
- probably immunosuppressive
properties
- anti-inflammatory effects
contribute
- Effective drugs include:
- prednisone
- cyclosporine
- cyclophosphamide
- mercaptopurine
- antilymphocyte globulin
return to menu I--return
to menu II
Summary of Clinical Immunosuppressive
Agent Use (adapted
from: Table 56-1,
Barbuto, J.A.M, Akporiaye, E.T. and Hersh, E.M.
Immunopharmacology, in Basic and
Clinical Pharmacology,
(Katzung, B. G., ed) Appleton-Lange, 1998, p. 931)
| Autoimmune
disease |
Immunosuppressive
Agents |
| Idiopathic
thrombocytopenic purpura |
prednisone*, vincristine,
mercaptopurine, azathioprine, high-dose gamma globulin, plasma
immune absorption |
| Autoimmune
hemolytic anemia |
prednisone*, cyclophosphamide,
chlorambucil, mercaptopurine, azathioprine, high-dose gamma
globulin |
| Acute
glomerulonephritis |
prednisone*,mercaptopurine, cyclophosphamide |
| Acquired
factor XIII antibodies |
cyclophosphamide
plus factor XIII |
| Miscellaneous
"autoreactive" disorders {systemic
lupus erythematosus, rheumatoid arthritis,
Wegener's gramulomatosis, chronic active
hepatitis, lipoid nephrosis, inflammatory bowel
disease} |
prednisone, cyclophosphamide,
azathioprine, cyclosporine |
| Isoimmune
Disease |
|
| Hemolytic
anemia of the newborn |
RHo(D)
immune globulin* |
| Organ
transplantation |
|
| Renal/Heart |
cyclosporine, azathioprine,
prednisone, antilymphocyte globulin
(ALG), OKT3 monoclonal antibody, tacrolimus |
| Liver |
cyclosporine, prednisone,
azathioprine, tacrolimus |
| Bone
marrow (HLA-matched) |
cyclosporine, cyclophosphamide,
prednisone, methotrexate,
antilymphocyte globulin (ALG), total body
irradiation, donor marrow purging with monoclonal
anti-T cell antibodies, immunotoxins |
*-Drug/treatment
of choice
Immunomodulating
Drugs
return to menu I--return
to menu II
return to menu I--return
to menu II
- Levamisole:
- enhances immune response:
- increases size of
delayed hypersensitivity
reactions /T-cell-mediated
immunity
- FDA approval: in
combination with flurouracil in
treating postsurgical Dukes class
C colorectal cancer
- reduces
recurrences-probable
mechanism:
return to menu I--return
to menu II
- Roquinimex -- investigational
- increases NK cell
number/reactivity
- stimulates T and B cells
- may stimulate immune
function (post-bone marrow transplants)
return to menu I--return
to menu II
- BCG (Bacille
Calmette-Guerin)
- Mycobacterium bovis-viable
strain; immunization against tuberculosis
- has been used:
- nonspecific
adjuvant
- immunostiumulant
in cancer
- Proposed Mechanism:
macrophage activation
return to menu I--return
to menu II
- Other Immune modulators-investigational
- Inosiplex, cyanoaziridine
agents (azimexon, ciamexon, imexon
- diethyl dithiocarbamate --
may slow HIV progression
- low-dose cyclophosphamide
administered before immunization with
tumor vaccine may increase immune
response
- indomethacin: reduced
suppressor macrophage effects
- cimetadine (and other H2
blockers) reduce suppressor lymphocyte
activity
return to menu I--return
to menu II
|
