Hubli Call Girls 👙 6297143586 👙 Genuine WhatsApp Number for Real Meet
Immunomodulators.ppt
1.
2. Immunomodulators are medications used to help,
regulate or normalize the immune system
Immunomodulators or biological-response modifiers
include both immunostimulatory and
immunosuppressive agents
10. Lympholytic property- Glucocorticoids size
& lymphoid content of the LN & spleen
Interfere with the cell cycle of activated
lymphoid cells (CMI is more affected than
humoral immunity)
Use: Immunosuppressant & anti-
inflammatory agent majority of conditions
11. It is a peptide antibiotic - act at an early stage
in the antigen receptor induced differentiation
ofT-cells & blocks their activation
It selectively suppress CMI
It is free of toxic effects on bone marrow & RE
system
12.
13. May be given IV or PO; bioavailability is low
Metabolized in the liver by CYP3A4 & excreted
in bile
Plasma t1/2 is biphasic 4-6 hr & 12-18 hr
Interactions:All nephrotoxic drugs enhance the
toxicity
Failure of immunosuppression with inducers
Hyperkalemia with potassium supplements
14. Standard drug for the transplantation of
kidney, pancreas, liver, & cardiac
transplantation
Cyclosporine+ methotrexate- prophylactic
regimen in prevention of GVHD after
allogeneic stem cell transplantation
17. Macrolide antibiotic produced by Streptomyces
tsukubaensis
On a weight basis it is 10-100 times more
potent than cyclosporine in inhibiting immune
responses
It has same M.O.A instead of cyclophilin it
binds to FKBP-12 inhibit calcineurin
18. It is valuable in liver transplantation because
its absorption is not dependent on bile
It is considered as standard prophylactic
agent ( with mtx or MMF ) in GVHD
It is also suitable for suppressing acute
rejection that has set in
19. Rejection type Hyperacute Acute Chronic
Mechanism Preformed recipient
antibodies react with
donor antigen &
activate complement
Cellular- Donor
antigen activates
recipientT cells
Humoral: Recipient
generates antibody
response to donor
antigen
Both humoral &
cellular in nature--
Chronic inflammation
caused by the
response of activated
T cells to donor
Antigen)
Time course Minutes to hours Weeks to months Months to years
Mode of damage Antibody-
dependent, cell-
mediated
cytotoxicity or
through activation of
the complement
cascade
CytotoxicT cell
mediated interstitial
& vascular damage
H- Antibody
directed against
endothelial cells
(Acute vascular
rejection)
ActivatedT cells
release cytokines i.e.
recruit macrophages
into the graft (chronic
inflammation i.e.
leads to intimal
proliferation of the
vasculature & scarring
of the graft tissue).
How suppressed Matching donor &
recipient blood types
Immunosuppression Cannot be suppressed
(Major cause of graft
loss)
21. GVHD is a major complication of allogeneic
bone marrow or stem cell transplantation
Occurs when transplanted immune cells attack
the cells of the recipient.
GVHD ranges from mild to life-threatening
Ameliorated by removingT cells from the donor
bone marrow before transplantation
22. Other uses: FistulatingCrohn’s disease,
Topically:Atopic dermatitis & Psoriasis
Hypertension, hirsutism, gum hyperplasia &
hyperuricemia are less marked than CSA
Tacrolimus is more likely to precipitate
diabetes, cause neurotoxicity, alopecia &
diarrhea. Dose-limiting toxicity is renal
23. Sirolimus binds the circulating immunophilin
FK506-binding protein 12 → an active
complex i.e. inhibits the kinase activity of
mTOR (mammalian target of rapamycin)
Blockade of mTOR – inhibition of interleukin
drivenT-cell proliferation
t1/2 of sirolimus is- 60 hrs & i.e. of everolimus
is 43 hrs
24. To prevent rejection of solid organ allografts
Prophylaxis & as therapy for steroid-refractory
acute & chronic GVHD in hematopoietic stem
cell transplant recipients
Sirolimus eluting coronary stents
Topically –in dermatological disorders & in
combination with cyclosporine in uveoretinitis
25. Prophylaxis of liver & kidney transplant
rejection
Others: Cardiac stents
Advanced renal cell cancer, hormone receptor-
positive Her-2 negative advanced breast cancer
Pancreatic neuroendocrine tumours
26. Myelosuppression (esp. thrombocytopenia)
Hepatotoxicity, diarrhea, headache,
hypertriglyceridemia & pneumonitis
↑ use in stem cell transplantation regimens
with tacrolimus has revealed an ↑ incidence
of HUS
27. Azathioprine : is a prodrug that is converted
first to 6-mercaptopurine (6-MP) & then to the
corresponding nucleotide, thioinosinic acid
They inhibit de novo purine synthesis & cause
damage to DNA
Cellular immunity as well as primary &
secondary serum antibody responses can be
blocked
28. Azathioprine is well absorbed PO & is
metabolized primarily 6-MP, XO splits much
of the active material to 6-thiouric acid
Much of the drug’s inactivation depends on
XO , patients who are also receiving
allopurinol for control of hyperuricemia
should have azathioprine dose-↓ ½ to 1/3
29. Uses: Maintaining renal allografts
Management of acute glomerulonephritis & in
the renal component of SLE
RA, Crohn’s disease & MS
Prednisone-resistant antibody-mediated ITP &
AIHA
A/E: BM suppression, skin rash, fever, nausea,
vomiting, diarrhoea & hepatic dysfunction
30. Inhibiting DHFRase & thymidylate synthase
It markedly depresses cytokine production &
cellular immunity & has anti-inflammatory
property
Uses: Autoimmune diseases like rapidly
progressive RA, MG, psoriasis, uveitis etc.
31. Semisynthetic derivative of mycophenolic
acid, isolated from - mold Penicillium glaucus
M.O.A: MPA, a selective, noncompetitive,
reversible inhibitor of inosine monophosphate
dehydrogenase (IMPDH) an important
enzyme in the de novo pathway of guanine
nucleotide synthesis
32. MMF undergoes rapid & complete metabolism
to MPA after PO or IV administration
The t1/2 of MPA is ~16 hours
Uses: For prophylaxis of transplant rejection, in
combination with glucocorticoids & a
calcineurin inhibitor
Prophylaxis & Rx of both acute & chronic GVHD
in hematopoietic stem cell transplant patients
33. Prevention of chronic allograft vasculopathy in
cardiac transplant recipients
New applications: Lupus nephritis, RA, IBD, &
some dermatological disorders
A/E: GI disturbances, headache, hypertension
Reversible myelosuppression (Neutropenia)
Predisposition for infections, esp.CMV
34. Leflunomide: It is a prodrug of teriflunomide
Dihydroorotate dehydrogenase
35. It inhibitsTNF-α, reduces phagocytosis by
neutrophils, ↑ production of IL-10, alters
adhesion molecule expression & ↑ CMI
Uses: Multiple myeloma- at initial diagnosis or
relapsed-refractory disease with dexamethasone
GVHD, ENL, Skin manifestations of SLE
36. A/E: Peripheral neuropathy, constipation, rash,
fatigue, hypothyroidism, & ↑ risk of DVT
Immunomodulatory derivatives of thalidomide
(IMiD’s):
Lenalidomide- MDS with 5q deletion, primary
and relapse/refractory myeloma
Pomalidomide- Relapse or refractory MM
37. Polyclonal: IGIV, Rho(D) Immune globulin
micro-dose, hyperimmune immunoglobulins
Monoclonal antibodies:
Muromonab-CD3: It is murine MAB against CD
3 glycoprotein expressed near to theTCR on
helperT cells
It obstructs approach of the MHCII-antigen
complex to theT-cell receptor
38. Acute renal allograft rejection & steroid
resistant acute cardiac & hepatic transplant
rejection
A/E: Initial doses are associated with cytokine
release syndrome with flu like symptoms
Occasionally aseptic meningitis, intragraft
thrombosis, pulmonary edema, seizures &
shock like state is produced
Rx- High dose corticosteroid pretreatment