-
IMMUNOSUPPRESSANTS
-These are drugs that suppress the immune
response.
-Their main therapeutic application is in
autoimmune diseases and organ
transplantation.
CLASSIFICATION
1.Calcineurin inhibitors: Cyclosporine ,Tacrolimus
2.Antiproliferative and cytotoxin agents :
Azathioprine,
methotrexate ,cyclophosphamide
3. mTOR(mammalian target of
rapamycin )inhibitors:Sirolimus
4.Glucocorticoids : Prednisolone
,methylprednisolone
5.Biologics :
(a)TNF-a inhibitors: Etanercept ,lnfliximab
(b)CL- I inhibitors: Anakinra
(c)Antibodies: Muromonab-CD3 , anti-thymocytes and
anti-ly111phocyte antibodies
MECHANISM OF ACTION
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1.CALCINEURIN INHIBITORS
-Cyc/osporine: Very lipophilic and essentially not soluble
in water
administered orally , i.v. and i.v. infusion
Mechanism of action :
enters in target cells
l
binds to cyclophilin
l
cyclosporine - cyclophili n complex
!
inhibit calcineurin and blocks activation of T cells and decresed
production of IL-2 and other cytokines
1.CALCINEURIN INHIBITORS
Uses:
-prevent and treat rejection episod ~UMAN
oRGAH
organ transplantation
like kidney.bone marrow.liver et.o --,;
L-treat autoimmune diseases
like myasthenia gravis, rheumatoid arthritis etc.
1.CALCINEURIN INHIBITORS
Adverse effects:
-Nephrotoxicity
-Hepatotoxicity
-Hypertrophy of Gums
-Hypertension
-Hyperglycemia
-Hyperlipidemia
-Increased susceptibility to infections
-Bone marrow toxicity is minimal
Drug Interaction : I
-Cyclosporine >< Aminoglycoside/Amphotericin I
BNancomycin/ I
NSAIDS: Nephrotoxicity is enhanced
-Cyclosporine x Rifampicin/Phenobarbitone/Phenytoin:
The
blood level of Cyclosporine is reduced due to
induction of its
metabolism
-Cyclosporine x Erythromycin: The pl",,." .... ~';!H
Cyclosporine
is increased as its metabolism is ir
2. ANTI PROLIFERATIVE AGENTS
-Azathioprine: -It is a purine antimetabolite
-Incorporation of false nucleotide
Mechanism of action : Taken up into the immune cells
l
Activated to 6-MP
l
Inhibits purine synthesis
l
lnhibi1ion of cell Proliferation and impairment of lymphocyte funlion
Uses :
-Used in combination with glucocorticoids or
cyclosporine for
prevention of rejection episodes in organ
transplantation
-Used in rheumatoid artt .. · - · · ·· !ase etc
Adverse effects :
-Hepatotoxicity
-Bone marrow suppresion
-Gastrointestinal side effects
3. mTOR Inhibitors
S,irollimus : It inhibits]T-ceH activlation and Proliferation.
-Mechanis1
1
m of ,action1:
ith an immunophilin
It forms comp lex w1 1
!
Inhibits a key·enzyme :in cell cyc:le p,rogressio:n
1
!
l'nhibits the response of interleuk.in-2
!,
That blocks activation ofT-cells and B-.cells
Uses : -To treat and prevent graph rejection reaction
Adverse effects :-MyelosupprE
-Headache
-Hepatotoxi
-Hypokalerr
-Risk of infe ..... u ,
I
-Thrombocytopenia
4.GLUCOCORTICOI DS
Prednisoloine : !Induce redistribution of lymphocyte·s that
decrease in
peripheral1blood, lymphocyte count.
Mechanism of a.c t1
i o1
n:
Inhibit proliferation 0f T~lymphocytes
1
!
Decrease expressio·n of interleukines
!
B,.l.ocks the activatio·n of r-.ce11s an.,d B,-c.ells
Uses : -~o prevent ,and treat rej ection episodes during
1
1
0rgan
1
tra nspll.antation.
1
-Autoimmu1ne diseases.
Adverse 8'f fects : -Osteoporo,sis
1
-Hyperglycemi;a
...Risk of Infection
-Po0r wound hrealing
1
-A vascul·ar necrosis of bone
ten,s.ion1
1
5. BIOLOGICS
lnfliximab : -It is a Chimeric antibody
(25% mouse derived, 75% human protein)
Mechanism of action :
It forms a relatively stable complex
l
Binds to soluble and membrane bound TNF
i
That blocks activation of T-lymphocytes
Uses : -Rheumatoid arthritis
-Crohn's Disease
Adverse Effects : -Infusion reactions like
fever,urticaria,hypoten
dysponea
-Opportunistic infection like
TB , urinart tract infection
