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2.  Antimetabolite
 Benificial in number of c/c inflammatory d/s
including crohns d/s, rheumatoid arthritis & in cancer
 Given orally, subcutaneously or I/M

3. DHFA
 Dihydro folate reductase
THFA
 This step is important in production of thymidine and
purine

4.  High doses, used in chemotherapy, inhibits cellular
proliferation.
 Low dose is used in treatment of IBD(12-25mg/wk).
 Interfere with inflammatory actions of interleukin-1.
 Stimulate increased release of adenosine, an
endogenous anti-inflammatory autocoid.
 Also stimulate apoptosis & death of activated T-
lymphocytes

5.  Induce & maintain remission in patients with crohns
d/s.
 Efficacy in ulcerative colitis is uncertain.
 To induce remission, 15-25mg given once weekly by
subcutaneous inj.
 If satisfactory response in 8-12wks, dose is reduced to
15mg/wk

6.  At high doses, cause BONE MARROW DEPRESSION,
MEGAIOBLASTIC ANAEMIA, ALOPACIA &
MUCOSITIS
 Folate supplimentation reduces risk of events without
impairing anti inflammatory effect.

7.  Dysregulation of TH1 response is present in IBD.
 Key proinflammatory cytokine in TH1 response is
TNF-alpha.
 INFLIXIMAB is a chimeric mouse
human monoclonal Ab to human TNF-
alpha
 Given I/v, therapeutic dose 5-10mg/kg & plasma
t1/2 is 8-10days

8.  TNF-alpha trimers bind to cell-surface TNF-alpha
receptors.
 INFLIXIMAB bind to soluble TNF-alpha trimers with
high affinity, preventing cytokine from binding to
receptors.
 It also bind to membrane bound TNF- alpha &
neutralises its activity.
 Also promote compliment activation & Ab-mediated
apoptosis & cellular cytotoxicity of activated T-
lymphocytes & macrophages.

9.  Used in a/c & c/c treatment of patients with moderate
to severe Crohns d/s & Ulcerative colitis.
 INFLIXIMAB induction therapy – dose 5mg/kg at 0, 2,
&6wks.
 In patients who respond can be treated with repeat
infusions every 8wks.
 Other anti-TNF agent approved are ADALIMUMAB &
CERTOLIZUMAB.

10.  Infection due to suppresion of TH1 inflammatory
response.
 Reactivation of latent TB, with dissemination.
 Other infections include pneumonia, sepsis,
pneumosistosis, histoplasmosis, listeriosis &
reactivation of hepatits B.
 May cause severe hepatic reactions leading to a/c
hepatic failure.
 May worsen CHF in cardiac disease.

11. o INTEGRINS are adhesion molecules on surface of
leucocytes that interact with another class of adhesion
molecules on the surface of vascular endothelium
known as SELECTIN, allowing circulating leucocytes
to adhere & subsequently move through the vessel wall
into the tissue.
o Integrins contain two subunits alpha & beta.
o NATALIZUMAB a humanized IgG4 monoclonal Ab
targeted against alpha-2 subunit.

12.  Used in patients with moderate to severe Crohns
disease.
 DOSE-300mg every 4 wks by I/V infusion & patient
should not be on any immunosuppressive treatment.
 ADVERSE EFFECTS- a/c infusion reactions & small
risk of oppurtunistic infections.