Anti-Inflammatory & Immunosuppressive Drugs 2 - PowerPoint PPT Presentation

Loading...

PPT – Anti-Inflammatory & Immunosuppressive Drugs 2 PowerPoint presentation | free to download - id: 3bf7ec-MGQzZ



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Anti-Inflammatory & Immunosuppressive Drugs 2

Description:

Anti-Inflammatory & Immunosuppressive Drugs 2 I-3 Fall 2011 Susan Masters, Ph.D. * * * * * * * 5-phosphoryibosyl-1-pyrophosphate (PRPP), xanthosine monophosphate; IMP ... – PowerPoint PPT presentation

Number of Views:99
Avg rating:3.0/5.0
Slides: 21
Provided by: physioUcs
Learn more at: http://physio.ucsf.edu
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Anti-Inflammatory & Immunosuppressive Drugs 2


1
Anti-Inflammatory Immunosuppressive Drugs 2
  • I-3 Fall 2011
  • Susan Masters, Ph.D.

2
The Inflammatory Cascade
Immunophilin ligands, mycophenolate
mofetil, DMARDs, anti-TNF, etc.
Perceived threat
Infection
Tissue injury
Adaptive immune system
Innate immune system
Anti-gout drugs
Leukocyte endothelial cell activation
Inflammatory mediators
Inflammation (redness, edema, warmth, pain,
tissue destruction)
3
Immunophilin Ligands
Cyclosporine
Tacrolimus
Sirolimus
4
Immune Cell Activation
Immunophilin ligands
5
Immunophilin Ligands Inhibit T-Cell Activation or
Proliferation
6
Immune Cell Activation
Mycophenolate mofetil, leflunomide, cytotoxic
drugs
7
A Theoretical Framework for Other
Immunosuppressants
8
Blocking Rapid Cell Division
9
A Big Advantage of Multiple Agents
isNon-Overlapping Toxicity
All these drugs increase the risk of infection
and lymphoma
10
Clinical Use of Immunosuppressants in
Transplantation
11
New Kids on the Block Biologic Products
Challenges
  • Pharmacokinetics
  • Parenteral
  • Cost (for long haul)
  • Long-term toxicity

12
Drugs for Gout
Acute Treatment (Anti-inflammatory)
NSAIDS (indomethacin) corticosteroids
Chronic Treatment (Decrease serum urate,
anti-inflammatory)
Low-dose colchicine, allopurinol, uricosuric drugs
13
Colchicine Inhibits Microtubule Assembly
Tubulin dimer
Activated macrophage
Sirolimus
Microtubule
Autumn Crocus
Tubulin dimer bound to colchicine
Toxicity
Diarrhea Extraordinarily toxic in OD
14
Manipulating Serum Uric Acid Levels
(Allopurinol, febuxostat)
15
Allopurinol Inhibits Uric Acid Production
Xanthine oxidase
Xanthine oxidase
Hypoxanthine
Xanthine
Uric acid
Reversible
Irreversible
Xanthine oxidase
Allopurinol
Alloxanthine
Febuxostat
Toxicity Acute gout, rash, hematologic
reactions, drug interactions
16
Uricosuric Drugs Inhibit Renal Reabsorption of
Uric Acid
UA
90 of uric acid filtered at the glomerulus is
reabsorbed in the proximal tubule
UA
UA
UA
UA
UA
UA
UA
UA
Probenecid
Toxicity Acute gout, allergic rxtn
UA
17
Summary
  • The immunosuppressants that are used to prevent
    transplant rejection and to treat autoimmune
    disorders inhibit T-cell function and
    proliferation
  • Newer biologic products, including ant-TNF drugs,
    are very selective in their action
  • Treatment of acute gout is with anti-inflammatory
    drugs prevention of more attacks is with
    colchicine and/or decreasing production of uric
    acid (allopurinol) or increasing uric acid
    excretion (probenecid)

18
Other Disease Modifying Antirheumatic Drugs
(DMARDS)
19
Mycophenolate Prevents GMP Synthesisin
Lymphocytes
DNA
GTP
IMP dehydrogenase
GMP
Inosine monophosphate (IMP)
Mycophenolic acid
De novo pathway of purine synthesis

PRPP
Guanine
GMP
Salvage pathway of purine synthesis (lacking in
lymphocytes)
20
How Do They Compare?
Lancet 372(9636)375-82, Aug 2008 1 year of
therapy
About PowerShow.com