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Dr. Waqas Nawaz
PMAS arid agriculture university rawalpindi

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  1. 1. SUBMITTED BY: 10-arid-850 10-arid-871 10-arid-881 11-arid-959 SUBMITTED TO: 11-arid-961 11-arid-962 11-arid-963 11-arid-964 11-arid-966 11-arid-967 11-arid-968 11-arid-969 Dr.Saif ur Rehman 11-arid-971 11-arid-972 11-arid-973 11-arid-975
  2. 2. Natural Man MadeInterferons Interferons (Recombinant)
  3. 3.  Interferons play an important role in the first line of defense against viral infections Interferons are part of the non-specific immune system Interferons are made by cells in response to an appropriate stimulus
  4. 4.  alpha (leukocyte interferon)  produced by virus infected leukocytes beta (fibroblast interferon)  produced by virus infected fibroblasts or epithelial cells gamma (immune interferon)  produced by certain activated T cells & NK cells
  5. 5. virus cells(Other stimuli:exogenous ds RNA,LPS, bacterialcomponents)
  6. 6. virus interferon
  7. 7. No replicationvirus Inhibitor y proteins
  8. 8.  IFN alpha and beta  induction of inhibitory protein synthesis IFN gamma  inc class II MHC molecules of APC  Inc ability of macrophages to resist viral infx and kill other cells if infected All IFN  inc class I MHC molecules  inc activity of NK cells
  9. 9.  block interferon binding to cells inhibit action of interferon-induced protein kinase inhibit NK function interfere with cell surface expression MHC block complement activation prevent apoptosis in host cell
  10. 10.  alpha  Hepatitis B & C, Hairy cell leukemia, Chronic myeloid leukemia, multiple myeloma, low grade lymphomas, Kaposi’s Sarcoma, Melanoma beta  Multiple Sclerosis, (Ulcerative colitis)
  11. 11.  gamma  Chronic granulomatous disease, Chronic Myeloid Leukemia, Renal cell Carcinoma
  12. 12.  Actimmune Alferon Avonex Betaserone Infergen Intron Wellferon, etc
  13. 13.  HCV is leading cause of liver disease 4 million Americans have been exposed  approx 3 million are infected HCV infection leads to decompensated cirrhosis and hepatocellular carcinoma HCV-related cirrhosis is the most common reason for OLT in the US NIH Consensus Development Conference Statement 2002
  14. 14.  Consensus Statement in 2002  treatment eligible patients  IVD users, consume alcohol, comorbidities (depression, HIV coinfections)  pegylated interferon with ribiviran better than peginterferon monotherapy or standard interferon- ribivarin
  15. 15.  Monotherapy  standard interferon 3 Million units inj tiw (Low Sustained virologic response) Combination therapy  standard interferon with ribivarin  pegylated interferon with ribivarin
  16. 16.  Limitations  monotherapy not very effective  cumbersome dosing (TIW)  multiple side effects
  17. 17. (Hepatitis C Data) Flu-like symptoms Headache Nausea, vomiting, diarrhea Depression, irritability, anxiety Injection site reactions, partial alopecia Hematologic abnormalities Autoimmune disorders
  18. 18.  Depression (77% Manns et al, Lancet 2001)  NIH consensus - “monitor patients for depression and prescribe antidepressants when necessary” Hematologic abnormalities  neutropenia and thrombocytopenia  treatment options include decreasing dose or giving hematopoietic growth factors
  19. 19.  HCV is an ideal setting for peginterferon  polyethylene glycol (PEG):interferon Pegylation was developed to overcome disadvantages of standard interferon  shields IFN from enzymatic degradation thus lowers systemic clearance  allows less frequent dosing  achieve higher/sustained serum [interferon]
  20. 20. 60% 56%50% 44%40% 29% monotherapy30% IFN+RBV20% Peg+RBV10%0% Pega2a IFN a2b+RBV Pega2aRBV P=<0.001
  21. 21.  peginterferon alfa-2b  linear molecule  weight 12 kDa peginterferon alfa-2a  larger, branched molecule  weight 40 kDa
  22. 22. Peg alfa-2b Peg alfa-2aVolume of 20 L 8LdistributionAbsorption half-life 4.6 50(h)Mean elimination 40 80half-life (h)
  23. 23.  Once weekly dosing alfa 2b  weight based dosing (1-1.5 mcg/kg/week)  high volume of distribution  kidney, heart, liver and throughout the bloodstream alfa 2a  fixed dose at 180 mcg/week  low volume of distribution
  24. 24.  Interferons are important in the nonspecific immune response Interferons are effective in the treatment of patients with chronic hepatitis Pegylated interferons are superior therapies for patients with HCV Side effects should be monitored closely