Immunology Drugs

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Author:
SOMnerd2014
ID:
55759
Filename:
Immunology Drugs
Updated:
2010-12-15 20:41:49
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Immunology Drugs
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Immunology Drugs
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  1. Glucocorticoids
    • ↑ IκB expression, ↓ NFκB in immune cells = ↑ apoptosis of activated immune cells
    • ↓ synthesis and release of proinflammatory cytokines (TNF-α, IL-1, IL-6,)
    • Neutrophils and monocytes show ↓ chemotaxis, ↓ enzyme release
    • ↓ T-cell production of IL-2 = ↓ T-cell proliferation
    • Activation of CTLs inhibited
  2. Antithymocyte globulin (ATG) & Antilymphocyte globulin (ALG)
    • Animal immunized with T-cells
    • Serum transfer containing anti-MHCs and anti-CDs
    • Bind circulating lymphocytes cause cytotoxicity
  3. Muromonab-CD3 (OKT-3)
    • Kidney Transplantation
    • Monoclonal Ab against CD3
    • Causes internalization of TCR, ↑ apoptosis
    • T-cell death due to complement activation
    • Margination and redistribution to nonlymphoid organs
    • T-cells disappear from circulation in mins, returning ~1 wk after cessation of OKT-3
  4. Daclizumab & Basiliximab
    • (Anti-CD25, Anti-IL-2R)
    • Abs to the α-subunit of IL-2 receptor of activated T-cells
    • Blocks IL-2 stimulation and increases apoptosis of activated T-cells
    • Low toxicity; without cytokine release, anaphylaxis still possible
    • Used in prophylactic combination (e.g., with CsA, glucocorticoids) to prevent acute renal rejection
  5. Cyclosporine (Cyclosporin A, CsA)
    • CsA enters cell and binds to cyclophilin (CyP)
    • CsA-CyP complex binds to calcineurin (PP2B), inhibiting its ability to dephosphorylate NF-ATc
    • NF-ATc is prevented from entering the nucleus, the transcriptional cascade required for T-cell activation doesn't occur
    • CsA inhibits signal transduction, and blocks transcription of genes, including IL-2, required for T-cell activation & clonal expansion
    • Metabolized by CYP3A4 (P-450) = drug interaction
  6. Tacrolimus (FK506)
    • Tacrolimus (FK506) enters the cell and binds to FKBP12 (FK binding protein 12)
    • FK506-FKBP12 complex binds to and inhibits the phosphatase activity of calcineurin (PP2B)
    • Inhibits signal transduction, and blocks transcription of genes, including IL-2, required for T-cell activation & clonal expansion
    • Metabolized by CYP3A4 (P-450) = drug interaction
  7. Sirolimus (Rapamycin)
    • Kidney Transplantation
    • Sirolimus binds to FKBP12 and the complex binds mTOR
    • Inhibition of CdK2, arresting cells at the G1→ S transition
    • Metabolized by CYP3A4 (P-450) = drug interaction
  8. Mycophenolate mofetil
    • Prodrug: hydrolyzed by mycophenolic acid (MPA)
    • MPA is a reversible inhibitor of inosine monophosphate dehydrogenase, in the de novo pathway of purine (GMP) synthesis
    • B and T lymphocytes are highly dependent upon de novo purine synthesis and are selectively inhibited
  9. Azathioprine
    • Kidney Transplantation
    • Prodrug cleaved to 6-mercaptopurine (6-MP), which inhibits de novo purine synthesis 6-MP is phosphorylated via the salvage pathway and incorporated into DNA disrupting replication, transcription, function
    • Metabolized by oxidation (xanthine oxidase) or methylation (thiopurine methyltransferase) in the liver before urinary elimination
  10. Infliximab & Adalimumab
    • Monoclonal Abs
    • TNF-α inhibitors
    • Decrease IL-1 and IL-6
  11. Entanercept
    • Human TNF-α receptor-IgG fusion protein
    • Neutralizes TNF-α in the blood and tissues.
  12. Antibody Drugs
    • ATG
    • ALG
    • Muromonab-CD3 (OKT-3)
    • Daclizumab & Basiliximab
    • Infliximab & Adalimumab
  13. TNF-α Inhibitors
    • Infliximab & Adalimumab
    • Etanercept
  14. Calcineurin Inhibitors
    • Cyclosporine (CsA)
    • Tacrolimus (Fk506)
  15. Antimetabolites
    • Mycophenolate mofetil
    • Azathiopine
  16. Glucocorticoid Toxicities
    • Supression of pituitary:adrenal axis leads to increased infection and malignancy
    • Growth retardation and poor would healing
    • Hypertension
    • Osteopenia
  17. ATG & ALG Toxicities
    • Serum Sickness
    • Anti-animal antibodies
  18. Muromonab-CD3 (OKT-3) Toxicities
    • Cytokine release syndrome
    • Hypersensitivity reaction
  19. Daclizumab Toxicities
    Low toxiciity
  20. Cyclosporine Toxicities
    • Nephrotoxicity
    • Gum hyperplasia
    • Predisposes patients to viral infection
  21. Tacrolimus Toxicities
    • Nephrotoxicity
    • Peripheral neuropathy
    • Hypertension
    • Plueral Effusion
    • Hyperglycemia (combination with glucocorticoids can lead to diabetes)
  22. Sirolimus (Rapamycin) Toxicities
    • Hyperlipidemia
    • Myelosupression (thrombocytopenia)
    • Leukopenia
    • Delayed wound healing
  23. Mycophenolate Toxicities
    • Leukopenia
    • Diarrhea
    • Vomiting
  24. Azathioprine Toxicities
    • Bone marrow supression
    • Hepatotoxicity
    • Toxic effects increased with allopurinol
  25. Chlorpheniramine & diphenhydramine (Benadryl)
    • 1st generation antihistamines
    • Vasoconstricts
    • Decrease vascular permeability
    • Short duration
    • Anti-nausea / anti-motion sickness
    • Causes Sedation
  26. Loratadine, fexofenadine, citrizine (Claratin, etc.)
    • 2nd and 3rd generation antihistamines
    • long duration
    • not anti-nausea
    • causes less sedation
  27. Sumatriptan
    • Serotinin agonist
    • Vasoconstrictor
    • Used for migrane headaches
  28. Misoprostol
    • PG16 analog
    • Oral treatment for gastric ulcers
  29. Glucocorticoids
    • end in "one"
    • inhibit arachadonic acid pathway
  30. Zileuton
    • Inhibits 5-lipoxygenase in leukotriene pathway
    • Used for asthma
  31. Zafirlukast
    • Leukotriene receptor agonist
    • Used for asthma

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