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PDA Block 2 > Immunopharmacology > Flashcards

Immunopharmacology Flashcards

1
Q

Steps in cell mediated cytotoxicity (6)

A
  1. Macrophage processing of antigen
  2. Presentation of antigen to T-lymphocyte
  3. Expression of IL-1 and IL-2 receptors on T-lymphocytes
  4. Secretion of IL-1 by macrophages
  5. IL-1 promotes IL-2 release from helper T-lymphocytes
  6. IL-2 acts on lymphocytes to promote replication of cytotoxic cells
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2
Q

Uses of Immunosuppression

A

Prevention of allograft rejection

Treatment of autoimmune diseases

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3
Q

Immunosupressant Drugs

  • Mechanisms
  • Uses
  • Side Effects
A
  • Mechanisms: block proliferation or interaction of immune cells or block actions or release of cytokines
  • Uses: treat autoimmune diseases and prevent allograft rejection
  • Side Effects: rapidly proliferating cells—bone marrow, liver or GI tract
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4
Q

Corticosteroids (Effect on immunity)

A

Reduce access of cells to target tissue

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5
Q

Prednisolone: Cell traffic or accumulation

A
  • Lymphocytopenia and monocytopenia - redistribution of cells out of vascular space
  • Prevent neutrophil adherence to endothelium
  • Inhibit action of chemotactic factors
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6
Q

Prednisolone: Cell Function

A
  • Interferes with macrophage antigen processing
  • Blocks the actions of lymphokines
  • Inhibits binding to Fc receptors
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7
Q

Prednisolone is used in combination with other drugs to treat ________ ________ and to prevent ______ _________

A

Autoimmune diseases; graft rejection

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8
Q

Prednisolone: Toxicity

A
  • Suppression of adrenal-pituitary axis. Acute adrenal insufficiency on abrupt withdrawal
  • Cushing’s syndrome
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9
Q

Prednisolone is contraindicated in the presence of ___________

A

Existing infection

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10
Q

Cytotoxic agents characteristics (4)

A
  1. These drugs kill rapidly proliferating immune cells
  2. Kill high percentage of precursor cells
  3. Relevant clone stimulated by antigen will be selectively killed
  4. Administered in low daily dosage to block immunoproliferation continually
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11
Q

Azathioprine

Metabolism:

Administration:

Function:

Uses:

Side Effects:

A

Metabolism: Metabolized to 6-mercaptopurine

Administration: Orally active

Function: Purine anti-metabolite that inhibits purine biosynthesis (both De Novo and Salvage pathways)

Uses: Inhibits rejction of transplanted organs and in some autoimmune diseases such as rheumatoid arthritis

Side Effects: Bone marrow depression; gastrointestinal and hepatic toxicity

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12
Q

Azathioprine mechanism of action

A
  • 6-Mercaptopurine is converted to Thioinosinic Acid which blocks the production of AMP and GMP from IMP
  • Thioinosinic Acid is further converted to ThioGMP which blocks synthesis of RNA and DNA by GMP
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13
Q

Cyclophosphamide

Administration:

Function:

Uses:

Side Effects:

Toxicity:

A

Administration: Orally active

Function: An alkylating agent that results in cross linking of DNA to kill replicating and non-replicating cells

Uses: Treatment of autoimmune diseases in combination with other drugs; not effective in preventing graft rejection

Side Effects: Bone marrow depression is major side effect

Toxicity: Toxic effect more pronounced on B cells (humoral immunity)

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14
Q

Methotrexate

Function:

Uses:

Toxicity:

A

Function: Inhibitor of dihydrofolate reductase - inhibits folate dependent steps in purine synthesis - inhibits DNA synthesis

Uses: Used to treat autoimmune diseases

Toxicity: Hepatic toxicity

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15
Q

Methotrexate mechanism of action

A

Conversion of dihydrofolate to its active form, tetrahydrofolate, is blocked by MTX inibition of enzyme dihydrofolate reductase (DHFR).

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16
Q

Mycophenolate Mofetil

Metabolism:

Administration:

Uses:

Function:

Side Effects:

A

Metabolism: Metabolized to active mycephenolic acid

Administration: Orally active

Uses: To treat autoimmune diseases - rheumatoid arthritis and refractory psoriasis

Function: Used w/ cyclosporine and corticosteroids to prevent renal allograft rejection (less toxicity)

Side Effects: Infection, leukopenia, anemia - should not be used with pregnancy (assoc. w/ pregnancy loss)

17
Q

Mycophenolate Mofetil mechanism of action

A

Lymphocyte selective immunosupressant

  • Inhibits IMP dehydrogenase: IMP →GMP (no effect on salvage pathway)
  • Lymphocytes cannot make GMP via salvage pathway
  • Inhibits lymphocyte proliferation and expression of cell surface molecules
  • More selective than azathioprine or methotrexate
18
Q

Cyclosporine

Classification:

Administration:

Uses:

Side Effects:

A

Classification: A lipophilic peptide antibiotic

Administration: Orally Active

Uses: To prevent rejection of transplanted organs. More effective than other agents used with fewer side effects - used for some autoimmune diseases

Side Effects: Nephrotoxicity is a major side effect (25-40% of patients with high doses) - Hepatotoxicity possible

19
Q

Cyclosporine Mechanism of Action

A
  • Binds to a cellular receptor and inhibits calcium dependent phosphatase - blocks activation of transcription factor (NFAT) necessary for IL-2 production
  • Inhibits mRNA synthesis that codes for lymphokines as IL-2
  • By blocking IL-2 synthesis, it blocks T-cell helper function so inhibits T-cell proliferation and cytotoxicity
  • Does not alter T-cell response to IL-2
  • Selective in its action
20
Q

Tacrolimus

Function:

Action:

Toxicity:

A

Function: Binds FK binding protein (FK BP-12), a cyclophilin-related protein. Same mechanism of action as cyclosporine

Action: Same as cyclosporine but 50-100 times more potent

Toxicity: Less nephro- and hepatotoxicity

21
Q

Cyclosporine and Tacrolimus Pathway

A
22
Q

Sirolimus

Function:

Action:

Uses:

A

Function: Inhibits T-cell activation and proliferation downstream of IL-2

Action: Binds FKBP-2 - complex does not bind calcineurin or affect calcineurin activity - binds and inhibits mTOR, a kinase involved in cell cycle progression - blocks G1 → S transition

Uses: Same as cyclosporine; coating of cardiac stents

23
Q

Sirolimus Pathway

A
24
Q

The Big Picture

A

PDA Block 2 (15 decks)

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