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pharmacology > Immunopharmacology > Flashcards

Immunopharmacology Flashcards

1
Q

define immunopharmacology

A

Immunopharmacology is a vast and complex area of pharmacology that focuses on
primary and secondary disorders of the immune system and the production of modulators of the immune system. It involves the production of vaccines and immunization, the treatment of inflammation, autoimmune diseases, allergies, fungal,viral and bacterial infections, infections due to parasites, and cancer

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2
Q

what do immunosuppressants inhibit?

A

inhibit normal immune response following organ transplantation or over reactive immune response associated with autoimmune disorders
-work best for primary immune response

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3
Q

immunosuppression following organ transplants

A
  • Acute rejection is defined as rejection that occurs 24 hours to several weeks following organ transplantation; it is mediated mainly by T cels and cytokine
  • decrease the amount of lymphocytes, divert lymphocyte traffic, or block pathways involved in lymphocytic response.
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4
Q

types of immunosuppressants

A
  1. ) steroids
  2. ) alkylating agents
  3. ) inhibitors of de novo purine synthesis
  4. ) inhibitors of de novo pyrimidine synthesis
  5. ) kinases and phosphatases inhibitors
  6. ) protein immunosuppressive drugs
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5
Q

corticosteroids

A
  • used for induction and maintenance of immunosuppression
  • reduce levels of circulating lymphocytes
  • block lymphocytes activation
  • block T cell lymphocyte proliferation-> inhibit IL-2 transcription
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6
Q

what never combine with steroids?

A

NSAIDs

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7
Q

what drugs to use for organ transplanation

A

steroids

cytotoxic drugs

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8
Q

why be cautious with steroids?

A

serious problem with long term utilization

-increases risk of infection, ulcers, hypoglycemia

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9
Q

cytotoxic drugs

A

azathioprine, cyclophosphamide, methotrexate

  • purine antimetabolite-> interferes with DNA synthesis
  • prevents clonal expansion of B and T cells
  • induction of maintenance of immunosuppression
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10
Q

cytotoxicity of cytotoxic drugs

A

leukopenia, thrombocytopenia, GI and liver dysfunction

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11
Q

alkylating agent

A

cyclophosphamide

-interferes with DNA synthesis

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12
Q

inhibitors of de novo synthesis

A

-inhibit inosine 5’-monophosphate dehydrongenase inhibitor
azathioprine, 6-mercaptopurine
2nd: mizoribine and mycophenolate mofetil (MMF)
methotrexate, polygentamate derivatives

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13
Q

MMF works by

A
  • inosine 5’-monophosphate dehydrogenase inhibitor
  • ester prodrug that is hydrolyzed to active drug
  • lacks cardiovascular side effects and chronic nephrotoxic syndrome
  • side effects: GI disorders, (N&V, diarrhea, ulcers, esophagitis) and bone marrow suppression
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14
Q

induction of maintenance immunosuppression drugs

A 
alkylating agents
steroids
inhibitors of de novo purine synthesis 
cyclosporine
tacrolimus 
kinases and phosphatases
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15
Q

inhibitors of de novo pyrimidine synthesis

A
  • inhibit dihydroorotate dehydrongenase
  • organ transplant medicine, usually in combination with steroids and tracrolimus
  • brequinar, leflunomide, malononitrilamides
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16
Q

kinase and phosphatase inhibitors

A

cyclosporine and tacrolimus

-organ transplants

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17
Q

cyclosporine

A

give IV or Per os

  • concentrates in red/white blood cells
  • metabolized by liver
  • excreted in feces
  • give 4-24 hours prior to organ transplant and continued for weeks
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18
Q

toxicity of cyclosporine

A

renal, gingival, neuronal, hepatic, systemic hypertension

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19
Q

cyclosporine MOA

A

associates with calcineurin

  • inhibits its phosphatase activity-> prevents translocation of members of nuclear factor of activated T (NFAT) from cytoplasm to nucleus of activated T cells
  • also blocks JNK and p38 signaling pathways that are induced by antigen recognition in T cells
20
Q

Tacrolimus

A

macrolide antibiotic

  • binds cytoplasmic protein FK506-binding protein 12-> inhibits phosphatase activity of calcineurin
  • also inhibits JNK and p38 pathways
21
Q

tacrolimus related to cyclosporine

A

metabolized by liver

  • given to patients that don’t respond to cyclosporine
  • not as widely distributed
  • same toxicity as cyclosporine
22
Q

sirolimus

A

-inhibits calcineurin
-binds cytoplasmic protein FK506-binding protein 12
used with cyclosporine, or other immunospuppressants

23
Q

protein immunosuppressants

A

antilymphocyte globulins: daclizumab, basilix-imab)

-inhibit acute graft rejection by binding to lymphocyte surface proteins

24
Q

protein immunosuppressants : rejection

A

Muromonab-> against CD3 that binds T cell receptor associated CD3 complex and alters T cells
-also used as induction of immunosuppression

25
Q

Belatcept

A

kidney transplant

  • inhibit calcineurin-> inhibits CS28 T cell co-stimulation
  • prevents T cell activation
26
Q

adverse affects of belatcept

A

anemia, neutropenia, UTI, headaches, peripheral edema

27
Q

other drugs to treat acute transplant rejection

A

rapamycin

  • macrocyclic lactone
  • antiproliferative effect on T cell proliferation
28
Q

what are the primary drugs to treat autoimmune disorders?

A

corticosteroids

29
Q

why should long term use of steroids to treatment of AD be avoided?

A

increased risk of infections, ulcers, hyperglycemia, osteoporosis

30
Q

what can be added if steroids aren’t enough for AD treatment

A

cyclophosphamide, azathioprine

31
Q

cyclophosphamide as a immunosuppressant for AD

A

interferes with DNA synthesis and function by alkylation

-affects B cells more than T

32
Q

azathioprine as a immunosuppressant for AD

A

purine anti-metabolite interferes with DNA synthesis

-affects rapidly growing cells such as those in bone marrow and GI tract

33
Q

as a immunosuppressant for AD: mercaptopurine

A
  • interferes with RNA/DNA synthesis after conversion into purine antagonist inside cells
  • active assessment of BM, liver and pancreatic diseases
34
Q

as a immunosuppressant for AD: leflunomide

A

prodrug
inhibitor of pyrimidine synthesis
-RA

35
Q

importance and cyclosporine monitoring

A
  • saturates tissues
  • variability of absorption
  • caution with other drugs b/c of many interactions
  • feeding/dosing schedule
36
Q

treatment of allergies

A
  1. ) fatty acids for systemic treatment: omega 3 fatty acids promote anti-inflammatory components
  2. ) Biotin: dry itchy skin
  3. ) antihistamines: H1 blockers (diphenhydramine, promethazine, chlorpheniramine)
37
Q

when would immunotherapy be used to treat allergies?

A

symptoms present for 4-6 months

-weekly/monthly injections

38
Q

when would corticosteroids be used to treat allergies?

A

severe symptoms that nothing else has worked for

-betamethasone, dexamethsasone, triamcinolone, methylprednisolone

39
Q

natural adjuvants: echinacea

A

stimulation of phagocytosis

-production of interferons as well as TNF

40
Q

natural adjuvants: acemannan or Aloeride

A
  • gel of aloe plant

- induces macrophage activity and production of IL-1

41
Q

natural adjuvants: beta-1,3 glycan

A

specific for beta-1,3 glycan receptor on macrophages leading to nonspecific destruction of pathogens

  • induces release of cytokines-> initiates immune cascade and triggers other cell lines, such as T-cells
  • stimulates bone marrow production
  • help people with: retroviral infections, tumors, chemo, atherosclerosis, weakened immune system and AIDS
42
Q

natural adjuvants: QS-21

A

adjuvant for vaccine specific antibody response and T cell response in presence of very low dose antigen

  • amplifies T and B cell mediated immune responses
  • complex of purified saponin
  • can give site pain of vaccine and myalgias
43
Q

natural adjuvants: detoxified Freund’s adjuvant

A

monophosphoryl lipid A + mycobacterial cell wall skeleton in an oil emuslion
-being tested

44
Q

what does immune globulin treatment do

A

prevention of virus penetration into cells
-low titers of antibodies to wide range of human viruses
used for: hep A, parvovirus, enterovirus infections
-hyperimmune globulin used for high titers of antibodies

45
Q

cytokines

A

IL-2 and interferon alpha

pharmacology (14 decks)

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