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MNI (immuno pharm) > L41- Immunopharmacology > Flashcards

L41- Immunopharmacology Flashcards

1
Q

list the immunosuppressive agents

A
  • glucocorticoids
  • calcineurin inhibitors
  • proliferation signal inhibitors
  • angiogenesis inhibitors
  • cytotoxic agents
  • other agents
  • immunosuppressive Antibodies
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2
Q

immunosupressive agents are used for the following clinical situations….

A

(dampen immune response)

  • organ transplantation
  • auto-immune disease
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3
Q

Glucocorticoids:

  • (1) general immune effects
  • (2) MOA in terms of immune system
A

1- anti-inflammatory, immunosuppressive effects

2:
-binds cytosolic glucocorticoid receptor
-receptor complex translocates to nucleus
-binds GREs (glucocorticoid response elements) in promoter region of genes
-down-regulation of many inflammatory mediators
+
-dec PG synthesis

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4
Q

______ is the preferred glucocorticoid for immunosuppression, explain

A

dexamethasone- long half-life, low mineralocorticoid effects

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5
Q

list the immune uses of glucocorticoids

A
  • prevent/treat transplant rejection
  • autoimmune disorders: RA, SLE, psoriasis, asthma, IBD
  • neuropathic and bone pain
  • palliative care: alleviate pain, nausea, fatigue
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6
Q

Glucocorticoids AEs:

  • (1) short term use AEs
  • (2) long term use AEs
A

1- HTN, hyperglycemia, immunosuppression, psychotic reactions, cognitive impairment

2- myopathy, Cushing’s syndrome, osteoporosis

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7
Q

Cyclosporin uses

A

(calcineurin inhibitor)

  • organ transplants
  • uveitis
  • RA
  • psoriasis
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8
Q

list the many AEs for Cyclosporin

A

(calcineurin inhibitor)

  • **nephrotoxicity (most common reason to stop drug –> RAAS activation + endothelin release)
  • tremor
  • HTN
  • hyperglycemia, hyperlipidemia
  • osteoporosis
  • hirsutism
  • gum hyperplasia

-CYP3A4 metabolism –> drug interactions

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9
Q

list the calcineurin inhibitors

A
  • cyclosporin

- tacrolimus

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10
Q

Calcineurin is a (1) type enzyme, which functions to activate (2) that is required for induction of (3).

A

1- phosphatase (dephosphorylation)

2- NFAT (T-cell specific transcription factor)

3- CK gene upregulation (IL-2 gene)

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11
Q

Cyclosporin MOA

A
  • forms complex with cyclophilin (an immunophilin)
  • complex inhibits calcineurin
  • prevents dephosphorylation of NFAT
  • no CK (IL-2) production
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12
Q

Tacrolimus uses

A

(calcineurin inhibitor)

  • transplant rejection: kidney, liver, heart
  • topical: psoriasis, atopic dermatitis
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13
Q

Tacrolimus AEs

A

(calcineurin inhibitor, less AE severity than cyclosporin)

  • nephrotoxicity, neurotoxicity
  • HTN, hyperkalemia, hyperglycemia
  • GI issues
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14
Q

Tacrolimus MOA

A

(calcineurin inhibitor)

  • forms complex with FKBP (FK-binding protein, an immunophilin)
  • complex inhibits calcineurin
  • prevents dephosphorylation of NFAT
  • no CK (IL-2) production
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15
Q

______ is the main proliferation signal inhibitor

A

Sirolimus

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16
Q

Sirolimus uses

A

(proliferation signal inhibitor)
-renal transplant

-Coronary Stents: sirolimus released –> inhibits restenosis of BV via reduction in cell proliferation

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17
Q

Sirolimus AEs

A

(proliferation signal inhibitor)

  • myelosuppression
  • hepatotoxicity
  • hypertriglyceridemia
  • pneumonitis
  • diarrhea
  • HA
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18
Q

Sirolimus MOA

A

(proliferation signal inhibitor- note it has similar structure to Tacrolimus a calcineurin inhibitor)

  • binds FKBP (FK binding protein, an immunophilin) [–> no calcineurin inhibitor]
  • inhibits serine-threonine kinase mTOR
  • blocks IL-2 driven T-cell proliferation
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19
Q

______ is the main angiogenesis inhibitor

A

Thalidomide

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20
Q

Thalidomide uses

A

(angiogenesis inhibitor)
erythema nodosum leprosum
multiple myeloma

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21
Q

Thalidomide MOA

A

(angiogenesis inhibitor)
mostly unclear:
-inhibits TNF-α synthesis
-inhibits angiogenesis

technically an immunomodulatory drug

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22
Q

list the Cytotoxic agents

A

antimetabolites:

  • azathioprine
  • methtrexate (MTX)
  • mycophenolate mofetil
  • leflunomide

alkylating agents:
-cyclophosphamide

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23
Q

Azathioprine:

  • (purine/pyrimidine) anti-metabolite
  • prodrug of (2) which functions to suppress (3)
A

1- purine

2- 6-MP (6-mercaptopurine)

3- B and T cell function, Ig production, IL-2 secretion

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24
Q

Azathioprine uses

A
  • organ transplant

- severe RA

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25
Q

Azathioprine:

  • (1) AEs
  • (2) drug interactions
A

1- BM suppression, GI issues, inc infections and malignancies

2- allopurinol –> give lower dose as inactivation requires xanthine oxidase

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26
Q

MTX uses

A
  • RA
  • psoriasis, psoriatic arthritis
  • ankylosing spondylitis
  • SLE
27
Q

MTX MOA

A

(low doses)
Rheumatic Diseases:
-inhibition of aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase
-AMP accumulation
-converted to adenosine extracellularly
-adenosine is potent inhibitor inflammation

28
Q

MTX AEs + contraindication

A
  • nausea, GI ulcerations
  • mucosal ulcers
  • leukopenia, anemia
  • hepatotoxicity, (rarely cirrhosis)
  • hypersensitivity pneumonitis

Contraindicated in pregnancy

29
Q

MTX toxicity can be reduced with co-administration of….

A
  • folic acid

- leucovorin

30
Q

Mycophenolate MOA

A
  • converted to mycophenolic aid
  • inhibits ionosine monophosphate dehydrogenase
  • dec Guanosine synthesis

-suppresses B, T cell activation – particularly susceptible to inhibition b/c lacking enzymes in salvage pathway

31
Q

Mycophenolate uses

A
  • prophylaxis transplant rejection

- SLE

32
Q

Mycophenolate AEs

A
  • n/v/d, abdominal pain
  • HTN, HA
  • reversible myelosuppression
33
Q

______ is the simple reason why anti-metabolites are effective as immunosuppressants

A

B/T-lymphocytes are particularly susceptible to inhibition b/c they lack the necessary enzymes for the salvage pathway

34
Q

Leflunomide MOA

A
  • prodrug of turiflunomide
  • turiflunomide inhibits dihyrdrooroate dehydrogenase
  • dec UMP levels
35
Q

Leflunomide uses

A
  • RA
  • SLE
  • myasthenia gravis
36
Q

Leflunomide AEs

A
  • diarrhea
  • rash, reversible alopecia
  • myelosuppression
  • inc aminotransferase activity
  • cardiogenic / teratogenic in animals
  • contraindicated in pregnancy
37
Q

Cyclophosphamide MOA (briefly / generally)

A
  • destroys proliferating lymphoid cells

- alkylates DNA / other molecules in resting cells

38
Q

Cyclophosphamide uses

A

SLE + others

39
Q

Cyclophosphamide AEs

A
  • infertility
  • BM suppression
  • hemorrhagic cystitis via acrolein
  • bladder cancer (rare) – general inc of infection and malignancy with long-term use
40
Q

list the ‘other’ agents of immunosuppression

A
  • hydroxychloroquine

- sulfasalazine

41
Q

Hydroxychloroquine MOA

A

unclear anti-inflammatory mechanism

42
Q

Hydroxychloroquine uses

A
  • RA (moderate effect, well-tolerated)
  • SLE

note- often in combination with MTX, sulfasalaxine and may require 3-6 mos to show clinical benefit

43
Q

Hydroxychloroquine AEs

A

(serious and rare)

  • hemolysis in G6PD deficiency
  • retinal damage (monitor vision)
44
Q

Sulfasalazine:

  • (1) structure
  • (2) metabolism allows for (3) function
A

Sulfasalazine = sulfapyridine + 5-aminosalicylic acid (5-ASA)

  • connected via diazo bond
  • Sulfasalazine is metabolized into moieties by bacteria in colon

Sulfapyridine —> RA Tx
5-ASA –> ulcerative colitis Tx

45
Q

Sulfasalazine uses

A
  • UC, CD
  • RA
  • ankylosing spondylitis
46
Q

Sulfasalazine AEs

A
  • n/v
  • HA
  • rash
  • neutropenia, hemolysis in G6PD def.

Rare: thyrombocytopenia, drug-induced lupus

47
Q

list the immunosuppressive POLYclonal Abs and their uses

A

ALG, ATG (antilymphocyte and antithymocyte globulin):

  • stem cell transplant
  • solid organ transplant

Rho(D) immune globulin: an IgG against Rho(D) Ag on RBCs
-prevents Rh hemolytic disease in newborns

48
Q

list the TNF-α inhibitor monoclonal antibodies

A
  • adalimumab
  • infliximab
  • etanercept
49
Q

list the ‘other’ immunosuppressuve monoclonal antibodies

A
  • omalizumab
  • basiliximab
  • rituximab
50
Q

list some of functions TNF-α signalling

A

-inc inflammation (macrophages)

  • inc cell infiltration (endothelium)
  • inc angiogenesis (endothelium)
  • inc CRP (hepatocytes)
  • cartilage degradation via MMPs (synoviocytes)
51
Q

match the Ab structure with the TNF-α monoclonal antibody:

  • (1) contains ligand-binding portion of human TNF-α receptor fused to Fc portion of human IgG
  • (2) chimeric monoclonal Ab
  • (3) fully human IgG1 anti-TNF monoclonal Ab
A

1- etanercept (not true mab)
2- infliximab
3- adalimumab

52
Q

list the uses for monoclonal anti-TNF antibodies

A

All:

  • RA
  • psoriatic arthritis
  • ankylosing spondylitis

Infliximab, Adalimumab:
-CD, UC

53
Q

monoclonal Anti-TNF antibodies:

  • screen for (1) before starting therapy
  • monitor for (2) during therapy
  • never give (3) to people on these Abs
  • most AEs result from (4) activity
A

1- Tb, HBV infections
2- CBC for cytopenias
3- live vaccinations + Pts w/ infections
4- TNF inhibition: inc infections, don’t give to infected Pts

54
Q

list the AEs of TNF inhibitors

A
  • inc risk of malignancies and GI ulcers
  • anti-drug Ab complexes formation –> interferes with efficacy + correlates w/ infusion site reaction
  • exacerbate HF
55
Q

Omalizumab:

  • (1) MOA
  • (2) uses
A

1- anti-IgE recombinant humanized monoclonal Ab –> prevents IgE from binding/activating mast cells and basophils –> prevents release of inflammatory mediators after allergen exposure

2:

  • asthma with allergy sensitization
  • chronic urticaria
56
Q

Basiliximab:

  • (1) structure
  • (2) MOA
  • (3) uses
A

1- chimeric human-mouse IgG

2- IL-2 receptor antagonist – binds and blocks IL-2 receptor

3- prevent transplant rejection

57
Q

Ritusimab:

  • (1) structure
  • (2) MOA
  • (3) uses
A

1- chimeric murine-human monoclonal Ab

2- binds CD20 on B cells –> depletion of circulationg B cells

3:

  • non-Hodgkin’s lymphoma
  • chronic lymphocytic leukemia
  • note: approved for RA
58
Q

Anakinra:

  • (1) structure
  • (2) MOA
  • (3) uses
A

1- recombinant human IL-1RA

2- IL-1 receptor antagonist –> prevents IL-1 binding its receptor

3- moderate to severe RA

59
Q

Abatacept:

  • (1) MOA
  • (2) uses
A

1- fusion protein –> interferes with T cell activation

2:

  • moderate to severe RA
  • polyarticular juvenile idiopathic arthritis
60
Q

list the immunostimulants

A

Aldesleukin
IFN-α, β, γ
BCG- bacillus calmette-guerin

61
Q

Aldesleukin:

  • (1) structure / MOA
  • (2) uses
A

1- recombinant IL-2

2- renal cell carcinoma, malignant melanoma

62
Q

list the functions for each IFN

A

IFN-α: HBV/HCV infections, hairy cell leukemia, CML, malignant melanoma, Kaposi’s sarcoma

IFN-β: relapsing MS

IFN-γ: chronic granulomatous disease

63
Q

BCG:

  • (1) structure
  • (2) MOA
  • (3) uses
  • (4) AEs
A

(Bacillus Calmette-Guerin)
1- attenuated live culture of Mycobacterium bovis

2- unknown –> active against tumors
3- Tx/prophylaxis urinary bladder carcinoma

4:

  • fever, chills, malaise
  • hypersensitivity, immune complex disease, shock

MNI (immuno pharm) (15 decks)

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