Rapid - Immunosuppressants Flashcards Preview

M2 - Pharm Rapid > Rapid - Immunosuppressants > Flashcards

Flashcards in Rapid - Immunosuppressants Deck (94):
1

Cyclosporine

  • Calcineurin inhibitor
    • binds cyclophilin → prevents IL-2 transcription → blocks T-cell activation
  • Use:
    • Transplant rejection prophylaxis
    • psoriasis
    • rheumatoid arthritis
  • S/E:
    • Nephrotoxicity
    • HTN
    • hyperlipidemia
    • neurotoxicity
    • gingival hyperplasia
    • hirsutism

2

Tacrolimus (FK506)

  • Calcineurin inhibitor
    • Binds FK506 binding protein (FKBP) → prevents IL-2 transcription → blocks T-cell activation
  • Use: Transplant rejection prophylaxis
  • S/E:
    • Nephrotoxicity
    • Peripheral neuropathy
    • Pleural effusion
    • HypERglycemia
    • HTN
    • hyperlipidemia
    • NO gingival hyperplasia or hirsutism

3

Sirolimus

  • aka Rapamycin
    • Binds FKBP → inhibits mTOR
    • Limits T-cell proliferation
  • Use: Kidney transplant rejection prophylaxis
  • S/E:
    • Pan"Sir"topenia (pancytopenia)
    • insulin resistance
    • hypERlipidemia
    • NOT nephrotoxic
  • Synergistic w/cyclosporine

4

Rapamycin

  • aka Sirolimus
    • Binds FKBP → inhibits mTOR
    • Limits T-cell proliferation
  • Use: Kidney transplant rejection prophylaxis
  • S/E:
    • Pan"Sir"topenia (pancytopenia)
    • insulin resistance
    • hypERlipidemia
    • NOT nephrotoxic
  • Synergistic w/cyclosporine

5

Daclizumab

  • Monoclonal Ab
    • Blocks IL-2 receptor
  • Use: Kidney transplant rejection prophylaxis
  • S/E:
    • Edema
    • HTN
    • tremor 

6

basiliximab

  • Monoclonal Ab
    • Blocks IL-2R
  • Use: Kidney transplant rejection prophylaxis
  • S/E:
    • Edema
    • HTN
    • tremor 

7

Azathioprine

  • Antimetabolite precursor of 6-MP
    • Blocks nucleotide synthesis → inhibits lymphocyte prolif
    • Activated by HGPRT
    • Degraded by xanthine oxidase
  • Use:
    • Transplant rejection prophylaxis
    • Glomerulonephritis
    • Hemolytic anemia
    • Rheumatoid arthritis
    • Crohn disease
    • other autoimmune conditions
  • S/E:
    • Leukopenia
    • anemia
    • thrombocytopenia
  • Toxicity increased by allopurinol

8

Mycophenolate mofetil

  • Reversibly inhibits IMP dehydrogenase
    • prevents purine synthesis
    • inhibits B and T cell proliferation
  • Use:
    • Transplant rejection prophylaxis
    • Lupus nephritis
  • S/E:
    • GI upset
    • pancytopenia
    • HTN
    • hypERglycemia 
    • Less nephrotoxic and neurotoxic
  • Assoc w/invasive CMV infxn

9

Corticosteroids

  • Multiple fcns
    • Inhibit NF-κB
    • decrease transcription of many cytokines → Suppress both B- and T-cell fcn
    • Induce apoptosis of T lymphocytes
  • Use:
    • Transplant rejection prophylaxis
    • many autoimmune and inflamm d/o
  • S/E:
    • Hyperglycemia
    • osteoporosis
    • central obesity
    • muscle breakdown
    • psychosis
    • acne
    • HTN
    • cataracts
    • avascular necrosis (femoral head)
    • iatrogenic Cushing syndrome.

10

Aldesleukin

  • Recombinant IL-2
  • Use:
    • Renal cell carcinoma
    • Metastatic melanoma 

11

Epoetin alfa

  • Recombinant EPO
  • Use: Anemias (especially in renal failure)

12

Filgrastim

  • Recombinant G-CSF → IL-3
    • Granulocyte stimulation
  • Use: Bone marrow recovery

13

Sargramostim

  • Recombinant GM-CSF → IL-3
    • Granulocyte and Macrophage stimulation
  • Use: Recovery of bone marrow

14

IFN-α

  • Recombinant cytokine
  • Use:
    • Chronic hepatitis B and C
    • Kaposi sarcoma
    • Leukemias
    • malignant melanoma

15

IFN-β

  • Recombinant cytokine
  • Use: Multiple Sclerosis

16

IFN-γ

  • Recombinant cytokine
  • Use: Chronic Granulomatous Disease (aids phagocytosis)

17

Romiplostim

  • Recombinant cytokine
    • thrombopoietin receptor agonist
  • Use: Thrombocytopenia

18

eltrombopag

  • Recombinant cytokine
    • thrombopoietin receptor agonist
  • Use: Thrombocytopenia

19

Oprelvekin

  • Recombinant IL-11 (oprelvekin → eleven)
  • Use: Thrombocytopenia

20

Immunosuppression targets

A image thumb
21

Alemtuzumab

  • Target: CD52
  • Use:
    • CLL
    • MS

22

Bevacizumab

  • Target: VEGF
  • Use:
    • Colorectal cancer
    • renal cell carcinoma

23

Cetuximab

  • Target: EGFR
  • Use:
    • Stage IV colorectal cancer
    • head and neck cancer 

24

Rituximab

  • Target: CD20 (B cells)
  • Use:
    • B-cell non-Hodgkin lymphoma
    • CLL
    • Rheumatoid arthritis
    • ITP

25

Trastuzumab / Herceptin

  • Target: HER2/neu (erb-B2) on chrom 17
  • Use: Breast cancer

26

Adalimumab

  • Target: Soluble TNF-α
  • Use:
    • Crohn's
    • Rheumatoid arthritis
    • Psoriatic arthritis

27

certolizumab

  • Target: Soluble TNF-α
  • Use:
    • IBD
    • rheumatoid arthritis
    • ankylosing spondylitis
    • psoriasis

28

Infliximab

  • Target: Soluble TNF-α
  • Use:
    • Crohn's
    • Rheumatoid arthritis
    • Ankylosing spondylitis
    • Psoriatic arthritis

29

Eculizumab

  • Target: Complement protein C5
  • Use: Paroxysmal nocturnal hemoglobinuria

30

Natalizumab

  • Target: α4-integrin (WBC adhesion)
  • Use:
    • Multiple sclerosis
    • Crohn disease
  • S/E: Risk of PML in pts w/JC virus

31

Abciximab

  • Target: Platelet GPIIb/IIIa
  • Use: prevention of ischemia in
    • Unstable angina
    • Percutaneous coronary intevention (stent)
    • Current MI

32

Denosumab

  • Target: RANKL
    • inhibits osteoclast maturation (mimics osteoprotegerin)
  • Use: Osteoporosis

33

Digoxin immune Fab

  • Target: Digoxin
  • Use: Antidote for digoxin toxicity
    • Symptoms:
      • QT lowering
      • ST scooping
      • T-wave inversion
      • yellow/blurred vision

34

Omalizumab

  • Target: IgE
    • prevents IgE binding to FcεRI
  • Use: Severe allergic asthma

35

Palivizumab

Target: RSV F protein

Use: RSV prophylaxis for high-risk infants

36

Ranibizumab

  • Target: VEGF
  • Use: Neovascular age-related macular degeneration

37

bevacizumab

  • Target: VEGF
  • Use: Neovascular age-related macular degeneration

38

Hyperacute Transplant Rejection

  • Within minutes
  • Pre-existing recipient antibodies react to
  • donor antigen (T2HS) → activate complement.
  • Widespread thrombosis of graft vessels → ischemia/necrosis.
  • Graft must be removed.

39

Acute Transplant Rejection

  • Weeks to months
    • Cellular: CD8+ T cells activated against donor MHCs (T4HS)
    • Humoral: similar to hyperacute, except Ab's develop after transplant.
  • Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate.
  • Prevent/reverse with immunosuppressants.

40

Chronic Transplant Rejection

  • Months to years
  • CD4+ T cells respond to recipient APCs presenting donor peptides, including allogeneic MHC.
  • Has both cellular and humoral components (T2HS and T4HS).
  • Recipient T cells react and secrete cytokines → proliferation of vascular smooth muscle, parenchymal atrophy, interstitial fibrosis.
  • Dominated by arteriosclerosis.

41

Graft-vs-Host Disease

  • Timing varies
  • Grafted T cells proliferate in immunocompromised host and reject host cells with “foreign” proteins (T4HS) → severe organ dysfcn
  • Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly.
  • Usually in bone marrow and liver transplants (rich in lymphocytes).
  • Potentially beneficial in bone marrow transplant for leukemia (graft-versus-tumor effect).

42

Bronchiolitis obliterans

Chronic lung graft rejection

43

Accelerated atherosclerosis

Chronic heart transplant rejection

44

Chronic graft nephropathy

Chronic kidney graft rejection

45

Vanishing bile duct syndrome

Chronic liver graft rejection

46

Methotrexate

  • Folate analog
    • competitively inhibits dihydrofolate reductase → decreases dTMP → decreases pyrimidine & DNA synthesis
  • Use: malignancy
  • S/E:
    • Oral, GI ulcers
    • Pancytopenia / BM suppresssion (reversible w/leucovorin)
    • Alopecia
    • Hepatotoxicity
    • Pulmonary fibrosis

47

Leflunomide

  • Reversibly inhibits dihydroorotate dehydrogenase → prevents pyrimidine synth
    • Suppresses T-cell proliferation
  • Use:
    • Rheumatoid arthritis
    • psoriatic arthritis
  • S/E:
    • Diarrhea
    • HTN
    • hepatotoxicity
    • teratogenicity

48

trimethoprim

  • Folate analog
    • inhibits bacterial dihydrofolate reductase → decreases pyrimidine & DNA synthesis
  • Use: + sulfamethazole for various bacterial infxns
  • S/E:
    • Megaloblastic anemia
    • leukopenia
    • granulocytopenia
    • (May alleviate with supplemental folinic acid).

49

pyrimethamine

  • inhibits protozoan dihydrofolate reductase → decreases pyrimidine & DNA synthesis
  • Use: Toxoplasmosis

50

Cyclophosphamide

  • Alkylating agent
    • Cross-links DNA at guanine N-7.
    • Requires bioactivation by liver.
  • Use:
    • Solid tumors
    • leukemia
    • lymphomas
  • S/E:
    • Myelosuppression
    • hemorrhagic cystitis: prevent w/mesna (thiol group binds toxic metabolites) or N-acetylcysteine

51

Anakinra

  • Recombinant cytokine: IL-1 receptor antagonist
  • Use: rheumatoid arthritis

52

Tocilizumab

  • Recombinant cytokine: IL-6 receptor antagonist
  • Use:
    • Giant cell arteritis
    • Rheumatoid arthritis

53

Muromonab

  • aka OKT3
  • mouse monoclonal antibody against human CD3  (co-receptor for T-cell receptor activation)
  • Use: kidney transplant rejection prophylaxis
  • S/E: Cytokine release syndrome (fever, myalgias, nausea, diarrhea)

54

OKT3

  • aka muromonab
  • mouse monoclonal antibody against human CD3  (co-receptor for T-cell receptor activation)
  • S/E: cytokine release syndrome (Fever, myalgias, nausea, diarrhea)

55

Levamisole

  • “Restores” depressed immune function of B & T cells, monocytes, and macrophages.
  • Its only clinical indication is as adjuvant therapy w/5-FU after surgical resection in patients with colon cancer

56

Thalidomide

  • Available only under restricted distribution program; can be prescribed only by specially licensed physicians
  • decreases TNF-α
  • Use:
    • Erythema nodosum leprosum
    • SLE
    • Organ transplants
  • S/E: Teratogenic → Limb defects (phocomelia, micromelia; “flipper” limbs)

57

Bacillus Calmette-Guerin (BCG)

  • Attenuated, live culture of the bacillus of Calmette and Guerin strain of Mycobacterium bovis
  • Mechanism unclear
  • Use: prophylaxis/Rx of carcinoma in situ of urinary bladder
  • Can cause positive PPD

58

Rho(D) Immune Globulin

  • IgG containing high titer of Ab's against Rh(D) Ag
    • binds Rho antigens → prevents sensitization
  • Use: prevents maternal anti-D IgG production in Rh- mothers (prev exposed to Rh+ blood) w/Rh+ baby

59

Kleihauer-Betke test

Postnatal maternal blood sample is analyzed to see how much fetal blood has entered maternal circulation so we can determine dose of RhoD immune globulin

60

Etanercept

  • TNF-α Inhibitor
    • Fusion protein (TNF-α + IgG1 Fc) → decoy receptor
  • Use:
    • Crohn's
    • Rheumatoid arthritis
    • Psoriatic arthritis
  • S/E: Infxn

61

Calcineurin Inhibitors

Prevent IL-2 transcription → block T-cell activation

  • Cyclosporine → cyclophilin
  • Tacrolimus → FK506

Note: gingival hyperplasia + hirsutism w/cyclosporine but NOT tacrolimus

62

mTOR Inhibitors

Bind FKBP → inhibit mTOR

  • Sirolimus / Rapamycin

Note: Pancytopenia; NOT nephrotoxic; synergistic w/cyclosporine

63

mTOR

  • serine/threonine protein kinase
  • regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, transcription
  • PI3 family
  • Inhibited by sirolimus/rapamycin

64

IL-2R Inhibitors

  • Daclizumab
  • Basiliximab

Note: use for kidney transplant rejection prophylaxis

65

6-MP Precursor

Antimetabolite precursor → blocks nucleotide synth → inhibits lymphocyte prolif

Activated by HGPRT; Degraded by xanthine oxidase

  • Azathioprine

Note: leukopenia; thrombocytopenia; conc increased by xanthine oxidase inhibitors

66

IMP Dehydrogenase Inhibitors

Reversibly inhibit IMP dehydrogenase → prevent purine synthesis → inhibit B and T cell responses

  • Mycophenolate Mofetil

Note: pancytopenia; invasive CMV

67

IL-2 Recombinant Cytokine

Aldesleukin

Use: Renal cell carcinoma; metastatic melanoma

68

EPO Recombinant Cytokine

Epoetin Alfa

Use: Anemias (especially in renal failure)

69

G-CSF Recombinant Cytokine

Filgrastim

Use: Recovery of bone marrow

70

GM-CSF Recombinant Cytokine

Sargramostim

Use: Recovery of bone marrow

71

IFN-α Recombinant Cytokine

IFN-α

Use: Chronic Hep B / C; Kaposi sarcoma; malignant melanoma

72

IFN-β Recombinant Cytokine

IFN-β

Use: Multiple sclerosis

73

IFN-γ Recombinant Cytokine

IFN-γ

Use: Chronic granulomatous disease

74

Thrombopoietin Receptor Agonists

  • Romiplostim
  • Eltrombopag

Use: Thrombocytopenia

75

IL-11 Recombinant Cytokine

Oprelvekin

Use: Thrombocytopenia

76

CD52 Blocker

Alemtuzumab

Use: CLL; MS

77

VEGF Blocker

  • Bevacizumab
    • Use: Colorectal cancer; renal cell carcinoma
  • Ranibizumab
    • Use: Neovascular age-related macular degeneration

78

EGFR Blocker

Cetuximab

Use: Stage IV colorectal cancer; head and neck cancer

79

CD20 Blocker

Rituximab

Use: B-cell non-Hodgkin lymphoma; CLL; rheumatoid arthritis; ITP

80

HER2/neu Blocker

Trastuzumab

Use: Breast cancer

81

C5 Blocker

Eculizumab

Use: Paroxysmal nocturnal hemoglobinuria

82

α4-Integrin Blocker

Natalizumab

Use: Multiple sclerosis; Crohn disease

83

Platelet GPIIb/IIIa Blocker

Abciximab

Use: Antiplatelet agent for prevention of ischemic complications in patients undergoing percutaneous coronary intervention

84

RANKL Blocker

Denosumab

Use: Osteoporosis

85

Digoxin Blocker

Digoxin immune Fab

Use: Antidote for digoxin toxicity

86

IgE Blocker

prevents IgE binding to FcεRI

Omalizumab

Use: Allergic asthma

87

RSV F Protein Blocker

Palivizumab

Use: RSV prophylaxis for high-risk infants

88

Dihydrofolate Reductase Inhibitors

Decrease dTMP → decrease pyrimidine & DNA synthesis

  • Methotrexate
  • Trimethoprim (bacteria)
  • Pyrimethamine (protozoa)

Note: mucosal ulcers; reversible BM suppression (leucovorin)

89

Dihydroorotate Dehydrogenase Inhibitors

Prevent pyrimidine synth

  • Leflunomide

Note: hepatotoxicity; teratogenicity

90

Alkylating Agents

Cross-link DNA at guanine N-7

  • Cyclophosphamide

Note: Myelosuppression; reversible hemorrhagic cystitis (mesna)

91

IL-1 receptor antagonist

Anakinra

Use: rheumatoid arthritis

92

IL-6 receptor antagonist

Tocilizumab

Use: Giant cell arteritis; Rheumatoid arthritis

93

Anti-CD3 Ab

Muromonab / OKT3

94

Immune Boosters

  • Levamisole
  • Thalidomide
  • Bacillus Calmette-Guerin (BCG)