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MOHD3 Exam 2 > Immunomodulatory Drugs > Flashcards

Immunomodulatory Drugs Flashcards

1
Q

Disease-modifying antirheumatic agents (DMARDs) target _____

A

inflammatory cytokines

CAN target both innate and adaptive

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2
Q

Activated T cells secrete ____ and express ____

A

IL-2

IL-2 receptor protein (CD25)

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3
Q

IL-2 stimulates ___

A

proliferation and clonal expansion of the antigen-specific T cell population.

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4
Q

___:Generally do not promote specific immune reaction

A

Immuno-stimulants

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5
Q

Require parenteral administration
Very short half-lives
Expensive

A

Cytokines

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6
Q

___: support prolonged exposure to developing immune reactions

A

Alum

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7
Q

BCG

A

Adjuvants: live attenuated bacillus calmette-guerin
Immuno-stimulants
Cancer therapy (bladder cancer)
Surface antigens interact directly with pattern recognition receptors on antigen presenting cells and increase their APC activity.

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8
Q

Interleukin-2 (Aldesleukin, Prokeukin) action:

A

increased proliferation of activated T cells, production of IFN-gamma, cytotoxic killer cell activity

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9
Q

Interleukin-2 treats: (2)

A

metastatic melanoma

renal cell carcinoma

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10
Q

Interleukin-2 adverse effects:

A

Serious capillary leak syndrome
Hypotension
Reduced organ perfusion
Can be fatal

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11
Q

IFN-gamma (Actimmune) action:

A

stimulates cell mediated cytotoxic immune response

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12
Q

IFN-gamma treats:

A

recurrent infections

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13
Q

IFN-alpha, IFN-beta produced by:

A

most cells in response to a variety of stimuli including viral infection

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14
Q

IFN-alpha, IFN-beta treats: (3)

A
  1. Chronic viral infection (hepatitis)
  2. Anti-proliferative activities used to treat some cancers: cell leukemia, melanoma, lymphomas
  3. Reduce episodes in multiple sclerosis
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15
Q

Immuno-stimulants (4)

A

BCG
Interluekin-2
IFN-gamma
IFN-alpha, beta

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16
Q

Adverse effects of ALL general immunosuppressants (5)

A
  1. Risk of infection
  2. Risk of cancer
  3. Loss of immune surveillance
  4. Susceptibility to tumor-promoting pathogens
  5. Posttransplant lymphoproliferative disorder (PTLD) = infection of B cells
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17
Q

Cyclophosphamide action:

A

Immunosuppressant

Cross-link DNA and kill proliferating cells –> prevent expansion of antigen-specific lymphocytes

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18
Q

Cyclophosphamide uses: (2)

A

Autoimmune disease

Bone marrow transplant

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19
Q

Cyclophosphamide adverse effects (4)

A

Myelosuppression
Nausea, vomiting
infertility

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20
Q

Azathioprine action:

Inactivated by:

A

Immunosuppressant: prodrug –> 6-mercaptopurine, 6-thioguanine
Inhibit purine synthesis

Xanthine oxidase

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21
Q

Azathioprine uses (2)

Adverse effects (3)

A

Renal and other transplantation
Auto-immune disease (lupus, rheumatoid arthritis)

Myelosuppression, nausea, vomiting

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22
Q

Mycophenolate Mofetil action

A

Immunosuppressant

Inhibits inosine monophosphate dehydrogenase –> prevents purine synthesis

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23
Q

Mycophenolate Mofetil uses (2)

Adverse effects (3)

A

Solid organ transplant
Auto-immune disease

Myelosuppression, nausea, vomiting

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24
Q

Methotrexate action

A

Immunosuppressant

Inhibit dihydrofolate reductase –> prevent synthesis of thymidine and purine nucleotides

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25
Q

Methotrexate uses

Adverse effects (3)

A

rheumatoid arthritis

Diarrhea, myelosuppression, modest hepatotoxicity

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26
Q

Have combined immuno-suppressive AND anti-inflammatory effects

A

glucocorticosteroids (Prednisone)

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27
Q

Glucocorticosteroids (Prednisone) immuno-suppressive action

A

Inhibit cytokine (IL-2, IFN-gamma) gene expression from antigen-activated T cells

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28
Q

First-line immunosuppressant for solid organ and hematopoietic stem cell transplantation

A

Glucocorticosteroids (Prednisone)

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29
Q

Glucocorticosteroids (Prednisone) uses:

A

Management of immune-based disorders:

autoimmune diseases, asthma, allergic reactions, systemic inflammation …etc.

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30
Q 
Adverse effects of \_\_\_\_:
Like Cushing's Syndrome
Glucose intolerance
Hypertension, fluid retention
Osteoporosis
GI disturbances
Ocular disturbances
Psychiatric disturbances
A

Glucocorticosteroids (Prednisone)

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31
Q

Calcineurin

A

Calcium dependent phosphatase that de-phosphorylates transcription factor, NF-AT –> cytokine gene expression in antigen activated T cells

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32
Q

Cyclosporine action

Uses: (3)

Adverse effects:

A

Calcineurin inhibitor

Kidney, liver, cardiac transplants
Autoimmune disorders
Some inflammatory diseases (asthma)

Nephrotoxicity, HTN, hyperglycemia, liver dysfunction, increased cancer incidence

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33
Q

Tacrolimus (FK506) action

A

Calcineurin inhibitor

10-100x more potent to cyclosporine

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34
Q

Serine/threonine kinase

Regulate translation of proteins required for cell proliferation induced by cytokines (IL-2)

A

mTOR (mammalian target of rapamycin

35
Q

Sirolimus action

Uses: (2)

Adverse effects: (5)

A

mTOR inhibitor

Preserve solid organ transplants
hematopoietic stem cell transplants

myelopsuppression, hyperlipidemia, hypertension, edema, hepatotoxicity

36
Q

Sirolimus antagonizes ____, synergizes with ____

A

tacrolimus

cyclosporine

37
Q

Variable domain of animal derived antibody with non-variable backbone of fully human antibody

A

Humanized antibodies

38
Q

Constant domain of human antibodies and selected ligand binding proteins

A

Fusion proteins

39
Q

Antibodies used in immunosuppression by:

A
  1. Depleting cell mediators of adaptive immune response

2. Blockade of critical receptor-ligand interactions

40
Q

____ uses antibodies used to suppress unwanted immune responses in Rh negative mothers against Rh-positive fetus

A

Rh(D) immune globulin

41
Q

Rh(D) immune globulin mechanism:

A

Opsonization and clearance of D antigens

Inhibit activation of maternal naive Rh(D) reactive B cells

42
Q

Drug (antibody) that blocks co-stimulatory receptors for immunosupression

A

Belatacept

43
Q

Belatocept =

A

fusion protein of high affinity B7 ligand with IgG Fc domain

44
Q

Belatocept uses:

Mechanism:

A

Kidney transplantation

Prevent interaction b/w B7 (on APC) and CD28 (on T cell)

45
Q

Comparable to calcineurin inhibitors in preventing transplant rejection

A

Belatocept

46
Q

Drugs (antibodies) used as immune-depleting agents (3)

A

Anti-T cell globulin (ATG)
Alemtuzumab
Basiliximab

47
Q

Anti-T cell globulin (ATG) =

Mechanism:

Effect:

Adverse effects:

A

Purified serum IgG

Blocks T cell surface receptors and opsonizes T cells

Prolonged T cell depletion

Cytokine release syndrome, serum sickness

48
Q

Cytokine release syndrome can be pretreated with

A

acetaminophen and antihistamine to prevent:

fever, chills, headache, nausea, malase

49
Q

Alemtuzumab =

Mechanism:

Effect:

A

humanized anti-CD52 antibody

Depletes broad variety of cells involved in adaptive and innate immune reactions

Prolonged depletion of T cells and other immune cells

50
Q

CD52

A

surface protein expressed on T and B cells, monocytes, macrophages and NK cells

51
Q

Basiliximab =

Mechanism:

Effect:

A

humanized anti-IL-2 receptor (anti-CD25) antibody

Blocks and opsonizes the alpha-chain of IL-2 receptor (CD25) that is present on ACTIVE T cells

Depletes only antigen-activated T cells

52
Q

___ and ___ activate macrophages, causing macrophages to ____

A

TNF-alpha, IL-1

Produce more inflammatory mediators

53
Q

____ activate neutrophils, causing them to produce ___

A

IL-6

Proteases that increase tissue destruction

54
Q

Anti-TNF-alpha agents (3)

A

Infliximab
Adalimumab
Etanercept

55
Q

Infliximab =

Mechanism:

Uses (2):

Complications:

A

Humanized antibody to TNF-alpha

Binds to TNF-alpha –> prevents interaction with its receptor

Rheumatoid arthritis, Crohn’s disease

Increased frequency of infection

56
Q

Adalimumab =

A

Human antibody to TNF alpha

57
Q

Etanercept =

A

Fusion protein = ligand binding domain of TNF alpha receptor + Fc domain of human IgG

58
Q

Anakinra =

Uses:

Characteristics:

Complications:

A

Anti-IL 1 agent
Competitive IL-1 receptor antagonist

RA

Short half-life, daily injection required

Increased susceptibility to infection

59
Q

Tofacitinib =

Uses:

Mechanism:

Complications: (2)

A

General Jak kinase inhibitor
Comparable to anti-TNFalpha agents in treating RA

Rheumatoid arthritis

Inhibits all activity of cytokines required for adaptive immunity and some inflammatory cytokines

Myelosuppression, risk of infection (herpes zoster)

60
Q

Arachidonic acid is converted to ____ by ____ (2)

A

prostaglandin H2

Cyclooxygenase-1 (COX-1)
Cyclooxygenase-2 (COX-2)

61
Q

Prostaglandin E (PGE2) produced in ___

A

most tissues

62
Q

Thromboxane (TXAs) produced in ____

A

platelets, macrophages

63
Q

Prostacyclin (PGI2) produced in ____

A

Endothelial cell, vascular smooth muscles

64
Q

PGE2 and PGI1 (dilates/constricts) blood vessels

A

Dilates

65
Q

TXA2 (dilates/constricts) blood vessels

A

Constricts

66
Q

PGI2 (inhibits/stimulates) aggregation of platelets

A

inhibits

67
Q

TXA2 (inhibits/stimulates) aggregation of platelets

A

stimulates

68
Q

____ is responsible for production of most prostanoids contributing to inflammatory reactions

A

COX-2

69
Q

COX-2 in induced by ____

A

pro-inflammatory cytokines (IL-1, TNF-alpha)

70
Q

COX-2 is inhibited by _____

A

glucocorticosteroids, cytokines associated w/ anti-inflammatory effects (IL-10)

71
Q

NSAIDs inhibit platelet ____

A

COX-1

72
Q

COX-1 effect in GI

A

decrease acid production

increase mucus formation

73
Q

Drugs that prevent GI ulcers from NSAID toxicity

A

Proton pump inhibitors
H2-receptor antagonists
Misoprostol (only NSAID induced)

74
Q

___ contracts uterine smooth muscle

A

PGE2

75
Q

___ relaxes uterine smooth muscle

A

PGI2

76
Q

Acetaminophen =

Uses:

Contraindications:

A

Non-selective COX-1/COX-2 inhibitor

NO anti-inflammatory activity
Used for analgesic and antipyretic ONLY

Alcohol –> hepatotoxicity

77
Q

Celecoxib =

Uses:

Effects:

A

COX-2 selective NSAID

Osteoarthritis, rheumatoid arthritis

Anti-inflammatory, antipyretic, analgesic

78
Q

Leukotrienes metabolized to ___ and ___ by ___

Effect:

A

LTB4, LTD4

5-lipoxygenase

Pro-inflammatory

79
Q

LTD4 (increases/decreases) capillary permeability

A

Increases

Promote localized edema

80
Q

LTD4’s effect on bronchial smooth muscle

A

Potent constrictor of bronchial smooth muscle –> difficulty breathing

81
Q

LTB4 attracts ____

LTD4 attracts ____

A

Neutrophils

Eosinophils

82
Q

Asthma’s major mediators

A

leukotrienes

83
Q

Zieuton =

Uses:

Adverse effect:

A

Leukotriene synthesis inhibitor
Inhibition of 5-lipoxygenase

Long term maintenance therapy for asthma (oral)

Liver toxicity, decrease metabolism of other drugs

84
Q

Zafirlukast, Montelukast =

Uses:

A

Leukotriene receptor antagonists

Maintenance therapy for asthma
Reduced bronchoconstriction and edema associated with inflammatory responses

MOHD3 Exam 2 (13 decks)

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