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Pharm II Test 4 > Immune Modulators > Flashcards

Immune Modulators Flashcards

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1
Q

Non-Selective Inhibitors- Available Drugs

A

Adrenocortical Steroids

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2
Q

Adrenocortical Steroids- Mech of Action

A

Compete for NF-kB and other nuclear activators= inhibit gene transcription= decreased pro-inflammatory cytokine production, suppression of antigen presentation, alteration of cell traffic, impaired chemotaxis

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3
Q

Adrenocortical Steroids- Kinetics

A

PO, IV, depo, intraretinal, topical

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4
Q

Adrenocortical Steroids- Toxicities

A 
impaired immune response
osteoporosis
diabetes mellitus
CNS effects (hyperphagia, psychosis)
obesity hypertension
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5
Q

Adrenocortical Steroids- Clinical Use

A

any disease with poorly regulated inflammation: RA, IBD, asthma

timing is important- cytokines peak early in the morning

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6
Q

Anti-proliferative Immunomodulators- Available Drugs

A 
Cyclophophamide-Cytoxan
Azathioprine-Imuran
Methotrexate
Mycopheolate mofetil
Leflunomide
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7
Q

Cyclophosphamide- Cytoxan- Mech of Action

A

alkylating agent activated by the liver, precise site of action on lymphocytes is unknown

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8
Q

Cyclophosphamide- Cytoxan- Kinetics

A

PO or IV

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9
Q

Cyclophosphamide- Cytoxan- Clinical Use

A

SLE
Granulomatous polyangiitis (Wegener’s)
Vasculitis

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10
Q

Cyclophosphamide- Cytoxan- Toxicities

A

severe bone marrow suppression and aplasia
hemorrhagic cystitis
bladder fibrosis
cancer

infertility, especially in women

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11
Q

Azathioprine- Imuran- Mech of Action

A

prodrug metabolized to 6-Mercaptopurine= weak immunomodulator

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12
Q

Azathioprine- Imuran- Kinetics

A

PO or IV

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13
Q

Azathioprine- Imuran- Clinical Use

A

decreasing use due to better drugs

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14
Q

Azathioprine- Imuran- Toxicities

A

BONE MARROW SUPPRESSION WHEN USED WITH ALLOPURINOL

GENETIC POLYMORPHISMS OF THIOPURINE S-METHYLTRANSFERASE CAN CHANGE DRUG LEVELS- CHANGE RATE OF DEACTIVATION

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15
Q

Methotrexate- Mech of Action

A

folate antagonist–> inhibit dihydrofolate reductase–> inhibit purine and pyrimidine synthesis

AT LOW DOSES ACTS AS AN ANTI-INFLAMMATORY

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16
Q

Methotrexate- Kinetics

A

PO, IV, IM

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17
Q

Methotrexate- Clinical Use

A

RA
other inflammatory arthritis
psoriasis
IBD

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18
Q

Methotrexate- Toxicities

A

ORAL ULCERS
pulmonary hypersensitivity
bone marrow suppression

PO folic acid may reduce side effects without blocking desired effects

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19
Q

Mycopheolate mofetil- Mech of Action

A

prodrug converted by plasma esterases to acid form

BLOCKS DE NOVO NUCLEOTIDE SYNTHESIS= INHIBIT B AND T CELL PROLIFERATION

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20
Q

Mycopheolate mofetil- Kinetics

A

PO or IV

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21
Q

Mycopheolate mofetil- Clinical Use

A

replacing azathioprine in clinical use, can reduce need for steroids

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22
Q

Leflunomide- Mech of Action

A

prodrug metabolized to an inhibitor of de novo pyrimidine synthesis

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23
Q

Leflunomide- Kinetics

A

EXTREMELY LONG HALF LIFE WITH EXTENSIVE ENTEROHEPATIC RECIRCULATION

24
Q

Leflunomide- Clinical Use

A

increasing use in many clinical scenarios, especially transplant and RA

25
Q

Leflunomide- Toxicities

A

hepatotoxicity

TERATOGENIC- administration of Cholestyramine can increase excretion if pregnancy occurs

26
Q

Calcineurin Inhibitors- Available Drugs

A

Cyclosporin

Tacrolimus

27
Q

Cyclosporin- Mech of Action

A

BIND CYCLOPHILIN A TO PREVENT NUCLEAR ACTIVATION OF LYMPHOCYTES AFTER ANTIGEN BINDING

28
Q

Cyclosporin, Tacrolimus- Clinical Use

A

T cell mediated disease

Prevent transplant rejection

29
Q

Cyclosporin, Tacrolimus- Toxicities

A

NARROW THERAPEUTIC WINDOW AND WIDE INTER- AND INTRAINDIVIDUAL VARIABILITY IN ABSORPTION AND METABOLISM

hypertension
hypercholesterolemia
nephrotoxicity
neurotoxicity

MANY DRUG INTERACTIONS- CYP450 INDUCERS WILL DECREASE DRUG LEVELS, CYP450 INHIBITORS (GRAPEFRUIT JUICE) WILL INCREASE DRUG AND CAUSE NEPHROTOXICITY AND NEUROTOXICITY

30
Q

Tacrolimus- Mech of Action

A

BIND FKBP TO PREVENT NUCLEAR ACTIVATION OF LYMPHOCYTES AFTER ANTIGEN BINDING

31
Q

Inhibitors of Mammalian Target of Rapamycin (mTOR)- Available Drugs

A

Rapamycin

32
Q

Rapamycin- Mech of Action

A

blocks singal transduction and cytokine activation
blocks co-stimulation and IL2-R activation

pro-apoptotic
ANTI-FIBRINOGENIC

33
Q

Rapamycin- Clinical Use

A

prevent transplant rejection, synergistic with the Calcineurin inhibitors

controversial use in coronary stenting

34
Q

Rapamycin- Toxicities

A

decrease IGF and lipoprotein lipase which can lead to severe hypertriglyceridemia and exacerbate the hypercholesterolemia of the Calcineurin inhibitors

nephrotoxicity, acute pulmonary interstitial pneumonitis

35
Q

Biologic Response Modifiers (BRMs)- Available Drugs

A 
Monomurab
Basailiximab
Dacluzimab
Abatacept
Rituximab
IVIg
36
Q

Monomurab- Mech of Action

A

Ab to CD3= T cell block

37
Q

Basiliximab, Dacluzimab- Mech of Action

A

Ab to IL2-R of activated cells preventing T cell proliferation/activation

38
Q

Abatacept- Mech of Action

A

CTLA IgG that binds CD80/86 on antigen presenting cells and inhibits CD28 coactivation of T cells

39
Q

Rituximab- Mech of Action

A

Bind CD20 and deplete B cells

40
Q

Rituximab- Clinical Use

A

originally designed for B cell lymphoma

potential for B cell mediated autoimmune disease- RA, SLE

41
Q

IVIg- Mech of Action

A

replace antibodies–> saturate the Fc receptor–> prevent immune activation

42
Q

Anti-TNF drugs- Available Drugs

A

Etanercept
Infliximab
Adalimumab

43
Q

Etanercept, Infliximab- Mech of Action

A

Partial human Ab that blocks TNF

44
Q

Adalimumab- Mech of Action

A

Fully humanized Ab that blocks TNF

45
Q

Etanercept, Infliximab, Adalimumab- Toxicities

A

Fungal infections

progressive multifocal leukoencephalopathy

46
Q

New Monoclonals- Available Drugs

A 
Tocilizumab
Mepolizumab
Eculizumab
Omalizumab
Denosomab
Anakinra
47
Q

Tocilizumab- Mech of Action

A

anti IL-6

48
Q

Tocilizumab- Clinical Use

A

RA

49
Q

Mepolizumab, Eculizumab- Mech of Action

A

anti IL-5

50
Q

Mepolizumab, Eculizumab- Clinical Use

A

HYPEREOSINOPHILIC SYNDROMES:
ASTHMA
SOME GLOMERULAR DISEASE

51
Q

Omalizumab- Mech of Action

A

anti IgE

52
Q

Omalizumab- Clinical Use

A

ASTHMA

CHRONIC URTICARIA

53
Q

Denosomab- Mech of Action

A

anti RankL

54
Q

Denosomab- Clinical Use

A

OSTEOPOROSIS

55
Q

Anakinra- Mech of Action

A

IL-1 antagonist

not actually a monoclonal antibody

56
Q

Anakinra- Clinical Use

A

RA

JUVENILE RA

Pharm II Test 4 (5 decks)

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