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IMM Exam 2 > Immunosuppressants and Immunomodulators > Flashcards

Immunosuppressants and Immunomodulators Flashcards

1
Q

immunosuppressant definition

A
  • drugs that increase risk of infection
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2
Q

immunosuppressants target - broad/narrow

A
  • broad targets/effects
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3
Q

age of immunosuppressant drugs

A
  • old drugs
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4
Q

immunomodulators definition

A
  • drugs that DO NOT increase risk of infection
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5
Q

Immunomodulators target - broad/narrow

A
  • narrow targets/effects
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6
Q

age of immunomodulator drug

A
  • new drugs
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7
Q

four characteristics of an inflammatory immune response

A
  • pain (dolor)
  • heat (calor)
  • erythema (rumor)
  • swelling (tumor)
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8
Q

eicanosanoids synthesized by

A
  • most cells
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9
Q

eicanosanoids role in inflammation

A
  • act as local vasodilators
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10
Q

what molecules do drugs affect in eicosanoid production/activity?

A
  • prostaglandins

- leukotrienes

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11
Q

what molecules do drugs affect in inflammatory cytokine production/activity

A
  • TNFa
  • IL-2
  • IL-5
  • IL-6
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12
Q

what molecules do drugs affect in leukocyte activation/proliferation?

A
  • Th-cells
  • B-cells
  • eosinophils
  • mast cells
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13
Q

what are eicosanoids derived from?

A

plasma membrane lipids

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14
Q

what creates arachidonic acid

A
  • from plasma membrane lipids

- by phospholipase A2

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15
Q

what are the three eicosanoids derived from arachidonic acid?

A
  • prostaglandin E2
  • Thromboxane A2
  • Leukotriene E4
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16
Q

prostaglandins E2 produced by

A
  • most cells
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17
Q

thromboxane A2 produced by

A
  • platelets
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18
Q

leukotriene E4 produced by

A
  • leukocytes
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19
Q

cyclooxygenase inhibitors inhibit what process

A
  • synthesis of prostanoids
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20
Q

big class of COX inhibitors

A
  • NSAIDs
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21
Q

COX1 constitutive/inducible

A
  • constitutive
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22
Q

COX1 responsible for

A
  • homeostatic functions
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23
Q

COX2 constitutive/inducible

A
  • inducible
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24
Q

COX2 responsible for

A
  • inflammatory response
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25
homeostatic effects of prostaglandins
- renal homeostasis - gastric mucosal production - platelet function
26
inflammatory effects of prostaglandins
- pain - inflammation - fever - limited homeostatic effects
27
toxic effects of prostaglandin inhibitors target
- renal homeostasis - gastric mucosal production - platelet function
28
therapeutic effects of prostaglandin inhibitors target
- pain - inflammation - fever - limited homeostatic effects - platelet function
29
selectivity of NSAIDS for COX
- vary in their selectivity
30
more toxicities associated with which COX inhibitors
- COX1 | - due to inhibition of homeostatic function
31
fewer toxicities associated with which COX inhibitors
- COX2 - but not no toxicities - due to inhibition of inflammatory effects
32
prostaglandin E2 (PGE2) role
- responsible for producing and maintaining gastric mucosal protection lining the inside of the stomach
33
prostaglandin E2 target toxicities of NSAID use
- long term use can lead to deterioration of mucous layer | - can lead to gastric bleeding or ulcers
34
thromboxane A2 (TXA2) role
- promotes platelet activation for clotting
35
thromboxane A2 toxicities of NSAID use
- long term use will increase risk of bleeding disorders
36
thrombaxane A2 target therapeutic of NSAID use
- inhibition of clotting may be therapeutic when treating patients to prevent MI or thrombotic/embolic stroke
37
aspirin MOA
- irreversibly inhibits COX1/2 through covalent modification | - of acetyl group
38
aspirin irreversible activation of COX-1 effect
- leads to inhibition of TXA2 | - avoiding vasoconstriction and platelet aggregation induced by this prostanoid
39
aspirin acetylation of COX-2 effect
- inhibition of prostaglandin production | - production of eicosatetraenoic acid as a substrate for new biologically active mediators aspirin triggered lipotoxins
40
aspirin approved uses
- pain - inflammation - RA, OA - fever - rheumatic fever - ischemic conditions
41
Off label uses of aspirin
- Kawasaki disease - prevention of pre-eclampsia - prevention of colorectal cancer
42
symptoms of Kawasaki disease
- conjunctivitis - swollen lymph nodes - swollen hands and feet - changes in oral mucosa - rash
43
diagnosis Kawasaki
- 4 out of 5 criteria | - + high fever
44
treatment for Kawasaki
- aspirin + intravenous immunoglobulin
45
definition of pre-eclampsia
- hypertension associated with pregnancy affect 2-8% of pregnancies worldwide
46
how aspirin helps prevent colorectal cancer
- inhibits production of PGE2 | - PGE2 associated with colon cancer
47
Aspirin toxicities
- Reye's syndrome - aspirin-sensitive asthma - acute/chronic aspirin poisoning
48
Reye's syndrome affects
- children treated with aspirin during viral infections | - treat with acetaminophen or ibuprofen instead
49
Reye's syndrome mortality
- 20-40% mortality | - long-term neurologic effects for many survivors
50
aspirin sensitive asthma mechanism
- shut down COX - increase rate at which arachidonic acid is converted to lipooxygenases into leukotrienes - leukotrienes cause bronchoconstriction
51
pediatric OD numbers
> 150mg/kg
52
OTC tablets of aspirin doses
- 81 mg - 100 mg - 300 mg
53
OTC drugs and aspirin
- many OTC drugs contain aspirin. | - read the label!
54
ibuprofen (Advil, Motrin, Nuprin) inhibits
- eicosanoids - its an NSAID - COX1/2 inhibitor
55
naproxen (Aleve) inhibits
- eicosanoids - its an NSAID - COX1/2 inhibitor
56
ibuprofen vs naproxen
- four dose/day vs two dose/day | - naproxen has a long biological half life
57
Vds of ibuprofen and naproxen
- low Vds due to plasma protein binding
58
COX2 selective inhibitors
- Celebrex (Celecoxib) | - Vioxx (Rofecoxib)
59
advantages of COX2 inhibitors
- fewer GI toxicities than COX1 inhibitors
60
disadvantages of COX2 inhibitors
- more CV toxicities (heart attack)
61
why Rofecoxib inhibitors can lead to more heart attacs
- inhibits synthesis of anti-clotting factor prostaclyin (PGI12) - increases risk of clotting
62
leukotriene inhibitors MOA
- inhibit synthesis or activity of leukotrienes
63
leukotriene inhibitors examples
- Zileuton | - Montelukast
64
Zileuton MOA
- inhibits lipoxygenase | - blocks SYNTHESIS of leukotrienes
65
Montelukast MOA
- leukotriene antagonist (inhibits receptors) | - blocks FUNCTION of leukotrienes
66
leukotriene inhibitor indications
- good for use in asthma
67
cortisol-derived synthetic drugs
- hydrocortisone - prednisone - methylprednisolone - dexamethasone
68
corticosteroids functions
- inhibitors of eicosanoid production
69
corticosteroids MOA
- alter transcription of cytokines genes in target cells
70
steroid hormones hydrophoblic/philic
- hydrophoblic | - pass through PM to reach their target receptors in the cytoplasm
71
corticosteroids and pro-inflammatory cytokines
- inhibit expression of pro-inflammatory cytokines
72
corticosteroids and anti-inflammatory cytokines
- induce expression of anti-inflammatory cytokines
73
examples of anti-inflammatory cytokines
- lipocortin/annexin 1
74
role of lipocortin
- inhibits phospholipase A2
75
specificity of corticosteroids?
- broad spectrum
76
corticosteroid toxicities
- immunosuppression | - hypercortisolism/cushing syndrome
77
corticosteroid oral inhalation effects
- thrush | - pneumonia
78
symptoms of hypercorticolism/cushing?
- weight gain - moon face - buffalo hump - thinning and fragility of skin - new or worsened high blood pressure - increased risk of fractures
79
moon face and buffalo hump caused by
- redistribution of fat by high corticosteroid levels
80
two proteins down regulated by corticosteroid use
- osteocalcin - weakens bone | - keratin - weakens skin
81
calcinuerin inhibitors MOA
- inhibit T-cell activation | - block TCR signaling through calcineurin
82
calcineurin inhibitor drug examples
- cyclosporin - tacrolimus Cows (Cal) Cycle Ta Cro (To Grow)
83
calcineurin role
- activates NFAT which is a transcription factor for IL-2
84
calcineurin inhibitor important toxicities
- malignancies (black box warning) | - non-hogkin's lymphoma
85
more important pro-inflammatory cytokines
- IL-1 - IL-2 - IL-3 - IL-6 - IL-8 - IL-11 - IL-12 - TNFa
86
JAK/Stat inhibitor drug example
- Tofacitinib JAK/STAT sitting together - citing
87
JAK/Stat inhibitor MOA
- inhibiting signaling through IL-2 receptor
88
process in JAK/Stat that Tofacitinib inhibits?
- when IL-2 binds to CD25 on T cells, JAK binds with STAT to trigger synthesis of new cytokines - Tofacitinib blocks this
89
cytokine antibody drug examples
- Adalimumab, Infiximab, Etaneracept (anti-TNFa) - Mepolizumab (anti-IL-5) - Tocilizumab (anti-IL-6) Cyto - signal AIN(En)TM - America's Intellectual Next Top Model
90
cytokine antibody MOA
- antibody molecules that bind to cytokines to render them inactive
91
Etaneracept
- antibody-like or non-antibody protein
92
administration of Anti-TNFa antibodies
- large proteins (GI will digest/too large to be absorbed) - must be administered IV or IM - expensive!!
93
Mepolizumab useful in treating
- eosinophilic asthma
94
DNA synthesis inhibitors MOA
- inhibits proliferation of T cells | - inhibits synthesis of purine nucleotides
95
DNA synthesis inhibitor drug examples
- Azathioprine - Mycophenolate - Methotrexate DAMM
96
Azathioprine MOA
- converted to MeTIMP and TGTP AZA don't know what ya heard about me but I'm a mutha fuckin' TIMP
97
MeTIMP role
- inhibits purine synthesis | - primary therapeutic effect
98
TGTP role
- aberrant nucleotide that incorporates into DNA instead of GTP - destroys daughter cells once they are produced
99
importance of administration of Azathioprine
- administered as a pro-drug first
100
Azathioprine toxicites
- mutagenicity if daughter T cell survives - acute myeloid leukemia - lung adenocarcinoma
101
Mycophenolate MOA
- inhibits inosine monophosphate dehydrogenase which catalyzes a step in GTP production
102
Methotrexate MOA
- inhibits dihydrofolatic acid reductase, which synthesizes a folate precursor - folate necessary for purine synthesis
103
methotrexate versus folate precursor
- competitive antagonist of folate precursor molecule for binding to the DHFR molecule - you must take supplemental folate
104
toxicities of DNA synthesis inhibitors
- embryotoxic/fetal toxic
105
Category D toxicity drugs
- Azathioprine | - Mycophenolate
106
Category X toxicity drugs
- Methotrexate
107
mTOR inhibitor drug example
- Sirolimus (Rapamycin) | (immature) mTOR (serious) Sirolomus (rapping) rapamycin
108
mTOR inhibitor MOA
- inhibits mTOR which carries the signal to the nucleus when IL2 binds T cells
109
Cytokine receptor antibodies drug examples
- Anakinra (IL-1R, various) (Ana Kendrick is Number 1) - Basilixumab (IL-2R, T cells) (Drop that Base at 2 AM) - Benralizumab (IL-5R, eosinophils) (Ben Folds Five) - Omalizumab (IgE, B cells) (OMG except it's E) - Rituximab (CD20, B cells) (Wear at Tux at age 20 people FRIENDS ARE GETTING MARRIED AND IT'S FUCKING TERRIFYING)

IMM Exam 2 (15 decks)

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