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Immunology II > Immunosuppressants/Immunomodulators > Flashcards

Immunosuppressants/Immunomodulators Flashcards

1
Q

immunosuppressants

A
  • drugs that increase the risk of infection
  • broad targets/effects
  • old drugs
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2
Q

immunomodulators

A
  • drugs that do not increase the risk of infection
  • narrow targets/effects
  • new drugs
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3
Q

What are eicosanoids?

A

a diverse family of signaling molecules derived from fatty acids, synthesized by most cells and act as local vasodilators

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4
Q

three steps of the inflammatory response that immunosuppressants/immunomodulators can affect

A
  1. eicosanoid production inhibitors
  2. inflammatory cytokine production inhibitors
  3. leukocyte activation proliferation inhibitors
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5
Q

Three examples of eicosanoids

A
  1. prostaglandin E2
  2. thromboxane A2
  3. Leukotriene E4
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6
Q

prostaglandin E2 are produced by

A

most cells

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7
Q

thromboxane A2 are produced by

A

platelets

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8
Q

leukotriene E4 are produced by

A

leukocytes

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9
Q

cyclooxygenases (COX1 and COX2)

A

arachidonic acid –> prostanoids

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10
Q

NSAIDS

A

COX inhibitors

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11
Q

COX-1

A
  • constitutively expressed
  • Homeostatic effect; on renal homeostasis, GI mucosal protection, and platelet function
  • toxic effects
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12
Q

COX-2

A
  • induced and contributes to the inflammatory response

- therapeutic effect

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13
Q

COX inhibitors (NSAIDS) vary/do not vary in their selectivity for COX1 vs COX2

A

vary

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14
Q

COX 1 selective NSAIDS are less/more toxic than COX 2 selective NSAIDS

A

more

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15
Q

NSAID toxicities

A
  1. gastric damage (bleeding, ulcers)

2. inhibition of platelet activation and clotting

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16
Q

NSAIDs that inhibit PGES

A

inhibit mucous layer formation that protects stomach

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17
Q

NSAIDS that inhibit thromboxane A2

A

inhibits platelet activation and clotting

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18
Q

T/F Aspirin is not the only NSAID that reversibly inhibits COX1/2 through covalent modification

A

false

it is the only NSAID that irreversibly inhibits

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19
Q

the acetyl/salicylate portion of acetylsalicylate irreversibly inactivates COX1?

A

acetyl

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20
Q

the salicylate molecule from acetylcalicylate has what other effects

A

anti-inflammatory

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21
Q

Aspirin approved uses

A
  • ischemic condtions
  • pain
  • inflammation ex. RA- rheumatoid arthritis
    OA- osteoarthritis
  • fever ex. rheumatic fever
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22
Q

Off-label use for aspirin

A
  1. kawasaki disease
  2. pre-eclampsia
  3. prevention of colorectal cancer
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23
Q

kawasaki disease

A

immune disorder of unknown etiology

characteristics: conjunctivitis, swollen lymph nodes, swollen hands and feet, changes in oral mucosa, rash

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24
Q

to diagnosis kawasaki disease

A

4 out of 5 characteristics plus fever

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25
standard of treatment for kawasaki disease
aspirin + IV immunoglobulin
26
pre-eclampsia
hypertension associated with pregnancy affecting 2-8 % of pregnancies worldwide
27
expression of PGE2 can/cannot lead to colon cancer
can
28
Aspirin toxicity examples
1. reyes syndrome | 2. aspirin sensitive asthma
29
Reye's syndrome
affects children treated with aspirin for a viral infection | -20-40% mortality, long term neurological effects for many survivors
30
arachidonic acid ----- (enzyme?) ---> prostanoids
cyclooxygenases
31
arachidonic acid ----- (enzyme?) ---> leukotrienes
lipoxygenases
32
aspirin sensitive asthma proposed mechanism
aspirin blocks COX so there is a shift where arachidonic acid forms increased number of leukotrienes via lipoxygenases that lead to broncho-constriction
33
acute aspirin toxicities
respiratory depression, CNS depression, sweating, dehydration, electrolyte imbalance, vasodilation, hypotenstion, coma, death * tend to only occur in children
34
chronic aspirin toxicities
nausea/vomiting, headache, tinnitus, hyperglycemia, delirium
35
pediatrics OD
> 150 mg /kg
36
kaopectate, peptobismol, alka seltzer, bengay, and goodys
contain aspirin
37
most frequently used NSAID
ibuprofen
38
Ibuprofen vx. naproxen
ibuprofen has a longer half life (12-17 hours compared to 2-4 hours) therefore two dose/day compared to the four doses per day required by ibuprofen
39
ibuprofen and naproxen have high/low Vd
low because they bind proteins in the plasma
40
ibuprofen is nonselective/selective for COX1 and COX2
nonselective
41
celecoxib and rofecoxib are nonselective/selective for COX1 and COX2
selective for cox-2
42
aspirin is nonselective/selective for COX1 and COX2
nonselective
43
naproxen is nonselective/selective for COX1 and COX2
nonselective
44
COX 2 inhibitor advantage is _____ and disadvantage is _____
fewer GI toxicities | increased CV toxicities
45
celebrex class name
celecoxib
46
rofecoxib trade name
vioxx
47
rofecoxib also inhibits the synthesis of ____ which is anti-clotting
PG12 prostacyclin
48
prostacyclins
PG12
49
prostaglandins
PGD2, PGE2, PGF2a
50
thromboxanes
TXA2 and TXB2
51
leukotriene inhibitors
inhibit the synthesis and activation of leukotrienes
52
leukotriene inhibitor indications
asthma
53
zileuton
inhibits synthesis of leukotrienes by inhibiting lipoxygenase
54
montelukast
inhibits function of leukotrienes by being a LT antagonists
55
corticosteroids (CSs) can inhibit all/some of the eicosanoids
all
56
all corticosteroids are derived from
cortisol- stress hormone
57
Mechanism of action for corticosteroids
alter transcription of genes in target cells
58
steroid hormones are hydrophobic/hydrophilic
hydrophobic- therefore pass through the plasma membrane to reach their target receptors in the cytoplasm which are then relocated into the nucleus
59
CSs inhibit/induce the expression of pro-inflammatory proteins
inhibit
60
CSs inhibit/induce the expression of anti-inflammatory proteins
induce
61
other name for lipocortin
annexin 1
62
lipocortin/annexin 1 is an anti-inflammatory/pro-inflammatory
anti-inflammatory
63
TNF alpha is an anti-inflammatory/pro-inflammatory
pro-inflammatory
64
CSs inhibit/induce the expression of lipocortin/annexin 1 and inhibit/induce the expression of TNF alpha
induce; inhibit
65
lipocortin inhibit
phospholipase A2 the enzyme that catalyzes cell membrane phospholipids ---> arachidonic acid
66
corticosteroid toxicities
1. immunosuppression | 2. Hypercortisolism
67
hypercortisolism
cushing syndrome - weight gain - moon face - buffalo hump - skin- thinning and fragility - vascular- new or worsened blood pressure - bones- increased risk of fractures
68
moon face and buffalo hump
related to redistribution of fat due to high corticosteroid levels
69
osteocalcin is decreased/increased during hypercortisolism leading to ______
decreased; weakens bones
70
keratin is decreased/increased during hypercortisolism leading to ______
decreased; weakens skin
71
calcineurin inhibitors
inhibit T-cell activation by blocking t cell receptor signaling through calcineurin
72
calcineurin toxicities
malignancies; Non-Hodgkin's lymphoma is the most common
73
corticosteroids can also decrease/increase the transcription of numerous cytokine genes
decrease
74
tofacitinib
jak/stat inhibitors
75
jak/stat inhibitors
inhibit signaling through the IL-2 receptor therefore inhibit cytokine production t-cell activation and proliferation
76
cytokine antibodies
inhibit cytokine function by directly binding to the cytokine so that it cannot bind receptor
77
cytokine antibodies that inhibit TNF
1. adalimumab 2. infliximab 3. etanercept
78
cytokine antibody that inhibit IL-5
mepolizumab
79
cytokine antibody that inhibits IL-6
tocilizumab
80
antibody drugs are large proteins therefore must be administered ____ or ______
IV or IM
81
anti-IL-5 mepolizumab
indicated for eosinophilic asthma
82
inhibitors of leukocytes proliferation and activation
DNA synthesis inhibitors 1. methotrexate 2. azathioprine 3. mycophenolate
83
methotrexate
inhibits DHFR and therefore the production of tetrahydrofolic acid (folate); inhibits purine production
84
azathioprine
inhibits purine synthesis and aberrant nucleotide that incorporates into DNA as tdGTP
85
toxicities of azathioprine
mutagenicity acute myeloid leukemia and lung adenocarcinoma (occcurs if daughter t-cell has survived with tdGTP)
86
mycophenolate
inhibits inosine monophosphate dehydrogenase; therefore inhibiting GTP production
87
``` DNA synthesis inhibitors 1. methotrexate 2. azathioprine 3. mycophenolate toxicities ```
d/x pregnancy category; embryo-toxic and fetal toxicity | methotrexate = category X
88
sirolimus
mTOR inhibitor- which in inhibits IL-2 production and therefore activation and proliferation of T-cells
89
anakinra
IL-1 receptor in various cells cytokine receptor antibody; inhibitor of leukocyte proliferation /activation by binding to cytokine receptor
90
basilixumab
IL-2 receptors on T cells cytokine receptor antibody; inhibitor of leukocyte proliferation /activation by binding to cytokine receptor
91
benralizumab
IL-5 receptors on eosinophils cytokine receptor antibody; inhibitor of leukocyte proliferation /activation by binding to cytokine receptor
92
omalizumab
IgE on B cells cytokine receptor antibody; inhibitor of leukocyte proliferation /activation by binding to cytokine receptor
93
rituximab
CD20 on b-cells cytokine receptor antibody; inhibitor of leukocyte proliferation /activation by binding to cytokine receptor
94
cytokine antibodies and cytokine receptor antibodies have mechanisms of action outside/inside the cell
outside
95
leukotrienes either block the synthesis of LOX or the activity of leukotrienes. they are indicated primarily for ______ due to the localized LT receptors in the bronchiole of smooth muscle
asthma
96
calcineurin examples
cyclosporin | tacrolimus
97
prastanoids
prostaglandins prostacyclins thromboxanes
98
Tofacitinib inhibits the inflammatory response by doing which of the following? A) Inhibiting COX2, but not COX1 B) Increasing the expression of annexin 1 in target cells C) Blocking an intermediate in the IL-2 intracellular signaling pathway D) Inhibiting mTOR E) Binding to the IL-2 receptor on T-cells
C) Blocking an intermediate in the IL-2 intracellular signaling pathway
99
2) In treating eosinophilic asthma, which of the following would probably have effects that most closely match those of benralizumab? ``` A) Omalizumab B) Mepolizumab C) Tocilizumab D) Infliximab E) Tocilizumab ```
B) Mepolizumab
100
3) Which of the following NSAIDs is LEAST likely to cause gastric damage with long-term use? ``` A) Celecoxib B) Ibuprofen C) Naproxen D) Ketorolac E) Indomethacin ```
A) Celecoxib
101
4) Which of the following targets a molecule found on the surface of an immune cell? ``` A) Etanercept B) Cyclosporin C) Dexamethasone D) Montelukast E) Rituximab ```
E) Rituximab
102
5) Where are you most likely to find the molecular target of montelukast? ``` A) Mast cells B) Bronchiole smooth muscle cells C) T-helper cells D) B-cells E) Eosinophils ```
B) Bronchiole smooth muscle cells
103
Which of the following drugs carries a warning of increased risk of non-Hodgkin’s lymphoma? ``` A) Azathioprine B) Tacrolimus C) Tofacitinib D) Methotrexate E) Adalimubmab ```
B) Tacrolimus
104
7) In which cell type would you expect to find the primary molecular target of cyclosporin? ``` A) Mast cell B) Antigen-presenting cell C) B-cell D) T-cell E) Eosinophil ```
D) T-cell
105
8) The enzyme dihydrofolate reductase (DHFR) is the molecular target of which anti-inflammatory drug? ``` A) Methotrexate B) Sirolimus C) Dexamethasone D) Zileuton E) Azathioprine ```
A) Methotrexate
106
9) Which drug has the widest range of clinical anti-inflammatory applications? ``` A) Celecoxib B) Hydrocortisone C) Adalimumab D) Sirolimus E) Ibuprofen ```
B) Hydrocortisone
107
10) Which drug is most likely to be used to prevent rejection following a kidney transplant? ``` A) Mepolizumab B) Indomethacin C) Methotrexate D) Cyclosporin E) Tocilizumab ```
D) Cyclosporin
108
11) Which drug induces the expression of the protein, lipocortin/annexin 1, as part of its mechanism of action? ``` A) Celecoxib B) Hydrocortisone C) Adalimumab D) Sirolimus E) Ibuprofen ```
B) Hydrocortisone
109
stages of reyes syndrome
``` toxicity of aspirin in children after viral infection stage I- fever and liver dysfunction stage II- lethargic stage III- light coma stage IV- deep coma stage V- seizures ```
110
kawaskis disease 5 symptoms and criteria
4 of 5 symptoms + fever (5 days of fever) 1. enlarged lymph nodes 2. rash 3. oral mucosa- cracked lips , red, cracked tongue 4. conjunctivae- red 5. swelling of hands and feet extreme irritability
111
kawaskis disease leads to what risk if not treated
vasculitis and coronary artery
112
treatment for kawaskis
treatment with IVIg and aspirin
113
The patient was admitted overnight due to signs and symptoms consistent with an aspirin overdose. How would this child have presented?
- acute poisoning respiratory depression, respiratory acidosis, CNS depression, sweating, dehydration, electrolyte imbalance, vasodilation, coma, death - chronic poisoning nausea, vomiting, headache, tinnitus, hyperglycemia - hidden salicylates
114
The parents of the next febrile child on rounds only want to use herbal medications to treat inflammation. How do you respond to this request?
just tell me and make sure they do not have drug interactions

Immunology II (11 decks)

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