Exam 4-FINALLLL Flashcards
(119 cards)
1
Q
Methotrexate Mechanism of Action
A
inhibits the critical enzyme that cycles the cofactor that makes folate DHFR-dihydrofolate reductase
DHFR is involved in the synthesis of thymine from uracil
2
Q
Methotrexate Side Effects and Interactions
A
ulcerative stomatitis, leukopenia, abdominal stress
Do not take NSAIDs before or during because they increase blood concentration of methotrexate
3
Q
Leflunomide
A
Prodrug of antirheumatic metabolite A77 1726 which suppresses lymphocytes proliferation and inhibits cytokine synthesis
side effect: liver toxicity
4
Q
Methotrexate
A
antimetabolite of folic acid
5
Q
Leflunomide Mechanism of Action
A
A77 1726 inhibits dihydro-orotate dehydrogenase required for pyrimidine biosynthesis
Inhibits tyrosine kinase associated with cytokines possibly interfering with T and B cell production
6
Q
Thalidomide indication
A
erythema nodosum leprosum (ENL)
7
Q
Thalidomide Mechanism of Action
A
Unclear
May decrease circulating TNF-(a) in ENL but increase it in HIV
8
Q
Echinacea
A
stimulates the innate immune system, increases phagocytosis and release from macrophages, Tcells of TNFs, interferons
possibly active polysaccharides
don’t use for more than 8 wks because can induce autoimmune process
9
Q
Astragalus
A
Chinese medicine for hepatitis, cancer, colds, URIs, heart disease
generally safe
10
Q
Levamisole
Immunostimulant
A
enhance 5-FU toxicity
mimics thymic hormone thymopoietin
inhibits most isoforms of alkaline phosphatase
restores depressed function of B/T cells, monocytes, macrophages
11
Q
Imiquimod
A
treats actinic keratosis external, genital, and perianal warts from HPV
Toll Like Receptor agonist-7 agonists, stimulates immune system to produce interferon(a) and others. Activates macrophages, NK, TH1, Bcells.
Topical creams
12
Q
active immunization involves stimulation with an antigen to develop immunological defenses against a future exposure
A
vaccine
13
Q
passive immunization involves administering pre-formed antibodies from an external source
A
antibodies: immunoglobulins, monoclonal antibodies
14
Q
Epoetin alfa, Darbepoetin alfa, granulocyte-colony stimulating factor, granulocyte macrophage colony stimulating factor
A
growth factors
15
Q
Active immunization vaccine
A
protection not immediate because body responds and produces antibodies
excess of TH2 cells produced-imbalance leads to asthma, allergies
16
Q
denaturing disinfectant kills pathogen, allows recovery of the surface antigens
A
killed pathogen vaccines
17
Q
pass the pathogen through many generations of host animals to yield low virulent strain
A
live/attenuated pathogen vaccines
18
Q
cowpox used in place of smallpox virus
A
live/ attenuated related strain vaccines
19
Q
isolate the surface antigen from the pathogen, purify it and reconstitute into a vaccine preparation
A
cellular antigen from a pathogen vaccine
20
Q
clone a piece of DNA encoding the surface antigen from the pathogen and over produce the antigen in E coli etc
A
genetically engineered pathogen vaccine
21
Q
simple vaccine
A
contains only one kind of antigen or strain
22
Q
multivalent vaccine
A
contains two or more kinds of antigens or strains that cause the same disease..full protection
23
Q
polyvalent vaccine
A
contains two or more kinds of antigens or strains that cause different diseases–convenience
24
Q
types of vaccine dosing
A
single dose, multiple dosing regimen, booster dose, co-administered vaccine
25
types of vaccines
viral, bacterial, toxoids, cancer/autoimmune
26
conjugate vaccines
covalently linked polysaccharide antigen and a carrier protein from the bacterium
27
toxoids
denatured toxin that has been inactivated
28
DNA vaccination advantage
expression of whole proteins, so HLA alleles do not matter
29
passive immunization-antibodies
```
immediate protection administered to people who are already ill and lasts 1-3 months
1. Immunoglobulins
2. Monoclonal Antibodies
neutralize toxic molecules
eliminate target cells
```
30
How antibodies can eliminate target cells
cell growth control
macrophage clearance
complement-mediated cytotoxicity
antibody dependent cell mediated cytotoxicity
31
human immunoglobulins
rabies, tetanus, hep B, Rho
32
animal immunoglobulins
digoxin immune fab--sheep IgG used for digoxin overdose. binds TO digoxin
33
antiithymocyte globulin
gamma globulin from rabbit immunized with human thymocytes
polyclonal mix
directly kills T lymphocytes
binds to cell surface molecules that regulate cell function
indication: kidney rejection, aplastic anemia if not suitable for bone marrow transplant
34
monoclonal antibodies
synthesized from a single clone of B lymphocytes or plasma cells
35
-ximab
chimeric antibody (2/3rd human)
36
-umab
human antibody
37
-zumab
humanized antibody (90% human)
38
muromonab
| attaches to T cell receptor
from mice that interacts with human CD3
instantly decreases T cells in blood, used 10-14 days and can't be used again
side effect: cytokine release syndrome
39
-omab
mouse antibody
40
basiliximab
| attaches to T cell receptor
chimeric maB that binds to IL2 receptor of activated Tcells
*IL2 aka CD25*
used with cyclosporine or tacrolimus+corticosteroids
41
belatacept
| attaches to T cell receptor
prevent kidney rejection
soluble fusion protein CTLA4-Ig contains CTLA4 fused to Fc domain of human IgG antibody
produced by recombinant DNA tech
binds CD80 and CD86
42
Ways to treat malignancies with MAbs
enhance effector function
pre-target
indirect arming
direct arming
43
rituximab
| for lymphomas
first MAb approved in USA for follicular lymphoma
| chimeric IgG binds to CD20 which is on 90% of non-Hodgkin's lymphomas
44
alemtuzumab
| for lymphomas
humanized MAb directed against CD52 which is on mature lymphocytes
used for Bcell chronic lymphocytic leukemia
45
brentuximab vedotin
| for lymphomas
chimeric IgG antibody specific for CD30+drug MMAE that disrupts microtubules+covalent linker
treatment of Hodgkin's lymphoma and sALCL (non)
binding internalizes ADC-CD30 complex, MMAE released, microtubules network disrupts, apoptosis
46
tositumomab
| for lymphomas
mouse IgG MAb linked to iodine131
antiCD20 for non-hodgkins
induces normal immune reactions and radioimmunoconjugates deliver cytotoxic ionization radiation
kills cells 1-2 mm away that are inaccessible to antibody
47
y-90-labeled ibritumomab tiuxetan
| for lymphomas
mouse IgG anti CD20 radiolabeld
48
trastuzumab
| anti-HER2
humanized IgG for breast cancer that overexpress HER2
inhibit HER2 signaling by blocking extracellular receptors. upregulates p27(kip1) to lead to cell cycle g1 arrest and growth inhibition
49
cetuximab
chimeric MAb binds to EGFR
50
panitumumab
human MAb binds to EGFR
51
infliximab
| for RA/Crohn's/ankylosing spondylitis
chimeric IgG binds to free and bound TNF(a)
| risk of infection esp Tb, severe hepatic rxns
52
adalimumbab
| for RA/Chron's
human mAb that against TNF(a)
| risk of infection
53
tocilizumab
| for RA
humanized mAb that inhibits IL6 receptor
| for people who failed other therapies
54
etanercept
| for RA/psoriasis/ankylosing spodylitis
```
dimeric fusion protein TNF receptor linked to Fc of IgG
binds TNF(a) to slow/stop joint damage, response 1-2 weeks
```
55
omalizumab
| for asthma
recombinant humanized mAb binds to circulating IgE to prevent its binding to mast cells and others. Cells can't recognize the allergens
56
mepolizumab
| for asthma/allergic rhinitis
humanized IL-5 antagonist mAb produced by recombinant DNA tech
57
efalizumb
| for psoriasis
recombinant humanized IgG that binds CD11a which is important in Tcel mediated steps in psoriasis pathogenesis.
inhibits CD11a interaction with ICAM mlcls...inhibits the APC T cell interaction and adhesion
58
Interferon (a)-2b
| cytokine
produced by recombinant DNA in E coli. to treat cancers and hep B
59
Interferon (b)-1a/b
| cytokine
produced by rDNA for neurological exaberations in relapsing MS
60
Interleukin-2
| cytokine
aka T-Cell growth factor
produced by rDNA, not glycosylated, no terminal alanine, serine substituted for Cys125 that normal IL2 has
cancers, induces a cytolytic response
61
Interleukin-11
| cytokine
aka platelet growth factor
produced by rDNA and one A.A. shorter than normal IL11
used after myelosuppressive chemotherapy
62
anakinra
| interleukin receptor agonist, cytokine
recombinant human IL1 receptor antagonist for RA.
slows degradation of joint, well tolerated
don't give with anti-TNF agents
risk of infection ex. Tb
63
G-CSF M-CSF GM-CSF Multi-CSF EPO TPO
growth factors that control expansion, proliferation, differentiation of myeloid cells
64
Granulocyte-Colony Stimulating Factor Analogs
| G-CSF
Fligastrim Pegfilgastrim
produced by rDNA to stimulate bone marrow to produce more WBCs
for neutropenia or after bone marrow transplant
65
Granulocyte-Macrophage-Colony Stimulating Factor
GM-CSF
Sargramostim
produced by rDNA in yeast, for bone marrow transplant
| hastens myeloid reconstitution
66
Granulocyte-Macrophage-Colony Stimulating Factor
GM-CSF
Erythropoietin
Epoetin for dialysis and chemotherapy. increases RBC
| Darbepoetin Alfa-has 2 extra carb chains=more stable=longer half life. For anemia from renal failure and chemotherapy
67
induction immunosupression
meds given right after transplant to prevent acute rejection for up to 30 days.
ex. methylprednisolone, atgam, thymoglobulin, OKT3, basiliximab
68
maintenance immunosuppression
meds given before, during, or after transplant with the intention to maintain them long term.
ex. prednisone, cyclosporing, rapamycin
69
anti-rejection immunosuppression
treat acute rejection up to 30 days after rejection
| ex. methylprednisolone, atgam, etc
70
RA pathophysiology
activated T cells stimulate macrophages and fibroblast-like synoviovytes
proinflammatory mediators (TNF(a) and ILs)/proteases generated
synovial inflammatory response
destroy cartilage and bone
71
biologics that treat RA
infliximab, adalimumab, anakinra, rituximad, tocilizumab, etanercept
72
DMARDs vs Biologics
```
DMARDs: oral-daily or weekly
target entire immune system
know if working w/in months
risk of infections
range of side effects
```
```
biologic: injection daily-monthly
target certain steps in inflame process
know if working w/in 4-6 wks
risk of serious infections
much more expensive
```
73
Skin anatomy
4 mm thick, largest organ in body
74
Epidermis
outer stratified layer, keratinocytes, hair follicle
4 layers:
stratum corneum, granular layer, spinous layer, basal layer
75
epithelial stem cells
in basal layer
slow cycling, potential to proliferate and regenerate
epidermal stem cells: quiescent stem sells, committed progenitors, wound repair
hair follicle stem cells: HF cycling, epidermal repair post injury
76
wound healing order
Hemostasis, inflammation, proliferation, remodeling
77
haemostasis: vasoconstriction, platelet aggregation, blood coagulation
NEURAL vasoconstriction: blood vessel constriction (epineph, prostaglandins, serotonin)
platelet aggregation: PDGF, TGF, IGF, thrombin
CONTACT/TISSUE FACTOR coagulation of blood: cascade, fibrinolytic cascade
78
Inflammation
vasodilation, increase vasc permeability, inflam cells, chemotaxis, cell response
neutrophils=main, macrophages
heat, redness, pain/swelling, raised temp
79
proliferation
stimulated by inflame response, replace lost epidermal/dermal tissue with scar tissue, scaffolding to laid for repair of wound, collagen ECM and granulation tissue formed
reepithelialization: epithelial cells,
angiogenesis: endothelial cells, new vessels
fibroplasia: fibroblast/myo-fibroblast differentiation, new ECM components
80
keratinocyte proliferation
keratinocytes detach, mirgrate, proliferate, differentiate, and stratify to neo-epidermis
81
fibroblast proliferation
keratinocyte (IL1 and TGF(b))>fibroblast>myofibroblast (tissue contraction during remodeling)
82
Angiogenesis
generates new vessel formation, brings in oxygen and nutrients
creates granulation tissue to fill in/heal wound
sprout UPWARDS
83
Remodeling
regression of blood vessels and granulation tissue
wound contraction and collagen remodeling
wound strength is 80% of original
no hair follicles or sweat glands
84
primary intention of healing
all tissue closed with suture material
| ex. surgery, clean cuts
85
secondary intention of healing
wound left open and close naturally
| ex. bed sores, burns
86
tertiary intention of healing
wound left open for number of days then closed if found to be clean
87
hypertrophic scar
rapid growth, (a)SMA+ myofibroblasts, collagen parallel to skin surface, vertically oriented vessels
surgery, burn wounds, rupture of wound common
88
keloid scars
constant growth, extend beyond margins of tissue damage, genetic, thick collagen bundles, more in pigmented skin
89
Negative pressure wound therapy
for lower extremity, chronic, diabetic wounds, ulcers
| vacuum pump, drainage tubing and a dressing set
90
```
TH1 phenotype
(psoriasis?)
```
older siblings, exposure at day care , Tb/measles/HepA infection, rural env, endotoxin
TNF(a) IFN(y) IL17
91
```
TH2 phenotype
(atopic dermatitis?)
```
use of antibiotic, western life/hygiene, urban, diet, sensitization to house mites/dust mites/cockroaches
IL4 IL5 IL13
92
psoriasis
chronic, lifelong disease. common in adults, hereditary, thick silvery scales
more in US and western countries
peaks at 16-22 and 57-60
9 susceptible regions. PSOR1 chromosome 6 (50%)
93
atopic dermatitis
comes and gos, children , environmental, red/inflamed skin
94
Koebner phenomenon
scratching causes areas next to plaque to be spread to
95
Environmental factors of psoriasis
physical trauma, infections, stress, drugs, alcohol, smoking, obesity
96
IL18
important part of psoriasis pathogenesis
| determines severity
97
psoriasis Th1
secrete INF(y) and TNF (a) leading to angiogenesis, epidermal neutrophiles and lymphocytes infiltration
98
psoriasis Th17
secretes IL17 IL22 and TNF(a) leading to activation of keratinocytes and endothelial cells
99
psoriasis pathogensis
1. epidermal keratinocyte proliferation
shortening of cell cycle, migration of neutrophils to cornified layer, silvery plaques
2. vascular alterations
hyperproliferation, dilation increased permeability, bright erythema
3. inflammation
T lymphocyte activation, IFK(y) TNF(a) IL17
RETE PEGS
100
4 types of psoriasis
1. plaque-most common, red/salmon color, covered by silvery patches, knees elbows, scalp chest lower back, limbs
2. guttate-dew drop like red spots on trunk region in young adults, erupt suddenly with infections and resolve naturally
3. pustular-localized eruption of sterile pustules, redness but no scales, trunk extremitires, palm soles and nails
4. erythrodermic-shed skin, appear suddenly whole body, scaly and itchy, alters thermoregulation
101
Atopic dermatitis
chronic or recurrent, kids (early)
50% develop other allergic symptoms w/in first year and can also develop asthma
dry skin, itching, redness, swelling, scaling, oozing
102
dermatitis distribution
infants: faces then hands and feet
older kids: skin folds esp elbow and knees
adults: face and hands
103
genes involved in skin barrier function
chromosome 1q21:Human EDC=epidermal diff complex
FLG mutations that encodes filaggrin
SCCE-degrades corneodesmosomes
SPINK5: increases protease activated Th2 responses
104
genes involved in immune system
CD14 monocyte differentiation
IL4, IL18 SNP associated with asthma and allergy
TLR2: children of farmers
TSLP: thymic stromal lymphopoietin
105
Atopic dermatitis immune responses
dry skin disrupts epidermal barrier, increased water loss=reduced lipids, entry of allergens, Th2 response (IL4 IL5 IL13)
=IgE
106
Types of dermatitis
contact: after being exposed
seborrheic: recurrent rash in scalp/brow/forehead/ears
nummular:coin shaped rashes itch and burn
neurodermatitis: thickened area cuased by itching and rubbing
stasis: lower legs, damage to vales in large veins
dyshidrotic eczema: small itchy blisters fingers/toes/hands feet
107
soap free cleansers
reduce irritation and dryness to increase absorption of topicals
108
emollient
moisturize and soften skin to reduce itching, trap moisture
| apply after bathing
109
topical corticosteroids
hydrocortisone, fluticasone, flucinonide, clobetasol propionate
many side effects
110
calcineurin inhibitor
block Tcell transduction AND IL2 transcription to suppress itching/inflammation
facial areas
111
cyclosporine
short term trtmnt works well but comes back. improves quality of life
112
UV light therapy
direct sunlight can help
113
antihistamines
reduce itch
114
biologics for atopic dermatitis
dupilumab: blocks IL4 and IL13
| xolair/omalizumab: asthma, IgE blocker
115
VitD3 analog
calcipotriene, calcitriol
| equivalent to medium-potent corticosteroid
116
VitA Retinoid
teratogenic, burn, sting
117
anthralin/dithranol
naturally occurs in bark of araroba tree, stains clothes brown/red
118
oral, systemic therapies
if cover 5-10% of body
methotrexate
cyclosporine-cyclophilin and NF-AT.
acitretin-oral retinoid, 8 wks. multiple prescreenings
otezla-inhibits phosphodiesterase 4 which degrades cAMP
119
biologics
target either Tcells or block inflame action of TNF(a)
Enbrel (etanercept) tumor necrosis factor receptor fusion protein
humira (adalimumab) antibody to TNF(a), blocks action with p55 and p75 surface receptors
remicade (infliximab) one mlcl drug binds to two TNF(a)s and can bind to soluble and membrane bound TNF
Amieve (alefacept) fusion protein of CD2 of LFA3, reduces # of T cells, CD4 CD8 cells
Ustekinumab: against IL12 and IL23
secukinumab (cosentyx) IL17A agonist
