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73 Cards in this Set
- Front
- Back
Tenecteplase difference from alteplase (in structure) (3)
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a)Asp117 to glutamine (removes mannose)
b)Thr103 by asparagine (puts on an oligosaccharide) c)tetraalanine put in to increase fibrin specificity |
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Tenecteplase activity vs alteplase activity (3)
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1)10-14x more fibrin specific = decr bleeding
2)80x more resistant to endogenous inactivator 3)8x slower clearance |
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Clinical use of tenecteplase and dosage (2)
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1)reduce AMI mortality ONLY
2)30mg to 50mg |
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Lanoteplase difference from alteplase (3)
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1)missing finger domain and growth factor domain
2)Asp117 to glutamine provides reduced clearance 3)37 +/- 11min half-life |
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Lanoteplase production/administration (2)
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1)produced in CHO cells
2)administered over 2-4minutes as IV bolus |
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Lanoteplase is more fibrin-specific than... (2)
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1)streptokinase
2)urokinase |
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Hemophilia
a)type of disease b)classified as...(2) |
a)group of genetic life-long bleeding disorders
b)type a (classical hemophilia) type b (christmas disease) |
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Classical hemophilia (type a) (3)
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a)hereditary
b)deficiency of clotting factor 8 c)x-linked (not in females) |
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Other name of clotting factor 8
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antihemophiliac factor (AHF)
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Christmas Disease (type b) (3)
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a)deficiency of factor 9
b)x-linked c)genetic |
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Factor 9 aka... (3)
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a)vitamin K-dependent clotting factor
b)binds to factor8-lipid complex and activates it c)essential step in the coagulation cascade |
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Degrees of hemophilia and are defined by...(3)
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1)severe
2)moderate 3)mild defined by amount of clotting factor |
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Treatment of Type A hemophilia (2)
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1)replace factor 8 for prophylaxis or acute bleeding episodes
2)by recombinant products or from plasma-derived factor 8 |
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% of hemophiliacs that are type A/B
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A-85%
B-15% |
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Treatment of Type B
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admin factor 9 from recombinant DNA or plasma derived
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2 types of coagulation pathways
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1)intrinsic
2)extrinsic |
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What is specific to the extrinsic pathway
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1)tissue factor is induced by tissue damage and it activates factor 7
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What is specific to the intrinsic pathway
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factor 7a activates factor 9
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Intrinsic coagulation pathway (4)
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1)after factor 9 is activated by factor 7a..
2)factor 10 is activated by 9a,8a,calcium and phospholipids 3)10a,Va,calcium and phospholipids produce thrombin from prothrombin 4)thrombin converts fibrinogen to fibrin |
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Extrinsic coagulation pathway (5)
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1)tissue factor is induced by tissue damage
2)TF activates factor 7 3)7a activates factor 10 4)10a,Va,calcium and phospholipids produce thrombin from prothrombin 5)thrombin converts fibrinogen to fibrin |
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Thrombin's substrate is...
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fibrinogen
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____ and ___ form clots
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fibrin and platelets
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Recombinant factor 8 (AHF) production (3)
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1)glycoprotien produced from cDNA
2)use CHO cells 3)highly purified and are microorganism free |
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4 recombinant factor 8's are available (and source of each)
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1)recombinate (CHO)
2)bioclate (CHO) 3)helixate (CHO) 4)kogenate (BHK) |
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Recombinant Coagulation Factor 9
a)brand name b)indication c)chemical structure (2) d)production |
a)Benefix
b)bleeding in hemophilia B patients c)glycoprotein, single chain protein d)CHO cells using cDNA |
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Recombinant Factor 9 (Benefix)
a)dosage form b)administration |
a)lyophilized powder, stored @ 2-8C
b)inject IV over several minutes |
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Recombinant Factor 7a
a)brand name b)why made? c)chemical structure d)production |
a)Novoseven
b)alternative to patients w/ inhibitor development to recombinant factor 8 c)glycoprotein d)BHK cells using cDNA |
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Human DNaseI
a)brand names (2) b)indications |
a)Dornase Alfa, Pulmozyme
b)CF |
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Dornase Alfa fxn (2)
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a)the DNA of destroyed neutrophils makes lung mucus even thicker
b)Dornase degrades this DNA to reduce thickness of mucus |
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Dornase Alfa
a)production b)chemical structure |
a)uses CHO cells
b)glycoprotein |
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Recombivax fxn
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HepB vaccine
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Superoxide Dismutase
a)fxn b)clinical indications (3) |
a)scavenges/destroys free superoxide radicals
b)oxygen toxicity in premature infants; MI; stroke |
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Epidermal Growth Factor (EGE)
b)clinical indications (2) |
1)for corneal/cataract surgeries
2)facilitates healing of surgery |
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Cytokines properties (2)
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1)soluble glycoproteins
2)aid in communication b/w cells, primary immune cells and hematological cells |
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Glycoproteins require/do (5)
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1)receptor binding onto specific membrane receptors
2)elicit cellular responses such as: 3)signal transduction 4)turn on genes 5)hematopoietic growth factors |
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Fxn of hematopoietic growth factors (3)
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Influence the maturation, differentiation and proliferation of circulating cells found in the blood
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Interferons
a)secreted by... b)potential fxns (3) |
a)leukocytes
b)antiviral b)anticancer b)biological response modifiers |
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Biotherapy
a)is different from standard chemotherapy using small chemical drugs via.. b)enhances.. |
a)act indirectly; don't act right @ site of problem
b)enhance normal immune interaxns w/ cells in specific or nonspecific fashion |
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Interferons are considered as ____ but chemotherapeutic agents...
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immune modulators
interact directly w/ cancer cells |
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Mechanism of interferons
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bind to receptors of neighboring cells to activate genes to produce proteins that interfere w/ translation of viral mRNA
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Interferon also activates ___ which... 11
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Protein kinase
transfer phosphate from ATP to an initiative factor (IF) required for protein synthesis making it not fxn properly |
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Interferon also activates ____ which... 22
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Oligonucleotide polymerase
synthesizes adenine trinucleotide which activates an endonuclease to cleave mRNA to stop viral protein synthesis |
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Interferon acts...
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INDIRECTLY
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Why did we need recombinant methods of producing interferons? (3)
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1)had to be extracted from white blood cells
2)HIGHLY EXPENSIVE to do this 3)could get an ounce of them from 630,000 gallons of plasma |
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Other fxns of interferons? (3)
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a)enhance T-cell activity
b)activates macrophages c)incr axn of NK cells |
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3 types of interferons (available commercially)
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a)alpha interferon
b)beta interferon c)gamma interferon |
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Beta interferon source
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secreted by fibroblasts induced by viruses or synthetic oligonucleotides
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Recombinant Interferon Alfacon-1
a)brand name b)produced by... c)synthetic version of... d)alternate name and why? |
a)Infergen
b)E. coli c)interferon alpha d)consensus interferon b/c uses common AAs from many interferons |
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Clinical use of Interferon alfacon-1
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prolong life of ppl w/ HepC
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Recombinant interferon gamma-1b
a)brand name b)produced by...(and sig of this) |
a)Actimune
b)E.coli (is naturally a glycosylated protein but doesn't need the glycosylation for activity) |
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Human Interferon Gamma-1b
a)use b)desc of the disease (2) |
a)chronic granulomatus disease
b1)autoimmune disease that affects the lungs b2)ppl w/ CGD have a lower capacity to perform phagocytic oxidation metabolism |
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Human Interferon Gamma-1b mechanism for management of CGD (2)
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1)activate phagocytes involved in host defense
2)enhance production of reactive oxygen radicals within phagocytes |
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Genetic basis CGD (3)
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1)x-linked
2)autosomal disorder of phagocytic oxygen metabolite generating system 3)leaves patients susceptible to severe infexns |
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Human Interferon Gamma-1b does what for CGD pts..
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extend time they spend w/o being hospitalized for infexns
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Human interleukins are involved in... (2)
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1)immune cell communication
2)soluble messengers b/w leukocytes |
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IL2
a)production b)category it is in c)fxn |
a)synthesized and secreted by T-cells
b)lymphokine c)stimulate the growth, differentiation, and activation of T-cells, B-cells and NK cells |
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IL2 chemical structure
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1)O-glycosylated
2)disulfide bond b/w cys 58/105 that is essential for activity |
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Recombinant IL2
a)generic name b)brand name c)indication (3) d)production by... |
a)Aldesleukin
b)Proleukin c)metastatic renal/melanoma cancer, breast cancer d)E. coli |
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Recombinant IL2 differs from native IL2 by... (3)
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1)no glycosylation
2)lack of N-terminal alanine @ position 1 (incr stability) 3)replacement of cysteine w/ serine @ 125 (incr stability) |
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Recombinant IL2
a)dosage form b)administration c)SEs (4) |
a)lyophilized powder w/ mannitol
b)IV infusion c)very toxic, shaking, chills, so need careful monitoring |
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Indication differences b/w interferon alpha 2a and 2b (3)
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2b is indicated for everything 2a is but 2b is also indicated for:
1)genital warts 2)HepB |
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Most toxic cytokine
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IL2
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Rosenberg's method of treating cancer (4)
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1)Put patients lympocytes & IL2 & cancerous cells in a test tube
2)This produces LAK cells (lymphocyte activated killer cells) 3)incubate these for a month to get TILs (tumor infiltrating lymphocytes) 4)TILs are 50-100x more powerful than LAK cells |
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Primary site of damage of RA (2)
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1)junction of synovium lining (inflammes area of synovial fluid)
2)this area is called the pannus which has high levels of macrophages via TNFalpha |
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Big target of RA treatment
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REMOVE TNFalpha
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Gamma interferon
a)also called b)source |
a)immune interferon or lymphokine b/c only secreted by lymphocytes
b)secreted by lymphocytes (CD4/CD8) and NK cells |
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Recombinant Interferon alpha-2a
a)brand name b)produced by... c)chemical structure (2) |
a)Rofereron-A
b)E. coli c1)non-glycoslyated protein that is still biologically active c2)lysine @ 23 to stabilize product |
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Recombinant Interferon alpha-2b
a)brand name b)produced by... c)chemical structure (3) |
a)Intron A
b)E. coli c1)nonglycoslyated protein c2)Arginine @ 23 to stabilize |
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Recombinant Interferon Beta-1b
a)brand name b)produced by... c)chemical structure |
a)Betaseron
b)E. coli c1)serine sub'd for cysteine @ 17 c2)glycosylated |
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Natural Interferon Beta-1b source
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human fibroblasts
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Betaseron is inducated for...
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relapsing MS
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Mechanism of MS
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autoimmune disease that demyleinates neurons; can result in disablement
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Recombinant Interferon Beta-1a
a)produced where b)it compared to human INF-B c)brand name |
a)CHO/mammalian cells
b)IDENTICAL c)Avenox |