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73 Cards in this Set

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Tenecteplase difference from alteplase (in structure) (3)
a)Asp117 to glutamine (removes mannose)
b)Thr103 by asparagine (puts on an oligosaccharide)
c)tetraalanine put in to increase fibrin specificity
Tenecteplase activity vs alteplase activity (3)
1)10-14x more fibrin specific = decr bleeding
2)80x more resistant to endogenous inactivator
3)8x slower clearance
Clinical use of tenecteplase and dosage (2)
1)reduce AMI mortality ONLY
2)30mg to 50mg
Lanoteplase difference from alteplase (3)
1)missing finger domain and growth factor domain
2)Asp117 to glutamine provides reduced clearance
3)37 +/- 11min half-life
Lanoteplase production/administration (2)
1)produced in CHO cells
2)administered over 2-4minutes as IV bolus
Lanoteplase is more fibrin-specific than... (2)
1)streptokinase
2)urokinase
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)
Classical hemophilia (type a) (3)
a)hereditary
b)deficiency of clotting factor 8
c)x-linked (not in females)
Other name of clotting factor 8
antihemophiliac factor (AHF)
Christmas Disease (type b) (3)
a)deficiency of factor 9
b)x-linked
c)genetic
Factor 9 aka... (3)
a)vitamin K-dependent clotting factor
b)binds to factor8-lipid complex and activates it
c)essential step in the coagulation cascade
Degrees of hemophilia and are defined by...(3)
1)severe
2)moderate
3)mild

defined by amount of clotting factor
Treatment of Type A hemophilia (2)
1)replace factor 8 for prophylaxis or acute bleeding episodes
2)by recombinant products or from plasma-derived factor 8
% of hemophiliacs that are type A/B
A-85%
B-15%
Treatment of Type B
admin factor 9 from recombinant DNA or plasma derived
2 types of coagulation pathways
1)intrinsic
2)extrinsic
What is specific to the extrinsic pathway
1)tissue factor is induced by tissue damage and it activates factor 7
What is specific to the intrinsic pathway
factor 7a activates factor 9
Intrinsic coagulation pathway (4)
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
Extrinsic coagulation pathway (5)
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
Thrombin's substrate is...
fibrinogen
____ and ___ form clots
fibrin and platelets
Recombinant factor 8 (AHF) production (3)
1)glycoprotien produced from cDNA
2)use CHO cells
3)highly purified and are microorganism free
4 recombinant factor 8's are available (and source of each)
1)recombinate (CHO)
2)bioclate (CHO)
3)helixate (CHO)
4)kogenate (BHK)
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
Recombinant Factor 9 (Benefix)
a)dosage form
b)administration
a)lyophilized powder, stored @ 2-8C
b)inject IV over several minutes
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
Human DNaseI
a)brand names (2)
b)indications
a)Dornase Alfa, Pulmozyme
b)CF
Dornase Alfa fxn (2)
a)the DNA of destroyed neutrophils makes lung mucus even thicker
b)Dornase degrades this DNA to reduce thickness of mucus
Dornase Alfa
a)production
b)chemical structure
a)uses CHO cells
b)glycoprotein
Recombivax fxn
HepB vaccine
Superoxide Dismutase
a)fxn
b)clinical indications (3)
a)scavenges/destroys free superoxide radicals
b)oxygen toxicity in premature infants; MI; stroke
Epidermal Growth Factor (EGE)
b)clinical indications (2)
1)for corneal/cataract surgeries
2)facilitates healing of surgery
Cytokines properties (2)
1)soluble glycoproteins
2)aid in communication b/w cells, primary immune cells and hematological cells
Glycoproteins require/do (5)
1)receptor binding onto specific membrane receptors
2)elicit cellular responses such as:
3)signal transduction
4)turn on genes
5)hematopoietic growth factors
Fxn of hematopoietic growth factors (3)
Influence the maturation, differentiation and proliferation of circulating cells found in the blood
Interferons
a)secreted by...
b)potential fxns (3)
a)leukocytes
b)antiviral
b)anticancer
b)biological response modifiers
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
Interferons are considered as ____ but chemotherapeutic agents...
immune modulators

interact directly w/ cancer cells
Mechanism of interferons
bind to receptors of neighboring cells to activate genes to produce proteins that interfere w/ translation of viral mRNA
Interferon also activates ___ which... 11
Protein kinase

transfer phosphate from ATP to an initiative factor (IF) required for protein synthesis making it not fxn properly
Interferon also activates ____ which... 22
Oligonucleotide polymerase

synthesizes adenine trinucleotide which activates an endonuclease to cleave mRNA to stop viral protein synthesis
Interferon acts...
INDIRECTLY
Why did we need recombinant methods of producing interferons? (3)
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
Other fxns of interferons? (3)
a)enhance T-cell activity
b)activates macrophages
c)incr axn of NK cells
3 types of interferons (available commercially)
a)alpha interferon
b)beta interferon
c)gamma interferon
Beta interferon source
secreted by fibroblasts induced by viruses or synthetic oligonucleotides
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
Clinical use of Interferon alfacon-1
prolong life of ppl w/ HepC
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)
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
Human Interferon Gamma-1b mechanism for management of CGD (2)
1)activate phagocytes involved in host defense
2)enhance production of reactive oxygen radicals within phagocytes
Genetic basis CGD (3)
1)x-linked
2)autosomal disorder of phagocytic oxygen metabolite generating system
3)leaves patients susceptible to severe infexns
Human Interferon Gamma-1b does what for CGD pts..
extend time they spend w/o being hospitalized for infexns
Human interleukins are involved in... (2)
1)immune cell communication
2)soluble messengers b/w leukocytes
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
IL2 chemical structure
1)O-glycosylated
2)disulfide bond b/w cys 58/105 that is essential for activity
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
Recombinant IL2 differs from native IL2 by... (3)
1)no glycosylation
2)lack of N-terminal alanine @ position 1 (incr stability)
3)replacement of cysteine w/ serine @ 125 (incr stability)
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
Indication differences b/w interferon alpha 2a and 2b (3)
2b is indicated for everything 2a is but 2b is also indicated for:
1)genital warts
2)HepB
Most toxic cytokine
IL2
Rosenberg's method of treating cancer (4)
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
Primary site of damage of RA (2)
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
Big target of RA treatment
REMOVE TNFalpha
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
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
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
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
Natural Interferon Beta-1b source
human fibroblasts
Betaseron is inducated for...
relapsing MS
Mechanism of MS
autoimmune disease that demyleinates neurons; can result in disablement
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