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Biotech Exam 2
Biotech Exam 2 material
102
Pharmacology
Graduate
10/28/2011

Additional Pharmacology Flashcards

 


 

Cards

Term
Deficiency of Clotting factor VIII (AKA antihemophiliac factor AHF)
Definition
classic hemophilia (type A)+
Term
Deficiency of factor IX
Definition
Christmas Disease (Type B)
Term
where is the mutation or deletion on a person with Christmas Disease (Type B hemophilia)
Definition
mutations or deletions on factor IX gene on long arm of X chromosome
Term
Factor IX is dependent on what vitamin?
Definition
vitamin K
Term
what does factor IX bind to?
Definition

factor VIII-lipid complex, thus activating factor X, an essential step in the coagulation cascade

 

Term
what type of protein is clotting factor VIII? where is it it made?
Definition
large glycoprotein synthesized mainly by liver, spleen and kidneys
Term
describe the amino acid composition of clotting factor VIII
Definition
composed of a single chain polypeptide containing 2332 amino acids (large protein)
Term
how is clotting factor VIII cloned (via E. Coli or mammalian cells)?
Definition
mammalian cells, since it is a glycoprotein.
Term
what is the concentration of clotting factor VIII in the plasma (in ng/ml)?
Definition
approx 200 ng/mL
Term
Brand names of clotting factor VIII drugs
Definition

Recomibinate

KoGENate

Bioclate

Helixate

Term

 this drug, a small protein (550 kDa, 415 AA in single chain), is indicated for control and prevention of bleeding episodes in patients with hemophilia B

 

Definition
rFactor IX, Benefix
Term
this drug is for patients who have antibody resistance to fact VIII or IX drugs
Definition
Novoseven (recombinant factor VIIa)
Term
How does Dornase Alfa/Pulmozyme work?
Definition
Also known as human deoxyribonuclease I (hDNase I). This drug is similar to the native enzyme. It is a glycoprotein containing 260 AA, and it works by degrading extracellular DNA to smaller fragments to reduce viscosity of CF airway mucus secretions
Term
what is the potential use for recombinant Superoxide Dismutase
Definition
potential to be useful in treatment of oxygen toxicity in premature infants; MI, and stroke.
Term
glycoproteins require what two things
Definition
1 receptor binding onto specific receptors for cellular response
2 hematopoietic growth factors (these influence maturation, differentiation and proliferation)
Term
Interferons are broad-spectrum antiviral and potential anticancer therapies, which means they are (BRM):
Definition
biological response modifiers
Term
interferons are considered ______ _______ but chemoterapeutic agents interact directly with the cancer cells
Definition
immune modulators
Term
describe the mechanism of antiviral properties of interferons:
(very long answer)
Definition
1. bind to receptors of health neighbor cells to activate genes to produce antiviral proteine
2. block viral translation via enzyme
3. protein kinase phosphorylates initiative factor that is required for protein synthesis
4. IF is inactive when Phosphorylated and cannot synthesis protein
5. Oligonucleotide polymerase synthesis adenine trinucleotide (AAA) to activate an endonuclease to prevent viral replication
Term
interferons other mechanism of action for antitumor action
Definition
1 enhance T cell activity
2 activate macrophage
3 increases cytotoxicity of NK cells (kill directly)
Term
what secretes alpha interferon and what induces it?
Definition
secreted by leukocytes and induces by viruses
Term
what secretes beta interfereon and what is it induced by?
Definition
secreted by fibroblats and induced by viruses or synthetic oligonucleotides
Term
gamma interferon (AKA immune interferon) is secreted by:
Definition
lymphocytes (CD4+ and CD+ and NK cells)
Term
Recombinant Interferon alpha-2a
Definition
Rofereron A
-interferon alpha
-165 AA
-produced by genetically engineered E coli
-non-glycosylated protein
-molecule has lysine at position 23
Term
recombinant interferon x-2b
Definition
Intron A
-interferon alpha
-165 AA
-nonglycosylated
-has arginine at position 23
Term
Recombinant Inteferon B-Ib
Definition
Betaseron
-interferon beta
-indicated for treatment of MS
-produced by human fibroblasts
-serine residue substituted for cysteine at position 17 (increase stability since cysteine is thiol and serine is a hydroxyl)
Term
inteferon beta-Ia
Definition
Avenox
-produced in mammalian cells
-has same AA sequence and CHO chain as natural INF-B
-admin 1x weekly IM (all other INF-B are SQ)
-flu like side effects
Term
interferon alfacon-1
Definition
Infergen
-synthetic version of INF alpha
-166 AA
-engineered in E coli
-AA sequence product of comparing sequences of several natural subtypes and assigning most freq. observed AA at each pos.
-homology of 88% with INF alpha 2 and 30% with INF beta
Term
alfacon is used as treatment for what? what can they do to increase half life?
Definition
hepatitis B and C, pegylated INF alpha 2a to increased half life (decreases visibility and CL by liver)
Term
recombinant human interferon gamma-Ib
Definition
Actiumune
-tx chronic granulomatus disease
-140 AA glycoprotein
-glycosylation not necessary for bioactivity
-activates phagocytes in host defense
+enchances oxygen radicals in phagoctes for more efficient killing
-extends time patients spend out of hospital
Term
what is the general action of interleukins
Definition
immune cell communication
Term
IL-2 (AKA lymphokine) is secreted by what? and stimulates what?
Definition
T-cells
-stims growth, differentiation and activation of T cells, B cells and NK cells
Term
where is the bond that is essential for Il-2's biological activity?
Definition
intramolecular disulfide bond between Cs 58 and Cys 105
Term
Il-2 Aldesleukin
Definition
-Proleukin
-metastatic renal carcinoma and metastatic melanoma
Term
how is IL-2 produced and how is different from the native protein?
Definition
-prod by inserting plasmid containing recomb IL-2 cDNA into E coli expression system
-differs from native by:
+absence of glycosylation
+lack of N-terminal alanine at position 1 (132 AA)
+serine for cysteine at pos 125
Term
Generic to Brand: Interferon alpha 2a
indication:
Definition
roferon-A
-hairy cell leukemia, AIDS related KS
Term
Generic to Brand: interferon alpha-2b
indication:
Definition
intron A
-hairy cell leukemia, genital warts, chronic hepatitis non-A, non-B/C, chronic hep B
Term
Generic to Brand: interferon alfacon-1
Definition
infergen, CIFN
Term
Generic to Brand: interferon beta-1a
Definition
Avonex
Term
Generic to Brand: interferon beta-1B
indication:
Definition
Betaseron
-relapsing-remitting MS
Term
Generic to Brand: interferon gamma-1b
indication:
Definition
Actimmune
-chronic granulomatous disease
Term
Generic to Brand: Aldesleukin
Definition
Proleukin
Term
Generic to Brand: Denileuin difititox
Definition
Ontak
Term
Generic to Brand: Oprelvekin
Definition
Neumega
Term
Generic to Brand: Etanercept
Definition
Enbrel
Term
Generic to Brand: interferon alpha-n3
indication:
Definition
Alferon N
genital warts
Term
Etanercept
Definition
Enbrel
-Rheumatoid arthritis
-rDNa prudced fusion protein that binds to TNFX (TNF alpha and beta) and blocks its intrxn with cell surface TNF receptors to reduce TNF stim
-recombinant human TNF receptor linked with a constant region (fc) human IgG1
-Fc region allows complex to be seen by macrophages
-reduces proinflamm mediators in pts. synovium to reduce RA related events
Term
IL-2 conjugated to Diphtheria Toxin
Definition
Denileukin Diftitox
-contains first 389 AA of diphtheria toxin to AA resides 2-133 of human IL-2
-targets IL-2 Receptors which are highly expressed in Cutaneous T-Cell Lymphoma (low grade nonhodgkin lymphomas)
-this brings diphtheria toxin directly to kill the CTCL target
Term
IL-11
Definition
Oprelvekin
-thromboporetic GF that directly stims prolif of hematopoietic stem cells and megakaryocyte progenitor cells
-induces megakaryocyte maturation to increase platelet production
-produced in E coli
-indication: preventing thrombocyopenia following suppressive chemotherapy
-monitor fluid retention
Term
what are Hematopoietic growth factors or CSFs?
Definition
cytokines that regulate hematopoiesis, lead to colony formation.
-glycoproteins produced by T-lymphocytes or macrophages
Term
how do CSFs work?
Definition
act on hematopoietic cells by binding to their specific membrane receptors to stimulate proliferatino, differentiation and maturation and functional activation of RBC, WBC and platelets
Term
what are the four types of CSFs?
Definition
1 granulocyte CSF (G-CSF)
2 granulocyte-macrophage CSF (GM-CSF)
3 macrophage CSF (M-CSF)
4 multi-CSF (IL-3)
Term
Generic/Brand for Filgrastim (GCSF)
indication:
Definition
-Neupogen
-decreases infections in pts. with non-myeloid cancers receiving myelosuppresive chemo
-Never shake the vial before dose is withdrawn for IV injection!
Term
Generic/Brand (GM-CSF) Sargramostim
Indication:
Definition
Leukine
-produced by recomb. in yeast S cerevisiae
-approved for accelerated myeloid cell recovery following autologous bone marrow transplantation (ABMT)
-reduces: periods of neutropenia, antibiotic utilizations, and hospitalizations with ABMT
Term
where is EPO produced?
Definition
kidney cells in response to low blood oxygen tension
Term
what does EPO do?
Definition
stimulates division and differentiation of erythroids progenitors in the bone marrow; increases production of RBC
Term
what has Epogen been approved for?
Definition
-treats anemia associated with CRF for patients by at least maintaining or elevating hematocrit or hemogloblulin levels
Term
Becaplermin (brand name and indication)
Definition
Regranex
-indicated for tx of diabetic foot ulcers
-prod. by inserting gene for B chain of PDGF into a yeast expression system
Term
Epidermal Growth Factor (EGF)
Definition
indicated for cataract and corneal surgery and is under development
Term
what is a polyclonal antibody?
Definition
when a large number of B-cells are ablet o bind to various epitopes of an antigen and hence produce a large number of antibodies (polyclonal Abs or antiserum)
Term
polyclonal antibodies consist of ______ antibodies that recognize different epitopes of antigen. It is derived from various clones of _____ ______.
Definition
-heterogenous
-plasma cells
Term
hybridomas have properties of both parent cells which are:
Definition
properties of B-lymphocytes to produce specific antibody and have immortal property of myeloma cells
Term
humanized antibodies have higher or lower affinity of binding to antigen than chimeric Abs?
Definition
lower
Term
What is Oncoscint CR?
Definition
murine MAb to diagnose colorectal tumors
Term
What is Oncoscint OV?
Definition
murine MAb in vivo dx of ovarian cancer
Term
what is Myoscint (imciromab)?
Definition
murine radiolabeled isotope that assess damage to myocardium after MI. helps dx pts who may end up with HF
Term
what are three advantages of using Mabs as diagnostic agents?
Definition
1. Abs demonstrate extremely precise specificity
2. Abs react with uniform avidity
3. Can be readily purified to homogeneity, providing reagent-grade materials for analysis.
Term
Trastuzumab
Definition
Herceptin
Humanized Mabs,
-Indicated for refrac breast cancer
-binds to HER2 extracellular domain
Term
Muromonab-CD3
Definition
Orthoclone-OKT3
-Murine Mab
-transplant rejection reversal
Term
Infliximab
Definition
Remicade
-Chimeric Mab
-anti-tumor necrosis factor alpha
-Chrohn's disease
Term
Abciximab
Definition
Reopro
-Chimeric
-LgG derived Fab2 frag blocks site on activated platelets
-indicated for prevention of reocclusion of coronary arteries during and after coronary angioplasty
Adjunct to PTCA for prevention of acute cardiac complications
Term
Rituximab
Definition
Rituxan
-Chimeric (IgG type)
-binds to CD20 antigen on B-cell lymphomas
-tx of B-cell non-Hodgkin's lymphoma
Term
Basiliximab
Definition
Simulect
-Chimeric
-binds to subunit of IL-2 on active T-cells to block IL-2x receptor
-prevents transplant rejection
Term
Daclizumab
Definition
Zenapax
-Humanized
-Binds to IL-2 subunit on active T cells, same MOA as Basiliximab
-prevents transplant rejection
Term
Palivizumab
Definition
Synagis
-Humanized
-Binds F protein on virus surface to prevent virus from infecting cells
-respiratory syncitial virus (RSV) prophylaxis
Term
Gemtuzumab/Ozoganicin
Definition
Mylotarg
-Fusion Mab
-humanized anti-CD33 Mab conj. w/ cytotoxic antibiotic calicheamicin
-Tx of CD33 positive AML
Term
Define genomics
Definition
study and analysis of genomes
Term
Genetic and physical mapping, as well as nucleotide sequencing are useful analyzation techniques for (genomics proteomics or bioinformatics?)?
Definition
genomics
Term
This type of sequencing uses a single DNA fragment atached to a bead then amplifies it by PCR (no cloning step)
Definition
454 Sequencing
-DNA is sequenced from bead using the enzymatic production of light as the read out
Term
This type of sequencing exploits the pH change caused by the release of H+ ions when nucleotides are incorporated into a strand of DNA
Definition
Ion torrent
Term
which is faster and less expensive sequencing: 454 or ion torrent?
Definition
ion torrent
Term
the Human genome project strategy used cloned contig sequencing, this involved (describe process)
Definition
1. construct physical map of chromosome using restriction enzymes
2. isolate and clone specific restriction frag
3. break frag into smaller pieces to sequence
4. assemble individual DNa sequence reads to reveal sequence of original restriction frag
5. position of sequence region on chrom. is already known by mapping
Term
TIGR used the two whole genome sequencing strategy, this involves (describe process)
Definition
1. isolate total DNA from cell
2. prepare shotgun library of entire chromosome
3. sequence all clones in library
4. assemble individual sequence reads into contigs
5. chromosome emerges as more sequences are read.
Term
Arcitumomab
Definition
murine MAb
-directed to carcinoembryonic antigen (CEA)
-colorectal, liver cancer
Term
Capromab
Definition
ProstaScrint Kit
Mab recognizes PSMA (prostate surfacemembrane antigen)
-specific for prostate adenocarcinomas
Term
what ar ethe murine Mabs
Definition
Muromonab, Oncoscint CR/OV, myoscint
Term
what are the solely humanized Mabs
Definition
trastuzumab (herceptin), Daclizumab (zenapax), Pavilizumab (Synagis)
Term
what is the fusion molecule Mab
Definition
Gemtuzumab Ozogamicin (Mylotarg)
Term
What is the purpose of Bioinformatics
Definition
-determines genes present in genome and their function
-compares DNA seqs and proteins to databases of all known DNa and proteins to identify and assign fxn to new genes
-aids in determining structure
-phylogenetic analysis
Term
what is BLAST utilized for?
Definition
computer search as an aid to identify new genes
-compares unknown protein or nucleic acid sequence to the database of all known proteins or DNAs
Term
what technologies are associated with proteomics
Definition
-microarrays (indirect protein detection)
-2D Electrophoresis (direct)
-Mass Spec (direct)
Term
this technique separates proteins by charge and then by size
Definition
2D electrophoresis
-must separate by charge first so you can discern between proteins that have the same MW
Term
the hybridization analysis of mRNA or DNA on a genome-wide scale
Definition
Microarray
(use this with 2D so you don't miss anything in sequencing)
microarrays are good for proteins that are turning over quickly
Term
% breakdown of the human genome (genes, transposons, miscellaneous, exons, introns)
Definition
30% genes
45% transposons
25% misc.
28.5 % introns and noncoding segments
1.5% exons
Term
where are the most significant changes in a gene
Definition
promoters, exons or introns
Term
what are the methods to detect SNPs?
Definition
1. restriction enzyme fragment length polymorphism (RFLP) - tells you loss or gain of RE in a gene
2. PCR product length variation
-presence or absence of target DNA
3. DNA sequencing
Term
alleles assoc. with diabetic nephropathy
Definition
-homozygoues RE Xba1 and enhancer 2 SNP-1
-SNPs at GLUT-1
Term
this tool shows us what genes are active in a given tissue under environmental conditions, drug tx, or stage of development
Definition
EST (expressed sequence tag)
Term
SNPs reveal the ____ ____ in an individual
Definition
genetic variations
Term
ESTs are the ___ _____ genes by an individual or tissue
Definition
actively expressed
Term
ALDH2 risk
Definition
homozygous variants cannot tolerate OH
heterozygotes can overcome discomfort and build tolerance but still susceptible to esoph. cancer
Term
nomenclature of CYP450 genes
Definition
CYP followed by number designating enzyme family, letter indicating subfamily, another number indicating indiv. enzyme, *1,2,3 indicates allele of enzyme
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