Biotech Products Flashcards
The strictly controlled structures make protein production a highly complex process that has so far proved impossible to replicate by chemical means. Why?
Even relatively small changes in the temperature, salt content or pH of the ambient solution can damage the structure and neutralize the function of the protein.
Recombinant DNA technology
modified DNA strand that is produced when a small piece of DNA is added to the genome (DNA molecule) of another organism.
Restriction enzymes are used to ____ certain sequences of DNA.
“cut”
What are the steps to make E Coli turn into a recombinant piece of technology?
- Plasmid is removed from E. coli cell and opened by the restriction enzymes.
- DNA codding for the targeted protein is inserted in the opened plasmid and plasmid is closed by ligase (recombination).\
- Introduction of recombined plasmid into E.coli host cells.
___________ are circular DNA molecules that replicate independently of the bacterial chromosomes.
Plasmids
_________ stage genetically modified E. coli bacteria are cultured and grown.
in the fermentation
The industrial-scale steel vessels in which fermentation takes place have capacities of ______ or more.
10,000 liters
___________ contains substances needed for the synthesis of the desired therapeutic protein.
The culture medium
Purification occurs two ways
The cultured cells secret the proteins into the culture medium. (taken about by centrifuge)
The proteins remain in the cells following biosynthesis.
(ground up and centrifuge)
____________ encompasses any technique that uses living organisms in the production or modification of products.
Biotechnology
Biotechnology products
refer to biopharmaceutical drugs generated through research in cell biology, genetics and recombinant DNA technology
Routes of Administration for biotechnology
B. Parenteral route because of the sensitive nature of most biopharmaceuticals, their dosage forms are limited to injectable solutions.
Why is oral a poor choice for biotechnology products?
- is unsuitable for most protein drugs, owing to their extensive degradation in GI tract.
- The highly acidic environment and proteolytic enzymes (e.g. pepsin, trypsin) immediately degrade the drug before it can be absorbed into the systematic circulation.
- The large molecular weight of proteins limits their ability to diffuse through the intestinal wall.
Insulin
is a hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body.
In type 1 diabetes, the body does
not produce insulin.
Type 2 diabetes, the body has
insulin resistance and relative insulin deficiency.
An _____ _____ is an altered form of insulin, different from any occurring in nature, but still available to the human body for performing the same action as human insulin.
insulin analog
The primary structure of insulin is made from two polypeptide chains named subunit ___ and ____.
These chains are connected by two ____ bridges.
A and B
disulfide
Insulin molecules have a tendency to form _____ in solution due to hydrogen-bonding.
dimers
in the presence of_____ ions in the blood, insulin dimers associate into hexamers.
zinc
Insulin is ____ and ______ in the body as a hexamer (a unit of six insulin molecules), while the active form is the monomer.
produced and stored
Monomers and dimers readily ______ into blood, whereas hexamers ________ poorly.
diffuse
The absorption of insulin preparations containing a high proportion of hexamers is ________
delayed.
____________ is the background insulin that is normally supplied by the pancreas and is present 24 hours a day, whether or not the person eats.
Basal insulin
____________ refers to the extra amounts of insulin the pancreas would naturally make in response to glucose taken in through food. The amount of bolus insulin produced depends on the size of the meal.
Bolus insulin
The person with type 1 diabetes must receive _______________ insulin through injections.
both basal and bolus
Why would you want to mix insulin?
to cover both basal and bolus needs.
is a unit of measurement for the amount of a substance, based on biological activity or effect.
The International Unit (IU)
Many biological agents exist in different forms or preparations. The goal of _________ is to provide a measure of the effect on the body a substance will have regardless of its mass.
IU
A ___________ preparation of a drug may have the same effect using a ________ amount, and that would also be 1 IU.
different different
There is ____ equivalence between IU measurements of different biological agents (e.g. insulin vs vitamin C).
no
What are two examples of doses insulin comes in?
U-500 and U-100
What is the scale on Insulin syringes set to?
scale is specially designed for insulin: a 100-unit calibrated scale intended for use with U-100 insulin
The labeling of insulin must state:
- The potency in USP insulin units per milliliter
2. The expiration date, which must not be later than 24 months after the date of manufacture
Hypoglycemia
is a condition that occurs when the blood sugar (glucose) is too low (
Hyperglycemia
is a condition in which an excessive amount of glucose circulates in the blood plasma (> 200 mg/dl).
Regular insulin
is structurally identical to human insulin synthesized through rDNA technology in a special non-disease-producing laboratory strain of E. coli bacteria.
are the analogues of human insulin of recombinant DNA origin.
Rapid-acting insulins
The changes in the structure of Rapid-acting insulin do not alter receptor binding, but blocks the formation of ____________ and _________
insulin dimers and hexamers.
Rapid-acting formulations consist of insulin in_____ form, while intermediate are based mainly on ______.
soluble, suspensions
Growth hormone deficiency
is a medical condition, caused by problems arising in the pituitary gland, in which the body does not produce enough growth hormone (GH, also called somatropin).
__________ with GH deficiency have a slow or flat rate of growth, less than 2 inches per year.
Children
____________ GH deficiency results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous visceral fat, decreased muscle mass, decreased bone density and low exercise performance.
In adults,
Growth hormone deficiency is treated by replacing ___________
growth hormone
Until 1985, growth hormone for treatment was obtained by extraction from human pituitary glands collected at autopsy. Since 1985 …
recombinant form of human highly purified GH produced by recombinant DNA technology.
__________ is a sterile, lyophilized powder intended for subcutaneous administration after reconstitution with Bacteriostatic Water for Injection, USP (with benzyl alcohol).
Somatropin
__________ is stable when refrigerated for up to 14 days following reconstitution with the diluent containing a preservative provided by manufacturer.
Somatropin
When sterile water for injection is used to reconstitute this product, each vial should be _________ and used within ___ hours because there is no preservative.
refrigerated, 24
An ____________ is a substance that prevents coagulation (clotting) of blood.
anticoagulant
____________, a recombinant hirudin derived from yeast cells, is a highly specific direct inhibitor of thrombin.
Lepirudin
Lepirudin may be used as an anticoagulant when heparins are contraindicated because of _____________ (low blood platelet count)
heparin-induced thrombocytopenia
tPA dissolves blood clotting by converting __________ , a component of blood, to the enzyme, ____________ which breaks down fibrin, the main constituent of a blood clot.
plasminogen, plasmin
is a protein involved in the breakdown of blood clots
Tissue plasminogen activator
Because the alteplase molecule is ________ it cannot easily diffuse across biological membrane and must be administered __________
large (527 amino acids), parentally, usually iv.
________________________ are glycoproteins that stimulate stem cells in bone marrow to form a specific kind of white blood cells (e.g. neutrophils) that defend the body against infection.
Colony Stimulating Factors (CSF)
__________ is a granulocyte colony-stimulating factor (G-CSF) analog used to stimulate the production of neutrophils in the bone marrow.
Filgrastim
________________is used in patients who are undergoing cancer treatment that causes low white blood cell counts (neutropenia) and puts the patient at risk of infection.
Filgrastim
rAHF is synthesized by a genetically engineered ______________-
Chinese Hamster Ovary (CHO) cell line.
Hemophilia
is a bleeding disorder, associated with low blood plasma clotting factor levels.
(rAHF)
Antihemophilic Factor (Recombinant)
_____________ is a glycoprotein hormone that stimulates the production of red blood cells by stem cells in bone marrow._______ is produced mainly by the kidneys, it is released in response to decreased levels of oxygen in body tissue
Erythropoietin (EPO)
(a deficiency of red blood cells production) is a complication of chronic renal failure, cancer and cancer therapy
Anemia
Epoetin Alfa
is approved for anemia related to cancer chemotherapy and chronic kidney disease.
Antibodies
are proteins produced by the B lymphocytes of the immune system in response to foreign proteins, called antigens.
Antibodies function as ____________ , binding to the antigen so that the antigen molecules can be recognized and destroyed by phagocytes.
as markers
Each tip of the “Y” of an antibody contains a ________ that is specific for one particular __________ on an antigen, allowing these two structures to bind together with precision
paratope, epitope
A typical antibody is composed of __________ and __________ connected by disulfide bonds.
two heavy chains, two light chains
A __________ is the same for all antibodies of the same class.
constant region
A ____________ gives the antibody is binding specificity and affinity
variable region
___________ are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell, in contrast __________ to antibodies which are made from several different immune cells.
Monoclonal antibodies (mAb or moAb), polyclonal
_____________ produces identical antibodies in almost unlimited quantities.
Hybridoma technology
___________ Murine MAbs, although in use, are considered to have limited therapeutic value.
Generation I:
Problem with Generation one Murine Mabs
Recognized by the human body as foreign substances, the murine MAbs often elicit a human immune response (known as HAMA or “human anti-mouse antibody” response) which neutralizes the foreign antibodies, prevents their ability to engage immune cells as intended, and accelerates their removal.
Generation II: Chimeric MAbs, which has a human constant region and murine variable region. What was better about these?
The immune response and incidents of HAMA reactions are much lower for chimeric Mabs.
Generation III: Humanized MAbs, which are 90% human, containing only 10% mouse protein in the variable region
-Nevertheless, induced antibody responses against humanized therapeutic mAbs have also been observed.
Generation IV: Human MAbs,
The human MAb are created in transgenic mice whose murine immunoglobulin genes are inactivated and replaced with human sequences.
The immunogenicity of fully human MAbs is lower and they are cleared at a lower rate from plasma due to the lack of mouse components.
The suffix, -omab, indicates
murine MAb
The suffix, -ximab, indicates
chimeric MAb
The suffix, -zumab, indicates
a humanized MAb
The suffix, -umab, indicates
human MAb
What can MAbs do with regards to cancer?
6
- trigger the immune system to attack cancer cells
- MAbs block the growth of cancer tumor
- MAbs stop new blood vessels from forming
- MAbs can deliver radiation drugs to cancer cells
- MAbs can deliver chemo drugs to cancer cells.
- MAbs can be used for cancer diagnosis
_________ can be used to reduce the body’s natural immunity in patients with organ transplants
MAbs
Rheumatoid arthritis has been linked to an overproduction of a protein called ____________, which causes inflammation in the joints.
tumor necrosis factor (TNF)
What inhibits TNF
Humira
Pregnancy tests rely on ___________ which bind to a hormone (human chorionic gonadotropin, hCG) which is made in the early stages of pregnancy
monoclonal antibodies
___________ is a form of treatment for genetic disorders or infections. When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nucleic acid (_____________) that will bind to the messenger RNA (mRNA) produced by that gene and inactivate it, effectively turning that gene “off”
Antisense therapy, antisense oligonucleotide
_____________ is an oligonucleotide that blocks translation of viral mRNA by binding to the complementary sequence of the mRNA transcribed from the coding segment of a key CMV gene.
Fomivirsen
