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48 Cards in this Set
- Front
- Back
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Are proteins INactive orally?
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Yes.
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Are some larger proteins taken up by the liver?
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Yes.
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Proteolytic cleavage can inactivate proteins and/or peptides.
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True.
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Small proteins and all peptides are rapidly filtered by the kidneys and lost in the urine.
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True.
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Insolubility leads to aggregation and phlebitis in the vasculature.
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True.
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Intravenous injections of proteins results in high blood levels initially.
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True.
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The immune system clears foreign proteins and can result in severe reactions.
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True.
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Subcutaneous injections can result in a loss of up to 80% of the dose.
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True.
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Formulation of proteins – key factors of the drug
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-Size
-Stability -Dose -Therapeutic index -Bioavailability |
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Formulation of proteins – key factors of the disease
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-Chronic or acute
-Local or disseminated -Accessible -Severity -Sex bias |
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Formulation of proteins – key factors of the destination
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-Local
-Systemic -Mucosal -Parenteral -Oral |
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Formulation of proteins – key factors of the kinetics
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-Pulsed
-Constant -First-order -Sustained |
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Formulation of proteins – key factors of the market
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Cost
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Main R&D
rationale: Biologicals vs. traditional drugs |
Replace or supplement natural proteins vs. testing new chemical entities, respectively
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Drug assay: Biologicals vs. traditional drugs
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Minute amounts in vivo vs. standard drug testing, respectively
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Type of clinical intervention: biologicals vs. traditional drugs
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biological vs. chemical
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Clinical issues with biologicals
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-Potential for “more physiological” therapy
-Integration of bio-therapy with traditional drug therapy -Drug delivery -Storage and transport of the items -Challenge in monitoring therapeutic levels |
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Stability: biologicals vs. traditional drugs
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Requires refrigeration vs more stable at room temp.
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Issues in handling biologicals: Storage
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-Usually require refrigeration.
-Freezing, thawing, and heat can denature proteins. |
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Issues in handling biologicals: Sterility
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Usually lacks a preservative
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Issues in handling biologicals: Preparation
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-Excessive agitation during reconstitution can denature proteins.
-The proper diluent is critical. -Proteins may adsorb onto plastic and glass. -Dosing calculations are based on units of activity vs. chemical weight. -Proteins are usually administered SC or IV. |
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Issues in handling biologicals: Home administration
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-transport
-storage -patient education |
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New delivery systems for biologicals - Step one: delivery of big, delicate molecules into the body
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-Transdermal (electric, ultrasound, or laser boost)
-Transnasal -Ophthalmic (eyedrops or lenses) -Implantable (polymer-based depot or pumps) -New oral (controlled release) -Pulmonary |
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New delivery systems for biologicals - Step two: targeting specific cells or tissues
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-Monoclonal antibodies
-Liposomes -Modified cells containing active genes (patient cells, donor cells) |
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Protein pharmaceuticals: Decomposition of chemical stability
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-deamidation
-racemization -hydrolysis (fragmentation) -oxidation -disulfide exchange reaction |
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Protein pharmaceuticals: Decomposition of physical stability
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-denaturation
-aggregation -precipitation -adsorption |
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Hydrophobic interaction is a primary driving force in protein folding.
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True.
deltaG = deltaH - TdeltaS |
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Denaturation of a protein
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Denaturation is the unfolding of a protein from its native structure to a more disordered arrangement.
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Denaturation may be partial or complete, reversible or irreversible and can result in loss of biological activity, aggregation, and precipitation (loss of solubility).
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True, denaturation may be partial or complete, reversible or irreversible and can result in loss of biological activity, aggregation, and precipitation (loss of solubility).
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Causes of denaturation of proteins
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Heating, pH changes, detergents, organic solvents, mechanical agitation of solutions, & denaturing agents, e.g. urea.
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Proteins may partially unfold and aggregate, owing to physical interactions, e.g. hydrophobic interaction.
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True, proteins may partially unfold and aggregate, owing to physical interactions, e.g. hydrophobic interaction.
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Proteins may also aggregate due to chemical reactions such as the disulfide exchange reaction.
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True, proteins may also aggregate due to chemical reactions such as the disulfide exchange reaction.
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The aggregation of proteins may be reversible or irreversible and lead to a loss of biological activity.
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True, the aggregation of proteins may be reversible or irreversible and lead to a loss of biological activity.
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Turbid solutions of proteins are caused by
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Precipitation of proteins is the macroscopic equivalent of aggregation – these particles form turbid solutions.
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Protein adsorption
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The adsorption of proteins occurs at air/water, oil/water, and solid/water interfaces.
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Adsorption increases with the hydrophobicity of the protein or surface.
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True, adsorption increases with the hydrophobicity of the protein or surface.
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At longer residence times, adsorbed proteins may unfold to optimize their interaction with the surface.
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True, at longer residence times, adsorbed proteins may unfold to optimize their interaction with the surface.
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Protein adsorption on hydrophilic surfaces is often at least partly reversible; adsorption on hydrophobic surfaces is often irreversible.
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True, Protein adsorption on hydrophilic surfaces is often at least partly reversible; adsorption on hydrophobic surfaces is often irreversible.
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Electric potentials can lead to enhanced adsorption, i.e. reduced adsorption with like charges.
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True, electric potentials can lead to enhanced adsorption, i.e. reduced adsorption with like charges.
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Is adsorption of a protein maximal at its isoelectric point?
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Yes, the adsorption of a protein is maximal at its isoelectric point.
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What does the quantity of adsorbed protein depend on?
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-The quantity of adsorbed protein is a few mg/m2
-depends on its nature -concentration -solution conditions -surface |
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Which has a longer expiration, liquid products from a manufacturer or reconstituted products?
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Since reconstituted products very rarely contain a preservative, liquid products from a manufacturer, such as insulin, have a much longer expiration.
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Factors to consider for the parenteral administration of protein drugs: concentration of protein drug
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-mg/mL
-µg/mL -ng/mL -pg/mL |
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Factors to consider for the parenteral administration of protein drugs: choices of diluent and additives
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-5% dextose
-NaCl injection -human serum albumin |
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Factors to consider for the parenteral administration of protein drugs: contact surfaces
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-glass
-polystyrene -polyvinylchloride (PVC) -polypropylene -polycarbonate |
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What are all the factors contributing to immunogenicity? (both structural and non-structural)
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-Sequence variation (whether from human or bacterial source)
-Glycosylation of the proteins -contamination and impurities -formulation -route of administration -dose -length of treatment -assay technologies -patient characteristics |
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What are some structural factors contributing to the immunogenicity?
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Sequence variation (whether from human or bacterial source)
-Glycosylation of the proteins |
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What are some non-structural factors contributing to the immunogenicity?
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-contamination and impurities
-formulation -route of administration -dose -length of treatment -assay technologies -patient characteristics |
