Phrm 866 Exam 3 Flashcards
Antibody — __#_ chains of Amino Acids Joined by _____ Bonds
4 chains
disulfide bonds
Antibodies are also known as ________
immunoglobulins (Ig’s)
The ___ end of an antibody has amino acids arranged in one of five constant sequences or patterns.
Fc
T or F: the Fc sequence of an IgG molecule is identical for all IgG molecules in all of us
true!!!
T or F: Fc sequence of all IgM molecules is identical in all of us, but different from that of IgG
true!!!
the ____ sequence an antibody, some aminoacids arranged in a highly variable sequence.
Fab
What are the 5 antibody classes
IgG IgM IgD IgA IgE
What antibody classes are seen as monomers only
IgG
IgE
IgD
which antibody class is seen as a pentamer and has J chain in the middle of the pentamer
IgM
what is the J chain?
The J chain is a polypeptide joined to the pentamer by disulfide bonds
which antibody class is seen as a polymer or monomer
IgA
The ________ portion of an antibody selectively binds to a particular antigenic determinant.
variable Fab
What is antibody specificity? (aka the lock and key mechanism)
An antibody coded for one antigenic determinant will bind to that determinant and no other.
Secretory _____ has a secretory Chain
IgA
Secretory IgA:
found where?
in body secretions…
predominantly those of the respiratory
and gastrointestinal tracts.
The SC chain is believed to protect the IgA molecule from __________ found in respiratory and gastrointestinal secretions
proteolysis by enzymes
IgM or IgG?
which one is seen has long term immunity/memory
IgG
IgM or IgG?
will have initial rising of antibody levels quickly (within first week or two of exposure)
IgM
IgM or IgG?
increase in this antibody is seen after exposure of an antigen for the SECOND time (after first response)
IgG
Antibody Naming Rules:
-o-
mouse
Antibody Naming Rules:
-u-
human
Antibody Naming Rules:
-zu-
humanizes
Antibody Naming Rules:
-xi-
chimeric
-xizu-
chimeric humanized
what does HAMA stand for
human against mouse allergic (reaction)
Therapeutic antibodies mainly delivered via ____ route
SQ
Many therapeutic mAbs are ____ concentration products
HIGH
Many therapeutic mAbs are high concentration products
often > ____ mg/mL
100 mg/mL
________ in viscosity with increasing protein concentration
exponential increase
Exponential increase in viscosity with protein concentration – will lead to:
- Difficulty in ________
- _______ times
- Increased ________ upon administration
“syringability”
long admin times
pain perception
types of incompatibilities of CSPs?
- Chemical incompatibility
- Physical incompatibility
- Y-site incompatibility
- Pharmacological incompatibility
Chemical or Physical Instability?
Denaturation
physical
Chemical or Physical Instability?
Deamidiation
chemical
Chemical or Physical Instability?
Aggregation
physical
Chemical or Physical Instability?
precipitation
phsyical
Chemical or Physical Instability?
Racemization
chemical
Chemical or Physical Instability?
oxidation
chemical
Chemical or Physical Instability?
adsorption
physical
Chemical or Physical Instability?
beta elimination
chemical
Chemical or Physical Instability?
disulfide exchange
chemical
Which type of incompatibility? (chemical, physical, Y-site, pharmacological)
Refers to formation of turbidity, haze, or a precipitate, or to sorption of drug to a container or IV delivery system
physical
Which type of incompatibility? (chemical, physical, Y-site, pharmacological)
Product is unsuitable for administration because of chemical reaction (oxidation, hydrolysis, deamidation, and so forth)
chemical…
Which type of incompatibility? (chemical, physical, Y-site, pharmacological)
Occurs when two or more drugs administered concurrently result in undesirable antagonistic or synergistic action
pharmacological
Labeling Guidelines:
Labeling required if the CSP…..
-is not _________
-is ______________
if NOT administered immediately
is administered by a different person
Labeling Guidelines:
Label conforms to what things?
federal, state and local laws and regulations
Labeling Guidelines: Labels are printed in \_\_\_\_\_\_ format, easy to read and free of \_\_\_\_\_\_
standardized format
free of obliterations
Labeling Guidelines:
Labels are firmly ______
affixed
Labeling Guidelines:
T or F: Metric system or apothecary measures should be used
FALSE
metric system only!!
Labeling Guidelines:
T or F: No locally assigned names, numbers or abbreviations
true!!
Minimum USP <797> label requirements:
_____ date
Use distinct labeling for solutions intended for what 5 things?
beyond use date
irrigation, cardioplegia, intrathecal and epidural injections and peritoneal dialysis
Minimum USP <797> label requirements:
T or F: Route of administration is needed
true! (do just let it up for interpretation!!)
Minimum USP <797> label requirements:
______ conditions
_______ labeling to emphasize the most critical aspects
storage conditions (fridge or freezing) Auxiliary labeling
T or F: it is best to use auxiliary labels all the time
False!! do not over use!! (like alert fatigue!! - we just become numb to it)
Minimum USP <797> label requirements:
Name of drug, preferably ______ (may do _____ if it helps decrease confusion)
prefer generic; may do trade name
Minimum USP <797> label requirements:
T or F: you must have other ingredients and volumes
true!!
HEPA Filters:
Remove _____% of all air particles ____ or larger
- 97%
0. 3 um (micrometers) or larger
Pinal highlighted what particle that is caught by the filter?
Pseudomonas diminuta ATCC!!
what does HEPA stand for?
high efficiency particulate airs
IV vs SC admin of Antibodies:
SC has lower ______ and ____
SC has greater _________
(compared to IV!)
lower bioavailability and Cmax
greater tmax
Antibodies are large usually > ____ kD
100
Antibody Lecture:
MW < 5 kD –> Mainly _______ absorption
MW > 100 kD –> Mainly _______ absorption
capillary
lymphatic
What is the term for this definition?
Occurs when two or more drugs administered concurrently result in undesirable antagonistic or synergistic action
Pharmacological Incompatibility
What is the term for this definition?
Product is unsuitable for administration because of chemical reaction (oxidation, hydrolysis, deamidation, and so forth).
chemical instability
What is the term for this definition?
Refers to formation of turbidity, haze, or a precipitate, or to sorption of drug to a container or IV delivery system
physical instability
Precipitation will occur whenever the _______of the drug is exceeded
solubility
Large ions (e.g., heparin) can form complexes with __________ (e.g., aminoglycosides) and precipitate
oppositely charged drugs
Turning insoluble drugs into _____ form helps solubilize them
ionic (ex: add a base to a poorly soluble acid)
Acidic drugs are generally less soluble (i.e., physically less stable) in ______ solutions
acidic
T or F: Lipids should never be added to dextrose before amino acids
true!!!
______ (a surfactant) can produce anaphylactic shock (paclitaxel)
Chremophor
Drugs solubilized with cosolvents can precipitate upon ______ (in a vial or in a vein)
dilution
T or F: Acid salts and bicarbonate are incompatible
trueee
______ is a Surface phenomenon
Adsorption
______ drugs can absorb into plastic administration sets, especially those made of PVC
lipophilic
Lipophilic drugs can absorb into plastic administration sets, especially those made of ____
PVC
Oil emulsions (e.g, PN) leach plasticizers from plastic containers, that is why they should be packaged in _____ containers only
glass
Hydrolysis is highly dependent on_______ and _____
temperature and pH
Laminar flow hoods have UV lamps – It is best to have the UV light on when the hood is _____
empty (because UV could damage drugs!!)
LVP (l a r g e v o l u m e p a r e n t e r a l )
Often used to administer __________
multiple medications
Y-site
Can reduce the potential for __________
Care must be taken in _______ site as needed
incompatibilities
flushing
ISO Classes:
_____ number = better air quality
lower number
For CSPs:
Store in _______ until time of use (except) if intended for prompt administration
Let reach __________ before administration
fridge
room temperature
what is the best type of HEPA filter
Type C
A HEPA filter vs HEPA A filter……
A HEPA = generic ass filer — 55% removing partilcles
HEPA A = a good filter (not best that is C) – 99.7% of removing particles
T or F: best to test and certify equipment for sterility/filter effectiveness when no one is using it
FALSE! – people are biggest contaminators– make it realistic — so have people use it
T or F: Laminar flow hoods are sterile
FALSE!! they are NOT - we try to make them clean as possible but they are never actually sterile
Protein Structure (primary, secondary, tertiary or quaternary?) amino acid sequence of a protein and all covalent modifications, except disulfides
primary
Protein Structure (primary, secondary, tertiary or quaternary?) local specific structures of a protein caused by hydrogen bonding, electrostatic, interactions, van der Waals forces, etc
secondary
Protein Structure (primary, secondary, tertiary or quaternary?) final 3-dimensional structure of a single protein chain resulting from intramolecular interactions
tertiary
Protein Structure (primary, secondary, tertiary or quaternary?) The 3-dimensional structure of a two or more protein chains resulting from inter-molecular interactions
quatenary
Unlike small molecules, ______ (here we will focus on peptides and proteins) possess a great deal of structural diversity due to their primary, secondary, tertiary and quaternary structures
biologicals
T or F: Chemical and physical instability can be very detrimental to the function and safety of biologicals
true af
what are the 5 forces that maintain the structure in peptides/proteins
covalent bonds electrostatic interactions polar-interactions hydrophobic interactions solvation
what type of interaction is hydrogen bonding
electrostatic
________ oxidation is not a major pathway for protein degradation and is difficult to predict.
methionine
T or F: Methionine oxidation is a major pathway for protein degradation and is difficult to predict.
FALSE - it is NOT a major pathway (but it is difficult to predict)
Almost all protein and peptide formulations are designed to be or near the pH of maximum stability of the protein, usually between pH ____ and ___
4.5 - 7.5
Recombinant Protein Production:
______ a gene into a cell allows for mass production (expression) of a protein
Transfecting
Recombinant Protein Production:
Synthesis for large peptides is expensive and difficult to perform in _______
large quantities
Recombinant Protein Production:
T or F: Bacteria do not provide post-translational modification
true!! bacterial does not! (but Chinese Hamster Ovary (CHO), COS, Baby Hamster Kidney cells, and yeast cells can do post translational modification)
Knipp Lecture:
_____ are Peptide/protein epitopes added to the protein
fusion tags
Knipp Lecture:
Fusion Tags – can help with _________ and tag sequence must __________
help w/ immunopurification
MUST NOT be similar to that of cell
T or F: Fusion tags can enable easier protein purification.
true!! (you are able to look for the tag…)
Knipp Lecture – Purification:
______ cells generate more proteins, and thus complicates purification
Mammalian
T or F: E. coli does not add post translation modiciations
true!! (it does not!! (bacteria does not!!)
Often glycosylation or another PTM can be detected as _____ by the immune system in humans
foreign (why what cell is used for making a biologic is important)
Upon completion of purification, the protein is now out of ___________ and formulations must be developed to stabilize it for clinical use.
its cellular environment
Epitope tagging is one way to improve purification through _____________ (antibodies on a column)
affinity chromatography
Lyophilized products have excipients that ______ to stabilize the dried protein
replace water
Proteins formulated in solution have excipients that ________ and stabilize the product.
increase water binding
_____ have multiple alcohol moeities that create preferential hydration.
Polyols
_______-bind metals that might cause oxidative stress of induce instability due to metal binding to the protein.
metal chelators
____________ can stabilize proteins through stoichiometric binding or by forming liposomal like structures
Phospholipids and fatty acids
______ is a good additive that possesses fairly high stability.
- It can prevent aggregation and surface adsorption on glass.
albumin
______ can be used to prevent oxidative damage to Met, protect disulfide bonds , and potentially stabilize a protein.
Antioxidants
Manual or automatic defrost freezers are best?
manual!! (Automatic will change temps all the time to keep it from frosting over…)
