PHRM 866 Exam 1 Flashcards
what are some biotech products
peptides
proteins
gene therapy
vaccines
Some therapeutic applications of biotech
factors to affect hemtopoyetic cells and blood coagulation
interferons/cytokines (infections and cancer)
hormones and derivs
enzymes
recombinant proteins for vaccines
cell therapy
Recombinant definition?
Using cells (microorganisms or mammalian) as “factories” to produce therapeutic proteins
Cloning definition?
Turning cells into the type of high quality biotech “factory” required for therapy
Example: monoclonal antibodies
MOST biotech drugs are administered by ______
injection
Biotech products are generally more _____, _____, and ______
potent, delicate, expensive,
Protein Drug Review: Primary Struc Secondary Struc Tertiary Struc Quat Struc
primary - chemical sequence
2nd: alpha coils or beta sheets
3rd: 3D structure
4th: multiple 3d units together
What aspect of protein structure results in longer circulation time in the blood?
a) Deamidation
b) Disulfide bridges
c) Tertiary structure
d) Quaternary structure
e) Glycosylation
E - glycosylation
Two examples of excipients used to enhance protein stability in injectable products in solution and in lyophilized form are ____, respectively
a) Glucose and threhalose
b) Heparin and glucose
c) Heparin and trehalose
d) Trehalose and heparin
e) Trehalose and glucose
C - heparin and trehalose
Which of these two products have higher incidence of immunogenicity in patients?
a) Epoietin (human recombinant)
b) IL-2
IL-2
Which of the follow ing is/are typically true of intramuscular (IM) administration of monoclonal antibodies (mAbs)?
A) bioavailability (F) is near 100%
B) bioavailability (F) is 50-80%
C) peak plasma concentration (Cmax) is reached in 2-5 minutes (tmax)
D) peak plasma concentration (Cmax) is reached in several days (tmax)
a) A and C
b) A and D
c) B and C
d) B and D
D
The volume of distribution (Vd) of monoclonal antibodies (mAbs) is:
a) much larger than blood volume, due to extensive extravascular binding
b) much larger than blood volume, due to FcRn (endocytic) rescue
c) approximately equal to total body w ater, reflecting distribution to aqueous fluids in the body
d) approximately equal to blood volume, since the drug is confined to the vasculature
e) none of the above
D - approximately equal to blood volume, since the drug is confined to the vasculature
Which of the follow ing two hematopoietic factors is associated with granulocytes?
a) GM-CSF
b) MGDF
A
The neutrophil count of a patient w ith neutropenia is:a) Below 180 cells/mm3
b) Below 1,800 cells/ mm3
c) Below 180 cells/cm3
d) Below 1,800 cells/ cm3
e) Below 1,600 cells/mL
B - b) Below 1,800 cells/ mm3
The majority of circulating erythropoietin is produced in the
a) liver
b) kidney
c) bone marrow
d) pancreas
e) RES
B - kidney
The follow ing is a long-acting insulin product
a) Humulin R
b) Humulin N
c) Humalog
B - N
USP <797> applies to ___________ of sterile preparations.
a) Compounding
b) Compounding and transportation
c) Compounding, transportation and storage
d) Compounding, transportation, storage and administration
C - Compounding, transportation and storage
Interferons fall in the follow ing category
a) Granulocyte colony-stimulating factors
b) Leukemia inhibitory factors
c) Stem cell factors
d) Interleukins
e) Cytokines
E - cytokines
Avonex®(IFN-b1a, Biogen Inc.) and Betaseron®(IFN-b1b, Berlex) are two different IFN products that
a) Come from the same cell type
b) Come from different cell type
A
Select a correct statement
a) The proteins in both Epogen®and Nupogen®are glycosylated
b) The protein in Epogen®is glycosylated, w hile the protein in Nupogen®is not
c) The protein in Nupogen®is glycosylated w hile the protein in Epogen®is not
d) Neither of proteins in Epogen®or Nupogen®are glycosylated
e) The aminoacid residue chains of both Epogen®and Nupogen®are too short to forthem be considered as proteins
B - The protein in Epogen®is glycosylated, w hile the protein in Nupogen®is not
Hemophilia A and B are associated w ith deficiencies in factors ___, respectively.
a) VI and VII
b) VII and VIII
c) VIII and IX
d) IX and X
e) VI and IX
C - VIII and IX
You are asked to dispense a new monoclonal antibody (mAb)-based drug,Mabtrema®. Due to modifications to the usual mAb structure, Mabtrema®is unable tobind to the neonatal Fc receptor (FcRn). Which of the follow ing properties w ould youexpect for Mabtrema?
a) the plasma half-life is longer than that of a typical mAb
b) the plasma half-life is shorter than that of a typical mAb
c) the plasma half-life is equal to that of a typical mAb
d) it binds Protein A with high affinity
e) it can be given orally
B - the plasma half-life is shorter than that of a typical mAb
Monoclonal antibodies (mAbs) are eliminated by all of the follow ing mechanismsEXCEPT:
a) proteolysis in the liver
b) metabolism by target cells
c) renal excretion of the unmetabolized parent drug
d) phagocytosis by the reticuloendothelial system (RES)
e) binding to antidrug antibodies (ADA) in the bloodstream
C -renal excretion of the unmetabolized parent drug
what amino acids are aromatic
phenylalanine
tryptophan
tyrosine
what amino acids are sulfur containing
cysteine
methionine
what amino acids are prone to deamidation
aspargine
glutamine
Glycosyl groups: will increase ______ and ______
stability and circulation time
Glycosylation vs PEGylation:
which one is natural and which one is synthetic
natural: glycosylation
PEGylation: synthetic
Glycosylation vs PEGylation:
both affect _____ and and help _______
affect PK
help reduce sorption
Biotech Stability Issues of Proteins:
Chemistry: (3 things)
Compounding: (3 things
Chem: denaturation, aggregation, deamidation
Compound: sorption, shear forces,foaming
Protein based meds come usually as _______ or ________
solutions or dry product for reconstitution
Sugars are used with biotech products why?
makes the drugs more stable
Hematopoeisis: related to?
production of blood cells
related to infection, allergic reaction, immune challenge, hemorrhage, inflammation, hypoxia
Hematopoeisis: begins in the _________ during early pregnancy
spleen/liver
During childhood, _____ is the primary hematopoetic site
bone marrow
Extramedular hematopoiesis (extremities) _________ with age
decreases
what does EPO stand for
erythropoietin
what does TPO stand for
thrombopoietin
what does G-CSF stand for
Granulocyte colony-stimulating factor
what does M-CSF stand for
Macrophage colony-stimulating factor
what does GM-CSF stand for
Granulocyte-macrophage colony-stimulating factor
what does IL stand for
Interleukin
neutropenia = Decreased blood neutrophil count below _________
1,800 cells/mm3
different causes of neutropenia?
chemotherapy, contaminant therapy, renal function
Hemophilia A is deficient of ________
Factor VIII
Hemophilia B is deficient of ______
Factor IX
EPO vs Filgrastim:
which one is glycosylated
EPO
IFN-a comes from ______
leukocytes
IFN-j comes from ______
fibroblasts
IFN (phi or psi?) weird symbol is from _____
activated t lymphocytes
what was the first human protein demonstrated to increase survival of cancer patietns
interferon!
what different effects do interferons have?
antiviral
antitumor
MS!
Hormones started as coming from animal extracts - but where the cons?
- contamination w/ other animal proteins
- risk of immunological side effects
- not all animal hormones have high homology w/ human counterparts
what enzyme gets replaced in cystic fibrosis
DNAse
what disease gets glucocerebrosidase?
Gauchers Disease
_______ is a biologic produced by a living
system that has been genetically engineered
Biopharmaceutical
USP:
Chapters > 1000 are _______
Chapters < 1000 are ______
> 1000: informational
< 1000: are enforcable
Revised USP 797:
became effective in ______
2008
797 Lecture:
______ are a major source of contamination
people
797 Lecture:
Immediate Use CSPs — relation to 797?
they are exempt form 797 requirements!!
797 Lecture:
examples of immediate use CSPs
patient bedside ambulance ER combat zone code
797 Lecture:
administration of immediate use CSPs must begin within ______ of start of preparation
1 hour
T or F: you can store ampuls
falseee
hazardous drugs is USP ____
800
radiopharmaceuticals is USP _____
825
1 fl oz = _____mLs
29.57 mL
1 pint = ______mLs
473 mL
1 gallon = _____mLs
3785
2 pints = ____ quarts
1
4 quarts = ____ gallon
1
1 g = _____ gr
15.432
1 gr = _____ mg
64.8
1 kg = ____ lbs
2.2
1 lb = _____ g
454
1 in = ____ cm
2.54
1 tsp = _____ mL
5 ml
1 tbsp = ____ mL
15 mL
how to find BSA?
square root of…
(height (in cm) x weight (in kg))/ 3600
average BSA for an adult?
1.73 m^2
units for BSA?
m^2
units of percentage strength should always be what?
GRAMS and MILLILITERS!!! (by the 100!)
ex: 75 g / 100 mLs = 75% w/v
units of ratio strength should always be what?
GRAMS and MILLILITERS!!!
units of milligram percent should always be what?
mg and mL!!!
of mg’s per 100 mL’s of liquid
should be annotated as 5mg%
what amino acid(s) is/are involved in disulfide exchange
cysteine
what amino acid(s) is/are involved in beta elimination and racemization
Ser, Thr, Cys
what amino acid(s) is/are involved in hydrolysis, racemization, and isomerization
Asp
what amino acid(s) is/are involved in deamidation, racemization and isomerization
Asn, Gln
monoclonal Abs naming:
- mo-
- xi-
- zu-
- mu-
each one goes with what type of antibody?
mo - murine/mouse
xi - chimeric
zu - humanized
mu - human
what are some examples of protein stabilizers?
sucrose
trehalose
mannitol
sorbitol
protein stabilizers are preferentially excluded from the _______
protein surface
more excipients will ______ the temperature level of when the protein will degrade
will increase the temp
______ prevent adsorption to the surface
surfactants
interaction b/w proteins and ice:
In a frozen matrix, proteins interact with the surface of ice, __________ structure
loosening of the native
An optimum freezing rate needs to be defined for each protein:
______ freezing rate with larger ice crystals (_____ surface area) would be preferable.
However, a slower rate can lead to a greater degree of macro cryoconcentration, as well as longer exposure to the cryoconcentrated and/or pH-altered medium, leading to ________
slower freezing rate
less surface area
leading to destabilization
Thawing of Proteins:
Proteins may get sheared at ice – liquid interfaces and lose ______
Concentration gradients created during freezing can _______ the protein during thawing
______ thawing rates are usually preferred for protein stability
their activity;
can harm the protein
faster rates
what is gliding force
how much force is needed to push the drug through a syringe.. (ex: humira/pre-filled syringe type things)
TPN preparations are considered ___________ preparations according to USP<797>
.a) Low Risk
b) Medium Risk
c) High Risk
B - medium
According to USP <797>, forLow Risk compounding, there should be not more than X commercially manufactured packages of sterile products and not more than Y entries into any one sterile container or package
X = #? and Y = #?
3;
2 entries
