Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Advanced Parenterals > Exam 2 Stuffs > Flashcards

Exam 2 Stuffs Flashcards

1
Q

Neutropenia = neutrophil count below ____ cells/mm^2

A

1800

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

2 major dose-limiting side effects of chemo

A

Neutropenia and infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What percentage of circulating erythropoietin is produced by the kidneys?

A

90%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What 3 things can have a major impact on neutrophil count and can lead to neutropenia?

A

Chemotherapy
Concomitant therapy
Decreased renal function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is hemostasis?

A

blood clot formation
hemo = blood
stasis = standing still

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

3 steps of hemostasis

A

Formation of the platelet plug
Activation of the clotting cascade
Propagation of the clot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Hemophilia A has a deficiency of what factor?

A

VIII (8)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Hemophilia B has a deficiency of what factor?

A

IX (9)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Another name for erythropoietin?

A

epoetin alpha

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How many AA residues does erythropoietin (epoetin alpha) have?

A

165

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the MW for erythropoietin (epoetin alpha)?

A

30.4 kDa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How many disulfide links does erythropoietin (epoetin alpha) have?

A

2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Erythopoietin (epoetin alpha) glycosylated or not?

A

glycosylated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Temperature for storage of erythopoietin (epoetin alpha)

A

2-8 degrees Celsius

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Epogen generic name

A

epoetin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Neupogen generic name

A

filgrastim

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Neupogen glycosylated or not?

A

Non-glycoslylated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Filgrastim is a G-CSF - what does this mean?

A

granulocyte colony stimulating factor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

MW for filgrastim

A

18.8 kDa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Which drug is not glycosylated unlike the naturally occurring human G-SCF

A

Filgrastim

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Vd of Filgrastim

A

150 mL/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Half-life of Filgrastim

A

3-4 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

In the 1970s, what impact did interferons (IFNs) have on the influenza virus?

A

Interfered with it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What kind of molecule are interferons?

A

Pleiotropic cytokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Which drug has diverse immunomodulatory properties?

A

Interferons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

IFN alpha comes from ___

A

leukocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

IFN J comes from ___

A

fibroblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

IFN psi (greek letter that looks like pitchfork) comes from ___

A

activated T-lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What was the first human protein that demonstrated an increase in survival of cancer patients?

A

Interferons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What effects do interferons have?

A

Antiviral effects
Antitumor effects
Positive effects in multiple sclerosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Pig and human insulin differs by ___ amino acids

A

1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Bovine and human insulin differs by ___ amino acids

A

3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What molecule started as purified extracts from animals?

A

hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How many peptide chains do somatotropic hormones have?

A

1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How many peptide chains do glycoprotein hormones have?

A

2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

How many peptide chains do pro-opiomelanocortin (POMC) derived hormones have?

A

1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Which types of hormones have the smallest molecular weight?

A

POMC-derived hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Which type of hormones have the largest molecular weight?

A

glycoprotein hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Which type of hormones have carbohydrates in them?

A

Glycoprotein hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What are examples of somatotropic hormones?

A 
Growth hormone (GH)
Prolactin (Prl)
Placental lactogen (PL)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What are examples of glycoprotein hormones?

A

Luteinizing hormone (LH)
Follicle-stimulating hormone (FSH)
Chorionic gonadotropin (CG)
Thyroid-stimulating hormone (TSH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are examples of POMC-derived hormones?

A 
Corticotropin (ACTH)
alpha melanocyte stimulating hormone
beta melanocyte stimulating hormone
beta lipotropin
gamma lipotropin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What types of hormones were used in the pre-recombinant era?

A

Somatotropic hormones
Glycoprotein hormone
POMC-derived hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Downfalls of animal-extracted hormones

A

Contamination with other animal proteins
Risk of immunological side effects
Not all animal hormones have high homology with the human counterpart

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Downfalls of human-extracted hormones

A 
Scarcity
Safety concerns (creutzfeldt-jakob disease)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

HumulinR/Humalog

Which is fast-acting?

A

Humalog (lispro)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

HumulinR/Humalog

Which is regular insulin?

A

HumalinR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Difference between human insulin and insulin lispro

A

2 amino acid difference

Lys and Pro AA’s are switched (aka why it was named was it was)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

HumalinN

Long-acting or fast-acting?

A

Long-acting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Humalog Mix 75/25

Long-acting or fast-acting?

A

Both!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Insulin Glargine

Long-acting or fast acting?

A

Long-acting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Amino acid difference between insulin glargine and human insulin?

A

3 amino acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

NPH insulin

Long-acting or fast acting?

A

Long-acting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

MOA of NPH insulin

A

suspension that gradually dissolves and absorbs into the body from the formulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

MOA of insulin glargine

A

solution that precipitates upon injection and forms a depot

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

NPH or insulin glargine

Has a peak on the glucose utilization rate graph

A

NPH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

NPH or insulin glargine

Does not have a peak on the glucose utilization rate graph

A

glargine (steady absorption)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Isoelectric point definition

A

pH value at which a protein has no net charge

aka is “zwitterionic”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

At what point is the solubility of a protein at its minimum

A

isoelectric point

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Why does insulin glargine precipitate when injected?

A

It is least soluble in the neutral pH, so it precipitates into a hexamer under physiological conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What pH is native insulin least soluble?

A

5.4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What pH is insulin glargine least soluble?

A

7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Insulin in solution exists in equilibrium between what 3 configurations? Why is it like this?

A

monomer
dimer
hexamer

This helps to maintain stability of the protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What ion is in the middle of a hexamer of insulin, stabilizing it?

A

zinc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Which insulin configuration is the most vulnerable to unfolding and denaturation?

A

monomer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Which insulin configuration acts at the receptor site?

A

monomer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Which insulin configuration is the most stable?

A

Hexamer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What ion serves as an anchor in the formation of the insulin hexamer formation and stabilizes insulin?

A

zinc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What pH is insulin glargine formated at?

A

4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

How long does it take for the insulin glargine depot to dissolve?

A

~24 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Importance of enzymes

A
  • biologic catalysts
  • capable of accelerating chemical rate reactions by a million-fold
  • they are proteins
  • essential for viability of cells and tissues
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

How many enzymatic reactions have been reported and how many proteins with enzymatic activity have been reported?

A

over 1,000

over 10,000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Deficient enzyme activity in metabolic pathways may produce what?

A

clinical symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

What can adenosine deamidase be used to treat?

A

severe combined immunodeficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

what can glucocerebrosidase be used to treat?

A

gaucher’s disease (glycolipids in lysosomes)

76
Q

What can DNAse be used to treat?

A

Cystic fibrosis

77
Q

What molecule consists of four chains of amino acids joined by disulfide bonds

A

antibodies

78
Q

another name for antibodies

A

immunoglobulins

79
Q

variable region of an antibody

A

Fab

80
Q

constant (fixed) region of an antibody

A

Fc

81
Q

What region of the antibody determines what class the antibody is from?

A

Fc region

82
Q

What are the different classes of antibodies?

A 
IgG
IgM
IgD
IgA
IgE
83
Q

True or false

Fc region of all antibodies of a certain class (e.g. IgG, IgM, etc) are the same

A

True

84
Q

Which antibodies exist only as monomers?

A

IgG
IgE
IgD

85
Q

Which antibody exists as a pentamer?

A

IgM

86
Q

IgM has a _____ located in the middle of the pentamer

A

J chain

87
Q

What is a J chain

A

polypeptide joined to the IgM pentamer by disulfide bonds

88
Q

Which antibody exists as a monomer or dimer (in excreted fluids)

A

IgA

89
Q

How does the Fab region of an antibody bind to an antigenic determinant

A

selectively

90
Q

What is antibody specificity

A

When an antibody coded for one antigenic determinant will bind to that determinant and no other

91
Q

Another term for antibody specificity

A

lock-and-key

92
Q

What is the first immunoglobulin made to fight a new infection?

A

IgM

93
Q

What immunoglobulin is produced that is more specific for the infecting antigen?

A

IgG

94
Q

mab naming

a

A

rat

95
Q

mab naming

axo

A

rat/mouse

96
Q

mab naming

e

A

hamster

97
Q

mab naming

i

A

primate

98
Q

mab naming

o

A

mouse

99
Q

mab naming

u

A

human

100
Q

mab naming

xi

A

chimeric

101
Q

mab naming

xizu

A

chimeric-humanized

102
Q

mab naming

zu

A

humanized

103
Q

Antibody half-life in circulation

A

days

104
Q

What are among the most stable natural proteins?

A

Antibodies

105
Q

Most proteins have a half-life of ___

A

minutes

106
Q

Stability of IgG is comparable to what?

A

serum albumin

107
Q

How are therapeutic antibodies administered?

A

Subcutaneously (so they are high in concentration)

108
Q

Implications of therapeutic antibodies

A
  • pharmacokinetics

- difficulty and pain associated with administration

109
Q

Antibodies are big or small?

A

BIG (>100 kD)

110
Q

Antibodies are mainly absorbed into what?

A

lymphatic system

111
Q

Molecules with MW <5 kD are absorbed into what?

A

Capillaries

112
Q

Molecules with MW >100 kD are absorbed into what?

A

Lymphatic system

113
Q

Liposomes and nanoparticles up to 200 nm are absorbed into what?

A

lymphatic drainage

114
Q

As the concentration of mabs increases so does ___

A

viscosity

115
Q

therapeutic mabs are usually ____ concentration

A

high

>100 mg/mL

116
Q

What does the high viscosity of mabs cause during administration?

A

difficulty in syringability
long administration times
increased pain perception upon administration

117
Q

Biopharmaceutical definition

A

biologic produced by a living system that has been genetically engineered

118
Q

Examples of biopharmaceuticals

A

mab’s
therapeutic proteins
vaccines

119
Q

What are biopharmaceuticals composed of?

A

proteins
glycans
polyneucleotides and lipids

120
Q

Which antibodies have the lowest immunogenic risk of generating anti-therapeutic antibodies (ATAs)?

A

Fully humanized mab’s

121
Q

Which antibodies have the highest immunogenic risk of generating anti-therapeutic antibodies (ATAs)?

A

murine (mouse) mab’s

122
Q

Which buffer has a large pKa range?

A

Phosphate (2.1, 7.2, 12.4)

123
Q

What are examples of protein stabilizers?

A

sucrose
trehalose
mannitol
sorbitol

124
Q

Why is freezing a stress to biologics?

A

Proteins interact with the surface of ice, which loosens the native structure

125
Q

Biologicals (like peptides and proteins) are stable or unstable molecules?

A

unstable!

126
Q

What structure of a protein involves amino acid sequence and all covalent modifications, except disulfide bonds

A

Primary structure

127
Q

What structure of a protein results from hydrogen bonding, electrostatic interactions, van der waals forces, etc?

A

Secondary structure

128
Q

What structure of a protein results from intramolecular interactions?

A

Tertiary structure

129
Q

What protein structure involves inter-molecular interactions between more than one protein chain?

A

Quaternary structure

130
Q

Examples of covalent bonds

A

Peptide bonds of backbone

Disulfide bonds

131
Q

Examples of electrostatic interactions

A

charge-charge
charge-dipole
dipole-dipole
HYDROGEN BONDING

132
Q

Polar interaction examples

A

aromatic-aromatic

oxygen or sulfer-aromatic

133
Q

Polar interactions are strong or weak?

A

Weak

134
Q

Hydrophobic interactions usually occur where?

A

core of proteins

135
Q

What are hydropphobic interactions driven by?

A

unfavorable interactions with water

136
Q

What type of interaction is van der waal forces?

A

hydrophobic

137
Q

What does solvation require?

A

hydration

138
Q

Definition of physical instability

A

changing in the physical structure of the protein that can occur through several different pathways

139
Q

Pathways of physical instability

A

Denaturation
Aggregation
Precipitation
Surface adsorption

140
Q

What is degradation of the globular protein structure - unfolding

A

denaturation

141
Q

what is it called when proteins clump into inactive multimeric units by association of hydrophobic surfaces, or other attractive forces for association?

A

Aggregation

142
Q

What is macroscopic aggregation into large particulates called?

A

Precipitation

143
Q

What is it called when a protein adsorbs on the surface of a glass vial and denatures?

A

surface adsorption

144
Q

Synthesis for large peptides is ___ and ___ to perform in large quantities

A

expensive

difficult

145
Q

True or false

Proteins can be readily produced by cells

A

True! They are natural products

146
Q

What allows for mass production of protein?

A

Transfecting a gene into a cell

147
Q

Advantages of recombinant protein production

A

Relatively inexpensive process
Ease of maintaining cell cultures
Relies on well defined molecular and cellular biology

148
Q

Where are biologics generated from?

A

biological source

149
Q

Different pathways of biologic production

A

Microbial
Mammalian
Plant
Gene therapy

150
Q

What do human proteins often have?

A

Post-translational modifications (PTMs)

151
Q

True or false

Bacteria provide post tranlational modification

A

False!

152
Q

What can be used to generate post translationally modified protein?

A

Chinese Hamster Ovary (CHO)
COS
Baby hamster kidney cells
Yeast cells

153
Q

What can post-translational modification be important in?

A

Immunogenicity

Pharmacodynamics

154
Q

What is a fusion tag?

A

When a peptide/protein epitopes are added to a protein

***sequence must not be similar to that of the cell

155
Q

What do fusion tags do?

A

Can help with immunopurification

156
Q

Affinity purification concepts in relation to fusion tags

A
  • you have to make sure the epitope tag does not interfere with protein function
  • since the tag is foreign, it may induce immunogenic response in humans
  • Enzyme cleavage sites before the tag can enable removal of epitope
157
Q

Does E.coli add Post translational modifications?

A

No

158
Q

The generation of proteins at a larger quantity requires what 2 things?

A

vectors

appropriate cell models for functional yields

159
Q

Some proteins require difficult purification steps which can affect what?

A

yield

160
Q

What is one way to improve purification through affinity chromatography?

A

epitope tagging

161
Q

True or false

The protein must be in the native form after it is purified?

A

True

162
Q

After protein purification, why is the protein so unstable?

A

It is out of its cellular environment

163
Q

What should be included in formulations that proteins are stabilized in?

A

as little as possible!
Buffering agents
essential excipients
protein

164
Q

What do polyols do to help stabilize biosimilars?

A

they have multiple alcohol moeities that create preferential hydration

165
Q

What do metal chelators do to help stabilize biosimilars

A

bind metals that might cause oxidative stress or induce instability due to metal binding to the protein

166
Q

What do amino acids do to help stabilize biosimilars?

A

they can be added to act in a case by case manner to increase stability

167
Q

What do surfactants do to help stabilize biosimilars?

A

in low concentrations can increase solubility and prevent film formation

Can be toxic in pediatric indications!!!

168
Q

What do phospholipids and fatty acids do to help stabilize biosimilars?

A

They can stabilize proteins through stoichiometric binding or by forming liposomal liek structures

169
Q

What do antioxidants do to help stabilize biosimilars?

A

they can be used to prevent oxidative damage to met, protect disulfide bonds, and potentially stabilize a protein

170
Q

What does albumin do to help stabilize biosimilars?

A

possesses fairly high stability
Can prevent aggregation and surface adsorption on glass

Bad - Can carry blood born pathogens and prions

171
Q

Buffer capacity definition

A

magnitude of the resistance to pH changes that a buffer exerts

172
Q

Protein formulations require ____ buffer capacities to resist pH changes

A

HIGH

pH can affect both chemical and physical stability!

173
Q

Immunogenicity definition

A

property of being able to evoke a humoral or cell-mediated immune response

Includes both antigens and allergens

174
Q

Immunogenic reaction examples

A

-Severe allergic or anaphylactic response
Reduction of efficacy
-induction of autoimmunity to endogenous proteins

175
Q

True or false

The relationship between antibody formation adn clinical outcome is always direct and quantative

A

FALSE

176
Q

True or false
The risk and benefit of antibody formation on the drug’s safety, efficacy and PK/PD parameters must be assessed and weighed against the benefits of therapy.

A

True

177
Q

True or false

Immunogenicity is a risk that needs to be evaluated with biologics

A

True

178
Q

True or False

Immune responses will be product and indication dependent

A

True

179
Q

True or False

Immunogenicity may affect efficacy

A

True

180
Q

True or False

Immunogenicity is predictable

A

False!

181
Q

Immunogenicity can often result in ______ effects on the patients

A

Little to no

182
Q

Biosimilar drug issues

A

Cellular and expression system critical
Post-translational modification
Cell extraction of protein is required
Cell purification is required

183
Q

Stability of biosimilar drug issues

A

Physical/structural instability
Chemical instability
Enzymatic stability

184
Q

Formulation issues with biosimilar drugs

A

Excipient choice depends on the route of administration and is carefully optimized for clinical use

185
Q

True or false

Immunogenicity is very important

A

True

186
Q

How should biosimilars be handled

A

VERY CAREFULLY

Advanced Parenterals (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions