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Biopharmaceutics > Term 2 > Flashcards

Term 2 Flashcards

1
Q

the most important responsibility of the rxist with biotech products

A

patient counselling

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2
Q

how may pre filled syringes can you give out at a time and why

A

1 weeks worth, sterility issues

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3
Q

how long is reconstituted interferon stable for? CSF?

A

interferon for a month if refrigerated, CSF must be used within hours

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4
Q

how do you minimize biotech SEs

A

give 650mg acetamin 30 minutes before injection, and many symptoms will disappear. HS to sleep off effects also good

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5
Q

for product evaluation, to dtermie if the drugs are equivalent must determine the

A

type of host cell used to generate the rHu protein-will be needed to determine post translational modifications

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6
Q

the dose required to obtain therapeutic response may be different from the dose necessary for biologic response. This results in

A

SEs not commonly seen at physiologic concentrations

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7
Q

how do you provide information to co workers on new biotech

A

pharmacy in service programs, monthly newsletter or bulletin, continuing education

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8
Q

what is the shelf life of most biotech

A

doesn’t exceed 12-18 months, even less after reconstituted. Can be as low as 3 months (interferon)

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9
Q

what is the expiration date for reconstituted biotech

A

2-30 days range; may not contain preservatives and 8-72 hour dating may be necessary

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10
Q

how do you avoid biotech products adhering to packaging

A

coat with HSA (human serum albumin)- should be added to solution prior to drug

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11
Q

should use in line filters with biotech products

A

NO- significant loss of protein

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12
Q

how to add diluent into a vial

A

against the side no into the product

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13
Q

what does parenteral route include

A

IV, IM, SC, intraperitoneal

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14
Q

advantages of parenteral

A

avoid presystemic degradation ie first pass resulting in highest dose of protein in biological system

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15
Q

how to increase mean residence time of short half life proteins and what might occur

A

switch to IM or SC- but changes in disposition may occur (difference in exercise, massage, heat, state of tissue, blood flow), can also have enhanced exposure to degradation enzymes (can take lymphatic route), presystematic degradation, trauma from injection

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16
Q

when protein is given SC or IM, a fraction can enter the lymphatic system, this is determined by

A

molecular weight (size determines if its taken up by capillaries to enter circulation)

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17
Q

why is oral often preferred

A

patient friendly, no medical intervention to administer, cost effective

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18
Q

why does oral route have low F, when can we not use it

A

protein degradation in GI (endopeptidases) and poor permeability for passive transport (especially high MW) - can’t use when high or constant F is required

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19
Q

types of peptidases

A

pepsins (active between 3-5, lose activity at higher pH), those active at neutral pH (trpsin, chymotrypsin, elastase)

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20
Q

what is an exopeptidase? give an example

A

proteases degrading peptide chains at their ends, carboxypeptidase A and B (eXo carboXy)

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21
Q

methods to improve oral F

A

encapsulation with nanoparticles, chemically modifying AAs, coadministering protease inhibitors

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22
Q

for oral vaccines, why are hurdles of degradation and permeation not necessarily prohibitive

A

only a small fraction of the antigen has to reach its target to illicit an immune response (can use liposomes, modified live vectors, etc to help improve antigen delivery)

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23
Q

nasal route advantages, and issues

A

easily accessible, fast uptake, lower proteolytic activity vs GI, avoid first pass, spatial containment of absorption enhancers. Reproducibility and safety are issues, low F

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24
Q

which two methods are quite equivalent for F

A

lungs and IV

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25
Q

Buccal route advantages and disadvantage

A

A-accessible, lower proteolytic activity, avoids first pass, spatial containment of absorption enhancers, can remove D- low F

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26
Q

Rectal route advantages and dis

A

A- accessible, lower proteolytic activity, partially avoids first pass, spatial containment of absoprtion enhancers, d-low F

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27
Q

transdermal route A and D

A

A- acessible, avoids first pass, can remove, sustained/controlled possible, d-low F

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28
Q

which routes of administration avoid first pass

A

transdermal, IV, nasal, buccal, PARTIALLY rectal,pulmonary

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29
Q

which routes of admin can’t contain spatial containment of absorption enhancers

A

oral, pulmonary,

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30
Q

pulmonary route A and d

A

A- easy, fast, lower proteolytic, avoid first pass, D- reproducibility, safety

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31
Q

if systematic action is required, these routes have little clinical relevance especially if simple protein formulations without absorption enhancing technology are used

A

nasal, buccal, rectal, transdermal -F is just too low

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32
Q

mechanisms to enhance F of proteins to increasing permeability of absorption barrier:

A

add ons (Fa/phospholipids, bile salts, enamine derivatives of phenylglycine, ester and ether non ionic detergents, saponins, salicylate derivatives), iontophoresis, liposomes

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33
Q

mechanism to enhance F or proteins by decreasing peptidase activity at site of absorption and along absorption route

A

protease inhibitors, modify molecular structure to enhance resistance to degradation, prolong exposure time

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34
Q

iontophoresis (what it is and what it depends on)

A

transdermal electric current through two electrodes on two places on skin- ionized molecules migrate through skin. Depends on current (pulsed or direct), pH, ionic strength, charge, temperature

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35
Q

for iontophoresis, how should the protein be charged

A

over the full thickness of the skin

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36
Q

are there size restrictions for iontophoreses

A

not clear, we know it is primarily dependent on charge and only potent proteins will be successful candidates

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37
Q

what is the present flux through the skin for iontophoresis

A

10ug/cm2/hr

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38
Q

as a rule, proteins are administered in____, and only ______ are delivered as colloidal dispersions

A

aq solutions, recombinant vaccines such as insulin

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39
Q

what is a colloidal

A

chemical mixture in which one substance is dispersed evenly throughout another ex// milk

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40
Q

what is the only drug currently administered using controlled release system

A

insulin

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41
Q

what does addition of chemical moiety do to a drug? What is a common example of this

A

can change half life and tissue distribution, can limit side effects, be used for better targetting. PEGylation

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42
Q

what is PEGylation and what can it do

A

COVALENTLY attaching PEG to another molecule (or encapsulating it- shields it from immune system to prevent immune response), can increase solubilty in water, can add targeting molecules to the PEGylated drug as well, improves T1/2

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43
Q

controlled release systems for parenteral delivery are either

A

open loop (continusous infusion with pump or osmotically driven), closed loop (feedback system with a biosensor pump combo ad encapsulated secretory cells- primarily langerhan)

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44
Q

describe open loop systems

A

mechanically driven pumps for continusous infusions, can have pulsatile or variable rate delivery, can have flexible input rates

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45
Q

issues for selecting a proper pump

A

must deliver drug for extended length of time, be safe, convenient

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46
Q

what to consider when a pump must deliver for an extended amount of time

A

have wide range of delivery rates, ensure accurate and precise stable delivery, contain reliable pump and electrical components, drugs must be compatible with pump intervals and maintain stability, provide simple means to monitor status and performance of pump

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47
Q

factors to consider for pump safety

A

biocompatible exterior if implanted, fail safe mechanism, sterilized interiors and exterors (if implantable), show no leakage, have Overdose protection

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48
Q

for open loop osmotic delivery systems, how is rate determined? What should be special about the protein solution?

A

influx of water through a rigid, external semi permeable membrane; water empties drug reservoir and release rate depends on characteristics of semipermeable membrane and on osmotic pressure differences over the membrane. Solution must be compatible to pump parts its exposed to

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49
Q

for a pump to be convenient, it should

A

be reasonable small and inconspicuous, have a long reservoir life, easy to program

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50
Q

disadvantage of open loop

A

fixed release rate which is not always desired (specifically osmotic driven)

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51
Q

reasons to switch to an insulin open loop pump

A

less pain, fewer hassles, less life interference, convenient, more flexible, more control, more likely to maintain desired BG levels

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52
Q

potential problems with pumps

A

may fail because of energy, problems with syringe, accidental needle withdrawal, leakage of catheter, problems at injection or implantation site, long term stability of drug may be problem, pump still has to collect data to adjust rate (ie with insulin still must take BG), invasive sampling of body bluids on regular basis

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53
Q

what must a protein be stable at to be used in a pump

A

37 celsius or ambient temperature (internal and external respectively)

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54
Q

close loop delivery systems- why created

A

developed for goal of insulin injections based on current blood readings, doesn’t require patient to maintain proper BG, readings in real time and regulated totally internally

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55
Q

what must a closed loop delivery system contain

A

a known relationship between plasma level and pharmacological effect, biosensor (measure plasma level of protein), algorithm, (calculate required input rate), pump system to administer drug at required rate over prolonged periods, NOT biodegradable polymer

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56
Q

protein delivery by microencapsulated secretory cells- what has been a major goal

A

implant of Langerhan cells in diabetics to restore insulin production in biodfeedback fashion

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57
Q

what is needed for protein delivery by microencapsulated secretory cells

A

cells should be protected from body environment (avoid rejection) (also desirable to keep cells from migrating in all direction), thin walls, robust, biocompatible polymeric membranes (should ensure transport of nutrients from outside medium to inside cell to keep them physiologically healthy but prohibit induction of undesirable immune responses ie block Abs and immune system cells)

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58
Q

in the case of insulin, what must microencapsulated cells be permeable to

A

glucose and relatively small sized hormones that are essential for biofeedback process

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59
Q

what is a key ingredient in Alzet for continuous infusion?

A

osmotic agents

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60
Q

reasons why drugs fail

A

active compound never reaches target site (rapidly eliminated or inactivated), drug doesn’t enter cell (high MW or hydrophilic), only small fraction reaches target site (accumulation of drug at target site is the exception not rule)

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61
Q

we generally don’t and can’t inject directly to a target except

A

skin, bladder, peritoneal cavities

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62
Q

what is the goal of targeted drug therapy

A

maximize therapeutic effect and avoid toxic effects elsewhere by specific delivery to action site and keeping it there until it is inactivated and detoxified

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63
Q

progress in drug targeting can be attributed to

A

revealing nature of anatomic and physiologic barriers that hinder access to target sites, insights into pathophys of disease at cellular and molecular level (specific receptors and homing devices to target them ie Abs), more technology (liposomes, PEG, etc)

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64
Q

necrotic tissue can hamper access to tumor tissue

A

fact

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65
Q

two types of targeting

A

passive, active

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66
Q

describe passive targeting

A

natural disposition pattern of carrier system is utilized for site specific delivery- usually macrophages in contact with circulation and accumulate in liver (Kupffer cells) and Spleen

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67
Q

special cells in liver that can be targeted

A

Kupffer cells

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68
Q

describe active targeting

A

change device or homing principle to select one particular tissue or cell type

69
Q

site specific delivery (active targeting) systems contain 3 units (what are they for)

A

active moiety (for therapeutic effect), carrier (protection and disposition), homing device (specificity, usually Abs, to target drug)

70
Q

when to target drugs

A

high total clearance, site has low blood flow, increase in rate of elimination, toxic

71
Q

to maximize target effect, release of drug from carrier should be restricted to

A

response compartment

72
Q

examples of colloidal particulate carrier systems for targeted delivery of proteins

A

biodegradable polycyanoacrylate nanoparticles, polylactic acid microspheres, LDL, albumin microspheres, liposomes

73
Q

in colloidal particulate carrier systems, what is the cut off size for permeation through batters

A

20 nm

74
Q

what factors control fate of particulate colloidal carriers in vivo

A

size, charge, surface hydrophobicity, presence of homing devices

75
Q

what happens to stable colloidal particulate systems with the cells of the mononuclear phagocyte system

A

if they are less than 5 um, they are recognized as foreign body like and phagocytosed

76
Q

what happens to stable colloidal particulate systems when they are larger than 5um and IB injected

A

tend to form emboli in lung capillaries on first encounter with this organ

77
Q

main component of liposome bilayer

A

phospatidylcholine

78
Q

what can vary in liposomes (be specific)

A

siz (30nm-10um), charge (negative or positively charged lipids incorporated), bilayer rigidity (selecting different phospholipids or adding lipids like cholesterol)

79
Q

when are homing devices not required to be covalently coupled to the outside bilayer leaflet of liposome? (and what is this phenomenon called)

A

if target tissue is liver (Kupffer cells), or spleen (macrophages) as this occurs by passive targeting

80
Q

how to extend the normally short half life of liposomes in blood circulation to hours and even days and what happens to them

A

PEGylation chains grafted on surface and stable bilayer structures used- can escape macrophage uptake and are sequestered in organs other than liver and spleen alone

81
Q

liposome encapsulated lymphokines (like interferon) and microbial products like MTP-PE can do what

A

activate macrophages and enable them to kill micrometastases or help stimulate immune reactions. Activating macrophages may also help fight macrophage located microbial/viral/bacterial disease

82
Q

why do liposomes have poor access to targets outside blood after IV injection?

A

high resistance against penetration through endothelial lining and relatively short circulation time- we should use target sites in blood circulation or those in cavities so that we can locally administer it (bladder, peritoneal, etc)

83
Q

advantages of liposomes as delivery systems

A

low toxicity, safe and experience, large aq core needed to stabilize many proteins, can manipulate their characteristics and control disposition by changing preparation techniques and bilayer constituents

84
Q

examples of current liposome systems for delivery

A

amphotericin b, doxorubicin, daunorubicin

85
Q

how to make monoconal Abs

A

start by immunizing mouse with antigen you want antibody to recognize, isolate antibodies from mouse spleen, fuse antibody forming cell with cancer cell to proliferate in culture (hybridomas), test to ensure specificity and efficiency

86
Q

what can occur when cancer cell has been targeted by MAb

A

binding can illicit immune response (body kills cancer cells), drugs can be attached to antibody and delivered to cancer cell (resulting in cell death), binding to a receptor can prevent activation (turn off survival and growth signals to cell, block entrance or exit of specific molecules to prevent survival

87
Q

what is the problem with mouse origin Abs? What can be done

A

can lead to problems in body such as production of HAMA (human anti mouse Abs) which may neutralize antigen binding site (prohibit further use of therapeutic MAbs). Can coadminister with immunosuppressant to minimize SEs, or use human MAb so no immune response (humanize mouse too)

88
Q

what portion of the antibody does the human immune system recognize? What is this section needed for?

A

Fc (causes the problem and immune system responds), needed to kill the cell with an immune response so if you don’t use it must attach a mechanism to kill the cells or design to change cell metabolism

89
Q

how to prevent production of HAMA

A

use only the Fab portion of antibody (but now must attach mechanism to kills cells or change cells metabolism), OR develop humanized or human MAbs

90
Q

it is considered ethical to immunize humans and isolate spleens to prevent HAMA

A

no

91
Q

how to make humanized Abs

A

build chimeric molecules with human Fc and mouse Fab, use human cells in culture to develop humanized Abs, completely human MAbs made my transfecting human antibody genes into mouse cells which will them produce human MAbs, transgenic mice can develop more humanized ABs

92
Q

murine also means

A

mouse

93
Q

chimeric means

A

partly human, partly murine

94
Q

what is the in vivo target of liposome delivery

A

macrophages

95
Q

which Ab recruits macrophages

A

Fc

96
Q

how can liposomes be passively targetted to the liver

A

Kupffer cells

97
Q

when can macrophages be activated to stimulate the immune system? (when liposome carriers are encapsulated with_____)

A

lymphokines

98
Q

can liposomes be given orally

A

no

99
Q

what is the FAB domain

A

antigen binding site, doesn’t cause HAMA

100
Q

what is the Fc domain

A

complement cascade site, activates immune system, causes HAMA

101
Q

why have bispecific antibodies been developed

A

enhance therapeutic potential of antibodies

102
Q

what are bispecific antibodies

A

manufactured from two separate antibodies to create a molecule with two different binding sites; they bring target cells or tissue (one binding site) in contact with other structures (second antigen binding site)

103
Q

what can the second antigen binding site on bispecific antibody do

A

bind to effector cells via cytotoxicity (triggers cytotoxicity) ex// T cell, NK cells, macrophages

104
Q

what are autologous T lymphocytes

A

come from the same individual; cultured outside of body and expanded in presence of IL 2 (stimulated) and given back to patient

105
Q

immunoconjugates- what are they and why are they used

A

combination between monoclonal antibody and active compound (usually drug known to kill cancer cells), developed because in many cases Ab or bispecific Ab alone lacks sufficient therapeutic activity. These are highly potent and toxic

106
Q

what can go wrong with conjugating drugs to immunoconjugates

A

inactivate Ab (lose targeting specificity), cause worsening immune response, change PK profile or make toxic

107
Q

what do immunoconjugates mainly focus on

A

cancer tx

108
Q

what kind of drug need to be used for immunoconjugates to be successful

A

highly potent are needed to give sufficient therapeutic activity

109
Q

not only existing drugs, but active drugs never used before because of toxicities should be reconsidered because of immunoconjugate technology

A

yes- we can conjugate them with Abs and make them more specific

110
Q

examples of immunoconjugate toxins as chemo agents to treat cancer ie immunotoxins (and what they do)

A

ricin, abrin, diphteria- extremely toxic all block intracellular protein synthesis at ribosomal level

111
Q

what does ricin bind to

A

it is an immunotoxin and it binds to galactose receptors

112
Q

ricin has two chains- what are they and what are they responsible for

A

A chain blocks protein synthesis at ribosomes (ie is responsible for killing), B chain is important for cellular uptake of molecule (endocytosis) and intracellular trafficking)

113
Q

how much ricin kills one cell

A

one molecule (minute quantities)

114
Q

what is the main target for natural ricin, how much immuno conjugated ricin accumulates at tumor tissue, how do we fix this

A

-natural target is liver, only 1% accumulates in tumor, to minimize liver targeting block/remove/mask the ligands on the ricin for galactose receptors on hepatocytes

115
Q

problems with immunoconjugates

A

covalent binding can change cytotoxic potential and decrease affinity of MAb for antigen, stability in vivo can be insufficient and fragmentation can lead to loss of activity and specificity, immunogenicity of MAb and toxicity of protein can change dramatically

116
Q

factors that interfere with successful targeting of proteins to tumor cells

A

tumor heterogeneity, antigen shedding, antigen modulation

117
Q

what is tumor heterogeneity and how do you overcome it

A

problem for successful targeting of proteins to tumor cells; hard to target because multiple receptors (make up of tumor cells is not constant) so not all tumor cells will react with one single targeted conjugate. Overcome by using cocktail of Mab or clone tumor to see what is exactly in it and design an antigen- but this is very expensive.

118
Q

what are clone specific antigens

A

unique for the clone forming the tumor- problem when focusing on them is that each patient probably needs a tailor made MAb

119
Q

what is antigen shedding and how do you overcome it

A

interferes with targeting of proteins to tumor cells; antigens are released form surface of tumor and can interact with circulating immunoconjugates outside the target area and form a complex which neutralizes homing potential of conjugates before target area has been reached. Target specificity is lost. Overcome- give Ab ahead of time by itself to bind to antigen shedding sites and saturate them, then give immunoconjugate (Ab with drug) and it will go to the tumor site

120
Q

qhat is antigen modulation and how do you overcome it

A

interferes with targeting proteins to tumor cells; lose active receptors with time during treatment (surface antigen is not replenished); upon endocytosis of surface antigen immunoconjugate complex, some antigens aren’t exposed on the surface anymore an there is no replenishment, so immunoconjugate will no longer be recognized by tumor. overcome- look for a receptor that doesn’t undergo modulation

121
Q

how to overcome problems related to tumor cell heterogeneity, shedding and modulation?

A

cocktail of MAbs, bystander approach induced (active part released from immunoconjugate after complex endocytosed and drug can be transported to neighboring cells), if shedding or modulation occurs choose different antigen/MAb combination, inject free MAb before immunoconjugate to neutralize free circulating antigen

122
Q

why might not MAb conjugates pan out

A

tumor cell heterogeneity, poor access to tumors, immunogenicity

123
Q

what two sites are recognized in bispecific Abs

A

tumor antigen, macrophages

124
Q

ricin is taken up by endocytosis after binding receptors for

A

galactose

125
Q

which organ is suitable for ex vivo gene therapy

A

liver

126
Q

what is a glycoprotein

A

predominantly protein, and polysaccharide; a protein produced by an animal cell with a sugar moiety(s) attached

127
Q

what is a preoteoglycan

A

predominantly polysaccharide (95%) and protein

128
Q

what does glycoconjugate include

A

glycoproteins, glycolipids, and proteoglycans

129
Q

bacteria can glycosylate

A

false- and non glycosylated proteins will often differ in their biological activity as compared to the active glycoprotein

130
Q

why is there a huge amount of variability in glycobiology

A

the monosaccharide units can be coupled in so many ways- you don’t find this with AAs of proteins or nucleotides of DNA

131
Q

there are ___(#) sugar commonly found in eukaryotes and they are

A

8: 4 alpha Ds (glucose, galactose, mannose, xylose), 1 alpha L (fucose), 3 N acetyl (alpha d glucosamine, alpha d galactosamine, alpha n acetlneuraminic acid aka sialic acid)

132
Q

sucrose is a common monosaccharide found in eukaryotic glycoproteins

A

false- find fucose, galactose, glucose, n acetyl alpha glucose and galactose, xylose, mannose, and n acetylneruaminic acid (sialic acid)

133
Q

for an oligmer with 10 bases (10 mer), how many linear oligomers that are structurally distinct are there for DNA, protein, and oligosaccharides

A

*6,13,18- DNA (4 possible bases) 1.04 x 10 6, protein (20 possible bases) 1.28 x 10 13, oligosaccarides (8 possible bases) 1.34 x 10 18

134
Q

after the synthesis of glycans, what are they known as

A

secondary gene products

135
Q

it is not possible to use recombinant glycan technology to produce large quantities of glycans for structural and functional studies

A

true

136
Q

two types of glycans of glycoproteins (structurally)

A

O linked (aka mucins)(galactose), N linked (asparagine linked) (glucose)

137
Q

o linked glycans structure

A

link between N acetylgalactosamine and hydroxyl group of either serine or threonine

138
Q

n linked glycans structure

A

all are linked through N acetylglucosamine and the amide group of the amino acid asparagine. Asparagine (ASN)-any AA (not proline)- Serine or threonine

139
Q

glycosylation does not affect biological activity

A

false- without these carbs attached, many don’t function therapeutically

140
Q

what are glycoforms and what makes them different, give an example

A

variations in glycosylation patterns of a glycoprotein- may have different biochemical and physiochemical properties ex// erythropeoitin (one O link, 3 N linked)

141
Q

what happens with the removal of terminal sugars at each site- what happens when you remove all sugar. What is the exception to this rule

A

terminal- destroys in vivo activity, all gives more rapid clearance and shorter T1/2. Exception= deglycosylation of hematopoietic cytokine granulocyte macrophage colony stimulating factor (GM-CSF)- removing carbs increasing specific activity 6 fold

142
Q

what happens when you remove galatose residues from IgG

A

less effective binding to the first component of the complement cascade

143
Q

n linked carbohydrates play an important role in what kinds of immunity

A

cellular and humoral

144
Q

what is humoral immunity

A

immunity associated with circulating antibodies, vs cellular which in within the cell itself

145
Q

sugars linked to proteins can help shield the surface of the glycoprotein from antibody recognition

A

true

146
Q

what can sugars linked to proteins do

A

protect from antibody recognition, help recognize binding sites and binding of biomolecules

147
Q

what is the name for the specific type of polysaccharide attached to proteoglycans

A

glycosaminoglycans (GAGs)

148
Q

what can the GAG chain be made of

A

chondrotin 4 and 6 sulfates, dermatan sulfates, heparan sulfates, hyaluronic acids, keraton sulfates

149
Q

what is the most abundant GAG and where is it found

A

chondroitin sulfate-cartilage, bone, and heart valves

150
Q

where is dermatan sulfate found

A

skin, blood vessels, heart valves

151
Q

what is a major component of the animal ECM

A

proteoglycans (it is the filler substance existing between cells in all organisms- they form large complexes with other proteoglycans, hyaluronan and fibrous matrix proteins such as collagen

152
Q

what are proteoglycans involved in

A

major component of animal ECM, binding molecules and water, regulating movement of molecules through matrix, can affect activity and stability of proteins and signalling molecules in the matrix

153
Q

what can individual functions of the proteoglycans be attributed to

A

protein core or the attached GAG chain

154
Q

how are the protein core of proteoglycans made

A

synthesized by ribosomes within the cell, then moved to golgi to have glycon moieties added on, then secreted as the complete proteoglycan into ECM in vesicles

155
Q

how many glycolipids (aa glycosphingolipids) have been isolated and identified from mammalian tissues

A

over 200

156
Q

what are mucins generally linked to

A

serine and threonine residues

157
Q

genetic variation or polymorphisms- what are they and how prevalent

A

variations in DNA sequences that occur in at least 1% of the population-most are due to single base differences

158
Q

what are single base differences in DNA called, how often do they occur and what is most common

A

single nucleotide polymorphisms (SNPs), occur 1 per 300-1000 bps, 2/3 are cytosine to thymine

159
Q

how many nucleotides does the human genome have- what does this mean for SNPs?

A

3 billion (about 3-10million SNPs are expected to exist between any two genomes)

160
Q

what is SNP scoring

A

correlating the prescence of SNPs with disease etiology and drug response

161
Q

what is a SNP map

A

cataloguing discovered SNPs within the human genome

162
Q

what is the goal of pharmacogenomics

A

maximize drug response while minimizing adverse effects

163
Q

give an example of a pharmacogenomic drug and what it is for

A

herceptin- used for metastatic breast cancer- give only to patients with HER2 (overexpressed in some tumors)- prescribing based on presence of this gene to predict drug efficacy (avoids giving to non responders and prevents exposure to life threatening SEs)

164
Q

almost all of the hepatic CYP450 have genetic polymorphisms that influence ability to metabolize drugs

A

true

165
Q

drugs affected by CYP2D6

A

BB (alter effect), antipsych (tardive dyskinesia), narcotics( SE), imipramine (change dose), tamoxifen (relapse breast cancer)

166
Q

drugs affected by CYP2C9, 2C19

A

warfarin, omeprazole

167
Q

who should you expose in clinical trials

A

least number of patients- more benefit decreased cost- limit it to those most likely to show response

168
Q

what are benefits of pharmacogenomics to health care

A

more powerful medicines (facilitate drug discovery, more targeted, max benefit decrease damage, create drugs based on disease), better safer drugs the first time (speed recover, increase safety, AE risk eliminated), advanced screening for disease, decrease overall cost to healthcare (decrease AE/failed drug trials/time to get drug approved), more accurate methods of determining appropriate doses (base on genetics vs age and weight), improvements in drug discovery and approval processes (can revive previously failed candidates, target on people capable of responding)

Biopharmaceutics (3 decks)

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