Brainscape's Knowledge GenomeTM

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


See full index

Health 31 > Biologics & drug development > Flashcards

Biologics & drug development Flashcards

1
Q

LO
- to know the different types of biological drugs and the differences to small molecules
- to know when an antibody approach is suitable for developing a therapeutic
- to know how to deliver antibody based drugs are being adapted to deliver new modes of action and improve efficacy

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

3 types of biological drugs examples

A

mabs,
proteins/peptides eg growth factors
RNA based therapeutics. microRNAs

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

list some classes of biologic drugs on market (pie chart)

A

mabs: majority
synthetic immunomodulators
vaccines
recombinant hormones

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

type of molecule that is developed to target mRNA for degradation?
(rel new class of biologic.)

A

RNAi based theraps:

antisense RNA molecules

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

how do antisense RNA mols target mRNAs for degradation + silence particular genes? ?? + use?

A

by admin. ANTIsense oligonucleotide that can be degraded to specifically target particular mRNAs for degradn

often sued for if have dysfunctional gene/ pathway: design oligonucleotide to silence it

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

why do small molecule drugs such as celecoxib sometimes end in ib?

A

= inhibitor small molecule drug

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

lead identification (LI) is done through what process?

A

high throughput screen

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

problems/ limitations with target identification process?

A

10,000 mols screened, only 1 approved drug maybe, after yeras and £billions

90% of drugs in development fail

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

primary screen is done using what process?

A

enzyme cell free assay

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

cell assays are done as part of primary or secondary screens?

A

secondary

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

3 things studied during in vivo studies?

A

function, moa and tox

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

how does antibody drug pipeline compare to the screening cascade w small molecule drugs (target identification, validation etc)?

A

rapid development time (few yrs)
4 steps

target -> synthetic antibody for target = drug :)
BUT have PK, PD complications :(

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

the 4 stages in antibody drug pipeline?

A

antigen prep
lead antibody discovery
lead optimisation
manufacturability assessment

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

how is the manufacture different between small molecules and large mols (biologics)?

A

small: chemicals synthesis
biologics: cell culture

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

bioanalytical assays for PK assessment for small mols are … and ….
eg

A

simple + specific
eg LC-MS/MS

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

bioanalytical assays for PK assessment for biologics are … and require …..
eg

A

complex + require biologic agents
eg ELISA

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

biologics: quicker to develop initially compared to small mols, but….

A

more effort to put in later to maintain, monitor px

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

small molecule drugs can get through cell membranes and get into cells easily to target what?

A

intracellular molecules

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

what sort of mols do small molecules target inside cells?/ their effect

A

intracellular mols…
kinases (enz)
inhibit phosphatases
or bind intarcellular signalling downstream of receptors

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

why are antibody drugs generally restricted to targeting transmembrane receptors such as TNFa or ligands?

A

too large to penetrate cells

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

lapantinib binds to what to inhibit the HER2 receptor to reduce breast cancer cell growth?

A

intracellular phosphorylation domain

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

where does the mab trastuzumab bind to target HER2 receptors to reduce breast cancer cell growth?

A

her2 receptor on cell membrane

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

give 2 inhibitors of HER2+ breast cancer cells

A

lapatinib (kinase inhibitor)
trastuzumab (mab)

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

what molecule can be developed when you want to target 2 differerent proteins or for 2 sites on the same proteins (bi paratopic)?

A

bi-specifics

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

how is a bi-specific antibody made? by …

A

joining 2 halves of different antibodies

and inhibits 2 actions. dual functionality

26
Q

how do antibody drug conjugates work (ADC)? to deliver drug to target cell eg cytotoxic compounds, chemos

A

delivery of payload -> target cells,
antibody targets specific antigen,
drug linked to antibody + delivered -> target cell

27
Q

why may you consider antibody drug conjugates for delivery of chemotherapeutic agent?

A

as want it to be selective to only cancer cells.

28
Q

ADC allows _____ delivery and stops …..

A

selective.

systemic/ generic activity of toxic drugs

29
Q

how can tissue penetration of antibody drugs be improved?

A

use small part of antibody: Fabs and scFvs instead

… more Fabs bound together: inc specificity

30
Q

why does tissue penetration of antibody drugs need to be improved?

A

large, so dont enter cells easily

31
Q

antibody oligonucleotide conjugates such as oliogonucleotide antisense allow silencing of?

A

intracellular drug targets

32
Q

delivery across plasma membrane is not a challenge for antibody oligonucleotide conjugates, true or false?

A

false

33
Q

antibodies used to target specific cell surface receptor and are conjugated to oligonucleotide via what?

A

linker

34
Q

why are most biologics given iv, sc or im?

A

oral BA poor due to enzymatic digestion in GIT

35
Q

why do biologics take longer to get to peak conc?

A

absorbed slowly due to large size

36
Q

is biologic distribution better or poorer compared to small molecules?

A

poorer

37
Q

biologics are eliminated mainly via intracellular lyosomal proteolytic degradation, binding to X allows for recycling of antibodies back into circ?

A

FCRn receptors

38
Q

true or false, biologics are prone to multiple interactions that impact on the pk and treatment response?

A

true

39
Q

what interaction that biologics are prone to may impact on PK + treatment response?

A
  • exposure to factors in blood eg platelets
  • binding to neonatal Fc receptors (FcRn)
  • immunogenecity eg prodn of ADA + neutralising antibodies
  • interactions w other drugs (polypharmacy)
40
Q

whats the critical requirement for biologic development in preclinical models during drug discovery/ development stages?

A

extensive PK/PD studies!

41
Q

what is romiplostim (Nplate 250)?

A

thrombopoietic mimetic (a fusion protein analog of it) for px w ITP (immune thrombocytopenia)

42
Q

how does romiplostim promote platelet production

A

bind to thrombopoietin receptor

43
Q

what is thrombopoeitin?

A

hormone that regulates platelet production

44
Q

binding of romiplostim to platelets affects ….

A

its clearance

45
Q

why is monitoring required for romiplostim?

A

high conc of drug in serum in px w low platelet count,
as count is boosted low conc of drug in serum as it becomes less effective

… as drug starts working, platelets inc = affects availabilty of drug

46
Q

production of 2 things that can cause immunogenicity to biologics?

A

production of anti drug antibodies (-> AEs)

neutralising antibodies (NAb)

47
Q

effect of production of neutralising antibodies (NAb) on biologics? cause immunogenicity

A

decrease in efficacy over time + potential treatment failure

48
Q

what is the moa of infliximab?

A

binds to TNFa and prevents TNFa binding to TNF receptor of target cells

49
Q

infliximab: mab drug used in what conditions 3…
and why?

A

RA, Crohn’s, Psoriasis
as all have inc TNFa

drug designed to mop up excess TNFa + prevent it from binding to TNF receptor

50
Q

infliximab is chimeric mab that binds to TNFa, what does this mean and why can it lead to immunogencity?

A

variable domans from mouse combined w constant domains from human to reduce immunogencity but still risk of immune response

51
Q

why might you see reduced conc of infliximab in serum after 6 months on treatment?

A

production of ADA in response
immunogenecity

52
Q

px taking infliximab, serum drug levels used to monitor what 2 things to check effectiveness of drug?

A

hm drug gone into circ
hm ADA developing
=== how effective drug is

53
Q

ADAs produced by body in response to being given (infliximab) drug. why dont you want these in circn? 2

A

AEs + could neutralise infliximab effectiveness

54
Q

why is there a lower risk of an immune response in patients that use adalimumab compared to some of the other mabs in its drug class?

A

full human antibody (no mouse)
(BUT still get some ADAs developing)

55
Q

what type of drug: adalimumab

A

TNFa mAb

56
Q

immunogenecity w adalimumab treatment. still get development and increase of what, w time?

A

ADAs.

57
Q

PK assessments can predict what?

A

treatment failure

58
Q

2 different management strategies for immunogencity that do not involve another drug for managing it?

A

switch treatment or treatment breaks

59
Q

why is methotrexate a good option to manage immunogenicity?

A

attentuated ADA production to TNFa mAbs

(diff MOA than TNFa antibody)

60
Q

what effect do inflammatory cytokines produced from conditions like RA have on simvastatin serum levels?

A

px w RA + other inflammatory conditions have elevated pro inflammatory cytokines, reduces CYP activity, reduces metabolism in liver + increases simvastatin exposure

61
Q

outline the DDI between tocilzumab and simvastatin?

A

causes increase CYP activity in liver as inflammation reduced, reduced simvastatin exposure

Health 31 (16 decks)

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