Brainscape's Knowledge GenomeTM

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


See full index

411 Oncology > L9 - Formulation considerations & targeted delivery of anticancer drugs > Flashcards

L9 - Formulation considerations & targeted delivery of anticancer drugs Flashcards

1
Q

What is cancer?

A

Diseases in which cells divide without control

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

Which method is chemotherapy most commonly delivered by?

A

Parenteral: IV injection or infusion

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

What are parenteral preparations?

A

STERILE preparations intended for administration by injection/infusion/implantation into human or animal body

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

What are FOUR advantages of parenteral/injectable formulations?

A

Rapid onset & PREDICTABLE effect

Predictable & high bioavailability

Avoid GI tract –> first-pass metabolism, pH degradation

Reliable in very ill/comatose patients (where swallowing not viable)

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

What are THREE disadvantages of parenteral/injectable formulations?

A

Frequent pain & injection site reactions (may be due to drug or excipients)

Psychological fears (needle)

Incorrect dose difficult to counteract

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

What are FOUR specialised parenteral routes for chemotherapy?

A

Intraarterial chemotherapy via catheter –> deliver chemotherapy directly to tumour, which reduces exposure to healthy tissue

Hyperthermic peritoneal chemotherapy –> deliver chemotherapy directly to lining of abdominal wall cavity during surgery

Intrathecal to CNS

Intravesicular to bladder

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

What are THREE biopharmaceutical problems with chemotherapy?

A

Poor aqueous solubility

Tissue damage/irritation

Unfavourable pharmacokinetics

  • Rapid in vivo breakdown
  • Poor distribution/cellular uptake
  • Lack of selectivity for target tissues
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is ONE pharmacodynamic problem with chemotherapy?

A

Non-specific targeting
- All proliferating cells are attacked, inc. normal cells

–> Off-target side effects

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

What are THREE implications of poor solubility for chemotherapy?

A

Difficulty for high dosing

Drug precipitation

Toxicities associated with excipients/solvent [which have been added to improve solubility]

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

What are THREE drug delivery systems to counteract poor solubility for chemotherapy?

A

Nanosuspension

Nanoencapsulation

Cyclodextrin inclusion/mocular encapsulation

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

What are TWO implications of tissue damage/irritation for chemotherapy?

A

Inadvertent extravasation of drug into tissue surrounding injection site –> tissue ncecrosis

Pain

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

What are TWO drug delivery systems to counteract tissue damage/irritation for chemotherapy?

A

Nanoencapsulation

Cyclodextrin inclusion

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

What is the most ideal solvent for formulation?

A

Water for injection

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

What are THREE ways of improving solubility?

A

Use of organic solvents for solvent-water systems

pH adjustment/salt formation –> eg. decreased pH allows basic drugs to be ionised & therefore more readily absorbed in water

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

What is post-injection drug precipitation?

A

Occurs in poorly water-soluble drugs solubilised in solvent systems/non-physiological pH

Occurs after SC, IM, IV injections

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

How does post-injection drug precipitation occur?

A

pH neutralisation (eg. tissue acts like buffer)

  • -> Drug concentration becomes more than solubility
  • -> Drug which was ionised becomes unionised again & precipitates
  • -> Poor absorption (IM/SC) or phlebitis (IV)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is phlebitis?

A

Inflammation of vein

18
Q

How does phlebitis occur?

A

Chemical irritation to endothelial cells

Release of inflammatory mediators

Drug precipitation (large particles) –> deposit on veins –> prolonged drug exposure –> increased irritation

19
Q

What are some strategies to resolve pain on injection, post-injection drug precipitation, decreased solubility?

A

Cyclodextrin use (molecular encapsulation)

Micro- or nanocarriers [macro sized particles can only be used in local site injections, not into bloodstream –> may precipitate]

  • -> Controlling drug diffusion –> no accumulation of drug
  • -> Prevent direct drug exposure to tissue
20
Q

What is the implication of rapid in vivo breakdown & rapid clearance for chemotherapy?

A

High drug doses/continuous infusion required

21
Q

What is a drug delivery system to counteract rapid in vivo breakdown & rapid clearance for chemotherapy?

A

Controlled/sustained release

22
Q

What are FOUR examples of parenteral controlled release strategies?

A

Dissolution-controlled depot

Encapsulation

Solidifying depot formulation

Implant or device

23
Q

What is a depot injection?

A

Slow-release, long-acting form of injectable medication

24
Q

What are TWO examples of dissolution-controlled release?

A

Nanosuspension

Micronised particles

25
Q

How does dissolution-controlled release work?

A

Reduce dissolution rate from formulation in tissue fluid

–> Decrease absorption rate

26
Q

What is a clinical example of microsphere-based long-acting depot?

A

Leuprorelin (LHRH/GnRH agonist)

Microspheres are suspended in vehicle –> called “suspension”

27
Q

How does solidifying depots work?

A

Polymeric formulation in sol form before administration into body –> once administered become gel –> drug released over long period of time

28
Q

Qhat is a clinical example of implant?

A

Zoladex (goserelin)

29
Q

How does implant work?

A

Polymer-based implant degrades by hydrolysis

–> Slowed degradation & erosion of polymer results in controlled release

30
Q

What are TWO implications of poor distribution for chemotherapy?

A

Higher Vd = more drug reaches tissues & need higher dose to reach high plasma concentrations = dose-limiting side effects

Cardiac toxicity of free doxorubicin

31
Q

What are TWO drug delivery systems to counteract poor distribution for chemotherapy?

A

Targeted drug delivery systems

Nanoparticles (lower Vd)

32
Q

What is the implication of lack of selectivity for target tissues for chemotherapy?

A

Low concentration results in suboptimal therapeutic effect –> high dose required

33
Q

What is a drug delivery system to counteract lack of selectivity for target tissues for chemotherapy?

A

Localised drug delivery systems

34
Q

What are FOUR advantages of liposomes?

A

Non-toxic & biocompatible –> very similar to own cells

Encapsulation of both hydrophilic & hydrophobic drugs

High drug loading

Easy surface modification –> actively targets tumour

35
Q

What is passive tumour targeting?

A

Drug permeates through leaky blood vessel walls [tumour angiogenesis] –> likely where tumour cells are

36
Q

What is active tumour targeting?

A

Drug has receptors added to surface that will bind to specific targets on tumour cells

Requires passive targeting to occur beforehand –> leave bloodstream & find tumour cell first before can bind

37
Q

How come drugs accumulate in tumours?

A

Tumours have lymphatic systems that do not work well –> drug not cleared from tumour & accumulates

38
Q

What are THREE important formulation parameters for passive tumour targeting?

A

Size (100-150nm)
Long-circulation –> not cleared by body quickly
Drug retention from carriers –> form drug in crystals to reduce drug release

39
Q

What is pegylation?

A

Form of long-circulation

Covalent coupling of non-toxic, hydrophilic PEG to drug

–> Prevents recognition/opsonisation & rapid clearance

40
Q

What are FOUR advantages of local drug delivery?

A

Reduce systemic side effects

Overcome BBB

Increased drug exposure to tumours

Effectively kill tumour cells due to high drug concentration, usually those left behind after surgery

411 Oncology (9 decks)

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