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S3 Case 4 - Endocrine > Delivering Drugs Through Impermeable Barriers > Flashcards

Delivering Drugs Through Impermeable Barriers Flashcards

1
Q

What is the structure of epidermis?

A

Stratum corneum
Stratum lucidum
Stratum granulosum
Stratum spinosum
Stratum basale
Basement membrane
Dermis

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2
Q

What are the different barriers?

A

Skin
BBB
Intestinal mucosal barrier
Paracellular + transcellular diffusion barrier

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3
Q

What are the challenges of impermeable barrier?

A

Lipid bilayers
Mucus
Enzyme transporters

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4
Q

What are the challenges of passive diffusion?

A

Macromolecules (eg. proteins, DNA)
Tight junction
Viscous mucus

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5
Q

What are the challenges of efflux mechanisms?

A

P-glycoprotein
Multidrug resistant proteins

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6
Q

What are the challenges of invasiveness?

A

Limitations of needle-based devices

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7
Q

What are the limitations of needle-based injections?

A

Specialist training
Invasive
Pain
Needle phobia

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8
Q

What is the injection degree for IM?

A

90

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9
Q

What is the injection degree for SC?

A

45

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10
Q

What is the injection degree for IV?

A

25

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11
Q

What is the injection degree for ID (intra-dermal)?

A

15

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12
Q

What are the chemical approaches (formulation-based) to overcome barriers?

A

Chemical penetration enhancers (CPEs)
Prodrug
Carrier

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13
Q

What are the physical approaches (device-based) to overcome barriers?

A

Iontophoresis
Electroporation
Ultrasound
Jet injector
Laser-assisted strategies
Microneedles

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14
Q

What are the job of CPE?

A

Modulate barrier function

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15
Q

How do pro-drugs work?

A

Inactive pro-moiety bonded to active drug via temporary linkage
Biotransformation = labile bond cleaved in vivo
= releases active drug
Pro-moiety non-toxic + rapidly excreted

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16
Q

What is an example of a prodrug?

A

Enalapril

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17
Q

How do Enalapril work as a prodrug?

A

Higher intestinal permeability
Bioactivated in the liver

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18
Q

How does a codrug work (“mutual prodrug”)?

A

Releases active drug with no inactive by-product

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19
Q

What are the uses of a carrier?

A

Improve drug solubility/permeability
Control drug release
Improve drug targeting

20
Q

What are the types of carriers?

A

Lipid vesicles - eg. micelles
Dendrimers
Nanoparticles - eg. nanospheres
Drug carrier conjugates - eg. cell-penetrating peptides
Viral carriers

21
Q

What is sonophoresis for?
Ultrasound

A

Drug delivery in the skin

22
Q

How does sonophoresis work?
Ultrasound

A

Ultrasound waves create vibration + heat
Acoustic cavitation
Increase kinetic energy

23
Q

What is acoustic cavitation?
Ultrasound

A

Creation + subsequent collapse of microbubbles create shockwaves
= disrupt skin barrier = increase skin permeability

24
Q

What is sonoporation?
Ultrasound

A

Drug delivery into cells across plasma membrane

25
Q

What is iontophoresis?

A

Continuous electrical current applied across membrane barrier
For transdermal drug delivery

26
Q

What is electrorepulsion?
Iontophoresis

A

Ionic drug propelled across membrane barrier

27
Q

What is electroosmosis?
Iontophoresis

A

Electorepulsion creates solvent flow, which carries along dissolved neutral/polar molecules

28
Q

What can the electrical field do?
Iontophoresis

A

Directly enhance membrane permeability, enhancing passive diffusion

29
Q

What is electroporation?

A

Drug delivery into cells
= short, intense electrical impulses

30
Q

How does electroporation work?

A

Destabilisation of lipid bilayer = transient pore formation
= drug diffuses passively through hydrophilic pores

31
Q

What is a jet injector?

A

Injects medication across skin

32
Q

What are the types of jet injectors?

A

Spring-loaded
Pressurised gas

33
Q

What is the mechanism of jet injectors?

A

High pressure jet of liquid erodes membrane barrier
Can deliver range of doses

34
Q

How does laser assisted strategies work?

A

Ablation
Enlargement of lacunar space
Thermal damage

35
Q

What does laser assisted strategies do?

A

Improve skin permeability
Improve depth of drug penetration

36
Q

What are microneedles?

A

Miniature needles
Minimally invasive
Patch or injector format
Dermal, ocular + oral drug delivery

37
Q

What are solid microneedles?

A

Microneedle pre-treatment
Followed by topical application of drug

38
Q

What are coated solid microneedles?

A

Drug formulation coats microneedle surface

39
Q

What are dissolving solid microneedles?

A

Drug encapsulated with microneedles, which dissolve/biodegrade in membrane barrier

40
Q

What are hydrogel-forming solid microneedles?

A

Drug diffuses into membrane from reservoir as hydrogel microneedles swell upon hydration

41
Q

What are hollow microneedles?

A

Drug injected from reservoir through orifice in microneedles

42
Q

What is bad about poke + flow microneedles?

A

Difficult to control amount

43
Q

What is bad about coated microneedles?

A

Small SA = limited amount given
Sharp waste

44
Q

What is bad about dissolving microneedles?

A

Not suitable for extended release
Limited amount of drug in needles

45
Q

What is good about hydrogel microneedles?

A

Increased dose over an extended time

46
Q

How would an oral insulin delivery work?

A

Needle in each pod
Come into correct contact with correct orientation
= inject insulin

S3 Case 4 - Endocrine (17 decks)

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