(PM3A) Skin Flashcards
What is the largest organ in the body?
The skin
How much of the human body mass does the skin comprise, as a percentage?
15%
How much water is lost through the skin everyday?
Give your answer as a volume.
Approximately 500mL
Name some key functions of the skin.
- Thermal insulation (from the fatty layer)
- Cutaneous sensation
- Metabolic functions
- Blood reservoir
How much of the body’s overall blood volume does the skin hold?
Approximately 5%
What is the integumentary system?
(1) A system which protects the body from damage
(2) It includes:
- Skin
- Sweat glands
- Oil glands
- Hairs
- Nails
What are the main layers of the skin?
(1) Epidermis
(2) Dermis
(3) Subcutaneous Tissue
What components of the skin comprise the epidermis?
(1) Stratum corneum
(2) Granular cell layer
(3) Spinous cell layer
(4) Basal cell layer
What components of the skin comprise the dermis?
(1) Sebaceous gland
(2) Erector pili muscle
(3) Sweat gland
(4) Nerves
(5) Hair follicle
(6) Collagen fibres
(7) Elastin fibres
What components of the skin comprise the subcutaneous tissue?
(1) Artery
(2) Vein
(3) Adipose tissue (fat)
Where does the stratum corneum thicken?
Load bearing areas
i.e. soles/ palms
What differs in the skin in load bearing areas?
The stratum corneum thickens
What happens when the stratum corneum is damaged?
(1) Damaged skin barrier
(2) Eczema
What happens when the stratum spinosa (spinous cell layer) goes wrong?
Spinous cell carcinoma
What happens when the stratum basale (basal cell layer) goes wrong?
(1) Hyper-proliferation (psoriasis)
(2) Basal cell carcinoma
How often does skin replace itself?
Every 28 days
How long does it take for the stratum basale to form the stratum corneum?
Approximately 14 days
What types of cell are within the epidermis?
(1) Keratinocytes
(2) Melanocytes
(3) Merkel cells
(4) Langerhan’s cells
What is a keratinocyte?
Cell within the epidermis
Produces keratin, a fibrous protein
Gives rise to protective properties
Produced in stratum basale layer
Dead, keratin-filled scale-like structures
Where are keratinocytes produced?
In the stratum basale layer
Where is keratin production increased in the body?
Areas with regular friction
e.g. palms and feet
What is a melanocyte?
Cell within the epidermis
Synthesises melanin - a pigment
What happens to the melanin produced by melanocytes?
Taken up by keratinocytes
Forms a pigment shield to protect nucleus from UV radiation
(1) Which cell produces melanin?
(2) Which layer is this in?
(1) Melanocyte
(2) Epidermis
What is a Merkel cell?
A sensory receptor for touch
Low-abundance cell
Have disc-like sensory nerve endings
Where are Merkel cells found?
In the epidermis of the skin
What is a Langerhan’s cell?
Dendritic cells which are produced in the bone marrow
Process microbial antigens
Become antigen-presenting cells (APCs)
Where are Langerhan’s cells found?
Epidermis of the skin
What is the largest component of the skin?
Dermis
What comprises the dermis?
Fibrous connective tissue
Richly supplied with nerve fibres, blood vessels, and lymphatic vessels
How many layers comprise the dermis?
Two
(1) Papillary
(2) Reticular
What is the papillary layer?
Layer within the skin (dermis)
Thin superficial layer
Produces structures like nipples and ridges, e.g. finger prints
Which layer of the skin gives rise to finger prints?
Papillary layer of the dermis
What is the reticular layer?
Dense + irregular connective tissue
Comprises 80% of the dermis thickness
Provides strength and resilience
Name 5 appendages of the skin.
(1) Hair
(2) Hair follicles
(3) Sweat glands
(4) Oil (sebaceous) glands
(5) Nails
How many types of sweat gland are there?
Two
(1) Eccrine
(2) Apocrine
Give another name for sudoriferous glands.
Sweat glands
What is an eccrine sweat gland?
Simple + coiled gland
Regulated by sympathetic autonomic nervous system
Prevents over-heating of the body
What is an apocrine sweat gland
Larger than eccrine sweat glands
Empty into hair follicles
Secretions contain sweat + fatty substances + proteins
How is odour produced on the skin?
Mixture of sweat, fatty substances, and proteins, with bacteria
Decomposes and produces odour
Describe the secretion pattern of an apocrine sweat gland.
Periodic
In bursts
Give another name for an oil gland.
Sebaceous gland
Where are oil/ sebaceous glands found?
All over the body
NOT palms or soles of feet
What do oil/ sebaceous glands produce?
Sebum
(1) What is the role of sebum?
(2) Where is it produced?
(1) Soften and lubricate skin and hair + bactericidal properties
(2) Oil/ sebaceous glands
How are oil/ sebaceous glands regulated?
Hormonal control
via androgens
What improves ease of administration through a nail?
Damage to nail - e.g. psoriasis
Define transdermal, as an administration route.
Through the skin
For systemic effect
Define local, as an administration route.
Effect close to site of administration
Define topical, as an administration route.
Effect on skin
Usually epidermis
What defines penetration in transdermal delivery?
Drug enters the skin
Passes through the stratum corneum
What defines permeation in transdermal delivery?
Drug passing THROUGH the skin
Systemic/ local
How can first pass hepatic metabolism be avoided by using the skin as a delivery route?
Transdermal delivery avoids first pass hepatic metabolism
(1) Does skin affect bioavailability?
(2) Why/ why not?
(1) Yes, it can do
(2) Skin is metabolically active
What mainly affects transdermal delivery?
Stratum corneum
What is the shunt route?
Permeation of a drug through hair follicles and sweat ducts
What is steady state permeation?
Permeation predominantly through the stratum corneum
How many cells thick is the stratum corneum?
Approximately 20 cells thick
Which gland are hair follicles mostly associated with?
Oil/ sebaceous glands
What is an example of a specialised apocrine gland?
Milk gland
What is the ‘brick and mortar’ model?
A model used to describe the structure of keratinocytes in the stratum corneum
Define transcellular route.
Through the cells
Usually through keratinocytes in the stratum corneum
Define intercellular route.
Around the cells
Usually around keratinocytes in the stratum corneum
What is the most common rate-limiting structure in transdermal delivery?
Multiple lipid bilayers
How many routes for micro-permeation are there in transdermal delivery?
Two
(1) Transcellular
(2) Intercellular
What are/ is the micro-permeation route(s)?
(1) Transcellular
(2) Intercellular
What is the most common lipid in the human stratum corneum?
Ceramides
Comprise approximately 41% of all lipids in stratum corneum
Give an example of an amphiphilic lipid.
Ceramide
Found in stratum corneum
How are crystalline areas formed in the stratum corneum?
Lipids (such as ceramides) packing closely together
(1) What is the role of a penetration enhancer?
(2) How does it achieve this?
(1) Increase transdermal delivery + drugs given transdermally
(2) Disrupts the crystalline areas formed by lipids in the stratum corneum
Where are crystalline areas found in the skin?
Stratum corneum
In the epidermis
What is the most common micro-permeation route?
Intercellular > Transcellular
When are shunt routes most often used in transdermal delivery?
For faster penetration (immediate effect)
For drugs which are unable to cross the lipid barrier
What is a permeant?
The molecule moving through/ into the skin
What is flux?
The rate of permeant moving through the skin
Measured in joules (J)
What is the permeability coefficient?
Speed of permeant transport
Kp
What does the unit Kp refer to?
Permeability coefficient
What are the units of Kp?
cm/hour
What is the diffusion coefficient?
Fundamental property of the permeant in a particular membrane
D
What is the diffusion coefficient symbol?
D
What does the symbol D refer to, with regard to skin.
Diffusion coefficient
What is the unit for diffusion coefficient (D)?
cm^2/hour
What is responsible for the driving force for diffusion?
Concentration gradient
How is flux calculated?
flux = Kp x concentration
Flux = aD/γh
What is the most accurate calculation for finding ‘flux’?
Flux = aD/γh
a = thermodynamic activity of the permeant in its vehicle
D = diffusion coefficient
γ = activity in the membrane
h = membrane (stratum corneum) thickness
What is a Franz cell used for?
Measuring diffusion for a delivery
What temperature must a Franz cell be kept at?
32ºC
Up to how long can a patch be used for to continually deliver a drug?
7 days
What is a lag phase in transdermal delivery?
The initial delay whilst an equilibrium is found across the membrane
Describe the order of a patch delivered drug.
Zero order
Until 10% of drug activity is lost
OR
>10% is present in receiver solution
Describe the gradient of a patch delivered drug.
Pseudo-steady state flux
What is described as the ‘driver’ for drug delivery?
Thermodynamic activity
What molecular weight is ideal for transdermal delivery?
300-500Da
What log P is ideal for transdermal delivery?
1-~3.5
What aqueous solubility is ideal for transdermal delivery?
> 100 mg/mL
What is the average patch size?
Approximately 10-25cm^2
How can estimation of drug flux be beneficial?
When deciding if a drug is appropriate for transdermal delivery
For which skin type are lotions preferred?
Normal-dry
For which skin type are creams preferred?
Dry
For which skin type are gels preferred?
Normal-oily
What formulations are preferred for a thick, scaly lesion?
Fatty, i.e. ointments/ pastes
What formulations are preferred for a wet, weeping lesion?
Aqueous based, e.g. cream, lotion, gel
What is the typical bioavailability for topical products (e.g. gels/ creams)?
1-3% bioavailability
What is the typical bioavailability for patches (e.g. fentanyl/ buprenorphine)?
30-70%
What is a suspension?
A saturated solution
What is occlusion?
Closing up/ blocking off
What is an enhancer?
A drug which reversibly interacts with skin to increase drug flux
How does an enhancer achieve its function?
Disrupts intercellular lipid structure in stratum corneum
What is the Hawthorne effect?
Patients modifying their behaviour in response to knowing they are being observed
e.g. falsifying reported adherence
How does the permeability of neonatal skin compare to that of adults?
It is more permeable
What does DIA mean?
Drug in adhesive
What is at the centre of a liposome?
Hydrophilic core
What can the hydrophilic core of a liposome be used for?
Trapping hydrophilic materials
What can the membrane of a liposome be used for?
Trapping lipophilic materials
What is iontophoresis?
A device used to drive a drug molecule into the skin
When is iontophoresis used?
To drive molecules into the skin
Often used for neutral molecules
What is iontophoresis currently approved for in the UK?
Hyperhidrosis
What are some proposed limitations to the method of iontophoresis?
Damage to drug stability
Changes in charge/ pH to drug
What is a microneedle used for?
To penetrate the stratum corneum, but not the pain receptors
What materials can be used to produce a microneedle?
(1) Carbon
(2) Silicon
(3) Polymeres
Which type of molecule may be able to be delivered using microneedles, as a revolutionary method?
Biologics/ biomacromolecules
i.e. insulin, vaccines, antibodies, hormones
How can microneedles be used to detect presence of skin conditions?
Coating microneedle tips in specific antibodies, to recognise presence of specific antigens
What is epidermolysis bullosa?
Skin condition causing insufficient anchoring of the epidermis to the dermis
This makes the skin fragile
(1) What gene mutation causes epidermolysis bullosa?
(2) Why?
(1) Laminin beta-3 (LAMB3)
(2) LAMB3 codes for an epidermal anchoring protein
What does epidermolysis bullosa cause?
Ulceration/ blistering due to epidermal fragmentation or detachment from the dermis
What does epidermolysis bullosa lead to over time?
Skin cancers
It is incurable
