The skin covers the entire
surface of the human body. In an adult, the skin has a surface area of about
1.8 square meters (20.83 square feet). The skin is sometimes called the cutaneous
membrane or the integument.
Accessory organs to the skin
The accessory organs to the skin include:
The hair,
Nails,
Sweat glands,
Sebaceous glands.
The skin and its accessory organs together make up the integumentary system.
Protective covering
Regulates body temperature
Manufactures Vitamin D
Sensory function
Temporary storage of fat
Screens out harmful
ultraviolet radiation
Anatomy of the skin
The skin has two regions:
The epidermis and The dermis.
The hypodermis is a subcutaneous tissue found between the skin and any
underlying structures, e.g. muscle. Usually, the hypodermis is only loosely
attached to underlying muscle tissue, but where no muscles are present, the
hypodermis attaches directly to bone.
For example, there are flexion creases where
the skin attaches directly to the joints of the fingers.
Epidermis
This is the outermost and
thinner region of the skin.
It is made up of stratified
squamous epithelium which is divided into several layers:
the deepest layer is the
stratum basale,
the most superficial layer is the stratum
corneum.
The epidermis is avascular (lacks blood vessels).
Layers of the epidermis
Stratum basale
The basal cells of the stratum
basale lie just superior to the dermis and are constantly dividing and
producing new cells that are pushed to the surface of the epidermis in 2-4
weeks.
As the cells move away from
the dermis, they get progressively farther away from the blood vessels in the
dermis.
Because these cells are not
being supplied with nutrients and oxygen (the epidermis itself lacks blood
vessels), they eventually die and are sloughed off.
Cells in stratum basale
Langerhans cells are macrophages found deep in the epidermis.
Macrophages are involved
in phagocytosis of microbes and then travel to lymphatic organs,
where they stimulate the immune system to react.
Melanocytes are located in the deeper epidermis.
Melanocytes produce melanin,
the pigment primarily responsible for skin color.
Melanin protects the skin from the damaging effects
of the ultraviolet (UV) radiation in sunlight.
Stratum Spinosum (Prickly Layer)
The stratum spinosum is
several cell layers thick.
These cells contain a weblike
system of intermediate filaments, mainly tension-resisting bundles of
pre-keratin filaments, which span their cytosol to attach to desmosomes.
Stratum Spinosum (Prickly Layer)
The keratinocytes in this
layer appear irregular (spiny) in shape, causing them to be called prickle
cells.
Scattered among the
keratinocytes are melanin granules and Langerhans’ cells, which are most
abundant in this epidermal layer.
Stratum granulosum (granular
layer)
The thin stratum
granulosum consists of three to five
cell layers in which keratinocyte appearance changes drastically.
Stratum granulosum (granular layer)
These cells flatten, their
nuclei and organelles begin to disintegrate, and they accumulate two types of
granules:
The keratohyaline
granules help to form keratin in the
upper layers.
The lamellated granules contain a
waterproofing glycolipid that is spewed into the extracellular space and is a
major factor in slowing water loss across the epidermis.
Stratum granulosum (granular
layer)
The plasma membranes of these cells thicken as
cytosol proteins bind to the inner membrane face and lipids released by the
lamellated granules coat their external surfaces.
This makes them more resistant
to destruction, i.e. the keratinocytes are “toughening up” to make the outer
strata the strongest skin region.
Stratum granulosum (granular
layer)
Like all epithelia, the epidermis
relies on capillaries in the underlying connective tissue (the dermis) for its
nutrients.
Above the stratum granulosum,
the epidermal cells are too far from the dermal capillaries, so they die.
Stratum Lucidum (Clear Layer)
Through the light microscope,
the stratum lucidum (“light”) appears as a thin translucent band just above the
stratum granulosum.
It consists of a few rows of clear, flat, dead
keratinocytes with indistinct boundaries.
Stratum Lucidum (Clear Layer)
In the stratum lucidum and stratum corneum above it, the gummy substance of the
keratohyaline granules clings to the keratin filaments in the cells, causing
them to aggregate in parallel arrays.
Note
The stratum lucidum is visible only in thick
skin(palms, fingertips, soles of the feet).
In thin skin, which covers the
rest of the body, the stratum lucidum appears to be absent and the other strata
are thinner
Stratum corneum (Horny layer)
The outermost stratum
corneum is a broad zone 20 to 30 cell
layers thick that accounts for up to three-quarters of the epidermal thickness.
Keratin and the thickened
plasma membranes of cells in this stratum protect the skin against abrasion and
penetration, and the glycolipid between its cells waterproofs this layer.
Stratum corneum (Horny layer )
The stratum corneum provides a durable “overcoat”
for the body, protecting deeper cells from the hostile external environment
(air) and from water loss, and rendering the body relatively insensitive to
biological, chemical, and physical assaults.
Stratum corneum (Horny layer)
The shingle-like cell remnants
of the stratum corneum are referred to as cornified, or horny, cells (cornu =
horn).
They appear as the dandruff
shed from the scalp and the flakes that slough off dry skin.
The average person sheds 18
kg of these skin flakes in a lifetime,
providing a lot of fodder for the dust mites that inhabit our homes and bed
linens.
Functions of the stratum
corneum
The waterproof nature of
keratin protects the body from water loss and water gain.
The stratum corneum also
serves as a mechanical barrier against microbe invasion.
This protective function of
skin is assisted by the secretions of sebaceous glands, which weaken or kill
bacteria on the skin.
The dermis
This is a deeper and thicker
region than the epidermis
It is composed of dense irregular connective
tissue.
The upper layer of the dermis
has fingerlike projections called dermal papillae.
Dermal papillae project into
and anchor the epidermis.
The dermis
The dermis contains
collagenous and elastic fibers.
The collagenous fibers are
flexible but offer great resistance to overstretching i.e. they prevent the
skin from being torn.
The elastic fibers stretch to allow movement
of underlying muscles and joints, but they maintain normal skin tension.
The dermis
The dermis also contains blood
vessels that nourish the skin.
There are also numerous
sensory nerve fibers in the dermis that take nerve impulses to and from the
accessory structures of the skin.
Hypodermis
Hypodermis, or subcutaneous
tissue, lies below the dermis.
The hypodermis is composed of
loose connective tissue, including adipose (fat) tissue.
Fat is an energy storage form that can be used
when necessary to supply the body with molecules for cellular respiration.
Adipose tissue also helps
insulate the body.
A well-developed hypodermis gives the body a
rounded appearance and provides protective padding against external assaults.
Excessive development of
adipose tissue in the hypodermis layer results in obesity.
Considerations in
dermatological therapy
The general pharmacokinetic
principles governing the use of drugs applied to the skin are the same as those
involved in other routes of drug administration.
Human skin is a complex series
of diffusion barriers.
Several variables
determine pharmacologic response to drugs applied to the skin
Factors that determine
response to dermatological drugs
Regional variation in drug
penetration:
For example, the scrotum,
face, axilla, and scalp are far more permeable than the forearm
These may require less drug for equivalent effect.
Factors that determine
response to dermatological drugs
Concentration gradient:
Increasing the concentration gradient
increases the mass of drug transferred per unit time, just as in the case of
diffusion across other barriers.
E.g. resistance to topical
corticosteroids can sometimes be overcome by use of higher concentrations of
drug.
Factors that determine response
to dermatological drugs
Dosing schedule:
Because of its physical
properties, the skin acts as a reservoir for many drugs.
As a result, the "local
half-life" may be long enough to permit once-daily application of drugs
with short systemic half-lives.
For example, once-daily
application of corticosteroids appears to be just as effective as multiple
applications in many conditions.
Factors that determine
response to dermatological drugs
Vehicles and occlusion:
An appropriate vehicle
maximizes the ability of the drug to penetrate the outer layers of the skin.
In addition, through their
physical properties (moistening or drying effects), vehicles may themselves
have important therapeutic effects.
Occlusion (application of a plastic
wrap to hold the drug and its vehicle in close contact with the skin) is
extremely effective in maximizing efficacy.
Dermatological vehicles
Topical medications usually
consist of active ingredients incorporated in a vehicle that facilitates cutaneous
application.
Factors that determine selection of a dermatological
vehicle
The solubility of the active agent in the
vehicle;
The rate of release of the agent from the
vehicle;
The ability of the vehicle to hydrate the stratum
corneum, thus enhancing penetration;
The stability of the therapeutic agent in the
vehicle;
Chemical and physical interactions of the vehicle and the active
agent.
Types of dermatological preparations
Depending on the vehicle,
dermatologic formulations may be classified as:
Tinctures
Wet dressings,
Lotions,
Gels,
Aerosols,
Powders,
Pastes,
Creams,
Ointments.
The ability of the vehicle to retard
evaporation from the surface of the skin increases in this series, being least
in tinctures and wet dressings and greatest in ointments.
Tinctures
Tinctures consist of an active
ingredient dissolved in alcohol
As the alcohol evaporates, it
cools and leaves behind a film of active ingredients
They are suitable for use on
the scalp,
Also used for applying high
concentrations of relatively toxic concentrations to a tiny area
Tinctures tend to be dry and
can be irritating
Tinctures
Examples:
Podophyllin is prepared as a
tincture for treating warts
Tincture of benzoin is used as
a vehicle for podophyllin
A wide variety of tinctures
are available for use on the scalp as cosmetics, tar products or as keratolytic
agents.
Wet dressings
These consist of an absorbent
product containing a water-based solution
They are an effective way to
cleanse and cool
They are useful for crusted,
infected conditions as well as for cleaning ulcers
Wet dressings
The skin can first be covered
with a cream or emollient cream and then covered with wet dressings
This reduces the drying effect
and improves debridement
The moisture and evaporation
provides a cooling effect which is a relief to the patient
However, excessive use leads
to drying out of the skin.
Lotions
Lotions are formulated either
as solutions or suspensions
They have a cooling effect
May be preferred to ointments
or creams for application on hairy areas.
Lotions in alcoholic bases can
sting if used on broken skin
Shake lotions e.g. calamine
lotion contain insoluble powders which leave a deposit on the skin surface.
Conversely, the low viscosity
of lotions may result in application
difficulties.
Gels
Pharmaceutical gels are
semisolid systems in which there is interaction (either physical or covalent)
between colloidal particles within a liquid vehicle.
The vehicle is continuous and
interacts with the colloidal particles within the 3D-network that is formed by
the bonds formed between adjacent particles.
Xerogels are gels in which the vehicle has been removed,
leaving a polymer network, e.g. polymer films.
Gels generally have a high
water content
They are suitable for
application on the face and scalp
Gels
Pharmaceutical gels may be
formulated to provide excellent spreading properties and will provide a cooling
effect due to solvent evaporation.
Similarly solvent evaporation
from liniments will provide a cooling effect.
Therapeutic agents that are
prone to hydrolysis should not be formulated into aqueous gels.
Powders
Dusting powders are used
rarely.
They reduce friction between
opposing skin surfaces
They should not be applied to
moist areas because they can cake and abrade the skin.
Powders
Talc is a lubricant but it does not absorb moisture.
It can cause respiratory
irritation.
Starch is less lubricant but absorbs water.
Pastes
Pharmaceutical pastes are
generally composed of ointment bases that contain a high concentration
(frequently 50% w/w) of dispersed drug.
The viscosity of pharmaceutical
pastes is greater than that of pharmaceutical ointments.
Due to the high solids
content, pharmaceutical pastes are often porous, allowing moisture loss from
the applied site.
Furthermore, pastes may act to
absorb moisture and chemicals within the exudates.
The opaque nature of pastes
(due to the high solids content) enables this formulation to be used as a
sunblock.
The chemical stability of therapeutic agents that are prone to
hydrolysis will be dramatically enhanced by formulation within pharmaceutical
ointments and pastes.
Pharmaceutical pastes are
generally not applied to the hair due to difficulties associated with removal.
Creams
Creams are emulsions of oil
and water
They are well absorbed into
the skin
They are cosmetically more
acceptable than ointments because they are less greasy and easier to apply
Ointments
These are greasy preparations
which are normally anhydrous and insoluble in water.
They are more occlusive than
creams
They are suitable for chronic,
dry lesions.
Pharmaceutical ointments are
semisolid systems that are applied externally, primarily to the skin and also
to mucous membranes, e.g. the rectum, the vagina/vulva and the eye.
Typically, medicated ointments
are used for the treatment of infection, inflammation and pruritus.
However, non-medicated
ointments are commonly used due to their emollient/lubricating properties.
In general, pharmaceutical
ointments persist at the site of application,
This enables the duration of drug release to be
greater than for many other topical dosage forms.
The increased viscosity of
pharmaceutical pastes ensures that a thick film of the dosage form is applied
to the site of action, which shows excellent persistence.
This property is particularly
useful if protection of an inflamed site is required, e.g. in eczema,
psoriasis.
Ointments may be easily spread on skin, being retained
at the site of application as an occlusive layer, thereby preventing moisture loss
from the skin.
This is particularly useful
whenever restoration of the physical characteristics of the skin is required
(e.g. due to inflammation).
Ointments are associated with lubricating/emollient
properties, properties that may be employed to reduce trauma of an affected
site upon spreading.
The hydrophobicity and
retention of ointments are useful attributes whenever applied to mucosa,
e.g. inflamed haemorrhoids,
eyelids, where fluid flow/inflammation at these sites would normally serve to
remove other formulations (e.g. oil in water creams) by dilution.
It should be noted, however,
that spreading of ointments on to moist surfaces may be difficult due to the
hydrophobic properties of most ointments.
Ointments-disadvantages
Pharmaceutical ointments are
generally greasy and difficult to remove (and are therefore often cosmetically
unacceptable).
Staining of clothes is often
associated with the use of pastes and
ointments.
Pharmaceutical ointments may
not be applied to exuding sites (however, this does not hold for pastes).
Ointments: Clinical uses
In certain clinical conditions
the site to which the ointment will be applied may be dry, e.g. psoriasis, or
moist.
If the area is dry, ointments
are often used to occlude the site, thereby retaining moisture.
This effect is considered to play an important
role in the treatment of certain clinical conditions.
Conversely, occlusive ointment
bases are not applied to sites in which there is fluid exudate.
Pastes
These are stiff preparations
containing a high content of finely powdered solids e.g. zinc oxide and starch
suspended in an ointment
They are used for
circumscribed lesions e.g. in lichen simplex, chronic eczema or psoriasis.
They are less occlusive than
ointments and can be used to protect inflamed, lichenified or excoriated skin.
Pastes
Pharmaceutical pastes are
generally applied as a thick layer at the required site and are therefore
considered to be cosmetically unacceptable.
The viscosity of pastes, may be problematic in ensuring
spreading of the dosage form over the affected site.
Aerosols
Dermatological sprays contain
particles that are coarser than those in inhalational sprays
They deliver the drug in the
form of a powder, a wet spray or a stream of liquid (especially local anaesthetics) or ointment- like
products
Aerosols allow the medication
to be applied in a uniform thin layer without anything else touching the
affected area
Thus it may reduce the
irritation that sometimes accompanies mechanical application of drugs to the
skin.
The rapid volatilization of
the propellant provides a cooling effect on the skin.
Dermatological formulations:
Clinical considerations
Acute inflammation with oozing,
vesiculation, and crusting is best treated with drying preparations such as
tinctures, wet dressings, and lotions
Dermatological
formulations: Clinical considerations
Chronic inflammation with xerosis, scaling, and
lichenification is best treated with more lubricating preparations such as
creams and ointments.
Tinctures, lotions, gels, and
aerosols are convenient for application to the scalp and hairy areas.
Dermatological formulations:
Clinical considerations
Emulsified vanishing-type
creams may be used in intertriginous areas without causing maceration.
Emulsifying agents are used to
provide homogeneous, stable preparations when mixtures of immiscible liquids
such as oil-in-water creams are compounded.
Some patients develop
irritation from these agents.
Substituting a preparation
that does not contain them or using one containing a lower concentration may
resolve the problem.
No comments:
Post a Comment