Transcript - SlideBoom

What Causes Eczema?
Exact cause unknown
 Over-reactive response by body's immune system
 More common in families with a history of other allergies or asthma

Factors that may cause eczema:

Adverse weather

Upper respiratory infections or colds

Household products

Animal dander

Coarse or rough materials

Other disease

Irritating substances

Allergies*

Genetic makeup*
What can worsen eczema?
Factors that may worsen eczema:

Allergies to pollen, mold, dust mites, or animals

Dry skin

Environmental irritants

Water

Extreme temperatures

Fragrances/dyes in skin lotions or soaps

Stress
What is happening when eczema occurs?
At Skin Level:
Irritant causes alterations in the structure and function of skin layers
 Splitting of layers of the epidermis,
= Protective function of the epidermis compromised.

This can lead to :
Penetration of irritants and bacteria
 Loss of water holding capacity = skin dries out, becomes flaky
& Hence thickening due to scratching.

What is happening when eczema occurs?
Elsewhere:
Effects of eczema can be seen deeper than skin level:
Increased levels of immunoglobins.
(Function: activation of white blood cells)
 Increased numbers of a type of white blood cells associated
with allergy.

Preventing Daniel’s eczema from
developing when he was an infant
Avoid Trigger factors:
1. Irritants
 Rough, irritable fibres
 Soap in excess, bubble baths, perfumed products
Solution:
 Wear cotton
 Applying emollient
Preventing Daniel’s eczema from
developing when he was an infant
2. Allergens (Links with atopic eczema)
 Droppings of house-dust mites.
 Food allergens
 Moulds and pollens
Solution:
 Regular vacuuming and use of anti-dust-mite bedding, wash bedding
t >60⁰.
 Avoid suspected food allergens.
 Daniel's environment should have been kept very clean
He also has hay fever and asthma - intensified by moulds and
pollen
Preventing Daniel’s eczema from
developing when he was an infant
3. Climate
● Extremes of temperature or humidity.
Overheating and sweating makes itching worse and also dries out
the skin.
Solution:
● Keep the environment cool.
4. Familial factors
● Genetics
Solution :
● If eczema, hay fever or asthma is known to run in the family, it can be
prevented as much as possible from birth.
Preventing Daniel’s eczema from
developing when he was an infant
5. Psychological stress
● May have used scratching as a weapon.
6. Illness
● such as teething or lack of sleep.
7. Breast feeding
● Breast feed exclusively for the first 6 months.
can prevent eczema from developing.
Why Daniel’s skin is worse since starting
his new job?

Frequent contact with water.

Irritant hand eczema. (dry, cracked and inflamed)


Contact with detergents
- breaks down the protective barrier of the skin.
Quick development of irritant hand eczema due to Daniel’s
history of eczema in childhood.
Side effects of using topical steroids
1. Immunosupression
Suppressed cell-mediated immunity by reduction T cell
proliferation and cytokine production
2. Osteoporosis
Increased risk of bone fracture
3. Tachyphylaxis
Reduced response to the steroid after repeated uses.
4. Skin atrophy
Repeated applications in the same area =
thinning of the epidermis and changes to tissue of dermis
Advantages of using higher dose with
shorter period:
1. Thick epidermis in affected region
= Lower dose may be ineffective
2. Shorter treatment period
3. Fewer uses of steroid can prevent tachyphylaxis and skin
atrophy
Drawbacks
1. Daniel is too young for high potent steroid.
2. Immunosupression will be severe during treatment period
- may cause secondary infection.
3. Steroid will be applied onto cracked skin
= increased absorption rate
= worsened side effects.
Advantages of using milder steroid
with longer period
1. It is a traditional treatment for mild eczema.
2. Mild steroid is enough to cure the disease because patient’s
condition is moderate.
3. It can reduce the risk of osteoporosis as it is a dose dependent
effect.
Drawbacks
1. Lengthened treatment
= increased chance of tachyphylaxis and skin atrophy.
2. If tachyphylaxis is developed,
- a higher dose of steroid will be required.
3. Steroid induced striae
= irreversible stretch marks on the skin.
Choice for treatment
Mild steroid for a relatively longer period.
1. It is safer for the patient.
2. Only two day gap before appointment with GP
What are the differences,
in terms of chemical structure,
between a steroid like
betamethasone used on the skin,
and steroids like nandrolone,
used (and abused) in sport?
-Absence of an –OH group
Absence of C=C
-Presence of –OH group
Nandrolone
Absence of a methyl grp.
-OH groups helps in binding
to the receptor
Presence of C=C
Betamethasone
-Presence of a –OH group
and a straight chain
Only 1 difference between
stuctures of Nandrolone and
testosterone:
Nandrolone
Testosterone
Nandrolone is abused in sport
because:
 Accelerates muscle growth
 Increases strength
 Enhances aggression
 Improves recovery.
International Olympic
committee Limit: 2 ng·mL-1
Diagnosis: urinalysis
Side effects

Acne

Sodium retention with oedema

Inhibition of spermatogenesis

Liver tumours

Abnormal liver function

Voice changes
How is the bioequivalence of topical
corticosteroids measured?
Medicines are bioequivalent if:

They are pharmaceutically equivalent or alternatives

Administration of same molar dose results in highly similar
bioavailibility.
Measuring bioequivalence:

Main: Vasoconstriction assay

Other: micro dialysis and tape stripping
Vasoconstriction Assay
Two types of vasoconstriction assay:
1. Visual assessment by human observers
2. Chromameter assay
Both techniques:


Rely on the drug’s blanching effect on the skin.
Both techniques begin with testing different skin sites by
applying the topical corticosteroid
Visual Assessment by Human Observers
Trained observers record the blanching of the skin at regular
time intervals


Arbitrary intensity scale of 0 – 4 (0 = no blanching)

Total Possible score (TPS) are calculated using data such as:


Max score = 4

No. of trained observers = T

No. of tested sites = S

No. of Subjects = V
TPS = 4 x T x S x V


% TPS = Actual Score x 100
TPS
Blanching profile is plotted using %TPS versus time
Chromameter Assessment

Objective instrumental approach
1. White light emitted onto test area.
2. Intensity of reflected light measured.
–
3 different wavelength filters
–
or photodiode array
3. Detected signal is converted into three sets of data:
I. luminosity,
II. amount of green or red
III. amount of yellow or blue
Chromameter Assessment
As skin blanching appears:
1. Luminosity increases
2. Amount of green or red decreases
3. Amount of yellow or blue slightly increases
Microdialysis



Assesses topical corticosteroids ability to penetrate stratum
corneum and into dermis
Successful for in vivo bioequivalence assessments
- But all drugs investigated were hydrophilic
Problem for assessment of lipophilic substances:
- The substance binds to membrane and other components
of microdialysis system.
Tape Stripping


Removal of stratum corneum to determine drug diffusion
through the skin
Problems:
–
Each tape doesn’t remove the same amount of skin
–
Different results from different labs
Considerations for Testing Bioequivalence
of Topical Corticosteroids


Difficult to determine dosage form of semi solid topical
corticosteroids
There are many pathways through the skin
–
Stratum corneum
–
Sweat glands
–
Hair follicles
Issues that the pharmacist should be aware of
when selling the hydrocortisone 1% Cream:
1. The potential for adverse effects
2. Differences in absorption rate in different areas of the
body
3. Is the cream suitable for what the patient wishes to treat?
4. Possible allergies
1. The potential for adverse effects

Epidermal Atropy

Telangiectascia

Striae

Premature aging

Rosacea

Greater potency = Greater potential for adverse effects

Topical steroids classified by potency

4 Groups (1,2,3 and 4)

Group 1 → 4, decreasing potency.

Hydrocortisone 1% Cream is in group 4
Issues that the pharmacist should be aware of
when selling the hydrocortisone 1% Cream:
1. The potential for adverse effects
2. Differences in absorption rate in different areas of the
body
3. Is the cream suitable for what the patient wishes to treat?
4. Possible allergies
2. Differences in absorption rate in different areas
of the body
For example:
 Forearm absorbs 1%
 Armpit absorbs 4%
 Face absorbs 7%
 Eyelids and genitals absorb 30%
 Palm absorbs 0.1%
 Sole absorbs 0.05%
Are Daniel's palms affected?
 A more potent cream may be required.
 Lower absorption rate due to thicker horny layer and epidermis


Hydrocortisone 1% cream should not be used on the face.
Issues that the pharmacist should be aware of
when selling the hydrocortisone 1% Cream:
1. The potential for adverse effects
2. Differences in absorption rate in different areas of the
body
3. Is the cream suitable for what the patient wishes to treat?
4. Possible allergies
3. Is the cream suitable for what
the patient wishes to treat?
Ointment vs. Cream

Daniel's hands: 'Dry, cracked inflamed'

Ointments: Dry eczemas

Creams: Weeping eczema

Daniel should purchase an ointment rather than a
cream
3. Is the cream suitable for what the patient
wishes to treat?
Is the eczema infected?

Risk of exacerbation of the infection

Infected eczema:
Red
'Weepy'
Yellow-ish crust
Pustules
Hot, itchy and sore


Daniel does not appear to have an infection.
Visit GP if eczema does not respond to topical steroid
treatment.

Issues that the pharmacist should be aware of
when selling the hydrocortisone 1% Cream:
1. The potential for adverse effects
2. Differences in absorption rate in different areas of the
body
3. Is the cream suitable for what the patient wishes to treat?
4. Possible allergies
4. Possible allergies


Read the leaflet
Check for allergies or sensitivities to ingredients before
use.
Daniel’s current treatment regime
Betamethasone valerate 0.1% ointment
– topical corticosteroid, potent
Zinc and ichthammol bandage
– reduce lichenification
– ichthammol reduces pruritus.
Dermol 500 Lotion
– Moisturising lotion
– Replacing lost moisture and aid moisture retention
– Reduce scaling, redness and itching
– Requires frequent application
Oilatum emollient – Emollient bath additive
– Soothes, smoothes and hydrates the skin
– Acetylated wool alcohols 5%, liquid paraffin 63.4%
Daniel’s current treatment regime

Ointment – best solution for his dry, cracked and inflamed
skin.

Hydrocortisone 1% cream – not suitable.

Side effects of systemic absorption of topical corticosteriods:


Hypothalamic pituitary-adrenal (HPA) axis suppression,

Cushing’s syndrome,

Hyperglycemia,

Glucosuria
Treatment should not be changed unless agreed with GP