**This sheet include all the sildes' material in bold
sand what dr said in light ..
We will continue our taking about acne
We said that acne is one of the most common
skin diseases which actually a lot of people suffer
from
In general we said that the is No cure but in realty
there are severe cases that need treatment
Some patient found that oral preparation is
effective but it is still questionable (wither these
drugs is really effective or the lesions resolve by
them selves ) ..
However we will take about what we need to
know about the treatment..
Drugs in acne
Retinoic acid and derivatives:
Retinoic acid (Tretinoin, Retin-A )
dapalene
Tazarotene
Isotretinoin
Isotretinoin is available in oral dosage form and
preserved for very sever acne cases because it is
very very toxic drug
Available
in cream,
gel and
ointment
dosage
forms
Oral
The most side effects that 1st three drugs have is
local irritation and sensitivity
But still the most sever side effect is for isotertioin
..
Lets discus every one of them separately
Tretinoin (Retin A), Adapalene, Tazarotene
Excellent choice for comedomal acne
Excellent choice for comedomal acne
Comedome means white &black vacuoles
which get with time smaller in size
So comodeletic effect drugs that dissolve such
comedome lead to disappearance of such
vacuoles
Improves follicular desquamation and
dyschromia
dyschromia with hyper or hypo pigmentation
inflammatory action (Adapalene best)
Adapalene has the best anti-inflammatory
effect among all retinoic acid derivatives
Use at night over entire face, exposure to
the sun increases irritation
It is preferd to use at night because it is
photosensitive and it might be degraded by
sun
Results in six to eight weeks. May
increase concentration over time
May increase the dose if there is no response
to applied dose
Degraded by prolonged exposure to the
sun and when used with benzoyl peroxide
(Adapalene most photostable)
So Adapalene Is the most photo stable , most anti-
inflammatory, less irritation (but we still advice to
use at night )
Side effects to Retinoids
Could lead to irritation (Tazarotene
most irritating, Adapalene least)
Sun sensitivity
Pustular eruption after Potential risk
of 3-- 4 weeks of use
Potential risk of hyper/
hypopigmentation
Contraindicated in pregnancy
(tumerogenic in animals)
We can generalized that all anti-acne preparation
have teratogenic activity so they are
contraindicated in pregnancy
Isotretinoin
It is orally given in capsule dosage form and this
drug is preserve for severe acne cases (even if
your patient improved after use it , we still say
don't use it except in severe cases because of its
huge side effects)
Systemic retinoid used for nodulo-- cystic
acne (caps.)
Most effective treatment with remission in
60 % after single course ( 15-- 24 weeks)
Requires long course treatment some times
up to six months
Reduces sebum production
Normalizes follicular keratinization (dr said
it inhibits keratinization )
Decreases inflammation
Extremely toxic: Teratogenic (can occur
with single exposure during gestation),
myalgias/arthralgias, photosensitivity, lipid
abnormalities, pancreatitis, leucopenia,
elevated platelets and ESR, proteinuria,
hematuria
Benzoyl Peroxide
Has bactericidal effect on P.acnes
No evidence of resistance
If combined with a topical antibiotic
(erythromycin or clindamycin) may help
in decreasing the emergence of
resistant of P.acnes species
As you know the problem in bacteria in
general is the resistance to anti-biotic and
chemotherapeutic agents , and we can
come over this problem by combining
drugs to gather for example( benzyl
peroxide with erythro or clindamycin)
Has mild comedolytic action(it dissolve
comodome) reduces inflammations ,and
decreases free fatty acids
Free fatty acids is aby product due to the
effect of lipase enzyme (which produced
by bacteria)
Such free fatty acids leads to irritation ( so
you must be careful with irritation, don't
touch the acne because it will leads to
disfigurement which is the major problem
with acne and this happen because most
people try to remove it (Remember that
the acne is not abases (if it is bacterial
abases yes you open and drain it then you
take an anti-biotic)
Available in cleansing liquid or bar,
lotion, cream, and gel
Adverse effects include: Irritation,
bleaches clothing and hair, allergic
contact dermatitis
Irritation which is common and shared
with all acne preparations
Even not just to acne , any skin
preparation which is locally applied will
lead to Irritation
Common question in exam
Which of the followings is common side effect between most
topically anti acne preparations ??
The answer is Irritation
But when we say proteinuria, hematuria ,
these side effects is just for isotretinon (not
common to all others)
Azelaic Acid
Has antimicrobial activity and inhibits
conversion of testosterone to
dihydrotetosterone
√ testosterone is synthesized in males (testes) and
in small quantities in females (ovaries)
√ testosterone which is the major androgen male
sex hormone is converted to more potent product
known as dihydrotetosterone which interacts with
androgen receptors
√ So Azelaic Acid has anti-androgenic effect by
inhibit this conversion
It is a dicarboxylic acid that is
bacteriostatic against P.acnes and
normalizes keratinization ( decrease
keratinization )
Most effective when used with other
agents
Comes as a gel and a cream
Side effects uncommon
Use in caution in teens with dark
complexions (dark skin) due to potential
risk of hypopigmentation
Topical antibacterials in Acne
Clindamycin
Erythromycin
Metronidazole
Sodium sulfacetamide
In addition to oral or systemic antibiotics
used against problems that related to
bacterial acne
Erythromycin, Clindamycin (locally applied)
Decrease P.acnes
Slow to act and percentage of free
fatty acids
Resistance often develops over time
Best used in combination with topical
retinoids/benzoyl peroxide
Combination therapy
5 % Benzoyl Peroxide and 3%
Erythromycin
5 %Benzoyl Peroxide and 1%
Clindamycin
Topical antibiotics and Azelaic acid or
Tretinion
Erythromycin
In topical preparations, erythromycin
base rather than a salt is used to
facilitate penetration
One of the possible complications of
topical therapy is the development of
antibiotic resistant strains of
organisms, including staphylococci
Adverse local reactions to
erythromycin solution may include a
burning sensation at the time of
application and drying and irritation
of the skin
Erythromycin is also available in a
fixed combination preparation with
benzoyl peroxide for topical treatment
of acne vulgaris
Clindamycin (locally applied)
10% absorbed, so, possibility of
Pseudomembranous colitis ( which is the
most dangerous side effect related to this
drug (also called antibiotic associated
colitis) , in this case we will stop this drug
and give the drug of choice which is
Vancomyocin )
The hydroalcoholic vehicle and foam
formulation (Evoclin) may cause drying
and irritation of the skin, with
complaints of burning and stinging
The water-based gel and lotion
formulations are well tolerated and
less likely to cause irritation.
Allergic contact dermatitis is
uncommon
Clindamycin is also available in fixed-
combination topical gels with benzoyl
peroxide, and with tretinoin
Metronidazole
- It is antibiotic and anti-parasitic
medication that is highly effective against
microorganism
- It is widely used in dentistry because in
oral cavity there are many anaerobic
bacteria
- In addition it has anti-acne effect
Effective in the treatment of rosacea
Rosacea داء الوردية : redness swollen face ,
this condition has a genetic background
also it has a role in certain mites that
normally present in skin , one of these
mites called ( Demodex brevis) which
cause this condition ( there is a role of
bacteria also ).
The mechanism of action is unknown,
but it may relate to the inhibitory
effects of neutrophil metronidazole on
Demodex brevis
It has an anti inflammatory effect by
direct effect on cellular function
Adverse local effects of the water-based
gel formulation include dryness,
burning, and stinging.
Less drying formulations may be better
tolerated
Caution should be exercised when
applying Metronidazole near the eyes
to avoid excessive tearing
Systemic antibiotics in acne
Primarily used for moderate to severe
inflammatory acne
Decrease P.acnes
Reduces amount of free fatty acids
Cases with high rates of resistance to
Erythromycin
Preferred agents include Tetracycline,
Doxycycline, Minocycline (those drugs
belong to tetracyclin group which differ in
pharmacokinetics parameters particularly
in …؟؟ مش واضحة بالريكورد
Hormonal control of acne
- We in general don't like to use hormonal
therapy especially with people normal
endocrine function
- Such pills or tablets (oral contraceptive
pills) consist of combination of estrogen
and progesterone (female sex hormones)
- So if you give this drug to females (or
even males (this could lead to irreversible
damage to the reproductive axis in the
body (this axis us responsible for
reproduction , pregnancy and sex)
- The severe side effect of this drug is due
to estrogenic component (progesterone
as compered to estrogen has few side
effects ) , so what they do nowadays is to
reduce as much as possible the
percentage of estrogen in order to
reduce side effect (which damage the
reproductive axis and lead to infertile in
men and women)
- Oral contraceptive pills are available with
different estrogen to progesterone ratios
Oral contraceptive pills in females
Increase production of sex
hormone binding globulin leading
to a decrease of circulating
androgens
Decrease ovarian androgen
production
Ortho tri cyclen (ethinyl estradiol and
norgestimate) , Estrostep (ethinyl
estradiol and norethindrone acetate)
FDA approved for the treatment of
acne
Norethindrone is progesterone
medication used in combination with
ethinyl estradiol
Oral antiandrogens (spironolactone)
can be useful
Spironolactone is an aldosterone antagonist
, it is found that is highly effective in certain
cases of acne and in case of female
hirsutism ( dense abnormal growth of hair
on a person's face and body, especially on a
woman.)
This drug absorb Na+ & water and increase
serum K+ level ( prevents your body from
absorbing too much salt and keeps
your potassium levels from getting too
low.) it can cause hyperkalemia
Oral corticosteroids, short course for
patients with severe inflammatory
disease ( for sever cases and last choice)
Summary
Mild acne: Topical therapy with
retinoid for comedomes, add Benzoyl
Peroxide or topical antibiotic if mild
inflammation present’
Moderate acne: Topical therapy plus
oral antibiotics for inflammatory
lesions, add Benzoyl Peroxide to
reduce antibiotic resistance. Consider
OCPs
Severe acne: Isotretinoin if topical
therapy and oral antibiotics fail
Advices to patients with acne
Avoid applying medication right after
washing face
Always remember that local application of
different dosage form is better on dry skin
Avoid over use of medication
Always start with applying a test dose
because there is a probability of having
severe irritation or sensitiveness on some
patients.
Apply on all acne prone areas
If face gets dry apply oil free
moisturizer
Always apply test dose
Start at low concentrations
Apply retinoids at night
Avoid use of at night Benzoyl Peroxide
Drugs in psoriasis )الصدفية(
Autoimmune disease (the immune system
is directed against normal tissues)
o A chronic skin condition, immune
mediated dermal inflammation
consists of painful reddened papules
that form plaques with distinct
borders. Other patches appear as
silvery yellow white scales
o Usually located in elbows, scalp,
knees, feet and genitalia (but any
parts of this skin could be affected also
by this condition)
Drugs in psoriasis
Topical
Coaltarointment
Calcipotriene
Tazarotene
Systemicc
PUVAA
Citretin
Alefacept
Coal tar ointment
Relieves itching, irritation, redness,
dryness, scaling caused by psoriasis,
seborrhea, or eczemaIt is a keratolytic
works by slowing bacterial growth and
loosening and softening scales
Calcipotriene
Derivative of vitamin D, acts by slowing
down the growth of skin cellsUsed
topically (cream; solution) in the
treatment of psoriasis Safe for longterm
application
Tazarotene (cream, gel, or foam)
It is a retinoid prodrug which is
converted to its active form, the
cognate carboxylic acid of tazarotene
Binds to all three members of the
retinoic acid receptor (RAR) (Retinoic
acid receptors) family: RARα, RARβ, and
RARγ but shows relative selectivity for
β, and γ and may modify ( alteration and
amplification) gene expression in stem
cells
Has anti-- inflammatory and anti
proliferative actions
Teratogenic and can cause burning,
stinging, peeling, erythema, and
localized edema of skin
UV light )using UV light for persons which
called phototherapy)
Patients with psoriasis noticed an
improvement in their skin after exposure to
sunshine
Of the many different UV rays emitted by
the sun, only UVA and UVB are helpful to
people with psoriasis’
(Not all wave lengths used in phototherapy like
UVC which is cause skin cancer but dose not
enter to atmosphere because our planet is
preserved by ozone layer )
Ultraviolet light reduces inflammation in
the skin, that s why it can be effective for
psoriasis and other inflammatory skin
conditions
PUVA (Psoralens + UVA)
Psoralens include psoralen; methoxsalen &
Trioxsalen, which are furocoumarins, can be
used both topically and systemically
( Furocoumarins are class of organic chemical
compounds produced by variety of plants )
Psoralens increase sensitivity to solar
radiation (given first and followed by UV)
Methoxsalen has the best oral
bioavailability, undergoes less first pass
effect and most effective
Effective in psoriasis, eczema, vitiligo (which
is decrease of pigmentation of certain area of
the skin), mycosis fungoides and cutaneous
T-cell lymphoma
PUVA MOA involves : (Mechanism of action)
inhibit DNA replication
Decrease in DNA-dependent
proliferation
Alteration of the immune system,
suppress T lymphocytes and epidermal
Langerhans cells
Inhibit mast cell release of inflammatory
mediators
Photo activation stimulates melanocytes
and induce their proliferation →
promotion of melanogenesis
Puva side effects include:
Nausea, blistering, painful erythema,
squamous cell carcinoma, malignant
melanoma (extensive PUVA therapy > 15
years) = ( with chronic use (more than 10
years)), cataract (patient should use UVA
absorbing eye glasses)
Acitretin
Related to isotretinoin
Given orally for severe pustular
psoriasis, good effect
Normalizes desregulated keratinocytes
and has anti-inflammatory action. Does
not suppress sebum
Accumulates in fat → prolonged
elimination t months after chronic use)
Hepatotoxic and teratogenic ½ (> 3
Adverse effects to Acitretin are similar to
other retinoids
More teratogenic than other retinoids
Should not be used in pregnant ladies or
those who might get pregnant while on the
drug or any time after at least 3 years of
discontinuation of therapy and also should
not donate blood
Alefacept
Immunosuppressant, stops the activity
of T lymphocytes
Given IM, major adverse effect
infection
Severe cases of psoriasis could be
managed with a high potency
corticosteroids or methotrexate
Keratolytic agents
Drugs that remove warts تواليل and other
lesions in which the epidermis produces
excess skin
Salicylic acid
o Solubilizes cell surface proteins resulting in
desquamation of keratotic debris
o Keratolytic in 36 % concentration, but
destructive in higher concentrations
When you apply Keratolytic agents you should
not exceed such percentages ,otherwise it will
burn your skin
o Can result in salicylism due to systemic
absorption
o Locally, can cause urticaria, erythema
multiforme, irritation, inflammation, and
ulceration
*It is applies to the warts and remove it but
many dermatologic prefer to use laser therapy
*warts may have viral involvement
**Don't forget that salicylic acid could be
absorbed to the circulation leading to
salicylism (toxicity) which is the main side
effects to aspirin ( which is acetylsalicylic acid)
Propylene Glycole
o Usually used as a vehicle for organic
compounds
o Develops an osmotic gradient through
the stratum corneum, thereby increasing
hydration of the outer layers of skin
o %70 Used alone as a keratolytic agent
in concentrations of 40 %, with plastic
occlusion, or in gel with salicylic acid
o 6 % It is also an effective humectant
()مرطب and increases the water content
of the stratum corneum
Urea
Has a humectant activity, i.e. softening
and moisturizing effect on the stratum
corneum
Increases water content as a result of
its hygroscopic characteristics
Urea is also keratolytic by altering
prekeratin and keratin, leading to
increased solubilization
Urea is available in a compatible
cream vehicle or ointment
It decreases the unpleasant oily feel of
dermatologic preparations (makes skin
preparations feel less greasy)
Podophyllum Resin & Podophyllotoxin
An alcoholic extract of Mandrake root or
Podophyllum Mayapple ) peltatum (
Used in the treatment of other verrucae( this
is another term for warts (paploma virus
infection leads to warts) ) Cytotoxic condyloma
acuminatum activity with specific affinity for
the microtubule protein of the mitotic
spindle. and Normal assembly of the spindle
is prevented, and epidermal mitoses are
arrested
Application should be restricted to wart
tissue only
A 25 % concentration of tincture of benzoin
podophyllum is used for resin in compound
condyloma acuminatum
Podophyllum Resin & Podophyllotoxin...
The patient should wash off the
preparation hours after the initial
application
23 Use during pregnancy is
contraindicated in view of possible
cytotoxic effects
Pure 0.5 % podophyllotoxin (podofilox)
is used for genital condylomas
Can cause N, V, (means nausea and
vomiting) muscle weakness, neuropathy,
coma, and even death
Flurouracil:
Antimetabolite that resembles uracil
and inhibits thymidylate synthetase,
thus interferes with DNA and may be
RNA synthesis
Used in multiple actinic keratosis
Aminolevulinic Acid:
Used in actinic keratosis ( keratinization
due to sun exposure which happen with
people who have sensitivity to sun light)
After topical application( 20 %) and
exposure to light, produces a cytotoxic
superoxide and hydroxyl radicals