**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