12/23/15

1.

Regional variation in drug penetration

- scrotum, face, axilla and scalp are more
permeable than forearm

2.

Concentration gradient

3.

Dosing schedule
-the local half life may be long enough to permit
once daily application of drugs with short
systemic half lives

4.

Vehicles and occlusion

12/23/15

Solubility of the active agent in the

vehicles
Rate of release of the agent from the
vehicle
Ability of the vehicle to hydrate the
stratum corneum
Stability of the therapeutic agent in the
vehicle
Interactions, chemical and physical, of
the vehicle, stratum corneum and active
agent
12/23/15

Acute inflammation with oozing, vesiculation

and crusting lesions
tinctures,

wet dressing, lotions

Chronic inflammation with xerosis, scaling

and lichenification
Creams

and ointments

12/23/15

Emulsifying agents used to provide

homogeneous, stable preparations when
mixtures of immiscible liquids such as oil-inwater creams are compounded

12/23/15

Antibacterial agents

The selection of a particular antibiotic depends upon the diagnosis

12/23/15

Topical Antibacterial Preparations

Bacitracin and
Gramicidin

Gram (+), Staph, Strep,

Pneumococci
Anaerobic cocci, Neisseria,
tetanus, diphtheria

Bacitracin poorly
absorbed through the
skin, systemic toxicity is
rare
Gramicidin: systemic
toxicity limits its use

Mupirocin

Gram(+) aerobic bacteria,

including methicillin resistant
S aureus

Treatment of impetigo
Intranasal mupirocin for
eliminating nasal
carriage of S. aureus

Polymixin B
Sulfate

Gram(-) organisms,
Pseudomona aeroginosa, E.
coli, Enterobacter, Klebsiella

Total daily dose should

not exceed 200 mg in
order to reduce
likelihood of
neurotoxicity and
nephrotoxicity

12/23/15

Topical Antibacterial Preparations

Neomycin and
gentamicin

Gram (-), E. coli,

Klebsiella, enterobater
Gentamicin:
P.aeroginosa, Staph,
Grp A b-hemolytic Strep

Both drugs are watersoluble and excreted in

urine
Neomycin causes
sensitization

Topical antibiotics in
acne

Clindamycin phosphate
Erythromycin base
Metronidazole
Sulfacetamide

Effectiveness of Topical
< systemic
administration
Suitable in mild to
moderate cases of
inflammatory acne

12/23/15

12/23/15

Clindamycin

Propionibacterium acnes
10% absorbed, rare cases of bloody diarrhea and
pseudomembranous colitis
Hydroalcoholic vehicle and foam formulation
maycause drying and irritation of the skin(burning
and stinging)

Erythromycin MOA:inhibitory effect on P. acnes

Complication: development of antibiotic-resistant
strains of organism
Adverse effect: burning sensation at the time of
application and drying and irritation of the skin

12/23/15

10

Metronidazole Acne rosacea

MOA: inhibitory effects on Demolex brevis or antiinflammatory agent by direct effect on neutrophil
cellular function
Adverse effects: dryness, burning and stinging
Acne vulgaris and acne rosacea
Sodium
sulfacetamide MOA: inhibition of P acnes by competitive inhibition
of PABA utilization

12/23/15

11

12/23/15

12

Topical
Clotrimazole
Miconazole
Econazole
Ketoconazole
Oxiconazole
Sulconazole
Ciclopirox
Olamine
Naftifine
Terbinafine
Butenafine
Tolnaftate

Oral
Griseofulvin
Terbinafine
Ketoconazole
Fluconazole
itraconazole

12/23/15

13

Topical azoles

Dermatophytes and yeast, Candida albicans

Miconazole: vulvovaginal candidiasis
Clotrimazole: vulvovaginal candidiasis
Ketoconazole: dermatophytosis and candidiasis
and as shampoo for the treatment of seborrheic
dermatitis
Once to twice daily x 2-3 weeks result in clearing
of superficial dermatophyte infection
Paronychial and intertriginous candidiasis: TID
/QID
Adverse reactions: stinging , pruritus, erythema,
local irritation

12/23/15

14

Ciclopirox
olamine

Inhibitory against dermatophytes, Candida, P

orbiculare
MOA: inhibit the uptake of precursors of
macromolecular synthesis; the site of action is
probably the fungal cell membrane
Uses: treatment of mild to moderate
onychomycosis of fingernails and toenails

Allylamine:Naftifin Highly active against dermatophytes but less

e and terbinafine active than yeasts
MOA: selective inhibition of squalene
epoxidase (key enzyme for the synthesis of
ergosterol)
Adverse reactions: local irritation, burning
sensation, erythema
12/23/15

15

Butenafine

MOA: inhibits epoxidation of squalene,

blocking synthesis of ergosterol

Tolnaftate

Against epidermophyton, miscrosporum,

trichphyton
Active against P orbiculare but not against
Candida
Recurrence after cessation of therapy is
common
Infections of the palms, soles and nails are
unresponsive

12/23/15

16

Nystatin and
amphotericin B

Topical therapy of Candida infections but

ineffective against dermatophytes
Nystatin : narrow spectrum and negligible
absorption from the GIT following oral
administration
-Paronychial and intertriginous candidiasis
BID/TID
-- oral candidiasis(thrush) 5 ml qid
-Vulvovaginal candidiasis 1 vaginal tab bid for
14 days then nightly for additional 14-21 days
Amphotericin B : broader spectrum; used IV in
the treatment of systemic mycoses
- Paronychial and intertriginous candidiasis

12/23/15

17

Oral Azoles
Derivatives

Oral treatment for systemic mycosis:

fluconazole, itraconazole, ketoconazole
MOA: affecting permeability of the cell
membrane of sensitive cells through alterations
of the biosynthesis of lipids, sterols, in the fungal
cell
Uses:
-Glabrous skin 200 mg OD x 2-3 weeks
-Palmar-plantar skin 200 BID x 4-6 wks
-Tinea vesicolor : 200 mg OD
Fluconazole: 100 mg mucocutaneus candidiasis
Itraconazole: onychomycosis 200 mg OD x 3
mos

12/23/15

18

Griseofulvin

12/23/15

Effective orally against dermatophyte infections

caused by epidermophyton, microsporum and
trichophyton
Ineffective against Candida and P. orbiculare
500 mg daily with meals (10 mg/kg)
Recalcitrant infections: 1 gm/d
Most effective in treating tinea infections of the
scalp( 4-6 weeks) and glabrous (nonhairy) skin(3-4
weeks)
Fingernails respond in 6 mos therapy
Toenails require 8-18 mos therapy
Contraindicated in patients with porphyria or hepatic
failure

19

Terbinafine

12/23/15

Treatment of onychomycosis 250 mg OD x 6 wks

(fingernails) and 12 wks for toenail infections

20

Acyclovir (Zovirax)
Valacyclovir
Penciclovir
Famciclovir
Synthetic guanine analogs with inhibitory
activity against members of the herpes virus
family

12/23/15

21

Treatment of external genital and perianal

warts
Actinic keratoses on the face and scalp
Biopsy-proven primary basal cell carcinomas
on the trunk, neck and extremities
MOA: stimulate peripheral mononuclear
cells to release interferon and to stimulate
macrophages to produce interleukins and
TNF
12/23/15

22

12/23/15

23

Applied to the wart tissue 3x/wk and left on

the skin for 6-10 hrs prior to washing off with
mild soap and water

Superficial basal cell Ca: 5x/wk application

to the tumor, including 1 cm margin
surrounding skin, for a 6-wk course of
therapy

12/23/15

24

Atopic dermatitis
Inhibit T-lymphocyte activation and prevent
release of inflammatory cytokines and
mediators from mast cells in vitro after
stimulation by antigen-IgE complexes
Most common side effect: burning sensation

12/23/15

25

12/23/15

26

Permethrin

Pediculosis humanus, Phtirus pubis, Sarcoptes

scabiei
Applied undiluted to affected area for 10
minutes and then rinsed off with warm water
Scabies: single applicaton of 5%cream is
applied, left for 8-14 hrs, then washed off
Adverse effects: transient burning, stinging,
pruritus

Lindane

Gamma benzene hexachloride

Concentrated in fatty tissues, including the brain
Pediculosis capitis or pubis:30 ml of shampoo is
applied to dry hair on the scalp or genital area
for 4 minutes and then rinsed off
Adverse effects: neurotoxicity and
hematotoxicity

12/23/15

27

12/23/15

28

Crotamiton

Scabicide with some antipruriticproperties

Two applications to the entire body from the
chin down at 24-hr intervals, with a cleansing
bath 48 hrs after the last application
Alternative to lindane

Sulfur

5% precipitated sulfur in petrolatum

Scabicide

Malathion

Organophosphate cholinesterase inibitor that

is hydrolyzed by plasma carboxylesterase
Applied to the hair when dry; 4-6 hours later,
the hair is combed to remove nits and lice

12/23/15

29

12/23/15

30

Hydroquinone, Monobenzone, Mequinol

Reduce

pigmentation of the skin

MOA: inhibition of the enzyme yrosinase, thus
interfering with the biosynthesis of melanin
Temporary lightening (hydroquinone and
mequinol)
Monobenzone: irreversible depigmentation

12/23/15

31

12/23/15

32

Trioxsalen and Methoxsalen

Psoralens

used for repigmentation of

depigmented macules of vitiligo
Psoralens must be photoactivated by long-wave
length UV in the range of 320-400 nm (UVA) to
produce a beneficial effect

12/23/15

33

Trioxsalen and Methoxsalen

Psoralens

intercalate with DNA and, with

subsequent UVA irradiation, cyclobutane adducts
are formed with pyrimidine
DNA photoproducts may inhibit DNA synthesis
Major long-term risks: cataracts and skin cancer

12/23/15

34

12/23/15

35

Topical medications useful in protecting

against sunlight contain either chemical
compounds that absorb UV light
Sunshades: opaque materials such as
titanium dioxide that reflect light

12/23/15

36

Designed to absorb UV light in the ultraviolet

B(UVB) wavelength range from 280 to 320 nm,
which is the range responsible for most of the
erythema and tanning associated with sun exposure

12/23/15

37

Chronic exposure to light induces aging of

the skin and photocarcinogenesis
Para-aminobenzoic acid and its esters are the
most effective available absorbers in the B
region

12/23/15

38

Benzophenones
Oxybenzones
Dioxybenzones
Sulisoenzone
Broader

spectrum of absorption from 250 to 360

nm

12/23/15

39

Dibenzoylmethanes
Parasol

and eusolex
Absorb wavelengths throughout the longer UVA
range, 320 nm to 400 nm, with maximum
absorption at 360 nm

12/23/15

40

Patients particularly sensitive to UVA

wavelengths include :
individuals

with polymorphous light eruption

Cutaneous lupus erythematosus
Drug-induced photosensitivity

12/23/15

41

Sun protection factor (SPF)

Measure

of its effectiveness in absorbing

erythrogenic ultraviolet light
Determined by measuring the minimal erythema
dose with and without the sunscreen to the
minimal erythema dose without sunscreen
Spf 15 or greater

12/23/15

42

Retinoic Acid and derivatives

Tretinoin

or all-trans-retinoic acid
Is the acid form of vitamin A
Effective topical treatment for acne vulgaris
Vitamin A alcohol: physiologic form of Vitamin A

12/23/15

43

Effects of retinoic acid on epithelial tissues

Stabilizes lysosomes
Increases RNA polymerase activity
Increases prostaglandin E2, cAMP, cGMP

12/23/15

44

Action in acne

Decrease cohesion between epidermal cells

Increase epidermal cell turnover

12/23/15

45

Expulsion of open comedones

Transformation of closed comedones into
open ones

12/23/15

46

Topical retinoic acid should be applied to dry

skin only
During the 1st 4-6 weeks of therapy,
comedones not previously evident may
appear and give the impression that the acne
has been aggravated by the retinoic acid
In 8-12 weeks optimal clinical improvement

12/23/15

47

The effects of tretinoin on keratinization and

desquamation offer benefits for patients
with photo damaged skin.
Prolonged used of tretinoin

promotes dermal collagen synthesis

new blood vessel formation
thickening of the epidermis, which helps
diminish fine lines and wrinkles

12/23/15

48

Most common adverse effects

Erythema
Dryness

12/23/15

49

Adapalene (Differin)

Derivative of naphthoic acid that resembles

retinoic acid in structure and effects
Less irritating
Effective in patients with mild to moderate acne
vulgaris

Tazarotene (Tazorac)

Acetylenic retinoid
Treatment of mild to moderately severe facial acne

12/23/15

50

Isotretinoin

Accutane is a synthetic retinoid restricted to

the treatment of severe cystic acne that is
recalcitrant to standard therapies
Act by inhibiting sebaceous gland size and
function
Drug is well absorbed, extensively bound to
plasma albumin
Elimination half life of 10-20 hours
Cyctic acne: 1-2 mg/kg given orally in two
divided doses daily for 4-5 months

12/23/15

51

Isotretinoin

Common adverse effects resemble

hypervitaminosis A
Dryness and itching of the skin
Reversible on discontinuation of therapy
Teratogenic

12/23/15

52

Benzoyl Peroxide

Penetrates the stratum corneum or fllicular

openings unchanged and is converted
metaolically to benzoic acid within the
epidermis and dermis

MOA: antimicrobial activity against P acnes and

to its peeling and comedolytic effects

12/23/15

53

Benzoyl Peroxide

Once daily application for the 1st week

Is an oxidant and may rarely cause bleaching
of the hair or colored fabrics

12/23/15

54

Drugs for Psoriasis

Acitretin

metabolite of the aromatic retinoid atretinate

Effective in the treatment of pustular forms
25-50 mg/d
Elevations in Cholesterol and TAG, hepatotoxicity
Teratognic

Tazarotene

Topical

acetylenic retinoid prodrug that is

ydrolyzed to its active form by an esterase
Tazarotenic acid binds to retinoic acid receptors
resulting in modified gene expression
Anti-inflammatory and antiproliferative actions
Adverse effects: sensory irritation and irritant
dermattis

Drugs for Psoriasis

Calcipotriene

Synthetic

vitamin D3 derivative
Effective in the treatament of plaque-type
psoariasis vulgaris of moderate severity
Improvement is noted following 2 wks of tx

Biologic agents

A.
B.
C.

Useful in adult patients with moderate to

severe chronic plaque psoriasis
Alefacept
Efalizumab
Etanercept

Drugs for Psoriasis

A.
-

B.
-

C.
-

Alefacept
Immunosuppressive dimeric fusion protein
Interferes with lymphocyte activation
Efalizumab
Immunosuppressive recombinant humanized IgG kappa isotype
monoclonal antibody that binds to CD11a subunit of leukocyte
function antigen-1
Adverse effect: immune-mediated thrombocytopenia
Etanercept
Dimeric fusion protein consisting of the extracellular ligandbinding portion of the human TNF receptor linked to the Fc
portion of human IgG
Binds specifically to TNF and and blocks interaction with
cell surface TNF receptors that play a role in the inflammatory
process of plaque psoriasis

Anti-inflammatory Agents

Topical corticosteroids
Hydrocortisone,

the natural glucocorticoid of the

adrenal cortex
Are only minimally absorbed following
application to normal skin
Penetration is increased several fold in the
inflamed skin of atopic dermatitis and in severe
exfoliative diseases such a erythrodermic
psoriasis

Anti-inflammatory Agents

Topical corticosteroids
Ointment bases tend to give better activity to
the corticosteroid than do cream or lotion
vehicles
Solubility of the corticosteroid in the vehicle is a
significant determinant of the percutaneous
absorption of a topical steroid

Anti-inflammatory Agents

Table 62-1

Anti-inflammatory Agents

Table 62-2

Anti-inflammatory Agents

Adverse effects
Possess

the potential to suppress the pituitaryadrenal cortex

Iatrogenic Cushings syndrome
Growth retardation
Atrophy : shiny,wrinkled cigarette paper"
appearing skin with prominent telangiectasia and
a tendency to develop purpura and ecchymosis
Steroid rosacea: persistent erythema,
telangiectasic vessels, pustules, and papules in
central facial distribution

Anti-inflammatory Agents

Corticosteroids
Contraindicated

in individuals who demonstrated

hypersensitivity to them

Anti-inflammatory Agents

Tar Compounds
Used

in the treatment of psoriasis, dermatitis,

lichen simplex chronicus
Adverse reaction: irritant folliculitis,
phototoxicity, allergic contact dermatitis

Keratolytic and Destructive Agents

1.
2.
3.
4.
5.
6.
7.

Salicylic acid
Propylene glycol
Urea
Podophyllum resin and podofilox
Fluorouracil
Nonsteroidal anti-inflammatory drugs
Aminolevulinic acid

Keratolytic and Destructive Agents

Salicylic Acid
Solubilize

cell surface proteins that keep the

stratum corneum intact desquamation of
keratotic debris
Keratolytic in concentrations of 3-6%
>6% destructive to tissues

Keratolytic and Destructive Agents

Propylene Glycol
40-70%

concentrations
Effective keratolytic agent for removal of
hyperkeratotic debris
Effective humectant and increases the water
content of the stratum corneum
Uses:

Ichthyosis palmar and plantar keratodermas

Psoriasis
Pytyriasis rubra pilaris
Keratosis pilaris
Hypertrophic lichen planus

Keratolytic and Destructive Agents

Urea
Softening

and moisturizing effect on the stratum

corneum
Increases the water content of the stratum
corneum, as a result of the hygroscopic
characteristics of this naturally occurring
molecule
Keratolytic : alterations in prekeratin and keratin
leading to increased solubilization
May break hydrogen bonds that keep the stratum
corneum intact

Keratolytic and Destructive Agents

Podophyllum resin and Podofilox

Podophyllum

resin is used in the treatment of

condyloma acuminata
Are active cytotoxic agents with specific affinity
for the microtubule protein of the mitotic
spindle
Treatment is self administered in treatment
cycles of twice-daily application for 3
consecutive days followed by a 4-day drug free
period

Keratolytic and Destructive Agents

Fluorouracil
Treatment

of multiple actinic keratoses

Inhibits thymidylate synthetase activity,
interfereing with the synthesis of DNA

Keratolytic and Destructive Agents

NSAIDs
Diclofenac
1

: actinic keratoses

Keratolytic and Destructive Agents

Aminolevulinic Acid
Endogenous

precursor of photosensitizing
porphyrin metabolites
Photosensitization of actinic keratoses using
ALA(Levulan Kerastick) and illumination with a
blue light photodynamic therapy
illuminator(BLU-U) is the basis for ALA
photodynamic therapy

Antipruritic Agents

Doxepin
Potent H1 and H2
receptor antagonist
Adverse effects:

Burning and stinging of

the treatment site

Pramoxine
Topical anesthetic

Trichogenic and Antitrichognic agents

Minoxidil
Reverse

the progressive miniaturization of

terminal scalp hairs associated with androgenic
alopecia
Vertex balding is more responsive to therapy
Cessation of treatment will lead to hair loss in 46 months

Trichogenic and Antitrichognic agents

Finasteride
5

reductase inibitor that blocks the conversion

of testosterone to dihydrotestosterone
Treatment for 3-6 months is necessary to see
increased hair growth

Trichogenic and Antitrichognic agents

Eflornithine
Irreversible

inhibitor of ornithine decarboxylase

that catalyzes the rate-limiting step in the
biosynthesis of polyamines