Topical agents

1. Treatments
MEDICINE 37:5 232 © 2009 Elsevier Ltd. All rights reserved.
Dermatological
pharmacology: topical
agents
Mahbub MU Chowdhury
Abstract
Topical therapies constitute an important aspect of dermatological treat-
ments. This article covers the principles of topical treatments, vehicles
used and a number of commonly used topical agents, including corti-
costeroids. Indications for use and common side effects of these topical
agents are mentioned.
Keywords calcineurin inhibitors; corticosteroids; creams; ointments;
retinoids; topical treatments; vitamin D analogues
Principles of topical therapy
Topical therapy allows direct delivery of drug to the skin with
minimal risk of systemic side effects. Problems include poor
compliance because of difficulty using the drug and inconven-
ience of applications. The effectiveness of topical drugs depends
on their ability to penetrate the epidermis. This is influenced by
the choice and concentration of drug, its vehicle or base, and the
age and degree of hydration of the skin.
• Substances enter aged skin more easily, but clearance into the
circulation is slower because of changes in the dermal matrix and
reduced vasculature, thus the skin may be more susceptible to
both beneficial and adverse effects of topical medication.
• Use of emollients to increase skin hydration before application of
topical agents such as corticosteroids may increase their penetration
five-fold. Occlusion of the skin will also increase drug penetration.
• The specific condition and body site to be treated is also im-
portant, for example absorption is greater at flexural sites and
less potent corticosteroids are therefore required.
Vehicles
An understanding of the available vehicles is important for effec-
tive prescribing of topical therapies. Vehicles hydrate the skin,
can have an anti-inflammatory effect and help the active drug
penetrate the skin.
• Creams are water-based products with a cooling and emollient
effect. They contain preservatives to prevent bacterial and fungal
growth, but the preservatives may lead to sensitization and al-
lergic contact dermatitis. Creams are less greasy than ­ointments
and are cosmetically better tolerated.
Mahbub MU Chowdhury MBChB FRCP is Consultant Dermatologist in the
Welsh Institute of Dermatology, University Hospital of Wales, Cardiff,
UK. Competing interests: none declared.
• Ointments contain no water; they are oil-based products pro-
viding an occlusive layer over the skin surface that helps to retain
water. This hydrates dry and scaly skin and enhances absorp-
tion, and ointments are therefore useful in chronic dry condi-
tions. They contain no preservatives.
• Lotions are watery suspensions that can be used over hairy and
large body surface areas. They have a drying, cooling ­effect.
• Gels are watery suspensions of insoluble drugs such as corti-
costeroids, salicylic acid and retinoids. Gelling agents are added
to aid their absorption.
Topical agents
A list of common topical agents is shown in Table 1.
Emollients
The term ‘emollient’ covers a diverse range of products, includ-
ing soap substitutes, bath additives, creams, ointments and even
aerosol spray products. They are important in the management
of itchy, dry skin conditions, giving symptomatic relief, and may
reduce requirements for topical corticosteroids. Their effects are
temporary and frequent applications are needed even after ini-
tial clinical improvement. Choice of emollient is guided by the
nature of the condition, its severity and patient preference. Emol-
lient creams, ointments and sprays are best applied following a
bath or shower. Many emollients contain preservatives and other
additives and sensitization may occasionally occur.
Topical corticosteroids
Topical corticosteroids are classified according to their potency
(Table 2). The cutaneous effects of topical corticosteroids include
vasoconstriction, reduced dermal blood vessel permeability and
inhibition of phospholipases, fibrin and kinins. In addition, inhi-
bition of phospholipases causes blockage of the arachidonic acid
pathway, which leads to a cascade of inflammatory mediators. Anti-
inflammatory effects thus occur, and corticosteroid responsive con-
ditions such as eczema usually exhibit clinical improvement within
2 weeks of starting treatment with a potent agent. Inflammatory skin
conditions involving delicate skin on the face, flexures or genitalia
require a mild or, at most, moderately potent corticosteroid. In con-
trast, palms, soles and markedly thickened skin (as may occur with
chronic scratching) often require a potent or very potent agent.
• The calcineurin inhibitors tacrolimus and pimecrolimus are
licensed treatments for atopic eczema
• Topical vitamin D analogues such as calcitriol can be used for
facial and flexural psoriasis
• UK National Institute for Clinical Excellence (NICE) guidelines
for the treatment of atopic eczema have been published,
including topical corticosteroids.3
• Retapamulin 1% ointment is a new antibacterial licensed
for treatment of impetigo, infected lacerations and sutured
wounds
What’s new?

2. Treatments
MEDICINE 37:5 233 © 2009 Elsevier Ltd. All rights reserved.
Corticosteroids should be applied once or twice daily. The
quantity applied can be assessed using the ‘fingertip unit’ (FTU)
concept – an amount of ointment or cream the length of an
adult fingertip is about 0.5 g and is sufficient to treat 300 cm2 of
affected skin (Figure 1).1 A single application for one arm or leg,
for example, requires 3 FTU or 6 FTU, respectively.
Failure to respond to topical corticosteroids may occur as a
result of incorrect diagnosis, skin infection or infestation, contact
allergy, poor compliance or inadequate application of treatment.
Under-treatment through use of too weak or inadequate amounts
of topical corticosteroids is a significant problem; it is now seen
more often in clinical practice than over-treatment through ­
long-term use of potent agents. The risk of side effects increases
with corticosteroid potency.
Topical retinoids
The topical retinoids are a unique group of drugs that are widely
prescribed for skin conditions, including psoriasis, acne and pho-
todamage. The first topical retinoids were synthetic derivatives
of vitamin A. Newer compounds (e.g. adapalene) have different
structural configurations, but also act via nuclear retinoid recep-
tors. Side effects of topical retinoids include skin desquamation
and erythema, producing mild irritant dermatitis.
Tazarotene is a selective retinoid receptor agonist with anti-
inflammatory and antiproliferative effects on keratinocytes. It is
used for plaque psoriasis affecting up to 10% of the skin area.2
It is applied once daily for up to 12 weeks and is available as a
0.05–0.1% gel. Side effects include local skin irritation, erythema,
burning, photosensitivity and worsening of psoriasis. Tazarotene
should be avoided in women of childbearing age, and on facial
and flexural skin. Combination treatment with topical corticoste-
roids and phototherapy is effective.
Adapalene is a topical retinoid drug used for acne. It is less
of an irritant than other, older retinoids and is effective in both
comedonal and inflammatory acne.
Tretinoin and isotretinoin are useful in comedonal acne, but
have little effect on inflammatory acne.
Topical vitamin D derivatives
Vitamin D analogues have become established as the first choice
topical therapies in the treatment of psoriasis. These products
are cosmetically acceptable because they are odourless and do
not stain or mark clothing or skin – a significant advantage over
traditional topical treatments such as coal tar and dithranol prod-
ucts. Topical vitamin D derivatives can be combined with topical
corticosteroids and phototherapy.
Calcipotriol is a vitamin D analogue that suppresses kerati-
nocyte proliferation and induces epidermal differentiation. It is
used in the treatment of mild-to-moderate plaque psoriasis affect-
ing up to 40% of the body surface area. It should not be used in
erythrodermic or pustular psoriasis. Maximal benefits are seen
after 8–12 weeks of once-daily or twice-daily application. Hyper-
calcaemia may occur if the recommended dose of 100 g per week
is exceeded. Other side effects include local irritation, pruritus
Topical corticosteroids
Potency Corticosteroid Risk of skin thinning
with long-term use
Mild Hydrocortisone Low
Moderate Clobetasone butyrate Some
Potent • Betamethasone
valerate
High
• Hydrocortisone
butyrate
Very potent Clobetasol propionate Very high
Table 2
Topical agents
Agent Indications Side effects
Corticosteroids Inflammatory
dermatoses
Striae, telangiectasiae,
bruising, contact
dermatitis,
depigmentation,
worsening of infection,
rebound phenomenon,
suppression of
hypothalamic–pituitary–
adrenal axis
Emollients Xerosis, eczema,
psoriasis
Folliculitis
Retinoids Psoriasis, acne,
photodamage
Skin irritation, erythema
Vitamin D
analogues
Plaque psoriasis Skin irritation,
pruritus, erythema,
hypercalcaemia
Coal tar Plaque psoriasis Skin irritation, staining,
folliculitis, skin cancers
Dithranol Plaque psoriasis Skin irritation, staining
Calcineurin
inhibitors
Atopic eczema Skin irritation, burning,
erythema, infections,
alcohol intolerance
Table 1
Figure 1 Demonstration of 1 fingertip unit (FTU).

3. Treatments
MEDICINE 37:5 234 © 2009 Elsevier Ltd. All rights reserved.
and erythema. Calcipotriol is contraindicated in pregnancy and
should not be used on the face.
Tacalcitol is used once daily, preferably at night. Its side
effects are similar to calcipotriol. It is not licensed for use in
­children.
Calcitriol is the newest topical vitamin D analogue. It is
licensed for use on the face and flexures in addition to psoriasis
on the trunk and limbs. It is applied twice daily up to a maximum
of 210 g per week.
Calcineurin inhibitors
Calcineurin inhibitors are a new class of topical immunomodula-
tors that act by reducing inflammation via T-cell suppression.
Tacrolimus and pimecrolimus have been appraised by the UK
National Institute for Health and Clinical Excellence (NICE).3
They are recommended as second-line treatment for moderate-
to-severe atopic eczema not controlled by topical ­corticosteroids
or when there is a high risk of adverse effects such as skin
­atrophy. The main side effects are skin irritation, burning, ery-
thema, infections and alcohol intolerance. Long-term effects such
as predisposition to skin malignancy are unknown. These treat-
ments should be started only by physicians (including GPs) with
a special interest and experience in dermatology.
Tacrolimus is used on all areas of the body, including the face
and flexures. In adults, 0.1% ointment can be used twice daily for
3 weeks initially; 0.03% is then used once or twice daily. In chil-
dren over the age of 2 years, 0.03% ointment only is licensed.
Pimecrolimus is available as a 1% cream and can be used
twice daily on sites including the face, neck and flexures in
adults and children aged 2–16 years. It can be used short term
or as intermittent long-term treatment to prevent flares. The side
effects are similar to those of tacrolimus.
New antibacterials
Retapamulin is a derivative of the antibacterial pleuromuti-
lin, a product of Pleurotus mutilus, an edible mushroom. This
1% ointment is a new antibacterial licensed for treatment of
­impetigo, infected lacerations and sutured wounds for patients
aged 9 months or above. It should be used on the infected area
twice daily for 5 days. Side effects include skin irritation, pain,
itching and redness. ◆
References
1 Long CC, Finlay AY. The fingertip unit: a new practical measure. Clin
Exp Dermatol 1991; 16: 444–46.
2 Chowdhury MMU, Marks R. Tazarotene: a new topical treatment for
psoriasis. Prescriber 1998; 9: 33–36.
3 National Institute for Health and Clinical Excellence. Pimecrolimus
and tacrolimus for atopic dermatitis (eczema). London: NICE, 2004.
Also available at: http://www.nice.org.uk/Guidance/TA82
(accessed 3 Feb 2009).