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Systemic Medication in
Dermatological Therapy
皮肤病的系统治疗
Professor Zheng Min
郑 敏 教授
Systemic Medication in
Dermatology

We list here only preparations we use
commonly for our patients with skin
disease.








Antihistamines drugs(sedative and non-sedative)
The Retinoids
Oral Antifungal Agents
Systemic Glucocorticoids
Antimalarial drugs
Cytotoxic (immunosuppressants) drugs
Immunoloregulation agents
Thalidomide
Systemic Medication in
Dermatology

Following medication also very
important in skin disorders therapy:

Antibacterials
• Erythromycin, Metronidazole……

Antivirals
• Acyclovir, Famciclovir

Anti-androgens
ANTIHISTAMINES IN
DERMATOLOGY
Antihistamines have been used in
dermatology primarily for the relief
of pruritus and the treatment of
urticaria and angioedema.
 Not all H1-type antihistamines have
similar beneficial therapeutic effects,
and nonresponders to one drug may
respond favorably to another.




Antihistamines are effective in blocking
experimental pruritus induced by
histamine;
They are of limited use in many pruritic
cutaneous diseases.
It has been suggested that the soporific
side effect of the traditional H1-type
antihistamines plays a role in the
treatment of pruritus.

Histamine which is present in mast
cells, basophils, and platelets in
association with their granules,
in gastric parietal cells
 and in nerve endings


is formed by the enzymatic
decarboxylation of the amino acid
histidine by histidine decarboxylase.
The biologic effects of
histamine

The biologic effects of histamine
result from its interactions with
tissue receptors, designated H1, H2,
and H3.
The biologic functions
mediated by H1 receptors

The biologic functions mediated by H1
receptors include





contraction of endothelial cells and smooth
muscle;
increases in venular permeability
increases airways resistance;
stimulation of cutaneous nerves and nasal
mucus secretion;
enhancement of chemotaxis of eosinophils
and neutrophils.
The biologic functions
mediated by H2 receptors

The biologic functions mediated by H2
receptors include





dilation of vascular smooth muscle and
bronchial smooth muscle;
increases in venular permeability, cardiac rate
and force of contraction, and airways mucus
production;
increases secretion of parietal cell acid;
stimulation of CD8+ T lymphocytes with
delayed-type hypersensitivity suppression;
inhibition of chemotaxis of neutrophils and
eosinophils.
Traditional, Classic, or First-Generation
H1-Type Antihistamines

The traditional, classic, or firstgeneration H1-type antihistamines
have in common with histamine a
substituted ethylamine moiety as an
integral part of the molecule
Ethylamine moiety present in H1 antihistamines
R1, aromatic and/or heterocyclic groups;
X, linkage such as nitrogen, oxygen, or carbon.
The activity of an H1-type antihistamine is
increased by the substitution of a halogen in the
para position of the phenyl or benzyl group of R1
First Generation H1type Antihistamines


Traditional H1type
antihistamines
have been
divided into
six groups based
on substitution at
the X position
with nitrogen,
oxygen, or
carbon.
Antihistamines have a
number of effects

In addition to their antihistamine actions,
the H1-type antihistamines have a
number of effects that include





sedation,
anticholinergic activity,
local anesthesia,
antiemetic activity,
anti-motion-sickness effects.

Moreover, they have a variety of
Antiinflammatory
 antiallergic properties that are
independent of H1 blockade.
 Some H1-type antihistamines possess
a-adrenergic receptor or cholinergic
muscarinic receptor blocking properties,
 while others possess antiserotonin
effects.

The side effects of antihistamines

The central nervous system (CNS)
effects
Sedation is the most common
 Other CNS effects include

• dizziness, tinnitus, disturbed coordination,
inability to concentrate, blurred vision, and
diplopia.
The side effects of antihistamines

Anticholinergic effects, including
dry mucous membranes,
 difficulty in micturition,
 urinary retention,
 dysuria,
 urinary frequency,
 and impotence.

The side effects of antihistamines

Infrequent side effects of H1-type
antihistamines include
headache,
 a sensation of tightness in the throat,
 tingling,
 numbness

CONTRAINDICATIONS AND DRUG
INTERACTIONS


When H1-type antihistamines are consumed in
combination with alcohol or other therapeutic
agents with CNS depressant effects, such as
diazepam, there may be an accentuation of the
central depressive effects.
There are limited guidelines for the use of H1type antihistamines in pregnant women.

Most drugs are classified as FDA category B, which is
defined as no risk to the human fetus despite possible
animal risks, or category C, in which risk cannot be
ruled out.
Low-Sedating or Second-Generation H1-Type
Antihistamines

Certain low-sedating H1-type antihistamines
affect the trafficking of cells in the skin and
other tissues, the release or generation and
release of inflammatory mediators, and the
expression of adhesion molecules.7
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Cetirizine
Loratadine
Fexofenadine
Acrivastine
Azelastine
Ebastine
Levocabastine
Second-Generation H1-Type Antihistamines
ANTIHISTAMINES IN
DERMATOLOGY




Antihistamines have been used in dermatology
primarily for the relief of pruritus and the
treatment of urticaria and angioedema.
Not all H1-type antihistamines have similar
beneficial therapeutic effects, and nonresponders
to one drug may respond favorably to another.
Antihistamines are effective in blocking
experimental pruritus induced by histamine;
It has been suggested that the soporific side
effect of the traditional H1-type antihistamines
plays a role in the treatment of pruritus
ANTIHISTAMINES IN DERMATOLOGY


Urticaria/Angioedema
Other Dermatologic Disorders



atopic dermatitis
systemic mastocytosis and urticaria
pigmentosa
Pruritus associated with other conditions
•
•
•
•
•
•
allergic contact dermatitis
other forms of eczematous dermatitis
lichen planus
mosquito bites
Infestations
pruritus secondary to underlying medical disorders
or of an idiopathic nature
The Retinoids in Dermatology
The Retinoids
Retinoids have diverse biologic
effects.
 They affect cell growth and
differentiation, morphogenesis,
 inhibition of tumor promotion and
malignant cell growth,
 immunomodulatory actions, and
 alterations in cellular cohesiveness

The Retinoids

Two classes of nuclear retinoid receptors
have been identified


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The RARs and RXRs are complex classes
of receptors


retinoic acid receptors (RARs)
retinoid X receptors (RXRs)
each composed of a, b, and g subtypes
In adult skin, most of the RAR is RAR-g
subtype.
The Retinoids in skin disorders


Severe cystic acne in a
female before (A) and
after (B) treatment with
oral isotretinoin.
CYSTIC ACNE
Cystic acne is unique
among the retinoidresponsive diseases in that
most cases of even the
greatest severity can be
successfully treated with
only one 4- or 5-month
course of isotretinoin at a
dosage of 0.5 to 2.0 mg/kg
body weight per day
The Retinoids

The most likely mechanism by which
isotretinoin leads to clinical improvement
in acne is inhibition of sebaceous gland
function with a reduced rate of sebum
excretion and alterations in skin-surface
lipid film chemistry.In addition, other
mechanisms include anti-inflammatory
effects, antibacterial effects, inhibitory
effects of microbial enzyme activity, and
desquamative effects on poral occlusion.
PSORIASIS
Generalize
d chronic
plaquetype
psoriasis
before (A)
and after
(B)
treatment
with
etretinate

When retinoids are used as
monotherapy for psoriasis vulgaris,
etretinate at a dosage of 0.5 to 1.0
mg/kg per day is superior to isotretinoin
Combining retinoids with
other effective therapies


Combining retinoids with other effective
therapies increases effectiveness and
minimizes toxicity.
Etretinate at lower doses has been used
in combination with
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photochemotherapy (PUVA),
anthralin,
ultraviolet radiation (UVB, 280 to 320 nm),
and topical glucocorticoids.
CUTANEOUS DISORDERS OF
CORNIFICATION

Darier's disease
Darier's disease before
(A) and after (B)
treatment with
isotretinoin.

pityriasis rubra pilaris
Chronic pityriasis
rubra pilaris before (A)
and after (B)
treatment with
isotretinoin.
CANCER
nevoid basal cell carcinoma syndrome
 xeroderma pigmentosum
 Low-Dose Isotretinoin for Basal Cell
Carcinoma

ACUTE TOXICITY
 Mucocutaneous
 Cheilitis
 Conjunctivitis
 Hair
Loss
Toxicities
SYSTEMIC TOXICITY
 Teratogenicity

It is currently recommended that women who
have taken etretinate avoid pregnancy for at
least 2 years after the discontinuation of
therapy.
 Arthralgias
and Myalgias
 Pseudotumor Cerebri
LABORATORY ABNORMALITIES
Hyperlipidemia
 Liver Toxicity
 Renal Toxicity

FACTORS IN THE DECISION TO USE
RETINOIDS
As with other medications, a
risk/benefit ratio should be used to
determine whether or not to treat a
dermatologic patient with synthetic
retinoids
 Factors to be considered include the
following:

FACTORS IN THE DECISION TO USE
RETINOIDS
1.
2.
Responsiveness of the disorder to
retinoids. The treatment of cystic acne
with isotretinoin is optimal, with shortterm exposure leading to long-term
remission.
Dose of retinoid required. The use of
retinoids in combination with other
effective treatments, such as RePUVA
(combination photochemotherapy) for
psoriasis, may allow dose reduction with
fewer side effects.
FACTORS IN THE DECISION TO USE
RETINOIDS
3.
4.
Availability of alternative treatments. In
some diseases (severe Darier's disease,
epidermolytic hyperkeratosis) synthetic
retinoids may be the only effective
treatment.
Chronicity of retinoid therapy. Diseases
that relapse rapidly on withdrawal of
synthetic retinoids require continuous
retinoid administration and, therefore,
are associated with increased risk of
chronic skeletal toxicity.
FACTORS IN THE DECISION TO USE
RETINOIDS
5.
Severity of the disease. Diseaseinduced limitations on educational,
psychological, or physical
development should be considered.
For example, early retinoid
treatment of lamellar ichthyosis
may prevent the development of
ectropion.
FACTORS IN THE DECISION TO USE
RETINOIDS
6.
Age of the patient. Children with
disorders of cornification requiring
chronic moderate- to high-dose retinoid
therapy are at highest risk of developing
bone toxicity. They are at risk of
premature epiphyseal closure and,
because of longer lifetime exposure to
the drug, they are at higher risk for
future development of the vertebral
changes resembling diffuse idiopathic
skeletal hyperostosis.
FACTORS IN THE DECISION TO USE
RETINOIDS
7.
8.
Sex of the patient. Retinoid teratogenicity
entails special risks for the female patient of
childbearing potential. Although isotretinoin
and acitretin are rapidly cleared from the body
within days, etretinate can be detected in the
serum for months or even years after the
discontinuation of therapy.
Presence of other disorders that may be
aggravated by retinoid use. Renal or hepatic
compromise, preexisting hyperlipidemia, or a
family history of hyperlipidemia or premature
atherosclerotic cardiovascular disease should
be considered in the therapeutic assessment.
FACTORS IN THE DECISION TO USE
RETINOIDS
9.
Concomitant use of other drugs with
similar toxicities. Other drugs that are
hepatotoxic (methotrexate), elevate
serum lipids (estrogens, glucocorticoids),
or rarely produce benign intracranial
hypertension (tetracycline) should be
avoided, if possible, or the patient must
be carefully monitored during the clinical
course.
Oral Antifungal Agents
in Dermatology
Oral Antifungal Agents

In order to eliminate refractory
dermatomycoses and onychomycosis,
physicians must familiarize
themselves with the systemic
antifungal agents available

Three new oral antifungal agents
that have been released are

the first oral allylamine, terbinafine (Lamisil)

the triazoles fluconazole (Diflucan)

itraconazole (Sporanox)
Rational selection of
therapy

Rational selection of therapy depends on


the mechanism of action of each agent
an understanding of
•
•
•
•
•
•
tissue pharmacokinetics,
spectrum of clinical activity,
potential adverse reactions,
significant drug interactions,
efficacy,
optimal dosage protocols.
Systemic Glucocorticoids Agents
in Dermatology
Systemic Glucocorticoids

Glucocorticoids are a mainstay of
dermatologic therapy because of
their potent immunosuppressive and
anti-inflammatory properties.
BIOLOGY of Glucocorticoids
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The major naturally occurring
glucocorticoid is cortisol (hydrocortisone).
The daily secretion of cortisol ranges
between 10 and 20 mg, with a diurnal
peak around 8 A.M.
Cortisol has a plasma half-life of 90 min.
It is metabolized primarily by the liver,
although it exerts hormonal effects on
virtually every tissue in the body.
The metabolites are excreted by the
kidney and the liver.
BIOLOGY of Glucocorticoids
Glucocorticoids profoundly affect the
replication and movement of cells
 Glucocorticoids affect cell activation,
proliferation, and differentiation

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They modulate the levels of mediators
of inflammation and immune reactions,
• as seen with the inhibition of
• IL-1, IL-2, IL-6, and TNF synthesis (or release)
BIOLOGY of Glucocorticoids

Macrophage functions—including
phagocytosis,
 antigen processing,
 cell killing
are decreased by cortisol
 this decrease affects immediate and delayed
hypersensitivity

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Glucocorticoids suppress monocyte and
lymphocyte function (both TH1 and TH2
cells)
BIOLOGY of Glucocorticoids

The multiplicity of biologic effects
produced by glucocorticoids
emphasizes that

currently there is no unifying
hypothesis to explain the therapeutic
efficacy of these extremely potent antiinflammatory and immunosuppressive
agents
DISEASES TREATED WITH
GLUCOCORTICOIDS

Skin diseases commonly treated with oral
glucocorticoids include

serious blistering diseases
• pemphigus,
• bullous pemphigoid,
• cicatricial pemphigoid,
• linear IgA bullous dermatoses,
• epidermolysis bullosa acquisita,
• herpes gestationis,
• erythema multiforme,
• toxic epidermal necrolysis),
DISEASES TREATED WITH
GLUCOCORTICOIDS
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sarcoidosis,
type I reactive leprosy,
capillary hemangiomas,
panniculitis, and
urticaria/angioedema.
Short courses of glucocorticoids, under
appropriate conditions, may be used for
• severe dermatitis
•
•
•
•
•
contact dermatitis,
atopic dermatitis
photodermatitis
exfoliative dermatitis
erythrodermas
COMPLICATIONS OF SYSTEMIC
GLUCOCORTICOID THERAPY

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Numerous complications are associated
with systemic glucocorticoid therapy
Complications increase with higher doses,
longer duration of therapy, and more
frequent administration.
However, osteoporosis and cataracts
develop with alternate-day dosing, and
avascular necrosis can be seen after only
short courses of glucocorticoids.
Complications of Glucocorticoid Therapy
THERAPEUTIC USE OF
GLUCOCORTICOIDS

Fundamental Principles
Before therapy with glucocorticoids is
begun, the benefit that can realistically
be expected should be weighed against
the potential side effects.
 In dermatology, this often means
assessing whether the disease is
serious enough to risk exposing the
patient to a toxic drug.

Alternative or adjunctive therapies
should be considered, especially if longterm treatment is contemplated.
Coexisting illnesses such as diabetes,
hypertension, or osteoporosis need to
be considered before instituting therapy
with glucocorticoids.
 The predisposition of the patient to side
effects should be included in an
assessment of risk.

Rationale for Choosing among Glucocorticoids

A number of considerations bear on the
choice of glucocorticoids.


First, a preparation with minimal
mineralocorticoid effect is usually picked to
decrease sodium retention.
Second, the long-term oral use of prednisone
or a similar drug, with an intermediate halflife and relatively weak steroid-receptor
affinity, may reduce side effects.

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Long-term use of drugs like dexamethasone,
which has a longer half-life and high
glucocorticoid-receptor affinity, may produce
more side effects without any better
therapeutic effects.
Third, if a patient does not respond to
cortisone or prednisone,
the substitution of the biologically active form,
cortisol or prednisolone, should be considered.
In general, even in severe liver disease,
substitution has not proved to be very
important.

Fourth, methylprednisolone is used for
pulse therapy because of its low
sodium-retaining characteristics and
high potency.
Route of Administration and Dosage
Schedules

Systemic glucocorticoids can be
administered





intralesionally,
orally,
intramuscularly,
intravenously.
The route and regimen are determined by
the nature and extent of the disease
being treated.
STRATEGIES TO REDUCE GLUCOCORTICOID
SIDE EFFECTS

Evaluation before Treatment

To minimize potential problems, the
baseline evaluation should include
• a personal and family history,
• with special attention to predisposition to
diabetes, hypertension, hyperlipidemia, and
glaucoma.

Evaluation during Treatment

At follow-up visits, patients receiving
chronic glucocorticoid therapy should
be questioned about
• polyuria, polydipsia, abdominal pain,
fevers, sleep disturbances, and
psychological effects.
Preventive Measures

GENERAL


A careful initial evaluation and followup, as discussed in the first two
sections above, are mandatory.
Exercise should be encouraged.
DIET Diet should be low in calories,
fat, and sodium and high in protein,
potassium, and calcium.

INFECTIONS


Patients with a positive PPD should be given prophylaxis
with isoniazid.
GASTROINTESTINAL COMPLICATIONS

There is ongoing debate over whether the incidence of
peptic ulcer disease is increased in otherwise normal
patients receiving glucocorticoids.

ADRENAL SUPPRESSION


Patients receiving daily glucocorticoid therapy
for longer than 3 to 4 weeks must be
assumed to have adrenal suppression that
requires tapering of the glucocorticoids to
allow for recovery of the HPA axis.
Tapering is best performed by switching from
a single daily dose to alternate-day doses,
followed by a gradual reduction of the amount
of the drug

OSTEOPOROSIS


Attention to the prevention of osteoporosis is
becoming increasingly important as newer
therapies that may deter bone loss become
available
ATHEROSCLEROSIS

Blood pressure, serum lipids, and glucose
levels should be measured serially.
Abnormalities should be treated with dietary
manipulation and medication as necessary.
Patients who smoke should be encouraged to
stop

AVASCULAR NECROSIS

Early detection is important, since early
intervention may prevent progression
to degenerative joint disease requiring
joint replacement.
Systemic Medication in
Dermatology(1)

We list here only preparations we use
commonly for our patients with skin
disease.






Antihistamines drugs(sedative and nonsedative)
Antimalarial drugs
Cytotoxic (immunosuppressants) drugs
Corticosteroids
Immunoloregulation agents
Thalidomide
Systemic Medication
in Dermatology(2)
We have to know main
dermatological uses, adverse effects,
interactions and cautions of all the
medications
 UV therapies are important
treatment in dermatological uses.

Systemic Medication in
Dermatology(3)

Following medication also very important
in skin disorders therapy:

Antibacterials
• Erythromycin, Metronidazole……

Antifungals
• Terbinafine, Griseofulvin, Itraconazole……

Antivirals
• Acyclovir, Famciclovir


Anti-androgens
Retinoids
Thank you for
your attention！