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Antihistamines & Corticosteroids
for Disorders of Skin
2007.9.21
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ANTIHISTAMINES
Diphenhydramine
Description
 A popular antihistamine due to its relative safety
after oral or parenteral administration
 An H1-antagonist of the ethanolamine class
 Ethanolamine H1-antagonists


Significant antimuscarinic activity and produce marked
sedation in most patients
Other members of this group

carbinoxamine, clemastine, dimenhydrinate (a salt of
diphenhydramine), doxylamine, phenyltoloxamine and
others
Diphenhydramine
 Drug Effects





For the usual allergic symptoms, irritant cough, airway drying
effect
Relief of nausea, vomiting, and vertigo associated with
motion sickness
Treatment of drug-induced extrapyramidal symptoms as well
as to treat mild cases of Parkinson's disease.
As an OTC hypnotic
Minimal gastrointestinal side effects
 Approval by FDA

Originally approved by the FDA in 1946 as a prescriptiononly drug but was later changed to non-prescription status
Diphenhydramine
Mechanism of Action-1
 Not prevent the release of histamine
(as do cromolyn and nedocromil)
 Competes with free histamine for binding at
H1-receptor sites
 Competitively antagonizes the effects of histamine
on H1-receptors

In the GI tract, uterus, large blood vessels, and bronchial
muscle.
 Suppresses the formation of edema, flare, and
pruritus that result from histaminic activity
Diphenhydramine
Mechanism of Action-2
 Greater anticholinergic activity than do other
antihistamines as ethanolamine derivatives


Antidyskinetic action of diphenhydramine
A direct suppressive action on the cough center and causes
sedation via CNS depression
 Topical diphenhydramine

Providing local relief from insect bites, minor burns, sunburn,
or minor abrasions

Due to an anesthetic effect resulting from decreased
permeability of nerve cell membranes to sodium ions
(preventing the transmission of nerve impulses)
 Occurrence of tolerance


Following prolonged use
Beneficial because of reduced sedative effects
Diphenhydramine
Pharmacokinetics-1
 Administered orally, topically, intravenously, or
intramuscularly
 Less soluble H1-antagonists

Slower onset of action & less likely to cause toxicity
 Onset of action following oral administration

15-30 minutes
 The time of peak concentrations

2-4 hours
 The duration of action ranges

4-6 hours
 The duration of the maximum sedative effect

1-3 hours
Diphenhydramine
Pharmacokinetics-2
 The onset of antiextrapyramidal effects following an
intramuscular injection

15-30 minutes
 Highly protein-bound


Widely distributed in body tissues and fluids
Crosses the placenta and is excreted into breast milk.
 Metabolism

In the liver to produce diphenylmethoxyacetic acid, which
then becomes conjugated
 Plasma half-life

2-8 hours
 Most unchanged drug and metabolites

Excreted renally within 24—48 hours of a dose.
Hydroxyzine
Hydroxyzine-HCl Tablet (Tab 25 mg)
Description
 A piperazine antihistamine (H1-blocker) structurally related to
buclizine, cyclizine, and meclizine
 Drug effects





Effective in treating histamine-mediated pruritus or pruritus
due to atopy or other allergic conditions
Used as a perioperative sedative and anxiolytic
Effective alternative treatment for anxiety disorders
Used to alleviate nausea and control emesis perioperatively
The intramuscular (IM) dosage form

Used for the symptomatic management of acute alcohol withdrawal
Hydroxyzine
 Known as one of the most sedating H1-blockers

a small study showed that hydroxyzine produced less sedation than
either azatadine or clemastine
 Approval by FDA


Originally approved by the FDA in 1956.
Officially discontinued all product lines of the Atarax® brand
name on May 4, 2004 by Pfizer
Hydroxyzine
Mechanism of Action
 Competes with histamine for H1-receptor sites on the
effector cell surface
 Blockade of H1-receptors

Suppression of the formation of edema, flare, and pruritus
that result from histaminic activity
 The dose-related sedative properties

At the subcortical level of the CNS
 Antiemetic actions secondary to its central
anticholinergic actions
 Antiarrhythmic, analgesic, local anesthetic, and
skeletal muscle relaxant properties
 Bronchodilatory and mild antisecretory effects
 Not used as potent analgesics
Hydroxyzine
Pharmacokinetics-1
 Administered orally or intramuscularly
 Rapidly absorbed following oral administration
 The onset of effect for hydroxyzine

15-60 minutes
 Thel duration of action

4-6 hours
 The inflammatory response and pruritus

Suppressed for up to 4 days
 Distribution of hydroxyzine


Not fully described
Unknown whether it crosses the placenta or is distributed
into breast milk
Hydroxyzine
Pharmacokinetics-2
 Metabolized in the liver
 Cetirizine

One of active metabolite; mostly excreted renally as
unchanged drug
 The elimination half-life of hydroxyzine

14—25 hours
Cetirizine
Zyrtec Tablet (Tablet 5 mg)
Description
 The active metabolite of hydroxyzine, a piperazine
H1-receptor antagonist
 Different from the parent compound by having greater
affinity for the H1-receptor
 Drug effects



Effective in the treatment of chronic idiopathic urticaria,
perennial allergic rhinitis, and seasonal allergic rhinitis
For the treatment of allergic asthma, physical urticaria
(triggered by physical stimuli)
For symptomatic relief of atopic dermatitis
Cetirizine
 Drug Effects



A higher incidence of somnolence than the non-sedating
antihistamines fexofenadine and loratadine
The cardiovascular safety in drug-interaction studies
elevated-dose studies, and clinical trials
Good tolerance in pediatric and elderly patients
 Approval by FDA

Initially FDA-approved on December 8, 1995


An expansion of labeling for use in infants as young as 6
months of age


For the treatment of allergic rhinitis and chronic urticaria
FDA-approved in October 2002
A chewable tablet

FDA-approved in March 2004
Cetirizine
Mechanism of Action
 High affinity for histamine H1-receptors
 Less affinity than terfenadine or hydroxyzine for calciumchannel, alpha-adrenergic, D2-dopamine, 5HT2-serotonin,
muscarinic receptors
 A low incidence of sedation compared with older antihistamines


The less lipophilic carboxyl group to the ethylamine side chain
reduces the penetration of cetirizine into the CNS
Dose-related drowsiness
 The action of cetirizine in the inflammatory response involving
a number of mediators




Affecting cell adhesion
Decrease of leukotriene C4 production
Suppression of neutrophil migration in IgE-mediated reactions
Reduction of eosinophil infiltration to nasal mucosa in patients
with seasonal allergic rhinitis
Cetirizine
Pharmacokinetics
 Administered orally
 Rapid onset (time to Cmax)

1 hour
 Long duration of action
 The overall bioavailability


Not altered by the presence of food, although the rate of
absorption can be slightly reduced
Poor penetration into the CNS
 Metabolized to limited extent via O-dealkylation
 The elimination half-life of cetirizine

6.5 -10 hours (mean 8.3 hours)
Astemizole
Description
 An oral H1-receptor antagonist similar in structure to
terfenadine, another H1-receptor antagonist
 Structurally related to haloperidol, a butyrophenone
antipsychotic
 Drug effects

Unlike other H1-antagonists, therapeutic doses of
astemizole produce insignificant anticholinergic activity or
sedation




Extremely long duration of action
Relieves symptoms associated with chronic idiopathic
urticaria and seasonal allergic rhinitis
Not be used PRN for the immediate relief of symptoms


Due to the poor penetration into the CNS
Due to its slow onset of action
Associated with QT prolongation and torsades de pointes
Astemizole
 Approval by the FDA

In December 1988 and came off patent in 1997
 Discontinuation from manufacture in the US by
Janssen Pharmaceutica in June 1999

Due to low prescription usage and the availability of other
agents with less propensity for adverse effects and drug
interactions
Fexofenadine
Allegra Tablet (Tab 180 mg)
Description
 An H1-receptor antagonist
 The active metabolite of another H1-antagonist,
terfenadine
 Drug effects
Both fexofenadine and terfenadine are non-sedating
 Unlike terfenadine, fexofenadine does not cause QT
prolongation when given in doses up to 800 mg/day
or when administered concomitantly with
ketoconazole or erythromycin

Fexofenadine
 Approval by FDA

First approved by the FDA in July 1996



for seasonal allergic rhinitis, subsequent approval was
granted in February 2000 for children as young as 6
years old
For the treatment of chronic idiopathic urticaria in
adults and children in February 2000.
Oral liquid formulation & Orally disintegrating tablet


Approved in October 2006 and in July 2007, respectively
For seasonal allergic rhinitis and chronic idiopathic
urticaria in children
Fexofenadine
Mechanism of Action
 Not prevent the release of histamine as do cromolyn
and nedocromil
 Competes with free histamine for binding at the H1receptor.
 relatively irreversible H1-receptor antagonism at
higher concentrations
 Lipophilic compared to first generation
antihistamines

Not readily cross the blood-brain barrier.
 Minimal CNS depression compared with other H1antagonists.
Fexofenadine
Pharmacokinetics
 Administered orally and is rapidly absorbed.
 the mean time to maximum plasma concentrations
following oral administration with tablets or oral
solution

2-3 hours and 1 hour, respectively.
 The mean time to maximum plasma concentrations of
the Orally Disintegrating Tablet (ODT) formulation


2 hours post-dose
The absolute bioavailability of fexofenadine: unknown
 The mean elimination half-life

14.4 hours in normal volunteers receiving 60 mg twice daily.
Loratadine
Loratadine Tablet (Tablet 10 mg)
Description
 An oral non-sedating H1-blocker similar in structure
to cyproheptadine and azatadine, other H1-blockers.
 Differs structurally from the other non-sedating H1blockers terfenadine and astemizole
 Administered once daily
 Drug effects


The CNS effects are less with loratadine compared to the
traditional H1-blockers (due to poor penetration into the CNS
and a low affinity for CNS H1-receptors)
Not associated QT prolongation or torsades de pointes.
(Unlike astemizole and terfenadine, loratadine)
Loratadine
 Approval by FDA

First approved in April 1993


An OTC loratadine oral solution


To relieve the symptoms associated with seasonal
allergic rhinitis
Approved in June 2006
An OTC 12-hour oral disintegrating tablet
(Claritin® RediTabs® 12 Hour)
Approved on December 12, 2006
 For the temporary relief of hay fever or other upper
respiratory allergies to include symptoms such as
rhinorrhea, sneezing, itchy, watery eyes, and itching
of the nose or throat

Loratadine
Mechanism of Action
 Competes with free histamine for binding at the H1-receptor.
Pharmacokinetics
 Administered orally
 The onset of action of loratadine
 1-3 hours
 Peak effects in 8-12 hours
 Duration of action greater than 24 hours
 The normal mean elimination half-lives of loratadine and its
metabolite
 8.4 hours (range 3-20 hours) and 28 hours, respectively.
 Elimination occurs through the fecal and renal routes
Ranitidine
Ranitidine Tablet (Tab 300 mg)
Description
 An antagonist at histamine H2-receptors.
 The actions and indications for ranitidine differ
little from other H2-blockers
 5-12 times more potent as a histamine receptor
antagonist (compared to cimetidine)
 Less affinity for the cytochrome P450 hepatic
enzyme system

Much less likely than cimetidine to interact with
other drugs
Ranitidine
 Drug effects

For the treatment of various gastrointestinal disorders
 Approval by FDA


First approved as Zantac® in June 1983
A non-prescription (OTC) formulation (75 mg tablets)
approved in December 1995
Ranitidine
Mechanism of Action-1
 Competitively inhibition of the binding of histamine to
receptors on gastric parietal cells (designated as the
H2-receptor)
 Reduction of basal and nocturnal gastric acid
secretion
 Decrease of the amount of gastric acid released

In response to stimuli such as food, caffeine, insulin,
betazole, or pentagastrin
 Reduction of the total volume of gastric juice

Indirectly decreasing pepsin secretion
Ranitidine
Mechanism of Action-2
 Aid of gastromucosal healing & protection of the
mucosa

From the irritant effects caused by aspirin and nonsteroidal
antiinflammatory agents
 Combination therapy with an H1-receptor antagonist



Stimulation of both H1- and H2-receptors expressed by
Human skin mast cells
Blocking both the initial and delayed histaminic response
Suppressing the formation of edema, flare, and pruritus that
results from histaminic activity
Ranitidine
Pharmacokinetics
 Administered either orally or parenterally
 Intramuscular (IM) administration

A bioavailability of 90-100% versus intravenous (IV) administration.
 The oral bioavailability of ranitidine

About 50-60%
 The duration of effects

8-12 hours.
 Partial metabolism (30%) in the liver
 Both the unchanged drug and its metabolites

Excreted in the urine and feces
 The half-life of the drug


2-3 hours but increases to roughly 5 hours in patients with renal
impairment (CrCl < 35 ml/min).
3-4 hours in elderly patients with decreased renal function
Cimetidine
Cimetidine Tablet (Tab 400 mg)
Description
 The first commercially available drug to be used for
peptic ulcer disease
 An oral H2-receptor antagonist similar to
famotidine, nizatidine, and ranitidine
 A known inhibitor of many of the isoenzymes of the
hepatic CYP450 enzyme system

Exhibition of many significant drug interactions with other
medications
 Used mainly for treating gastrointestinal disorders
 Approval by FDA

First approved in 1977
Cimetidine
Mechanism of Action
 Blocking the effects of histamine at the receptor located on the
basolateral membrane of the parietal cell (designated as the H2receptor)
 Decreasing the amount of gastric acid
 Not reducing acid-output as dramatically as the proton-pump
inhibiting medications (e.g., omeprazole)
 Exhibition of weak anti-androgenic effects
 Combination therapy with an H1-receptor antagonist

Suppression of the formation of edema, flare, and pruritus that
results from histaminic activity by blocking both the initial and
delayed histaminic response
Cimetidine
Pharmacokinetics
 Rrapidly and completely absorbed in the GI tract
 Oral bioavailability: 60-70%

 Distribution throughout body tissues

Found in breast milk, and crosses the placenta.
 Extensively metabolized predominately to a sulfoxide metabolite
following oral administration
 Half-life

2 hours in patients with normal renal function.
Management of Acute Urticaria and
Angioedema
 Antihistamines (both H1 and H2)

The first-line drugs

H1 antihistamines
 Diphenhydramine:12.5 to 100 mg per dose every 4 hrs

Nonsedating agents
 Cetirizine, Loratadine, or Fexofenadine

For stabilizing any respiratory insufficiency &
hemodynamic instability in the emergency
department
 Hydroxyzine (10 to 100 mg daily at bedtime)

Can be tried when other H1 antihistamines are
inadequate

Decrease of histamine-induced urticarial reaction
by adding an H2 blocker (e.g., ranitidine or
cimetidine)


Histamine receptors in the skin: H1 (85%) & H2 (15%)
Doxepin (25 to 100 mg/day)

An excellent alternative as it has both H1 and H2 activity
Treatment for Hereditary Angioedema
 Life-threatening acute attacks
 Not usually respond satisfactorily to treatment with
epinephrine in normal dosage, antihistamines, or
steroids
 Active airway management

The mainstay of treatment
 Fresh frozen plasma (C1 inhibitor)

Effective in abolishing acute attacks
 High-dose epinephrine with caution
Second-Line Therapy for Anaphylaxis
 All patients with anaphylaxis should receive
histamine-1 (H1) blockers
 Diphenhydramine


The most commonly used H1 antihistamine
The typical dose


A loading dose


50 mg every 4 to 6 hours in adults or 5 mg/kg/day in divided
doses for the pediatric population
1 to 2 mg/kg intravenously (IV) to a maximum of 100 mg
for severe reactions
Too large a dose or too rapid administration

Marked sedation and hypotension
 Cf) Diphenhydramine: intravenous (or oral) (Rosen’s)

Adult


50 mg, up to 400 mg/24 hr, titrated to effects
Pediatric

1 mg/kg, up to 300 mg/24 hr, titrated to effects
 Chlorpheniramine



The alkylamine family (chlorpheniramine maleate)
Administration to children by the same routes
At a standard dose of 10 to 20 mg or 0.35 mg/kg/day in
divided doses
 Histamine-2 (H2) blockers



Effective in shock refractory to epinephrine, fluids, steroids,
and H1 blockers
Common in refractory urticaria; however, clear evidence of
benefit from controlled trials is lacking
Ranitidine and cimetidine
 Ranitidine: intravenous (or oral)


Adult: 50 mg
Pediatric: 1 mg/kg
 Cimetidine


Should not be used for patients who are elderly (side
effects), with multiple comorbidities (interference with
metabolism of many drugs) have renal or hepatic impairment
Or whose anaphylaxis is complicated by beta-blocker use
(prolongs metabolism of -blockers and may prolong
anaphylactic state)
 After the initial intravenous dose of steroids and
antihistamines, the patient may be switched to oral
medication (Table 34-2)
Management of Dermatologic
Disease
 Antihistamines (H1 antagonists)

Used frequently in the management of dermatologic disease,
particularly in the control of pruritus
 The first-generation antihistamines


Diphenhydramine and hydroxyzine
Used PO, IM, or IV
 The second-generation antihistamine agents (newer
agents)



Astemizole, cetirizine, fexofenadine, and loratadine
Offer the advantages of reduced dosing frequency and less
sedative effect
More costly
 The use of topical antihistamine preparations


Discouraging because these agents are readily absorbed
Dosing is therefore difficult to predict
 Suggested dosing, administration schedules, and
routes of therapy
 H2 antagonists (ranitidine or famotidine)

Some benefit in the patient with an allergic-mediated event,
in particular urticaria
 Other recommended antipruritic therapies

Domeboro solution (aluminum sulfate diluted 1:10 with water)
soaks, potassium permanganate baths, and oatmeal baths
CORTICOSTEROIDS
CORTICOSTEROIDS
 The production of the adrenal gland (cortex)

More than 50 different steroids, grouped into three classes
according to their effects



Glucocorticoids
Mineralocorticoids
Androgenic steroids
 Major effects of Corticosteroids



Anti-inflammatory
Antipruritic
Vasoconstrictive properties
Glucocorticoids
 Cortisol

The most abundant steroid produced by the adrenals
representative of this class
 Involved in the regulation of a number of metabolic
pathways

Including gluconeogenesis, fat redistribution, protein
metabolism, and calcium balance
 Some mineralocorticoid effects
 Active in the synthesis of medullary catecholamines
as well as beta-adrenergic receptors

Important role in the maintenance of vascular tone and
cardiac contractility
Glucocorticoids
 Other hemodynamic effects


Maintaining endothelial integrity
Controlling vascular permeability
 Total daily production of cortisol

Approximately 25 mg in the nonstressed state
 Free forms

Only 5 to 10 percent is free and physiologically active
 Bound forms

The remainder is bound to plasma proteins, principally (80
percent) cortisol-binding globulin
Mineralocorticoids
 Aldosterone


The principal mineralocorticoid produced by the adrenals.
Alteration of electrolyte and fluid balance by facilitating
sodium resorption and hydrogen and potassium excretion
 Regulation of Aldosterone


ACTH has a minor influence on its secretion
the primary regulators: the renin-angiotensin system and
serum potassium levels
Mineralocorticoids
 Stimulation by the diminished glomerular filtration
seen in volume depletion



→ Release of prorenin from the juxtaglomerular apparatus
→ Release of aldosterone from the adrenals
→ Resorption of sodium and water in the distal tubules at
the expense of potassium loss
 Minor degrees of hyperkalemia

Directly stimulate the adrenals to secrete aldosterone
 The net result


Increase of serum volume while depleting potassium
Edema and hypertension
Adrenal Androgens
 Under the control of ACTH
 The same diurnal rhythm as cortisol
 A minor contributor to total androgen levels in the
male
 Significant source in the female

Leading to some of the signs of adrenal insufficiency in
these patients
Mechanism of Action
 Lipocortins

Peptides induced by corticosteroids at the cellular level
 Phospholipase A2


the breakdown of leukocyte lysosomal membranes to release
arachidonic acid
Antagonized by lipocortins

decrease of the subsequent formation and release of
endogenous inflammatory mediators including prostaglandins,
kinins, histamine, liposomal enzymes and the complement
system
Mechanism of Action
 Early anti-inflammatory effects of topical
corticosteroids

Inhibition of macrophage and leukocyte movement and
activity in the inflamed area by reversing vascular dilation
and permeability
 Later inflammatory processes


Capillary production, collagen deposition, keloid (scar)
formation
Inhibition by corticosteroids

Decrease of edema, erythema, pruritus, plaque formation and
scaling of the affected skin
Hydrocortisone
Ala Cort Cream (Cream1% ) Cortef Tablet (Tab 10 mg)
Description
 A steroid hormone secreted by the adrenal cortex
 Both mineralocorticoid actions and glucocorticoid
actions
 Commercially available forms




The unchanged hormone
Hydrocortisone acetate, hydrocortisone cypionate
Hydrocortisone sodium phosphate, hydrocortisone butyrate
Hydrocortisone valerate, and hydrocortisone sodium succinate
Hydrocortisone
 Hydrocortisone


The preferred glucocorticoid for replacement therapy in
patients with adrenal insufficiency
Although some patients require concomitant administration
of a more potent mineralocorticoid, such as fludrocortisone,
to treat this condition
 Topical hydrocortisone


Low potency topical corticosteroids
the safest for chronic use and may be used on the face or
intertriginous areas, with occlusion, and in infants and young
children
 Approved by the FDA in 1951
Hydrocortisone
Pharmacokinetics
 Rapidly absorbed following an oral dose
 The time of peak effects following oral and IV
administration

Within 1-2 hours
 The onset and duration of action

Depend on type of injection (e.g., intra-articular or IM
injection) and the extent of the local blood supply
 Distribution of Methylprednisolone


Quickly distributed into the kidneys, intestines, skin, liver,
and muscle
Distribute into breast milk and cross the placenta
Hydrocortisone
Pharmacokinetics
 Metabolism

Topical preparations of hydrocortisone


Metabolized in the skin
Systemic hydrocortisone


Metabolized by the liver to inactive metabolites
Excretion in the urine
 The biologic half-life of hydrocortisone

8-12 hours
Methylprednisolone
A-Methapred Powder for Injection (Injection 125 mg)
Description
 A synthetic glucocorticoids used orally or parenterally
as antiinflammatory or immunosuppressive agents
 Very little mineralocorticoid activity

not used to manage adrenal insufficiency unless a more
potent mineralocorticoid is administered concomitantly.
 Originally approved by the FDA in 1957
Methylprednisolone
Pharmacokinetics
 Route of administeration



Orally
Methylprednisolone sodium succinate: by IM or IV injection
or by IV infusion.
Methylprednisolone acetate: by IM, intra-articular,
intralesional, or soft tissue injection.
 The time of peak effects following oral and IV
administration

1-2 hours
Methylprednisolone
Pharmacokinetics
 The duration of absorption of methylprednisolone
from an intra-articular injection site

Over about 7 days
 Distribution of Methylprednisolone
 Metabolism
 The biologic half-life of methylprednisolone

18—36 hours
Prednisone
Prednisone Tablet (Tab 1 mg)
Description
 the most commonly-prescribed oral corticosteroid.
 Potency relative to hydrocortisone

Roughly 4 times as potent as a glucocorticoid
 Diuration of action

Intermediate between hydrocortisone and dexamethasone
 Common Uses

Allograft rejection, asthma, systemic lupus erythematosus,
and many other inflammatory states
 Very little mineralocorticoid activity
 First approved by the FDA in 1955
Prednisone
Pharmacokinetics
 Rapidly absorbed across the GI membrane following
oral administration
 The time of peak effects

1—2 hours
 The plasma elimination half-life

1 hour
 The biological half-life of prednisone

18—36 hours
Many Medical indications for Glucocorticoid
therapy
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1. Rheumatoid arthritis
2. Psoriatic arthritis
3. Gouty arthritis
4. Bursitis and tenosynovitis
5. Systemic lupus erythematosus
6. Acute rheumatic carditis
7. Pemphigus
8. Erythema multiforme
9. Exfoliative dermatitis
10. Mycosis fungoides
11. Allergic rhinitis
12. Bronchial asthma
13. Atopic dermatitis
14. Serum sickness
15. Allergic conjunctivitis
16. Uveitis
17. Retrobulbarneuritis
18. Sarcoidosis
19. Löffler's syndrome
20. Berylliosis
21. Idiopathic thrombocytopenic
purpura
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22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
Autoimmune hemolytic anemia
Lymphomas
Immune nephritis
Tuberculous meningitis
Urticaria
Chronic active hepatitis
Ulcerative hepatitis
Regional enteritis
Nontropical sprue
Dental postoperative
inflammation
Cerebral edema
Subacute nonsuppurative
thyroiditis
Malignant exophthalmos
Hypercalcemia
Trichinosis
Myasthenia gravis
Organ transplantation
Alopecia areata
Management of Acute Urticaria and
Angioedema
 Topical steroids

No value
 Systemic steroids

should be reserved for pressure urticaria, vasculitis
urticaria, and intractable chronic urticaria
Second-Line Therapy for Anaphylaxis
 All patients with anaphylaxis should receive
corticosteroids
 Treatment of anaphylaxis refractory to the first-line
treatments or associated with complications
 Prevention of recurrences
 Others

Antihistamines, asthma medications, and glucagon, etc.
Systemic corticosteroids
 Late onset of action


Approximately 4 to 6 hours after administration
Limited benefit in the acute treatment of the anaphylactic
patient
 Clinical Uses


Most useful in persistent bronchospasm or hypotension
Should be used to prevent the biphasic reaction of
anaphylaxis
 Rare cases of deterioration after corticosteroid
administration

The result of anaphylactic sensitivity to this medication
Systemic corticosteroids
 Hydrocortisone (Solu-Cortef)


Adult: 250 to 500 mg (or 1g; Rosen’s) IV
Children: 5 to 10 mg/kg; up to 500 mg
 Methylprednisolone (Solu-Medrol)




Adult: 125 to 250 mg IV
Children: 2 mg/kg; up to 125 mg (40-80 mg IV; Rosen’s)
Produces less fluid retention than does hydrocortisone
Preferred for elderly patients and for those patients in whom
fluid retention would be problematic (e.g., renal and cardiac
impairment)
 Acceptable regimen after the anaphylactic episode

Corticosteroid IV followed by oral prednisone over 7 to 10
days
Management of Skin Disorders
 Potential indications for systemic corticosteroids

Urticaria, angioedema, and toxicodendron dermatitis (rhus,
poison ivy, or poison oak) and other contact or allergic
dermatitides
 Treatment benefits

Dermatologic syndromes (erythema multiforme, toxic
epidermal necrolysis, and vasculitis)


Reduction of pruritis & urticaria


Small bursts of prednisone (40 mg daily for 4 days) in one
study
Poison ivy or oak


best treated with systemic steroids only after consultation with
a dermatologist.
Systemic steroids; oral prednisone (1 mg/kg body weight) with
a slow 2- to 3-week taper.
Other contact or allergic dermatitides

Benefit from an abbreviated course (4 days) of oral prednisone
Management of Skin Disorders
 Relative Contraindication or cautions of oral
corticosteroids

In those with diabetes, hypertension, active peptic ulcer
disease, psychiatric disease, and immunodeficiency.

Close follow-up is needed if oral corticosteroids are
prescribed to these patients.
Topical corticosteroids
 Powerful and useful tools in the management of
dermatologic disease.
 Numerous agents

Different in concentration, base components, and cost
 Familiarity with a single agent in each potency class

Sufficient to safely and effectively treat any steroidresponsive skin ailment
Topical corticosteroids
 Measurement of corticosteroid potency or strength
(i.e., the anti-inflammatory property)

Rated by vasoconstricting ability on a scale of one to seven,
with lower scale numbers correlating with more potent
corticosteroids



Group 1 agents: the most powerful corticosteroids
Group 7 agents: the least potent
Table 245-7 for a listing of topical corticosteroid agents relative
to group potencies
 Use of the appropriate-strength topical steroid

Strongly encouraged at the start of therapy
 The use of a less powerful agent

Not likely to spare the patient from potential adverse effect
or produce adequate control of the disease
Topical corticosteroids
 Hydrocortisone




The most frequently used topical corticosteroid in the
outpatient setting
Used safely on most body surfaces, including the face,
genitalia, flexure creases, and intertriginous zones
Safe for use in infants and children
A poor choice for the treatment of diseases involving the
palms and soles

Relatively low-potency in penetration of skin
 Triamcinolone acetonide & fluocinoline acetonide



Corticosteroids of moderate potency
Useful in severely inflamed skin and on the thicker skin
(the scalp, trunk, extensor surfaces, palms, and soles)
Should not be applied to the face or genitals or used in the
infant
Topical corticosteroids
 Fluorination in many corticosteroids


Greatly increases the potency
Increases the risk of adverse reactions

Should not be used in pregnancy
 Recommendations of corticosteroid potency
relative to dermatologic disease
Topical corticosteroids
 Different skin surfaces

Different response rate varies relative to the absorption of
the steroid into the deeper tissues
 The relatively thin skin surfaces of the face

Respond very rapidly to the use of group 7 agents
 The thicker skin of the palms and soles

Requires a highly potent steroid
Topical corticosteroids
 Irritations that resolve with an effective, higher
potency application when using a low-potency agent

Raw & inflamed skin


More rapidly and readily absorbs medication
Treatment regions involving skin surfaces in frequent contact

Intertriginous areas


The apposition of two skin surfaces produces enhanced absorption
of drug
Areas of skin surfaces enclosed under tight clothing
(the diaper area)

Enhanced absorption of the agent due to the occlusive effect
of the garment
Topical corticosteroids
 Washing the skin before corticosteroid application

Unnecessary
 The medication applied in thin layers

Massaged daily into the skin
 Advised directions for corticosteroid application in
the treatment course

Early application with extra medication per dose or more
frequent medication administrations


Not desired
A reduced frequency of application or a decreased amount
of medication as the disease process responds to therapy
can cause relapse.
Topical corticosteroids
 Optimum application regimens

Not been determined in most dermatologic syndromes
 The more potent agents from the steroid groups


Applied two to three times daily for 1 to 2 weeks followed by
a drug-free week
Additional therapy

Required as determined by the disease and by the particular
patient's response to the initial therapy
 The Less potent agents

Applied three times daily for 2 to 4 weeks followed by a 7day steroid-free period.
Topical corticosteroids
 Estimate the amount of topical corticosteroid to prescribe
according to the burn rule of 9's


Calculate the percentage of body surface area requiring therapy
Providing the amount of topical corticosteroid in grams for a single
application
 In general, 9 g of topical steroid will cover 9 percent of the body
surface area in a thrice-daily application for 1 day
 Description of topical corticosteroid amount to be dispensed
relative to the coverage area and duration of therapy
Tachyphylaxis of corticosteroids
 Tachyphylaxis

The decrease in responsiveness to a drug as a result of
enzyme-mediated events.
 Acute tolerance to the vasoconstricting ability in
relation to topical corticosteroids


Decreasing progressively over time after a topical steroid has
been applied.
As soon as 4 days into the treatment course in all potency
groups
 Strategy to counter the development of tachyphylaxis


Interrupted application schedules
ex.) an initial thrice-daily application for 2 weeks, followed
by 1 week without using the drug and a repeat of the cycle.
스테로이드제 치료가 도움이 되는
주요 피부질환
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Atopic Dermatitis
Toxic Shock Syndrome
Urticaria
Contact Dermatitis
Diaper Dermatitis
Erythema Multiforme
Pemphigus Vulgaris
Herpes Zoster
Exofoliative Dermatitis
Acneiform Eruptions
Seborrheic Dermatitis
Exogenous Photosensitivity
Disorders
 Contact Dermatitis of the
Face
 Alopecia Areata
 Hand and Foot Dermatitis
 Psoriasis
 Lichen Simplex Chronicus
 Human Scabies
 Pediculosis Corporis
 Venous Stasis Dermatitis and
Venous Leg Ulcers
 Erythema Nodusum
 Noninfectious Intertrigo
 Candida intertrigo
항히스타민제 치료가 도움이 되는
주요 피부질환
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Drug eruptions
Atopic Dermatitis
Urticaria
contact dermatitis
Erythema Multiforme
Contact Dermatitis of the Face
Lichen Simplex Chronicus
Human Scabies
Pediculosis Corporis
Venous Stasis Dermatitis and Venous Leg Ulcers
References
 Tintinalli’s Emergency Medicine, 6th ed.
 Internet web site

http://www.accessmedicine.com/content.aspx?aID=609483
 Drug Information provided by Gold Standard, Inc. 2007
 Marx: Rosen’s Emergency Medicine: Concepts and
Clinical Practrice. 6th ed.