Transcript URTICARIA Etymology: New Latin urticria,Latin urtica, nettle

URTICARIA
Etymology: Latin urtica, nettle
Prof. IHAB YOUNIS, M.D.
Classification
1- Ordinary Urticaria
• Acute
• Chronic
2- Immune complex urticaria
• Serum sickness
• Urticarial vasculitis
3- Physical urticaria
4- Contact urticaria
5- Angioedema
1- Ordinary Urticaria
Acute Urticaria
• First described in the English literature in
1772
• The natural course of the acute disease
lasts up to 6 weeks
Etiology
• Urticaria affects 15 -20% of the population
at some point in their lives
• Females have a slightly higher prevalence
(61%) than males
• A definitive provoking agent can be
identified in 40 -50% of cases of acute
urticaria
• Histamine is the
most important
biochemical
mediator
• It is released
from mast cells
and basophils
• Histamine is the ligand (a molecule that
binds to a receptor) for at least 2 types of
receptors, H1 and H2
• The activation of H1 histamine receptors
on smooth muscle cells and endothelial
cells leads to cellular contraction and
increased vascular permeability
• The activation of H2 histamine receptors
causes vasodilation resulting in
extravasation of plasma into the dermis
• Acute urticaria may be caused by an
immune or a non-immune mechanism:
Immune-mediated urticaria
Caused by 3 of the 4 types of immune
mechanisms:
Type I: allergic IgE response is initiated by
antigen-mediated IgE immune complexes that
bind and cross-link Fc receptors on the surface
of mast cells and basophils. The types of
antigens that bind to IgE are varied and include:
• Recent infection from a viral syndrome or
an upper respiratory illness
• Medications : eg, ACE inhibitors, aspirin,
nonsteroidal anti-inflammatory drugs,
sulfa-based drugs, penicillins,
cephalosporins, tetracyclines, diuretics,
opioids.(usually occurring within 36h of
drug administration. It is unusual to
develop urticaria from a drug taken
continuously for months)
• Food and food additives :e.g. nuts, fish,
shellfish, eggs, chocolate, strawberries,
salicylate, benzoates.Many cases go
unreported and usually, reactions occur
within minutes
• Parasitic infections (e.g. Ascaris,
Ancylostoma, Strongyloides,
Echinococcus, Trichinella, Filaria)
• Physical stimulants : e.g. cold, pressure,
aquagenic
• Chemicals :e.g. latex, ammonium
persulfate in hair chemicals
• Intravenous radiocontrast media
• Arthropod bites(bees and wasps)
• In one recent study, causes were identified
as:
-Upper respiratory tract infection in
39.5%
-Analgesics in 9%
-Food intolerance in 0.9%
Type II: responses are mediated by
cytotoxic T cells. The disease process
activates byproducts that cause urticarial
vasculitis or bullous pemphigoid
Type III: immune-complex disease is
associated with systemic lupus
erythematosus and other connective
tissue disorders that activate urticaria
Non–immune-mediated
• Some chemicals can directly induce mast
cell degranulation, presumably by altering
the membrane properties
• Common agents are opiates, antibiotics,
curare, radiocontrast media, azo dyes,
aspirin, aspirin derivatives and
radiocontrast media
Clinically
• Wheals:edematous,
evanescent,
erythematous
plaques
• Lesions vary from
several millimeters
to large, continuous
plaques
Plaques have
smooth
surfaces with
polycyclic
curved borders
• Lesions show an intense erythema in the
newest areas, with a trailing clearing
region in older areas
• Individual lesions remain for less than 24
hours, exhibiting a transitory and migratory
behavior
• Greater than 80% of new-onset urticaria
cases resolve in 2 weeks and greater than
95% of new-onset cases resolves by 3
months
Treatment
• Avoidence of the cause
• Antihistamines
• Systemic corticosteroids
Chronic Urticaria
Urticaria that persists for longer than 6 weeks
Etiology
1-Medications: common drugs include
aspirin, nonsteroidal anti-inflammatory
drugs, opioids, penicillins, cephalosporins,
angiotensin-converting enzyme inhibitors,
and alcohol
2-Infections:
• Viral infections are a frequent cause due
to a non-specific effect of circulating proinflammatory cytokines or chemokines,
either acting on mast cells or leading to
expression of adhesion molecules on
endothelial cells
• Bacterial infections (e.g.sinusitis or
urinary)and parasitic infestations are a
rare cause of chronic urticaria
3-Contactants: Contact urticaria syndrome
refers to the onset of urticaria within 30-60
minutes of contact with an inciting agent.
The lesions may be localized or
generalized. Precipitating factors include
latex (especially in health care workers),
plants, animals (e.g. caterpillars, dander),
medications, and food (e.g. fish, garlic,
onions, tomato)
4-Foods and food additives:
• Numerous foods (Shellfish, eggs, nuts,
strawberries) have been blamed as a cause of
urticaria. However, an allergic cause for all ordinary
urticarias was found in fewer than 3.5%
• Reactions to additives is considered to be important
in fewer than 10% of patients
• More frequently implicated food additives are azo
dyes e.g. tartrazine (gives food lemon-yellow color)
and amaranth (gives food a deep red color)
5-Arthropod assault: It is the most
common cause of papular urticaria.
Although patients who are bitten by
mosquitoes are likely to be aware of the
source of the problem, patients with
scabies, bedbug bites, flea bites, or other
similar problems may not be aware
6-Inhalents:Grass pollens, mould spores,
animal danders, house dust and even
tobacco smoke, may rarely provoke
urticaria
7-Autoimmune disease: SLE, cryoglobulinemia, juvenile rheumatoid arthritis, and
autoimmune thyroid disease
8-Malignancies: Little evidence exists to
support the concern that chronic urticaria
is a cutaneous sign of occult internal
malignancy
9-Emotional factors: their role remains
controversial
Investigations
• CBC with differential: Elevated eosinophil
count may be found in parasitic infections
or drug reactions
• Stool ova and parasites: Consider this test
in patients with GIT tract symptoms, an
elevated eosinophil count, or a positive
travel history
• Skin testing may be useful if contact
urticaria is suggested
• Provocation tests
Treatment
1-Avoid the cause
2-Prevent scratching by cooling the
skin:cold compresses or cooling lotions
that contain menthol (Dermocalm)
3-Systemic therapy:
• 2nd and 3rd generation antihistamines are
the drugs of choice
• If sedation is required a 1st generation
antihistamine (especially hydroxizine) is
used
• If there is no response to non sedating
antihistamines, double the dose or use
another non sedating drug or add a
sedating antihistamine or use a
combination of H1 & H2 antihistamines
• In refractory cases, when all diagnostic
and therapeutic methods have been
exhausted, a 2-week course of
corticosteroids (starting at 40 to 60 mg
prednisone or equivalent) will temporarily
suppress the disease
• Plasmapheresis has been effective in
some severe, unremitting cases
• The use of many other immunosuppressive agents in the treatment of
urticaria including tacrolimus, azathioprine,
cyclophosphamide, intravenous
immunoglobulin,IFN-α has been reported
• Antileukotriene medications such as
zileuton (Zyflo), zafirlukast (Accolate) and
montelukast (Singulair), have been used
off-label especially in combination with
antihistamines
2-Immune-complex urticaria
A-Serum sickness
Etiology
• Immune complexes consisting of antigen
and IgG activate complement and are
deposited in tissues including skin (type III
reaction)
• Complement-containing immune
complexes generate an influx of
polymorphs into the vessel wall, where
proteolytic enzymes are released causing
the widespread vasculitic lesions seen
• Drugs : e.g.allopurinol , barbiturates,
captopril , cephalosporins, griseofulvin,
sulfonamides, penicillin and radiocontrast
media
• Heterologous serum used in the
prophylaxis and/or treatment of botulism,
diphtheria, gas gangrene, organ transplant
rejection, and snake and spider bites
• Blood products
• Hormones
• Vaccines
Clinically
• Onset is after 1-3 weeks
• Fever in almost all patients
• Skin symptoms: Urticaria (95%),
morbilliform or scarlatiniform rash,
palpable purpura
• Arthritis (10-50%), usually in the
metacarpophalangeal and knee joints
• Facial edema
• Generalized lymphadenopathy and
splenomegaly
Treatment
• NSAI e.g. Ibuprofen 200-800 mg PO qid
and antihistamines provide symptomatic
relief
• Severe cases may warrant a brief course
of corticosteroids e.g. Prednisone 20-40
mg/d PO
B-Urticarial Vasculitis
Etiology
• Type III like serum sickness
• Most cases are idiopathic
• Rarely causes like those of serum
sickness can be found
• 2.1% of 1310 patients with urticaria were
found to have urticarial vasculitis
Clinically
• Wheals last for more than
24 hours in a fixed
location
• Often accompanied by a
painful or burning sensation
• Lesions resolve with postinflammatory
pigmentation
• Overall, the disease has a relatively
benign course lasting an average of 3
years
• Systemic involvement is common:
-The most frequent symptom is
arthralgia (50%)
-Abdominal pain, nausea and vomiting
(20 %(
Investigations
• Investigations should include a search for
the occasional associated disease, and for
systemic involvement e.g.
-CBC
-ESR
-Urinalysis
-Renal and liver function
-Immunoglobulins
-Chest X-ray
-Serum complement and
Histopathology
• There is leukocytoclastic vasculitis of small
vessels
• Perivascular
infiltrate of neutrophils with leukocytoclasis together
with eosinofills
• Vessels are dilated and their walls show
fibrin deposition
• Later, the infiltrate may become a mixture
of lymphocytes and neutrophils
Treatment
• For patients with cutaneous involvement
only, antihistamines or NSAIDs may provide
symptomatic relief
• If these agents do not work, prescribe
colchicine (0.6 mg PO bid/tid),
hydroxychloroquine(50 mg/d PO initial; can
be increased by 50 mg/wk to 300 mg/d), or
dapsone (6.5 mg/kg PO)
• If all other treatment modalities have failed
or if the patient has systemic involvement,
consider initiating treatment with systemic
steroids (0.5-1.5 mg/kg/d PO (. If the
patient requires long-term treatment with
corticosteroids, consider every-other-day
dosing of the steroid or the addition of
azathioprine as a steroid-reducing agent
3-Physical urticarias
• They are a distinct subgroup of urticarias
in which a specific physical stimulus
induces reproducible whealing
• It accounts for 19% of urticaria cases in a
dermatology clinics
• whealing caused by physical stimuli
usually occurs in minutes at the site of
contact with the skin and persists for less
than 2h
A-Dermographism
• It is a triple response (erythema, edema,
flare) which may arise from firm stroking of
the skin
• It is postulated that mast cells sensitized
with immunoglobulins (especially IgE)
react to an antigen induced by mechanical
stimulation of the skin and release their
mediators
• This reaction is normal but in 5% of normal
people this physiological response is
sufficiently exaggerated to warrant the
term dermographism
• Patients complain of whealing and itching
at sites of trauma, friction with clothing or
scratching the skin
• The rash tends to
last less than an hour
• The condition tends
to improve or
disappear gradually
over a few years
• It is easily diagnosed by using
the dermographometer which
has a spring-loaded stylus, the
pressure of which can be adjusted
to a predetermined setting
• Stroking the skin
at a pressure of
less than 36g/mm
induces a linear
itching weal
within 10min.
Treatment
• Low-sedating H 1 antihistamines are often
effective, sometimes in low doses
• For the more severely affected patients
some improvement may be obtained with
UVB or PUVA therapy
B- Delayed pressure urticaria
• The underlying mechanism is unclear
• It occurs to some degree in up to 37% of
patients with chronic ordinary urticaria,
although they may not be aware of it
unless directly questioned
• whealing occurs at sites of sustained
pressure applied to the skin after a delay
of 30min to 9h, but usually 4-8h, and lasts
12-72h
• Wheals occur frequently under tight clothing
on the hands after manual work, the buttocks
after sitting and on the feet after walking
• Lesions may be itchy, but are often tender or
painful, particularly on the soles and scalp
• It may be accompanied by systemic
symptoms of malaise, flu-like symptoms,
arthralgia, myalgia and leukocytosis
• Delayed pressure urticaria responds
poorly to antihistamine therapy
• Cetirizine in high doses (10mg three times
a day) has been advocated as being more
specific, as it also inhibits eosinophils
• Although non-steroidal anti-inflammatory
drugs may be helpful, they may
exacerbate the ordinary urticarial wheals
• Systemic steroids can provide
symptomatic relief but in doses that are
usually unjustifiable for long-term therapy,
although they can be used short term for
exacerbations
• The prognosis is variable: the symptoms
fluctuate in severity; they may show
spontaneous improvement or last for many
years
C-Heat urticaria
•
•
•
•
1-Cholinergic urticaria
Cholinergic urticaria is common
It occurs in about 0.2% of patients in an
outpatient dermatologic clinic
It occurs in 5-11% of persons with urticaria
The prevalence is higher in persons with
atopy
• Seems to be more common in men than in
women
• The condition usually begins in people
aged 10 -30 years, with an average age at
onset of 16 years
• The average duration was 7.5 years, with
a range of 3-16 years in one study
Etiology
A rise in core body temperature resulting in
sweating causes the rash. Common triggers
include:
• Exercise
• Hot baths/showers
• Fever
• Occlusive dressings
• Eating spicy foods
• Emotional stress
• The pathogenesis is still not clear
• Intracutaneous injection of cholinergic
agents such as acetylcholine produces
wheals in approximately ⅓ of patients
• Thus, acetylcholine released from
sympathetic nerve endings of sweat
glands has been hypothesised to induce
histamine release in some way
• Cholinergic agents released at the nerve
ending may become excessive and
stimulate the sensory nerves directly,
resulting in cholinergic itching and pain
• Aspirin aggravated the condition in 52% of
patients
Clinically
• Lesions appear usually within a
few minutes after the onset of
sweating, and they last from a
half-hour to an hour or more
• Often, itching, burning, tingling, warmth, or
irritation precedes the onset of numerous
small (1- 4 mm in diameter)
pruritic wheals with large
surrounding flares
• Lesions may appear anywhere on the
body, except on the palms or the soles
and rarely in the axillae
• Sometimes, flares are the
only presentation. Patients
who are more severely affected may
experience systemic symptomatology,
such as fainting, abdominal cramping,
diarrhea, salivation, and headaches
Treatment
• A few patients find that they can bring on a
severe attack by suitable exertion, and in this
way can achieve freedom for up to 24h
• Sometimes, an attack can be aborted by
rapid cooling
• Some patients get partial relief from
antihistamines used either regularly or before
they forecast attacks, but most have to
modify their lifestyle by reducing exercise
• For selected severely affected patients not
responding to antihistamines, the attenuated
androgen danazol(1X3) improved whealing.
Usefulness is limited by its side-effects and,
due to potential abuse in sport
• Beta-blockers, such as propranolol, have
been reported to be useful
2-Localized heat urticaria
• This is one of the rarest forms of physical
urticaria
• Localized warming of skin at temperatures
varying from 38 to 50°C for 2-5min induces
whealing at the test site lasting 1h
• Treatment with antihistamines or induction of
tolerance by repeated heat exposure may be
helpful
D- Cold urticaria
• The population most affected is young
adults age 18 to 25 years
• Patients with cold urticaria may also have
dermographism and cholinergic urticaria
• Severe reactions can be seen with
exposure to cold water. Swimming in cold
water is the most common cause of a
severe reaction. This can cause a massive
release of histamine resulting in low blood
pressure, fainting, shock, and even death
Clinically
• Occurs in two forms:
- The common form presents with the
rapid onset of urticaria on the face,
neck, or hands after exposure to cold
-The rare form is hereditary and
manifests as urticaria all over the body
9 to 18 hours after cold exposure
• It lasts for an average of 5 to 6 years
• Cold urticaria is diagnosed by holding an
ice cube against the skin of the forearm for
1 to 5 minutes. Urticarial wheals should
develop in positive cases
Treatment
• Patients with cold urticaria should learn to
protect themselves from a rapid drop in
body temperature
• Regular antihistamines are not generally
effective
• Cyproheptadine (Triactin), doxepin and
ketotifen (Zaditin) have been found to be a
useful treatment
E-Aquagenic urticaria
• It is a rare condition in which urticaria
develops within 1 to 15 minutes after
contact with water
• Urticaria lasts for 10 to 120 minutes
• It does not seem to be caused by
histamine release like the other physical
urticarias. Most investigators believe that
this condition is actually exquisite skin
sensitivity to additives in the water such as
chlorine
• Aquagenic urticaria is diagnosed by
applying tap water and distilled water to
the skin and observing the reaction
• Treatment is with capsaicin cream(Zostrix)
applied to the irritated skin. Antihistamines
are of questionable benefit since histamine
is not the causative factor in water urticaria
F-Solar urticaria
• It is rare
• Urticarial lesions appear minutes after
sunlight exposure and disappear rapidly after
sun avoidance
• It is most common in females & young adults
• Phototesting is required to make the
diagnosis with testing against UVA, UVB,
and visible light
• Antihistamines, broad-spectrum sunscreens,
and graded exposure to increasing amounts
of light or PUVA desensitization are effective
treatments
4-Contact Urticaria syndrome
• Much of the epidemiologic data regarding
contact urticaria syndrome is from
occupational studies, which may therefore
skew the reported etiologies. Little data
exist regarding CUS in the general
population
Classification & Etiology
• Can be classified into 2 broad categories:
1-Nonimmunologic contact urticaria : does
not require presensitization of the patient's
immune system to an allergen . It is
mediated by prostaglandins and not
histamine
• 2- Immunologic contact urticaria:
presensitization is required.It is a type 1
hypersensitivity reaction mediated by
immunoglobulin IgE antibodies specific to the
eliciting substance
• Some of the more commonly reported
causes of NICU include balsam of Peru
( perfumes & deodorants, insect
repellents, toothpastes) , benzoic acid
(food preservative), cinnamic
alcohol(perfumes)
• Reported causes of ICU include natural
rubber latex, raw meat and fish, semen,
many antibiotics, some metals (e.g.
platinum, nickel)
Clinically
• Wheals occur at sites of contact with the
allergen, usually therefore on the hands
and round the mouth.They disappear in 24
hours
• Extracutaneous manifestations include
rhinitis, chest wheezing and conjunctivitis
Treatment
• Avoidance of the cause
• Antihistamines
5-Angioedema
• Angioedema and urticaria are varying
manifestations of the same process
• Postcapillary venule inflammation results
in fluid leakage and edema in both
conditions. However, angioedema involves
vessels in the layers of the skin below the
dermis, while urticaria is localized
superficial to the dermis
• Occurs in 40% of patients with urticaria but
can occur alone
• Women tend to have more occurrences
than men do
• It commonly involves the lips, eyelids, face,
extremities, and genitalia in an asymmetrical
manner
• Angioedema can also involve the
gastrointestinal tract and cause abdominal
pain, nausea, vomiting, and diarrhea
Types
1-Ordinary angioedema:Has the same
multiple etiology and frequent lack of
precise diagnosis as in chronic urticaria
2-ACEIs induced angioedema: related to
the ability of ACEI to prolong bradykinin
survival and potentiate its effects.
Symptoms may be severe and laryngeal
involvement may be life-threatening. Can
occur at any time during treatment
3-Hereditary angio-oedema:
-1% of all cases of angio-oedema
-Due to C1 esterase inhibitor deficiency
transmitted as an autosomal dominant trait
-Onset is usually in early childhood
-May be precipitated by local trauma (e.g.
dental procedures, tonsillectomy)
-Often associated with laryngeal edema,
nausea, vomiting, colic and urinary
symptoms
-Ordinary urticaria does not occur
-Treatment : Danazol orally (1 X 3) or
Epsilon- aminocaproic acid IV
ANTIHISTAMINES
General consideration
• The first H1-antihistamine was discovered
by Jeff Forneau and Daniel Bovet in 1933
in their efforts to develop a guinea pig
animal-model for anaphylaxis at Ryerson
University(Toronto). Bovet went on to win
the 1957 Nobel Prize in Physiology
• Benadryl® was the first antihistamine
introduced in 1945
• IMS Health reports that prescription
antihistamine sales in the USA totaled
more than $4.3 billion in 2001
Histamine receptors
There are four known histamine receptors:
• The H1 receptors: found in smooth muscles,
on vascular endothelial cells, in the heart,
and in the central nervous system.
Stimulation causes systemic vasodilation &
increased cell permeability
• The H2 receptors: found in gastric parietal
cells,vascular smooth muscles,
neutrophils,CNS, heart & uterus.
Stimulation causes gastric acid secretion
& smooth muscle relaxation
• The H3 receptors:found in CNS &
peripheral nerves
• The H4 receptors:found in bone marrow &
leukocytes
H1 Antihistamines
First- Generation H1
(sedating)
antihistamines
Chemical name
Trade
name
Anallerge,
Allergyl
Content
Pheniramine
Avil
Chlorphenoxamine
Allergex
Hydroxyzine
Atarax
Acrivastine
Semprex
75mg/tab
10mg/ts
20mg/tab
3.5mg/ts
10&20mg/
tab
8 mg/tab
Chlorpheniramine
4mg/tab
2mg/ts
Adult
dose
1x1 up to
1x4
Pediatr.
dose
1x1 up to
1x2
1x1 up to ½x1up to
1x1
1x3
1x2
1x2
1x2 for
No syrup
the 2conc
1x1
No syrup
Chemical name
Content
Adult dose
Cyproheptadine
Trade
name
Triactin
4 mg/tab
2 mg/ts
1x3
Pediatr.
dose
1x2
Clemastine
Tavegyl
1x2
1x2
Dimethindene
Fenistil
1 mg/tab
0.5 mg/ts
1 mg/tab
4 mg/cap
0.5 mg/ts
1x3 (tab)
1x1 (cap)
1x1 up to
1x2
1x1= qd = once a day(from the Latin quaque die)
1x2= bid= two times a day(from the Latin bis in die(
1x3= tid = three times a day (from the Latin ter in die)
1x4=qid = 4 times a day (from the Latin quater in die)
Side Effects
• Occur in about 25 percent of patients
• Sedation is the most common problem,
however, there are considerable individual
variations
• The sedative effect ameliorates in most
individuals within a few days
• Other CNS effects include dizziness, tinnitus,
disturbed coordination, inability to concentrate
& blurred vision
• A Canadian study on the relation between
H1-type antihistamines and automobile
fatalities suggested that antihistamines
may affect driving skills sufficiently to
result in fatal automobile accidents
• The CNS effects at times may be
stimulatory (nervousness, irritability,
insomnia, tremors) especially with
Anallerge, Avil, Allergex
• Anticholinergic effects, include: dry
mucous membranes, difficulty in
micturition, urinary retention, dysuria,
urinary frequency, and impotence
• Allergic contact dermatitis may develop
after the topical application
• Accentuation of the central depressive
effects when taken in combination with
alcohol or other therapeutic agents with
CNS depressant effects, such as
diazepam
• Metabolism occurs via the hepatic
microsomal cytochrome P-450 system. Thus,
the half life may be prolonged by patients
receiving microsomal oxygenase inhibitors
such as ketoconazole, erythromycin, doxepin
or cimetidine
• Other side-effects of these antihistamines
include tachycardia, with prolongation of the
QT interval on ECG and other arrythmias
Use in pregnancy
Drug
Anallerge
Avil
Allergex
Atarax
Triactin
Tavegyl
Fenistil
Safety
B
B
No available
information
C
B
B
C
B = Usually safe but
benefits must
outweigh the
risks
C = Safety for use
during
pregnancy has
not been
established
Second-Generation H1
(Low-sedating)
antihistamines
Chemical Trade
name
name
Content
Loratidine
Claritine,
Lorano,
Mosedine,
Loratan
10 mg/tab
Cetrizine
Zyrtec,
10 mg/tab
Histazine1,
Cetrac
Evastine,
10 mg/tab
Kestin
Ebastine
Adult
dose
1x1
Pediatr.
dose
½-1x1
1x1
½-1x1
1x1
No syp
Cetirizine
• It is a metabolite of hydroxyzine and is
less sedating than it
• It is not metabolized in the liver
• Peak plasma concentrations are achieved
in 1 h
• It suppresses cutaneous wheal-anderythema reactions for as long as 24 h
• When assessed by actual driving, the
critical tracking test, and the divided
attention test, cetirizine was more sedating
than placebo and loratadine
• When assessed by pharmacodymanic
comparisons, cetirizine was not more
sedating than other second-generation
H1-type antihistamines
• There are no restrictions on the ability to
take cetirizine with other medications
• Cardiac side effects have not been reported
• Food may decrease the rate of absorption
but does not interfere with the extent of
absorption
Loratadine
• Peak serum concentrations are achieved in 1
to 1.5 h
• Causes no greater sedative or anticholinergic
side effects than does a placebo
• It is metabolised in the liver via the CYP3A4
pathway. Concurrent administration of
loratidine with ketoconazole or erythromycin
(both CYP3A4 inhibitors) was associated
with significantly increased plasma
concentration and elimination
• Cardiac side effects have not been reported
• There are no restrictions on the ability to take
this agent with food or other medications
• Two cases of hepatotoxicity with liver failure
have been reported
• Small amounts of loratadine are excreted in
breast milk
Ebastine
• Has peak plasma concentrations at 2.6 h
• It is metabolised in the liver via the CYP3A4
pathway. Concurrent administration of
ebastine with ketoconazole or erythromycin
causes significantly increased plasma
concentration and elimination
• The effects of impaired renal function and
hepatic cirrhosis on its pharmacokinetics are
minimal
• It has no sedative or cardiac side effects ,
nor does it interact with alcohol or diazepam
Third-Generation H1
antihistamines
Chemical
name
Fexofenadine
Desloratidine
Levocitrizine
Trade
name
Content
Dose
adult
Dose
ped
Telfast,
Fexon,
Allerfen
Aireus,
Desa
120/180
mg/tab
1x1
No liquid
5 mg/tab
1x1
Not
available
Xyzal
5 mg/tab
1x1
Not
available
Fexofenadine
• It is the metabolite of terfenadine
• Ppeak plasma concentrations occur at 2.6 h.
• Plasma half-life is greater in individuals over
65 years of age and in those with renal
impairment
• Pharmacokinetics in patients with hepatic
disease do not differ from those in healthy
subjects
• Has no anticholinergic effects
• It lacks adverse effects at doses up to 480
mg/day
• QT interval was not affected when
administered with erythromycin or
ketoconazole
Desloratadine
A survey published in 2003 concluded:
"When severity of disease was controlled for
analysis amongst loratadine-dissatisfied
patients who converted to desloratadine,
there was a consistent pattern favoring
desloratadine, with statistically significant
results reported for sum of adverse effects,
nighttime awakening due to symptoms,
symptom severity just prior to the next dose,
and overall satisfaction (p < 0.05)."
Levocetrizine
• Studies done in 2001 & 2002 showed that
levocetrizine was more potent at
suppressing weal and flare than ebastine,
fexofenadine, and loratadine
• Skin rash (rarely), headache, and fatigue
have been reported as side effects
• It does not produce any deleterious effect
on cognitive and psychometric functions
H2-Type Antihistamines
• They are less hydrophilic, which
presumably accounts for their lack of CNS
effects
• Although these agents were originally
developed to treat peptic ulcer disease,
they have been used in the treatment of
dermatologic disorders because of the
presence of H2 receptors on the
cutaneous microvasculature
Chemical
name
Cimetidin
Trade
name
Tagamet,
Cimetidine
200 & 400
mg tab
Ranitidine
Zantac,
Ranitac
Antodine,
Famotin
150 & 300 150 mg bid
mg tab
20 & 40 mg 20 - 40 mg
tab
bid
Famotidine
Content
Dose
400-800 mg
bid
• Combined H1 and H2 antihistamine therapy
is statistically more effective than H1
antihistamines alone in controlling the
symptoms of chronic urticaria
• Famotidine is the safest of this group as
cimitidine commonly causes mental
confusion in elderly patients
• Ranitidine does not have these side effects
but interacts with fentanyl, midazolam,
nifedipine, theophylline, and warfarin
Other Therapeutic Agents
with Antihistaminic Activity
Ketotifen(Zaditen)
• It prevents histamine release from mast cells
• Ketotifen also is an H1-type antihistamine
and a calcium-channel blocker
• Sedation and weight gain are side effects
• Dose: Adults 1x2 (1 mg / tab)
Pediatr. ½ -1x1 (1mg / ts)
Doxepin (Sinequan)
• Is a tricyclic antidepressant
• Acts on both H1 and H2 receptors
• More potent than chlorpheniramine in
inhibiting experimental wheals induced by
histamine
• Dose10-150 mg/d
• Not available in Egypt