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URTICARIA
Etymology: Latin urtica, nettle
Prof. Ihab Younis
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
A-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& 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 : e.g. 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, Filaria)
•Physical stimulants : e.g. cold, pressure, aquagenic
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•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, and
radiocontrast media
Clinically
•Wheals :edematous, evanescent, erythematous plaques
•Lesions vary from several millimeters to large, continuous plaques
•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
B-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 pro-inflammatory
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:
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• 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 immuno-suppressive 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)
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•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 reaction 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
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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
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
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•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 longterm 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
•It 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 halfhour 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
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•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 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
•In evaluating any response to therapy, one must always consider that the condition can clear
spontaneously
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 help
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 water contact
•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
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•It 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 a rare type where 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, & 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 (NICU) : 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(ICU): 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
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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 (1x3)orally 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 > $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
Content
Adult dose
Pediatr.dose
Chlorpheniramine Anallerge,Allergyl 4mg/tab 2mg/ts
1x1 up to 1x4
1x1 up to1x2
Pheniramine
Avil
75mg/tab 10mg/ts
1x1 up to1x3
½x1up to 1x1
Chlorphenoxamine Allergex
20mg/tab 3.5mg/ts 1x2
1x2
Hydroxyzine
Atarax
10&20mg/tab
1x2 for the 2conc No syrup
Acrivastine
Semprex
8 mg/tab
1x1
No syrup
Cyproheptadine
Triactin
4 mg/tab 2 mg/ts
1x3
1x2
Clemastine
Tavegyl
1 mg/tab 0.5 mg/ts 1x2
1x2
Dimethindene
Fenistil
1 mg/tab
1x3 (tab)
1x1 up to
4 mg/cap0.5 mg/ts
1x1 (cap)
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)
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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
Safety
Anallerge
B
Avil
B
Allergex
No available information
Atarax
C
Triactin
B
Tavegyl
B
Fenistil
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 name Trade name
Content
Adult Pediatr.
dose
dose
Claritine, Lorano, Mosedine,Loratan 10 mg/tab 1x1
½ -1x1
Zyrtec, Histazine1,Cetrac
10 mg/tab 1x1
½ -1x1
Evastine, Kestin
10 mg/tab 1x1 No syp
Loratidine
Cetrizine
Ebastine
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-and-erythema reactions for as long as 24 h
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•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
Trade name
Content
Adult
Pediat.Dose
Dose
Fexofenadine
Telfast,Fexon,Allerfen 120/180mg/tab
1x1
No liquid
Desloratidine
Aireus,Desa
5 mg/tab
1x1
Not available
Levocitrizine
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)."
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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
Chemical name
Trade name
Content
Dose
Cimetidin
Tagamet, Cimetidine 200 & 400 mg tab 400-800 mg bid
Ranitidine
Zantac, Ranitac
150 & 300 mg tab 150 mg bid
Famotidine
Antodine, Famotin
20 & 40 mg tab
20 - 40 mg bid
•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
•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
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