Antihistamines in the Treatment of Chronic

8/11/2019 Antihistamines in the Treatment of Chronic

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I Juregui (Service of Allergy, Hospital de Basurto, Bilbao, Spain), M Ferrer(Department of Allergology, Clnica Universitaria de Navarra, Pamplona, Spain), J

Montoro (Allergy Unit, Hospital La Plana, Villarreal (Castelln), Spain), I Dvila

(Service of Immunoallergy, Hospital Clnico, Salamanca, Spain), J Bartra (AllergyUnit, Service of Pneumology and Respiratory Allergy, Hospital Clnic (ICT),Barcelona, Spain), A del Cuvillo (Clnica Dr. Lobatn, Cdiz, Spain), J Mullol

(Rhinology Unit, ENT Service (ICEMEQ), Hospital Clnic, Barcelona, Spain), J Sastre(Service of Allergy, Fundacin Jimnez Daz, Madrid, Spain), A Valero (Allergy Unit,

Service of Pneumology and Respiratory Allergy, Hospital Clnic (ICT), Barcelona,Spain)


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The most common causes of consultation indermatology, allergology and emergency

care.

The H1 antihistamines are the first linesymptomatic treatment for chronic urticaria,according to the most recent Europeanconsensus


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Chronic urticaria and angioedema had asimilar processes

characterized by a vascular skin reaction with

edema and dilatation of the postcapillary venules

and lymphatic vessels of the dermis


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SUPERFICIAL DERMIS,

AND THE RESULT IS WHEAL

PRODUCTION

DEEP DERMIS AND

SUBCUTANEOUS

CELLULAR TISSUE AND THE

RESULT IS SWELLING IN THE

OVERLYING TISSUE


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Is the appearance ofwheals on a recurrent

basis, more than twice a

week, and during over 6consecutive weeks

The wheals persist formore than an hour, less

than 24-36 hours

The lesions may beindurated and painful.

physical (triggered byspecific physical stimuli)

or idiopathic .


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Histamine is a key in the papule-erythema reaction typical of

urticaria, alleviate the itching

and reduce the number, size andduration of the urticarial lesions.


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induces

decrease in preformed histamine, tryptase) and

neoformed mediators prostaglandins, leukotrienes) of the mast

cells and basophils.

The effect is independent of the H1 receptor, is considered to be

due to drug membrane on interactions .

inhibition of the transmembrane flux of calcium and intracellular cAMP .

Stabilization of the mast cell and basophil membranes,


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Inhibition of cytoplasmictranscription factors

which activates with H1 activationand migrates towards the nucleuswhere it interacts with nuclear DNA

stimulating the transcription of cytokines,chemokines and adhesion molecules, and thegeneration of nitride oxide (NO)


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all H1 antihistaminesinhibitioning skin

reaction tohistamine

cetirizine was foundthe most significant

effect versus otherantihistamines

No correlation betweeninhibition of the skinreaction to histamine andthe clinical efficacy of the

different drug


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The skin drug concentration is also dependentupon the apparent distribution volume (Vda)

or ratio between the amount of drug in thetissues and its concentration in plasma.

Vda decreases with increasing drug binding tothe plasma proteins, and is directly

proportional to tissue affinity for the drugcompound


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H1 antihistamines the non-sedating (AH-2G)

are the only drugs with first class evidence and

grade A recommendation(they are regarded as

the first line symptomatic treatment option) The first generation H1 antihistamines (AH-

1G) should be reserved for those patients not

controlled with AH-2G, All the antihistamines are more effective in

alleviating itching (pruritus) than in reducing

the frequency, number and size of wheals


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(AH-1G) have

sedative effect

The most widely used inapplication to CU:

the ethanolamines(diphenhydramine,clemastine), hydroxyzine,dexchlorpheniramine.

The most classical is

piperidines such as cyproheptadine,

azatadine andketotifen.

Ketotifen proved to be

more effective thanclemastine in a studyinvolving 305 patientswith CU :

effects was similar(20-21% of patients)


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The AH-2G are considered to be the first-linesymptomatic treatment for CU, and are theonly drugs with class 1 evidence and grade A

recommendation.

Doubt the efficacy of combining different

AH-2G with each other or with AH-1G,forcing them to compete for the samereceptors and increasing the risk of drug

interactions and adverse effects


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Table 4 presents several randomized clinicaltrials comparing cetirizine in CU versus both

hydroxyzine and loratadine , of similar clinicalefficacy but with a safety profile superior tothat of hydroxyzine.


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Pregnancy:

Most antihistamines are classified as

belonging to category :

B (risk not demonstrated in animals,

with no human studies) or

C (demonstrated risk in animals orlack of animal or human studies)


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Category B includes the AH-2G,

cetirizine and loratadine;nevertheless, the AH-1G are

considered the drugs of choice,

since they offer greater cumulative

experience


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Chronic urticaria in pediatrics:

There are pediatric formulations for the

following drugs :1. hydroxyzine and alimemazine (>6

months)

2. dexchlorpheniramine (> 1 year),3. diphenhydramine, clemastine,

promethazine, cyproheptadine and

ketotifen (>2 years)


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For the indication of CU, only cetirizine,loratadine and desloratadine are

approved for treatments in patients upto 2 years of age

while ebastine and levocetirizine areonly for urticaria in children over 6

years of age


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In patients with liver or kidney failure,a reduction of the dose of all AH-2G is

advised


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Antidepressants with antihistamine

action

Tricyclic antidepressants have beensuccessfully used, including amitriptylineor doxepin, which possesses potent H1

antihistamine effect and H2 antihistamineactivity


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H2 antihistamin

In view of the above, the routine use of H1-H2antihistamine combinations is presently notjustifi ed.


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Associations of antihistamines to

leukotriene antagonists

Not approved for use in CU


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Dermographism(factitious urticaria)

This is the mostfrequent type ofphysical urticaria and

CU. Respone to AH

Cholinergic urticaria 10% of all young adults

tends to respond tocertrerizinantihistamine

treatment.

Acquired cold urticaria AH2G are

recommended, thoughin 90% of cases thecondition is idiopathic

and responds toantihistamine therapy

Solar urticaria

characterized by thedevelopment of wheals withinminutes after exposure of theskin to ultraviolet

No respone AH

Delayed pressure urticaria

develops on areas of the skin towhich pressure has been applied(soles, buttocks and waist, palms ofthe hands after carrying heavy bagsor tools)

No respone AH


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The H1 antihistamines arethe first line symptomatic

treatment for chronic

urticaria

Physical urticaria

respond well to

antihistamines

The combination ofH2 antihistamines

may prove effective

in chronic urticaria

There are not

enough data torecommend

combination with

leukotriene

antagonits


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Authors suggest that before moving on

to another therapeutic level,antihistamine dose escalation should be

considered


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Antihistamines in the Treatment of Chronic

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