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Microsoft word - anti histamines

Review article
Five decades of Antihistamines - an objective analysis
Balakrishnan D *
*Senior Assistant Professor of ENT, Madras Medical College and
Civil Surgeon at the Peripheral Hospital, Chennai 600082 India.
Adapted from a guest lecture delivered by the author at the
Fifth National Conference of The Association of Paediatric
Otolaryngologists of India 18-20 September 1998 Trivandrum,
India. This is a review article, coloured with two decades of
personal experience. Each statement in this article is
substantiated by bibliography. The unwieldy list of references
has been intentionally pruned in the interest of fluency and
brevity.

Preface
The antihistamine is a commonly used drug. The number of antihistamines is
bewildering. This number keeps on increasing. Little distinction can be made between
the different compounds on the basis of efficacy. They do vary somewhat, however,
with respect to potency, dosage, relative incidence of side effects, and the type of
preparations available. Naturally, a physician would desire to choose a preparation that
will afford the greatest therapeutic success with minimal side effects. Unfortunately,
none of the antihistamines meet these criteria. Additionally, individuals vary significantly,
in their responses to antihistamines. This fact also adds to the physician’s conundrum.
But fortunately, all the available H1 blockers can be conveniently classified into several
classes. It would seem wise for the physician to get familiar with a few representative
compounds from the different classes and to base his choice on this knowledge.
Introduction
In the latest issue of Current Index of Medical Specialities (CIMS, a common
compendium of drugs in India), eighteen different generic antihistamines are listed. The
number of trade formulations exceeds 120. Very frequently, new antihistamines are
launched. Each company claims that theirs is the best. The usual refrain is an
introduction of minor changes in the chemical structure with a claim for a new name.
This article is an objective analysis of the newer antihistamines. I have tried to be very
concise, without sacrificing information and fluency.
The hypersensitivity reaction

The most important player in the ‘allergy-reaction’ is the mast cell. First, the mast cells
get sensitized to an antigen. On subsequent re-exposure, they degranulate and release
histamine and similarly acting substances. This causes the typical reaction of itching,
nasal stuffiness, watery eyes and nose, sneezing, bronchospasm etc. This occurs within
the first several minutes and is aptly called the Early Phase Reaction. In approximately
half the patients, a late phase reaction also occurs in the next 3-10 hours. This phase is
characterised by an inflammatory infiltrate i.e. increased number of eosinophils,
basophils and mast cells in the affected tissue. It is during this late phase that several
other mediators like leukotrienes, prostaglandins and platelet activating factor are
produced. The net interactive mediator effect is mucosal engorgement. Additional
inflammatory response results in further symptoms. Patient remains hypersensitive to
antigen exposure for several hours to several days. With repeated exposure, the late
phase can become chronic.
Histamine inhibitors
In 1910, Dale and Laidlaw discovered histamine. After the discovery of histamine, thirty
six long years had to be spent in painstaking research before a compound to block its
action could be found. But this phenolic ether amine was never used in humans
because it was too toxic. Another seven years had to pass before the first clinically
useful anti histamine, Pyrilamine could be synthesized. Soon, several compounds made
their appearance. They are now collectively called the first generation anti histamines.
They were all lipid-soluble and consequently crossed the blood-brain barrier – resulting
in sedation. Some have the unsavoury side effect of producing neural stimulation also,
leading to tremulousness. Even convulsions can result with supra therapeutic doses. In
the last 15 years, newer methods of synthesis led to the development of less lipophillic
antihistamines. Consequently, they are less liable to reach the brain and thus less liable
to produce sedation. These were called second generation antihistamines. Inspite of
their side effects, several first generation antihistamines are still usefully employed for
specific indications (Table1).


Clinical considerations

The Antihistamines are competitive inhibitors of histaminic action, either at the H1 or the
H2 receptor sites. They prevent the action of histamines, rather than reverse it. Hence
they are better given before histamine liberation occurs i.e. before the antigen challenge
occurs. Despite claims to the contrary, as a class, they lead to some degree of dry
mouth, sedation, lassitude and gastro intestinal symptoms. In a clinical situation when a
patient presents to you with signs of severe allergy, the drug of choice is adrenaline a
potent physiological antagonist of histamine. Further, several antihistamines do not
block the production of late phase mediators. This is why sometimes we need drugs
other than antihistamines like steroids (Table 2).

Properties of newer antihistamines
In table 3, the salient properties are indicated. Briefly put, all new antihistamines except
cetirizine,are less sedating. Terfenadine has a potential to lead to cardiac arrhythmia.
Loratidine can be given once a day. In view of the diurnal variation of the inhalational
allergy, this antihistamine can usefully be given in the night, so that it can cover the
early morning period.

Table1. First generation Antihistamines still in use
Drug

Table2. Drug therapy of allergy
Type
stabilise mast cell membrane / prevent degranulation
Table3. Second generation Antihistamines which are commonly used
Drug

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