Antihistamin
es
By Hassan Imran
Histamine
Histamine is a chemical messenger mostly
generated in the mast cells, thrombocytes
and basophils. Histamine mediates a wide
range of cellular responses including:
Allergic reactions
Inflammatory reactions
Gastric secretions
Synthesis
Histamine is formed by the decarboxylation of
the amino acid histidine by the enzyme
histidine decarboxylase, which is expressed
in cells throughout the body.
Location
Histamine is present in all the tissues including
lungs, skin, blood vessels and GI tract. High
concentration of histamine is found in mast
cells and basophils. Histamine also functions
as a neurotransmitter in the brain.
It also occur as a component of venom and in
the secretions of insect stings
Release of histamine
The stimuli for the release of histamine from
tissues include:
Toxins from organisms
Allergies ( food, drugs, pollen) and anaphylaxis
Venoms from insects
Destruction of cells as a result of trauma etc
Actions
The released histamine in response to various
stimuli exerts its effects through various types
of histamine receptors i.e. H1, H2, H3 and H4.
However H1 and H2 are the targets of clinically
used drugs.
Actions
Histamine increases the production of nasal
and bronchial mucus, resulting in respiratory
symptoms. It also constricts the bronchioles
resulting in symptoms of asthma.
Histamine stimulates the parietal cells in the
stomach causing an increase in acid secretion
through activation of H2 receptors.
Actions
Histamine promotes vasodilation of small
blood vessels and capillaries. Histamine
increases the permeability of the vessels
resulting in leakage of protein and fluids in the
tissue (edema).
Histamine causes itching and pain through its
action on the sensory nerve endings.
Action
Lowers the blood pressure by reducing the
peripheral resistance (vasodilation).
Histamine H1 receptors mediate many
pathological responses including:
Allergic rhinitis
Allergic conjunctivitis
Atopic dermetitis
Urticaria
Bronchoconstriction and asthma
Anaphylaxis
Urticaria
The term antihistamine refers primarily to H1
receptor blockers. H1 receptor blockers are
divided into first and second generation drugs.
First generation
Chlorpheniramine
Cyclizine
Meclizine
Hydroxyzine
Diphenhydramine
Dimenhydrinate
Doxylamine
First generation
The first generation drugs are still widely used
because they are effective and inexpensive.
Most of the first generation antihistamine drugs
penetrate the CNS and cause sedation. They
also interact with other receptors (cholinergic,
alpha adrenergic and serotonin receptors)
producing a wide variety of unwanted adverse
effects.
Second Generation
Acrivastine
Cetirizine
Levocetrizine
Loratadine
Desloratadine
Fexofenadine
Second Generation
The second generation drugs are specific for
peripheral H1 receptors, because they are
made polar (mainly by adding carboxyl groups).
Therefore the second generation agents do not
penetrate the blood brain barrier and cause less
CNS depression than the first generation drugs.
Ophthalmic Anti-
Histamines
Azelastine
Olopatadine
Ketotifen
These drugs are used for the treatment of allergic
conjunctivitis.
Therapeutic Uses
Allergic and inflammatory conditions:
H1 receptor blockers are useful in treating and
preventing allergic reactions caused by antigen
acting on immunoglobulin E antibody.
Oral antihistamines are the drugs of choice in
treating allergic rhinitis and urticaria because
histamine is the principle mediator released by
the mast cells.
Allergic conjunctivitis:
Topical antihistamines decrease itching and
normalize the increased permeability in allergic
conjunctivitis.
Motion sickness and
nausea
Some H1 receptor blockers such as
diphenhydramine, dimenhydrinate and cyclizine
are the most effective agents for preventing he
symptoms of motion sickness.
They are not as effective if symptoms are already
present thus should be taken prior to expected
travel.
The antiemetic action of H1 receptor blockers may
be due to blockade of M1 muscarinic receptors.
Adverse effects
The first generation H1- receptor blockers
interact not only with histamine receptors but
also with muscarinic cholinergic receptors, alpha
adrenergic receptors and serotonin receptors.
Adverse Effects
Sedation:
First generation H1 anti histamines bind h1
receptors and block neurotransmitter effect of
histamine in the CNS. Sedation is less common
with second generation drugs science they do
not readily enter the CNS.
Other effects
First generation antihistamines exert
anticholinergic effects leading to:
Dryness in the nasal passage
Dry mouth (Xerostomia)
Blurred vision
Dry eyes
Retention of urine.
References
Lippincott, Illustrated Reviews Pharmacology.
Basic and Clinical Pharmacology 12 Edition
Katzung.
Essentials of Medical Pharmacology 6th edition,
KD Tripathi.
Ocular therapeutics Pharmacology and clinical
application by Paul U. Fechner and Klaus D.
Teichmann.
