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DR AAKANKSHA SINGH
What is an antihistamine?
A drug that reduces or eliminates the effects mediated
by the chemical histamine
Histamine is released by your body during an allergic
reaction and acts on specific histamine receptors
The term antihistamine usually refers to H1 receptor
antagonists (actually inverse agonists)
Antihistamines compete with histamine for binding
sites at the receptors. Antihistamine cannot remove
the histamine if it is already bound
Histamine: Histamine was first identified in 1910
and recognized in the 1920s as a major
pathogenic mediator of allergic disorders.
Histamine receptor antagonist was introduced in
1937, and from 1942 to 1981, more than 40
compounds have reached the market.
Histamine is derived from the decarboxylation of
the aminoacid histidine, a reaction catalyzed by
the enzyme L-histidine decarboxylase
it is an endogenous substance synthesized
and stored in and released by
(a) mast cells, which are abundant in the
skin, GI, and the respiratory tract,
(b) basophils in the blood
Allergies are caused by hypersensitivity reaction
involving antibody class IgE (which are located on
mast cells in the tissues and basophils in the blood)
When an allergen is encountered, it binds to IgE,
which activates the mast cells or basophils, leading
them to release massive amounts of histamines.
Pharmalogical effects of Histamine
1)Histamine promotes( intestinal and Bronchiolar )
smooth muscle contraction which is an H1 receptor
2)Histamine significantly increases gastric acid and
gastric pepsin secretion which is an H2 receptor
3) Vasodilation of arterioles and precapillary sphincters
which is an H1and H2 receptor mediated effect
The different Histamine receptors
LOCATION EFFECT TREATMENT
H1 Throughout the body, specifically in
smooth muscles, on vascular
endothelial cells, in the heart and the
Mediate an increase in
vascular permeability at
sites of inflammation
induced by histamine
Allergies, nausea, sleep
H2 In more specific locations in the body
mainly in gastric parietal cells, a low
level can be found in vascular smooth
muscle, neutrophils, CNS, heart, uterus
Increases the release of
H3 Found mostly in the CNS, with a high
level in the thalamus, caudate nucleus
and cortex, also a low level detected in
small intestine, testis and prostate.
receptor, may function to
H4 They were recently discovered in 2000.
They are widely expressed in
components of the immune system
such as the spleen, thymus and
unkonwn In addition to benefiting
research in the h4
receptor may lead to the
treatment of autoimmune
Clinical Symptoms Associated With
mild to moderate
• erythema, urticaria, and/or
• skin reactions, tachycardia,
hypotension, mild respiratory
• severe hypotension,
cardiac arrest, bronchospasm,
CLINICAL CLASSIFICATION OF H1
1) HIGHLY SEDATIVE
3) MILD SEDATIVE
First generation H1 antihistamines
4) SECOND GENERATION ANTIHISTAMINICS
5)NEW SECOND GENERATION- Levocetrizine
Hydroxyzine can be administered orally or via
intramuscular injection. When given orally,
hydroxyzine is rapidly absorbed from the gastro-
intestinal tract. The effect of hydroxyzine is notable in
hydroxyzine is rapidly absorbed and distributed in oral
and intramuscular administration, and is metabolized
in the liver; the main metabolite (45%) is
formed is cetirizine
is an antihistamine with anticholinergic properties
used to treat allergic conditions such as hay
fever or urticaria. It has relatively strong sedative
effects, Pheniramine may cause
drowsiness, bradycardia and sleep disorders. Overdose
may lead to seizures, especially in combination with
Cetrizine is the carboxylic metabolite of first
generation H1 antihistamine hydroxyzine.
It is rapidly absorbed after oral administration.
A single 10 mg oral dose causes significant histamine
wheal suppression in 20-60 minutes and lasts for 24
Indication – urticaria
It is formulated as 1o mg tablets and a 1mg/ml syrup.
It is the most recently introduced second generation
More potent in supressing the histamine wheal in
healthy volunteers with low sedation.
It is licensed for patients over 6 years of age in dosage
of 5 mg daily for the indication of urticaria.
Terfenadine and fexofenadine
Terfenadine was an antihistamine formerly used for
the treatment of allergic conditions.
Terfenadine is a prodrug, generally completely
metabolized to the active form fexofenadine in the
liver . Due to its near complete metabolism by the liver
immediately after leaving the gut, terfenadine
normally is not measurable in the plasma. Terfenadine
itself is cardiotoxic(specifically cardiac
arrhythmia caused by QT interval prolongation). at
higher doses, while its major active metabolite is not.
Terfenadine, in addition to its antihistamine effects,
also acts as a potassium channel blocker . Since its
active metabolite is not a potassium channel blocker,
there is no cardiotoxicity associated with fexofenadine.
Fexofenadine is absorbed by oral route with peak
plasma levels being achieved at 1 to 3 hours after
After a single dose 80% is recovered unchanged in the
faeces and 12% excreted in urine.
dose of fexofenadine 30,60,180mg
It is a piperidine tricyclic selective long acting H1
antihistamine with minimal sedation
Loratadine is given orally, is well absorbed from
the gastrointestinal tract, and has rapid first-pass
Its metabolite desloratadine, which is largely
responsible for the antihistaminergic effects.
Indication – is administered as 10 mg capsules and
syrup(1mg/ml) for the treatment of chronic urticaria
Systemic and topical doxepin
Doxepin is tricyclic antidepressent drug with potent
H1 and H2 antihistamine activity.
It has proved useful when given systemically in the
treatment of severe urticaria.
Doxepin has also been formulated as a 5% cream with
indication of pruritus in eczematous dermatitis.
Although effective,5% doxepin cream may cause
significant drowsiness because of percutaneous
It can also cause allergic contact dermatitis (dermatitis
Topical doxepin should be used for 8 days at the most.
The classical H1 antihistaminics are well absorbed from
oral and parenteral routes,metabolized in liver and
excreted in urine except fexofenadine which is
excreted in faeces
Duration of action of most agents is 4-6 hours,except
newer antihistamines which act for 12-24 hours or
Interacting drug group Examples
These drugs may increase serum levels
Several H1 antihistamines
Azole antifungal agents Fluconazole at doses 300 mg daily or
H2 antihistamines cimetidine
These drugs may decrease serum levels
Several H1 antihistamines
Antibacterial Rifamycin,rifabutin (risk with
Diphenhydramine may increase serum Levels of these drugs
Beta blockers Metoprolol,propanolol,,risk bradycadia
Development of tolerance after continued regular
administration of H1 antihistamines is frequently
perceived as a problem.
In a comparison of several antihistamines
administered daily for 3 weeks ,hydroxyzine(75mg
daily) proved to be the most effective in suppressing
intracutaneously injected histamine wheel.
Hydroxyzine showed greatest degree of tolerance in
contrast chlorpheniramine showed little or no
tendency to produce subsentivity.
allergic rhinitis , Atopic dermatitis, hay fever,
2)Sedation and hypnotics. :
these agents to be used has sleep-aids, i.e.
The newer H1 antagonists, by contrast, cause
minimal or no sedation.
USE IN PREGNANCY AND
Chlorpheniramine, one of the first-generation
antihistamines, is reportedly safe in pregnancy. There
is little information on the use of the new
antihistamines during pregnancy although
loratadine are considered relatively safe for use during
pregnancy(FDA category B).H1antihistamines are
excreted in small amounts in breast milk (<0.1% of a
maternal dose). Breast-fed infants whose mothers
have ingested first-generation antihistamines may
experience irritability, drowsiness or respiratory
depression;no symptoms have been attributed to
second-generation antihistamines to date.
1)first generation- generally mild,sedation,diminshed
alertness,light headache and tendency to sleep
2)dryness of mouth,alteration of bowel
movements,urinary hesitancy and blurring of vision
4)local application can cause contact dermatitis
Acute overdose produces central
Death is due to respiratory and cardiovascular failure
H2 receptor antangnists
Peptic Ulcer and Duodenal Disease
Gastric Ulcer: reduce symptoms
promote healing for benign gastric ulcers
Gastroesophageal Reflux Disorder (erosive esophagitis)
acid hypersecretion -- caused by gastrin-secreting
Systemic mastocytosis and multiple endocrine
cimetidine --------CNS effects (uncommon): elderly:
confusion states, delirium, slurred speech (most
associated with cimetadine)
(granulocytopenia , thrombocytopenia , neutropenia ,