The document discusses histamine and antihistamines. It describes how histamine is synthesized from the amino acid histidine and acts as a messenger in various tissues through four receptors: H1, H2, H3, and H4. The H1 receptor is located in blood vessels and smooth muscles and its activation causes effects like vasodilation. Antihistamines like diphenhydramine and loratadine block the H1 receptor to relieve allergic symptoms. H2 receptor antagonists like famotidine and ranitidine are used to inhibit gastric acid secretion by blocking the H2 receptor in the stomach. The document outlines the mechanisms of action, pharmacokinetics, side effects and uses of

1. Srija Bose, Sridebesh Ghorui
B.Pharm, 3rd Year , Section-A
Roll No.- 18601916033,18601916034
Guru Nanak Institute Of Pharmaceutical Science And Technology
HISTAMINE AND ANTIHISTAMINICS

2. CONTENTS
2
TOPIC
Introduction
Synthesis, Storage And Destruction
Mechanisms Of Action
Histamine Receptors, It’s Location Mechanisms And Their Effects
H1 Receptor Antagonist
H2 Receptor Antagonist
Pharmacological Action Of Histamine Antagonist
Pharmacokinetics
Side Effects Of Antihistamine
Uses Of Antihistaminic Drugs
Conclusions
References

3. INTRODUCTION
• Histamine meaning “tissue amine”(histos-tissue).
• Histamine =Beta-imidazolyl ethylamine
• Synthesised from histidine (amino acid) and degraded by oxidation and methylation
• Histamine is a biogenic amine found in tissues, including mast cell, basophile, lymphocytes,
neurones, and gastric enterochromaffin like cell.
• It is an autacoid that is a molecule secreted locally to increases or decreases the activity of nearby
cells.[1]
3

4. SYNTHESIS, STORAGE AND
DESTRUCTION MECHANISMS OF ACTION
4
[1]

5. HISTAMINE RECEPTORS, IT’S LOCATION MECHANISMS
AND THEIR EFFECTS
RECEPTORS H1 Receptor H2 Receptor H3 Receptor
Location and
effects
• Blood vessel-
1. Endothelium: releases of
NO and PGI2- Vasodilation
2. Smooth muscle of larger
vessels- vasoconstriction
• Smooth muscle- contraction
• Brain- transmitter
• Afferent nerve ending and
ganglionic cell – stimulation
• Heart:
Atria: +ve chronotropy
Ventricles: +ve inotropy
• Blood vessel: dilation
• Gastric glands: acid
secretion
• Brain-transmitter
• Uterus: relaxation
• Brain (presynaptically):
inhibition
• Certain blood vessel:
vasodilation.
Receptor types
and
mechanisms
Gq
IP3, DAG
Gs
cAMP
Gi/o
cAMP
[1,2]
5

6. 6
HISTAMINE
RECEPTORS
[3]

7. H1 RECEPTOR ANTAGONIST
Highly sedative Moderately sedative Mild sedative
• Promethazine
• Diphenhydramine
• Pheniramine
• Meclizine
• Chlorpheniramine
• Clemastine
[1]
7
1st generation
Sedation (penetrate BBB)
They interact with other
receptors producing variety of
adverse effects
2nd generation
They are made polar by the addition
of carboxyl groups, so they can't
penetrate BBB and show less
sedation.
They are specific for peripheral H1
receptor
• Fexofenadine
• Loratadine
• Cetirizine
• Ebastine
• Rupatadine [1]

8. H2 RECEPTOR ANTAGONIST
8
• The pharmacological and clinical utility of H2 antagonist for inhibition of gastric acid secretion in
the treatment of GI disorder.
• cimetidine
• ranitidine
• famotidine
• Nizatidine [2]

9. Pharmacological Action Of Histamine Antagonist
H1 receptors H2 receptors
9
1st Generation
Antagonism of histamine:
• block the histamine induced-
vasoconstriction
• Causes low BP
Antiallergic: Hypersensitivity
are suppressed
CNS: cause sedation because
they penetrate BBB
Anticholinergic: H1 blocker
antagonise muscarinic action
of acetylcholine.
2nd Generation
• absence of CNS depressant.
• Higher selectivity towards H1
receptors.
• No anticholinergic side effects.
• Additional anticholinergic
activity, apart from histamine
blocked.
• Inhibit late phase allergic
reaction by modifying the
action of leukotrienes, PAF
(platelet activating factor),
cytokines, etc.
Heart:
• Atria: +ve chronotropy
• Ventricles: +ve inotropy
BV- constriction
Gastric gland- histamine
released by enterochromaffin
cells in stomach is blocked from
binding on parietal cell H2
receptors.[1]

10. PHARMACOKINETICS
ABSORPTION DISTRIBUTION METABOLISM EXCRETION
• H1 antagonist are
well absorbed from
oral and parenteral
routes.
• Following oral
administration, the
peak plasma
concentration is
achieved in 1-3 hour
and effect usually last
for 4-6 hours for 1st
generation drugs.
• For 2nd generation
drugs effect last for
12-24 hours.
• This agents distributed
widely through out the
body including CNS
for 1st generation
agents. The newer
compounds penetrate
brain poorly.
• H1 antagonists are metabolised by
CYPs(Cytochrome P450 system)
in the liver.
• The plasma concentration of
active or inactive metabolised of
H1 antagonists depends on CYP
system activity.
• Only acrivastine, cetirizine,
levocetirizine, fexofenadine,
desloratadine prevent this
metabolic pathway to a relevant
extent which makes them more
predictable regarding their
desirable effects.
• These are excreted
unchanged in the
urine.
• Exceptions are –
 Fexofenadine-
excreted through
faeces
 Epinastine-
excreted through
both urine and
faeces.
[2]
10

11. SIDE EFFECT OF ANTIHISTAMINE
H1 ANTIHISTAMINE
1st generation 2nd generation
 Sedation
 Diminished alertness and
concentration
 Fatigue
 Restless, nervous, unable
to sleep
 Dryness of mouth
 Alternation of bowl
movement
 Blurred vision
 Teratogenic in animals
Eg: Hydroxyzine, Cyclizine
 Drowsiness
 Fatigue
 Headache
 Nausea
 Dry mouth
H2 ANTIHISTAMINE
Constipation
Diarrhoea
Difficulty
sleeping
Dry mouth and
skin
Headache
Ringing in ear
A runny nose
Trouble
urinating
[1]
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12. USES OF ANTIHISTAMINE DRUGS
• Allergic disorder: Antihistamines do not suppress AG: AB reaction, but block the effects of
released histamine—are only palliative. They effectively control certain immediate type of
allergies, e.g. itching, urticaria, seasonal hay fever, allergic conjunctivitis and angioedema of lips,
eyelids, etc.
• Motion sickness: Promethazine, diphenhydramine, dimenhydrinate and meclozine have
prophylactic value in milder types of motion sickness;
• Vertigo: Cetirizine is the H1 anti histamine having additional anticholinergic, anti-5-HT, sedative
and vasodilator properties which has been widely used in vertigo.
• Parkinsonism: Promethazine and some other afford mild symptomatic relief in early cases – based
on anticholinergic property.
• Sedative, Hypnotic, anxiolytic: Antihistamines with CNS depressant action have been used as
sedative and to induce sleep, especially in children.
• Common cold: Antihistamines do not affect the course of the illness but may afford symptomatic
relief by anticholinergic (reduce rhinorrhoea) and sedative actions. The newer non sedating
antihistamines are less effective in this respect.[1]
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13. CONCLUSION
• Histamine is an important chemical messenger that exhibits significant physiological effects
mediated through its receptors. A through knowledge of drugs is very much useful to treat the
clinical conditions arising due to imbalance of histamine in the body.[1]
• Drugs with antihistamine action are the most commonly prescribed medication in daily
dermatological practice, both adults and children.
• H1 receptors act on the gene transcription of inflammatory mediators.
• H2 antagonist are practically non-sedative because its not permeable through BBB.
• When a person has a problem in metabolising and breaking down histamine, it's level build up and
lead to worrying symptoms like rashes, itching, swelling, redness etc.[2]
• All who have histamine intolerance in any kind need to take steps and manage it by taking specific
diets and supplements –
Protein- Dairy products, egg whites, peanuts
Vegetables - Tomatoes (Red one has higher histamine than white or yellow one), spinach,
pumpkin etc
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14. REFERENCE
1. TRIPATHI KD “Essentials Of Medical Pharmacology”, Seventh Edition, Jaypee Brothers
Medical Publishers, 2013, Chapter 11 “Histamine And Antihistaminics”, Page No- 159-169,
ISBN: 978-93-5025-937-5
2. Brunton Laurence L. “Goodman & Gilman’s The Pharmacological Basis Of Therapeutics”,
13th Edition ,Mc Graw Hill Education, Chapter 39 “Histamine, bradykinin& Their Antagonists”
Page no.- 713& 719,ISBN-978-1-25-958474-9.
3. photo_51686184_stock-vector-histamine-receptor-function-target-tissue-and-organs-histamine-
action
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