full detail of antihistamin

1. Prepared By:- Miss. Anamika Singh

2. A substance that plays a major role in many
allergic reactions, dilating blood vessels and
making the vessel walls abnormally permeable.
Antihistamines work by preventing the release
of histamine from certain cells (mast cells)
thereby blocking the allergic reaction.

3. Histamine was first discovered in 1910 by the British
physiologist Sir Henry Hallett Dale (photo, right) as a
contaminant of ergot generated by bacterial action. It
was first synthesized before its significance was known,
and due to its wide range of biological activity, has
become one of the most important biologically produced
amines in medicine and biology. The word 'histamine'
comes from histos, which means tissue. By 1937, the
first "antihistamine" had been synthesized by Etienne
Fourneau, which was the H1 receptor antagonist, thymo-
ethyl-diethylamine. However its activity was too weak,
and it was too toxic for clinical use in the treatment
of Histadelia. In 1942, Bernard N. Halpem synthesised
the first clincally used antihistamine - phenbenzamine.

4. In humans histamine is found in nearly all tissues of the body, where it is
stored primarily in the granules of tissue mast cells. The blood cells called
basophils also harbor histamine-containing granules.

5.  Formed from the amino acid Histadine in a
decarboxylation reaction with the enzyme Histadine
decarboxylase.
 Occurs primarily in mast cell and basophiles

6. H1 Smooth Muscle ,Endothelium,
Broconstruction , Vasodilatation , Separation of
endothelial cell, pain and itching, allergy motion
sickness.
H2 Gastric ,Partial cell , basophils , gastric
acid secretion inhibition of IG-E depend
degranulation.

7. H3 The H3-receptor is a promising
potential therapeutically target for many
(cognitive) disorders that are caused by a
histaminergic H3R dysfunction, because it is
linked to the central nervous system
and its regulation of other neurotransmitters. ...
This receptor has been proposed as a target for
treating sleep disorders.
H4 Highly expressed in bone narrow and
white blood cell mediate mast cell chemo taxis .

10. Metabolism of histamine take by the enzymatic
activation.
Enzyme that metabolism involve are .
1) Histamine n-methyl transfer age (HMT)
2) Diamine oxidase
 Histamine is metabolized as N-methyl
imidazole acetic acid imidazole acetic acid
riboside .Both are excreted through urine

11. Based on pharmacological profile ,the H1
antihistamine are divided into two major group
First generation or classical Antihistamine
Second generation or non –sedative antihistamine
 The SAR of antihistamine is a discussed with
reference to the first generation antihistamine.

12.  Ar is aryl :- Phenyl substituted phenyl, hetro aryl
group like -2 pyridil .
 Ar1 :- second aryl or methyl group .
 X :- Connecting atom O,C,N .
 (CH2)n :- Carbon chain usually ethyl .
 NRR1:- Basic terminal function amine group
Ar
Ar1
(CH2)n N
R
R1
X

13.  The diaryl substitution is essential for significant
receptor H1 receptor affinity .The optimal
antihistaminic activity depend upon the co-
planarity of two aryl substitution .
Ar:- Phenyl substituted phenyl, and hetroaryl
group like 2-pyridil .
Most of the H1 antihistaminic process substituent
one of the aryl ring (Mainly in Phenyl Ring ) and
this influence the potency of the compound .Aryl
ring may be linked in eg:- promethazine

14. The X-connecting moiety of H1 antihistaminic may
be simple carbon chain or saturated carbon oxygen
moiety ,which serve as special group for required
pharmacophore.
Antihistaminic containing a carbon atom in the
connecting moiety {eg:- Carbinoxamine } exhibit
charity ,which leads to sterio-selective binding at
receptor X=Oxygen { amino alkyl ether analogue}
X=Nitrogen {Ethylene –diamine derivatives }
X=Carbon ( Mono amino propyl analogue }

15. The carbon chain consist of two or three atom in
H1 antihistamines , which leads to the distance
between the central point of diaryl ring system
and the terminal nitrogen atom is the extended
conformation of these compound in he range of 5-6
Angstrom.
Ar
Ar1
(CH2)n N
R
R1
X

16. Branching of this carbon chain leads decrease in
antihistaminic activity {exception is promethazine
which is more potent than its non branched
counterpart.
If the carbon atom adjacent in the terminal
nitrogen atom in the branched ,the possibility
asymmetry exist however it will not affect the
binding affinity with the receptor .

17. The terminal should be tertiary amine for
maximum activity the terminal nitrogen may be a
part heterocyclic ring eg:-chlorcyclizine which
also retain high antihistaminic activity .the amino
moiety deserve the protonation on interaction
with H1 receptor due to the basicity with
pka8.5-10

18.  It is not used in therapeutically but in the past it
has been used to test acid secreating capacity of
stomach.
To test bronchial hyperactivity in asthmatics.
For diagnosis of pheochromocytoma ,but
pharmacological test are risky .
In pulmonary laboratory ,histamine aerosol has
been used as provocative test of bronchoil
hyperactivity .
To distinguish between real to pseudo
anesthesia .

19. H1 antagonists, also called H1 blockers, are a class
of medications that block the action of histamine at
the H1 receptor, helping to relieve allergic reactions.
Agents where the main therapeutic effect is mediated
by negative modulation of histamine receptors are
termed antihistamines; other agents may have
antihistaminergic action but are not true
antihistamines.[
In common use, the term "antihistamine" refers only
to H1-antihistamines. Virtually all H1-antihistamines
function as inverse agonists at the histamine H1-
receptor, as opposed to neutral antagonists, as was
previously believed.[

20. Bioavailability :- 40-60%
Protein Binding :-98-99%
Metabolism :- liver
Excretion :- urine
Uses :- Diphenhydramine is used to relieve red,
irritated, itchy, watery eyes; sneezing; and runny nose
caused by hay fever, allergies, or the common cold.
Diphenhydramine is also used to relieve cough caused
by minor throat or airway irritation.
Antihistamine Drug

21. Diphenylhydramine hydrochloride

22. Route of administration:- Oral ,
Rectal,intavasculer,Intramusculer
Uses :- Dimenhydrinate is used to
prevent and treat nausea, vomiting,
and dizziness caused by motion
sickness. Dimenhydrinate is in a
class of medications
called antihistamines. It works by
preventing problems with body
balance.

23. Route of administration :- Mouth
Metabolism:- Hepatic
Bioavailability :-oral (20%)
intranasal (70.8%)
Execration :- Urine
Uses:- Doxylamine is an antihistamine used to treat
sneezing, runny nose, watery eyes, hives, skin rash,
itching, and other cold or allergy symptoms. It is
also used as a short-term treatment for sleep
problems (insomnia). It is used in the combination
drug pyridoxine/doxylamine to treat nausea and
vomiting of pregnancy.

24. Bioavailability :- 39.20%
Metabolism:- Hepatic
Execration :-Urine
Uses :- Clemastine fumarate is the fumaric acid salt of
clemastine. An antihistamine with antimuscarinic and
moderate sedative properties, it is used for the
symptomatic relief of allergic conditions such as rhinitis,
urticaria, conjunctivitis and in pruritic (severe itching)
skin conditions.

25. Uses: Diphenhydramine Hydrochloride is used to
relieve red, irritated, itchy, watery eyes; sneezing;
and runny nose caused by hay fever, allergies, or the
common cold. Diphenhydramine is also used to
relieve cough caused by minor throat or airway
irritation.

26. Route of administration :- Mouth
Intravenous s
Metabolism:- Hepatic
Execration :-Urine
Uses:-Tripelennamine is an
antihistamine. Tripelennamine blocks the effects of
the naturally occurring chemical histamine in the
body. Tripelennamine is used to treat sneezing; runny
nose; itching, watery eyes; hives; rashes; itching; and
other symptoms of allergies and the common cold.

27. Uses :-Chlorcyclizine is a first generation
phenylpiperazine class antihistamine used to treat
urticaria, rhinitis, pruritus, and other allergy symptoms.
Chlorcyclizine also has some local anesthetic, ant
cholinergic, and antiserotonergic properties, and can be
used as an antiemetic.

28. Uses :- Meclizine Hydrochloride is used to prevent
and control nausea, vomiting, and dizziness caused
by motion sickness. It is also used for vertigo
(dizziness or lightheadedness) caused by ear
problems. Meclizine is an antihistamine. It works to
block the signals to the brain that cause nausea,
vomiting, and dizziness.

29. Uses:-Buclizine is a piperazine-derivative
antihistamine used as an antivertigo/antiemetic
agent. Buclizine is used in the prevention and
treatment of nausea, vomiting,
and dizziness associated with motion sickness.
Additionally, it has been used in the management of
vertigo in diseases affecting the vestibular apparatus.

30. Uses:- Chlorpheniramine is an antihistamine used
to relieve symptoms of allergy, hay fever, and the
common cold. These symptoms include rash, watery
eyes, itchy eyes/nose/throat/skin, cough, runny
nose, and sneezing.

31. Uses:-Triprolidine is an antihistamine used to relieve
symptoms of allergy, hay fever, and the common
cold. These symptoms include rash, watery eyes,
itchy eyes/nose/throat/skin, cough, runny nose,
and sneezing.

33. Uses :-It is used to treat symptoms of the
common cold and allergies, such as sneezing,
itching, rashes, and hives.

34. Route of administration :- IV,IM
Topical
Metabolism:- Hepatic
Execration :-Urine
88%
Uses:- Promethazine is used to prevent and
treat nausea and vomiting related to certain
conditions (such as before/after surgery, motion
sickness). It is also used to treat allergy symptoms
such as rash, itching, and runny nose.
Bioavailability :-

36. Uses:-Trimeprazine (also known as Alimemazine),
a phenothiazine used as antipsychotic drug.
This drug is used in Russia under brand name
TERALIGEN and has anti-histamine, sedative, and
anti-emetic (anti-nausea) effects. Teraligen is used
to treat neurosis, depression and anxiety of
different origins.

37. Route of administration :-Oral
Metabolism:- Hepatic
Execration :-Kidney
Protein Binding :- 96 -99%
Uses :-Cyproheptadine is an antihistamine used to relieve
allergy symptoms such as watery eyes, runny nose,
itching eyes/nose, sneezing, hives, and itching. It works
by blocking a certain natural substance (histamine) that
your body makes during an allergic reaction.

38. Uses:-Azatadine is an antihistamine, which blocks
the effects of the naturally occurring chemical
histamine in the body. Azatadine is used to
treat sneezing; runny nose; itching, watery
eyes; hives; rashes; and other symptoms
of allergies and the common cold.

39. Uses:-Astemizole is an antihistamine.
Antihistamines prevent sneezing, runny nose,
itching and watering of the eyes, and other allergic
symptoms. Astemizole is used treat allergies, hives
(urticaria), and other allergic inflammatory
conditions.

40. Metabolism:- Hepatic
Execration :-Kidney
Protein Binding :- 97 -99%
Bioavailability :-100%
Uses :- Loratadine is an antihistamine medicine that
relieves the symptoms of allergies. It's used
to treat: hay fever. conjunctivitis (red itchy
eyes)

41. Metabolism:- Hepatic
Execration :-Urine
Protein Binding :- 88-96%
Bioavailability :-70%
Uses:-Cetirizine is used to temporarily relieve
the symptoms of hay fever (allergy to pollen, dust, or
other substances in the air) and allergy to other
substances (such as dust mites, animal dander,
cockroaches, and molds).
These symptoms include sneezing; runny nose; itchy,
red, watery eyes; and itchy nose or throat.

42. Metabolism:- Hepatic
Execration :-Urine
Protein Binding :- 90%
Bioavailability :-70%
Uses:-Levocetirizine is used to relieve runny
nose; sneezing; and redness, itching, and tearing of
the eyes caused by hay fever, seasonal allergies,
and allergies to other substances such as dust
mites, animal dander, and mold. It is also used to
treat symptoms of hives, including itching and
rash.

43. H2 antagonists, sometimes referred to as H2RAs[1] and also
called H2 blockers, are a class of medications that block the
action of histamine at the histamine H2 receptors of
the parietal cells in the stomach. This decreases the
production of stomach acid. H2 antagonists can be used in the
treatment of dyspepsia, peptic ulcers and gastroesophageal
reflux disease. They have been surpassed by proton pump
inhibitors (PPIs); the PPI omeprazole was found to be more
effective at both healing and alleviating symptoms of ulcers
and reflux oesophagitis than the
H2 blockers ranitidine and cimetidine.[2]
H2 antagonists are a type of antihistamine, although in
common use the term "antihistamine" is often reserved
for H1 antagonists, which relieve allergic reactions. Like the
H1 antagonists, some H2 antagonists function as inverse
agonists rather than receptor antagonists, due to
the constitutive activity of these receptors.[3]

44. Metabolism:- Liver
Execration :-Urine
Protein Binding :- 13-25%
Bioavailability :-70%
Uses:-Cimetidine is used treat ulcers; gastroesophageal
reflux disease (GERD), a condition in which backward
flow of acid from the stomach causes heartburn and
injury of the food pipe (esophagus); and conditions
where the stomach produces too much acid, such as
Zollinger-Ellison syndrome.

46. Metabolism:- Liver
Execration :-Urine
Protein Binding :- 15-20%
Bioavailability :-45%
Uses:-Famotidine belongs to a class of drugs known
as H2 blockers. This medication is also available
without a prescription. It is used to prevent and
treat heartburn and other symptoms caused by too
much acid in the stomach (acid indigestion).

47. Metabolism:- Liver
Execration :-Urine
Protein Binding :- 15%
Bioavailability :-50%
Uses:-Ranitidine is used treat ulcers; gastroesophageal
reflux disease (GERD), a condition in which backward
flow of acid from the stomach causes heartburn and
injury of the food pipe (esophagus); and conditions
where the stomach produces too much acid, such
as Zollinger-Ellison syndrome.

48. Proton-pump inhibitors (PPIs) are members of a class
of medications whose main action is a profound and
prolonged reduction of stomach acid production.
Within the class of medications, there is no clear
evidence that one agent works better than another.[1][2]
They are the most potent inhibitors of acid secretion
available.[3] This group of medications followed and
largely superseded another group of medications with
similar effects, but a different mode of action, the H2-
receptor antagonists.

49. Metabolism:- Liver
Execration :-Urine
Protein Binding :- 95%
Bioavailability :-35-76%
Uses :-Prescription omeprazole is used alone or with
other medications treat symptoms of gastroesophageal
reflux disease (GERD), a condition in which backward
flow of acid from the stomach causes heartburn and
possible injury of the esophagus (the tube between the
throat and stomach) in adults and children 1 year of ...

50. Metabolism:- Liver
Execration :-Kidney
Protein Binding :- 97%
Bioavailability :-80%
Uses:-Lansoprazole reduces the amount of acid your
stomach makes. It's used for indigestion, heartburn
and acid reflux and gastroesophageal-reflux-disease
(GORD). Lansoprazole is also taken to prevent and
treat stomach ulcers.

51. Metabolism:- Liver
Execration :-Kidney
Protein Binding :- 97%
Bioavailability :-80%
Uses:-Pantoprazole is used to allow the esophagus to
heal and prevent further damage to the esophagus in
adults with GERD. It is also used to treat conditions
where the stomach produces too much acid, such as
Zollinger-Ellison syndrome in adults. Pantoprazole
is in a class of medications called proton-pump
inhibitors.

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