HISTAMINICS PHARMACOLOGY

1. REFAT JAHAN
BATCH-2017-2018

2. Contents
 1.Introduction
 2.Synthesis,storage and destruction
 3.Histamine receptors
 4.Pharmacological action
 5.Pathophysiological roles
 6Betahistine
 7.Uses and histamine release

3. Introduction
 Histamine is a biogenic amines present in many
animals and plant tissues.
 It is also present in venoms and stinging
secretions.
 Its pharmacology was studied by Dale in the
beginning of 20th century.
 Tissues rich in histamine are skin ,gastric and
intestinal mucosa ,lungs ,liver and placenta,also
present in blood, body secretions and pathological
fluids.
 Non mast cells histamine occurs in brain,
epidermis, gastric mucosa.

4. Synthesis storage and destruction
 Histamine is beta imadazolylethylamine.
 It is synthesised by decarboxylation of
amino acid histidine.
 Degraded rapidly by oxidation and
methylation.
 Histamine is present mostly within storage
granules of mast cells.

6. Histamine receptors
 There are 4 types of histaminergic receptors:-
 H1 receptors:-increases Ca2+smooth muscle
contraction,increase in capillary permeability.
 H2 receptors:-increases cAMP increase gastric
acid secretion
 H3 presynaptic autoreceptors:- decreases cAMP
decreases histamine levels in brain
,lungs,skin,gastric mucosa
 H4 receptors:- decreases cAMP chemotaxis,
cytokine secretions

8. PHARMACOLOGICAL ACTIONS
 1.Blood vessels:-
Causes marked dilatation of smaller blood
vessels like arterioles, capillaries and venules.
On s/c injection flushing, increased heart rate
and cardiac output with no fall in BP are produced.
Rapid iv injections and large doses causes fall
In BP and this can be blocked only by a
combination of H1 and H2 antagonist
Dilation of cranial vessels causes pulsatile
headache.
If injected intradermally, it elicits triple
response:-RED SPOT,WHEAL,FLARE

9.  2.Heart:-
Direct effect of histamine on insitu
heart are not prominent.
 3.Visceral smooth muscle:-
Cause bronchoconstriction, asthma
patients are highly sensitive.
Large doses causes abdominal cramps
and colic by increasing intestinal
contraction.
Human uterus is not much affected.
Smooth muscle contraction is a H1
response.

10.  4.Glands:-
Causes marked increase in gastric secretions-
primarily of acid but also of pepsin.
This is a direct action exerted on parietal cells
through H2 receptors.
Histamine can increase other secretions also,
but the effect is hardly desirable.
 5.Sensory nerve endings:-
Itching occurs when histamine is injected iv
or subcutaneously.
Higher concentration injected more deeply
cause pain.

11.  6.Autonomic ganglia and adrenal medulla:-
These are stimulated and release of
adrenaline occurs which can cause a secondary rise
in BP.
 7.CNS:-
Histamine does not penetrates blood brain
barrier-no central effects are produced on iv
injections.
Intracerebroventricular administrations
produces rise in BP, cardiac stimulation,
hypothermia, vomiting and ADH release.
These effects are mediated through both H1
and H2 post synaptic receptors.

12. PATHOPHYSIOLOGICAL ROLES
 1.Gastric secretion:-
It mediates secretion of HCL in the stomach.
H2 blockers not only suppress acid secretion induced by
histamine but also markedly diminish that in response
to Ach and gastrin.
 2.Allergic phenomenon:-
Helps in mediation of hypersensitivity reaction.
Histamine is causative in urticaria,
bronchoconstriction and anaphylactic shock.H1
antagonist are effective in controlling these
manifestations.
Histamine is not involved in delayed or retarded type of
allergic reaction.

13.  3.As transmitters:-
Histamine is afferent transmitters which initiates
the sensation of itch and pain at sensory nerve
endings.
 4.Inflammation:-
Histamine is a mediator of vasodilator and other
changes that occurs during inflammation.

14.  5.Tissue growth and repair
Because growing and regenerating tissues
contains high concentration of histamine,it has
been suggested to play an essential role in the
process of growth and repair

15. BETAHISTINE
 It is orally active,somewhat H1 selective
histamine analogue.
 Used to control vertigo in patients of
meiner’s disease,acts by causing
vasodilation in the internal ear.
 It is contraindicated in asthma and ulcer
patients.

16. USES AND HISTAMINE RELEASE
 Histamine has no therapeutic use:-
 A variety of mechanical, chemical and
immunological stimulus are capable of releasing
histamine from mast cells.
1Tissue damage
2.Antigen
3.Polymers like dextran and PVP
4.Some basic drugs like morphine,atropine
5.Surface acting agents

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