Histamine and

Antihistaminics
Dr Nitin Kothari

 Autacoids
Local hormones
Produced by tissues or endothelial cells
which after being released locally, act at
the site or near the site of their release
Histamine, serotonin, bradykinin

 Histamine
Found at- skin, GIT mucosa, brain, lungs, CsF,
BM, snake venom, sting secretion
Mast cells are the predominant site of storage
of histamine in most of the tissues. Turnover
slow.
Non-mast cells- stomach, brain. Turnover rapid
Release of histamine
Immunologic allergan + IgE bind to mast cells
Chemical and mechanical release- degranulation
of mast cells

Drugs that liberate histamine

Morphine
D-TC
Radiocontrast media
Polymixin B

Synthesis, Storage, Release,

Metabolism

 Histamine receptors
4
G- protein coupled
Only H3- presynaptic- inhibitory type
H4- on eosinophil, basophil, CD4Tcells play role in chemotaxis

Rece
ptor
type

H1

H2

Distribution

function

Smooth muscles

contraction

Blood vessels

vasodilatation,
increased capillary
permeability

CNS-

neurotransmitter

Sensory n ending

pain, itching

Blood vesselsvasodilatation,
increreased
capillarypermaebility
CNS- neurotransmitter
Gastric glands- acid
sectretion

 Smooth muscle contraction- H 1

action
Bronchoconstriction
Spasmodic contraction of
intestinediarrhoea

 CNS
Both H1 and H2
Wakefulness
H2 blockers also cause drowsiness

Sensory n endings
Urticaria response to insect bite and sting

Gastric glands
H2 receptors on parietal cells

 Blood vessels
Histamine causes marked dilatation of smaller blood
vessels, including arterioles, capillaries and venules.
Larger arteries and veins are constricted.
Histamine.
On s.c. injection flushing, especially in the blush area,
heat, increased heart rate and cardiac output, with
little or no fall in BP are produced.
Rapid i.v. injection causes fall in BP which has an early
short lastingH1 and a slow but more persistent H2
component. With low doses only the H1 component is
manifest since H1 receptors have higher affinity. Fall in
BP due to large doses is completely blocked only by a
combination of H1 and H2 antagonists.

 Marked dilatation of smaller blood vessels,

including arterioles, capillaries and venules.
How?
H1 receptor
directly- H1 receptors mediating vasodilatation are
located directly on the vascular smooth muscle.
indirectly- mediated through endothelium dependent
relaxing factor (EDRF): the receptor being located on
the endothelial cells.

H2 receptor
H2 receptors mediating vasodilatation are located
directly on the vascular smooth muscle.

 Histamine also causes increased capillary

permeability due to separation of endothelial
cells exudation of plasma. This is primarily a
H1 response.
Injected intradermaly, it elicits the triple
response consisting of:
Red spot: due to intense capillary dilatation.
Wheal: due to exudation of fluid from capillaries
and venules.
Flare: i.e. redness in the surrounding area due to
arteriolar dilatation

 Heart
Negative chrontropic-H2 action
Negative ionotroic-H2 action
Negative dromotropic- H1 action

 Antagonist
H1 receptor- conventional
antihistaminic
H2 receptor- H2 blocker

H1 receptor antagonists
First Generation

Second Generation
( introduced after
1980)

DOA

Short to intermediate

Longer duration

Sedation

more

less

BBB permeability

more

Less

Antimuscarinic side
effect

more

less

Anti pruritic,
antiemetic,
antitussive

good

poor

FGA
Highly sedative
Diphendramine, Dimenhydrinate
Promethazine
Hydoxyzine

Moderately sedative

Pheniramine
Cyproheptadine
Meclizine
Cinnarizine

Mild sedative

CPM
Clemastine
Dexchlorpheniramine
Triprolidine

 Antihistaminic with high

anticholinergic action
DP-2
Diphenhydramine
Dimenhydrinate
Promethazine
Pheniramine

 SGA

Cetirizine
Levocertizine
Terfenadine
Fexofenadine
Astemizole
Loratadine
Desloratadine
Azelastine
Rupatadine
Ebastine

 P/A
Smooth m cell- block histamine
effect bronchoconstriction
Blood vessels- Fall in BP reversed but
H2 blocker also needed
Triple response blocked
Large art- constriction antagonised

 CNS FGA- variable degree of CNS

depression. This appears to depend on
the compounds ability to penetrate
blood-brain barrier and its affinity for
the central (compared to peripheral) H1
receptors. Excitement and convulsions
are frequently seen at toxic doses.
SGA- are practically nonsedating.

 Certain H1 antihistamines are

effective in preventing motion
sickness. It is not certain whether
this is due to antagonism of
histamine in the brain or reflects
antimuscarinic property of these
drugs. Promethazine also controls
vomiting of pregnancy and other
causes.

side effects
FGA- marked but mild
Sedation, diminshed alertnes, light
headedness, motor incoordination,
tendency to fall asleep, impairment of
psychomotor performance
Caution- dont drive vehicle
Anticholinergic S/E
Dont use in children regularly
pregnanacy- caution though no evidence
of malformation

 Epigastric distress and headache are

also common.
paradoxical- Local application can
cause contact dermatitis.

SGAs
Terfenadine- Torsade pointus
( polymorphic ventricular
tachycardia)- QT prolongation
Dont use with ketoconazole,
eryththromycin
Fexofenadine- metbolite of terfadine
lack cardiac arrhythmia
Astemizole- same ADR with terfadine

 Acute overdose
central excitation, tremors,
hallucinations, motor incordination,
flushing, hypotension, some other
feture of belldona poisoning
Death is due to CV and resp failure

T/U

Allergic disorders
Insect bite, ivy poisoning
Pruritides
As sedative, hypnotic, anxiolytic
Vertigo

 T/U because of anticholinergic

properties
Motion sickness- anticholinergic or
antihistaminergic?
Parkinsonism
Acute muscle dystonia
Preanesthetic medication
Common cold
Cough

 Allergic disorders
block effects of released histaminepalliative effects

 Pruritides
Independent of H1 action
Chlorpheniramine, dipheniramine
more effective

 Sedative, hypnotic, anxiolytic

Induce sleep but promethazine- not
in < 2 years
severe resp depression
deaths are reported
BZDs are better

Hydroxyzine-anxiolytic

 Vertigo
Cinnarizine
H1 antihistaminic, sedative, anticholinergic,
anti- 5-HT, vasodilator
Modualte Ca fluxes
Attenuates vasoconstrictor action of many
endogenous substances

Dimenhydrinate

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