Histamine and Antihistaminics 4.

Glands
HISTAMINE  Histamine causes marked increase in
gastric secretion—primarily of acid but
also of pepsin.
PHARMACOLOGICAL ACTIONS  This is a direct action exerted on parietal
1. Blood vessels cells through H2 receptors.
 Histamine causes marked dilatation of
smaller blood vessels, including
5. Sensory nerve endings
arterioles, capillaries and venules.
 Itching occurs when histamine is injected
 Rapid i.v. injection causes fall in BP. i.v. or intracutaneously.
 Dilatation of cranial vessels causes
 These are reflections of the capacity of
pulsatile headache. histamine to stimulate nerve endings.
 Larger arteries and veins are constricted
by histamine: mediated by H1 receptor on 6. Autonomic ganglia and adrenal medulla
vascular smooth muscle.  These are stimulated and release of Adr
 Histamine also causes increased capillary occurs, which can cause a secondary rise
permeability due to separation of in BP.
endothelial cells → exudation of plasma.
This is primarily a H1 response.

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7. CNS
 Injected intradermally, it elicits the triple
aw
Histamine does not penetrate blood brain
response consisting of: barrier—no central effects are seen on i.v.
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Red spot: due to intense capillary dilatation. injection.

Wheal: due to exudation of fluid from
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capillaries and venules. PATHOPHYSIOLOGICAL ROLES

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Flare: i.e. redness in the surrounding area

1. Gastric secretion
due to arteriolar dilatation.
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Histamine has dominant physiological role in

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mediating secretion of HCl in the stomach.

2. Allergic phenomena
 Mediation of hypersensitivity reactions
was the first role ascribed to histamine.
 It is an important, but only one of the
mediators of such phenomena.
 Histamine is causative in urticaria,
2. Heart
angioedema, bronchoconstriction and
 Direct effects of histamine on in situ heart
anaphylactic shock. The H1 antagonists
are not prominent, but the isolated heart,
are effective in controlling these
especially of guinea pig, is stimulated—
manifestations to a considerable extent,
rate as well as force of contraction is
except asthma and to a lesser extent
increased.
anaphylactic fall in BP in which
leukotrienes (especially LTD4) and PAF
3. Visceral smooth muscle
appear to be more important.
 Histamine causes bronchoconstriction;
patients of asthma are highly sensitive.
3. As transmitter H1 ANTAGONISTS
 Histamine is believed to be the afferent These drugs competitively antagonize
transmitter which initiates the sensation of actions of histamine at the H1 receptors.
itch and pain at sensory nerve endings.
 Nonmast cell histamine occurs in brain, PHARMACOLOGICAL ACTIONS
especially hypothalamus and midbrain. It 1. Antagonism of histamine
is involved in maintaining wakefulness;  They effectively block histamine induced
H1 antihistaminics owe their sedative bronchoconstriction, contraction of
action to blockade of this function. intestinal and other smooth muscle and
triple response—especially wheal, flare
4. Inflammation and itch.
 Histamine is a mediator of vasodilatation  Constriction of larger blood vessel by
and other changes that occur during histamine is also antagonized.
inflammation.  Action of histamine on gastric secretion is
 It promotes adhesion of leukocytes to singularly not affected by these drugs.
vascular endothelium.
2. Antiallergic action
Betahistine  Many manifestations of immediate

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 It is an orally active, somewhat H1 aw hypersensitivity (type I reactions) are
selective histamine analogue, which is suppressed.
used to control vertigo in patients of  Urticaria, itching and angioedema are
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Meniéré’s disease: possibly acts by well controlled.

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causing vasodilatation in the internal ear.  Anaphylactic fall in BP is only partially

 It is contraindicated in asthmatics and prevented.
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ulcer patients.
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VERTIN 8 mg tab., 1/2 to 1 tab. QID. 3. CNS

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 The older antihistamines produce variable

degree of CNS depression.
 The second generation antihistaminics are
practically nonsedating.
 Certain H1 antihistamines are effective in
preventing motion sickness.
 Promethazine also controls vomiting of
pregnancy and other causes.
 Promethazine and few other
antihistaminics reduce tremor, rigidity
and sialorrhoea of parkinsonism.
 Some older antihistamines, especially
cyproheptadine, have appetite stimulating
effect.
 Some H1 antihistamines are also effective
antitussives.
4. Anticholinergic action leukotrienes or by antiplatelet activating
 Many H1 blockers in addition antagonize factor effect.
muscarinic actions of ACh.  These newer drugs have the advantage of
not impairing psychomotor performance
PHARMACOKINETICS (driving etc. need not be contraindicated),
 The conventional H1 antihistaminics are no sleepiness.
well absorbed from oral and parenteral  Some patients do complain of sedation.
routes, metabolized in the liver and  Their principal indications are:
excreted in urine. (i) Allergic rhinitis and conjunctivitis, hay
 They are widely distributed in the body fever, pollinosis—control sneezing, runny
and enter brain. but not blocked nose, and red, watering, itchy
 The newer compounds penetrate brain eyes.
poorly accounting for their low/absent (ii) Urticaria, dermographism, eczema.
sedating action.
 Duration of action of most agents is 4–6
hours, except meclozine,
chlorpheniramine, mesolastine,
loratadine, cetirizine and fexofenadine

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which act for 12–24 hours or more. aw
SIDE EFFECTS AND TOXICITY
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 Sedation, diminished alertness and (iii) Acute allergic reactions to drugs and
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concentration, motor incoordination, foods.

fatigue are the most common. They have poor antipruritic, antiemetic and
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 Patients should be cautioned not to antitussive actions.

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operate motor vehicles or machinery

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requiring constant attention. USES

 Second generation compounds are largely 1. Allergic disorders
free of CNS effects.  They effectively control certain
 Dryness of mouth, alteration of bowel immediate type of allergies, e.g. itching,
movement, urinary hesitancy and blurring urticaria, seasonal hay fever, allergic
of vision can be ascribed to conjunctivitis and angioedema of lips,
anticholinergic property. eyelids, etc. However, their action is
 Epigastric distress and headache may be slow—Adr alone is life-saving in
felt. laryngeal angioedema.
 The antihistaminics are ineffective in
SECOND GENERATION ANTIHISTAMINICS bronchial asthma: reasons may be—
• Absence of CNS depressant property. (i) Leukotrienes (C4, D4) and PAF are more
• Higher H1 selectivitiy: no anticholinergic important mediators than histamine.
side effects. (ii) Concentration of antihistamines attained
• Additional antiallergic mechanisms apart at the site may not be sufficient to block high
from histamine blockade: some also inhibit concentration of histamine released locally in
late phase allergic reaction by acting on the bronchi.
2. Other conditions involving histamine 7. Preanaesthetic medication
Antihistaminics block symptoms produced Promethazine has been used for its
by histamine liberators; afford symptomatic anticholinergic and sedative properties.
relief in insect bite. 8. Cough
3.Pruritides  Antihistaminics like chlorpheniramine,
 Many conventional antihistamines have diphenhydramine and promethazine are
antipruritic action independent of H1 constituents of many popular cough
antagonism. Though relief is often remedies.
incomplete, older antihistaminics  They have no selective cough suppressant
chlorpheniramine, diphenhydramine, action, but may afford symptomatic relief
cyproheptadine remain the first choice by sedative and anticholinergic property.
drugs for idiopathic pruritus. 9. Parkinsonism
4. Common cold  Promethazine and some others afford mild
 Antihistaminics do not affect the course of symptomatic relief in early cases— based
the illness but may afford symptomatic on anticholinergic and sedative property.
relief by anticholinergic (reduce 10.As sedative, hypnotic, anxiolytic
rhinorrhoea) and sedative actions.  Antihistamines with CNS depressant
5. Motion sickness action have been used as sedative and to

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 Promethazine, diphenhydramine, aw induce sleep, especially in children.
dimenhydrinate and meclozine have  However, promethazine has produced
prophylactic value in milder types of serious respiratory depression in young
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motion sickness; should be taken one hour children; few deaths are on record; it is not
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before starting journey. indicated in children aged 2 years or less.

 Promethazine can also be used in morning
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sickness, drug induced and postoperative

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vomiting, radiation sickness.

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 Use of cyproheptadine is often made in

anorectic patients for improving appetite.
Such use in underweight children is
inappropriate, because its CNS depressant
action can affect learning.
6. Vertigo
 Cinnarizine is the H1 antihistamine
having additional anticholinergic, anti-5-
HT, sedative and vasodilator properties
which has been widely used in vertigo.
 It modulates Ca2+ fluxes and attenuates
vasoconstrictor action of many
endogenous mediators.
 Side effects are sedation and mild g.i.
upset.
 Dimenhydrinate is another effective
antivertigo antihistaminic.