Histamines

 Chemical messenger that mediates a
wide range of cellular responses,
including allergic and inflammatory
reactions, gastric acid secretion, and
neurotransmission in parts of the brain.
 Plays an important role in gastric acid
secretion.

 Occurs in practically all tissues.
 High amounts found in lung, skin, and
the GIT.
 Found at high concentration in mast cells
or basophils.
 Occurs as a component of venoms and in
secretions from insect stings.

 Histamine is an amine formed by the
decarboxylation of the amino acid
histidine by histidine decarboxylase

A. Immunologic Release
 Mast cell sensitized by IgE antibodies attached to their
surface membranes, degranulate explosively when
exposed to the appropriate antigen.
 This type of release requires energy.
 Degranulation leads to the simultaneous release of
histamine, adenosine triphosphate (ATP), and other
mediators that are stored together in the granules.
 Histamine released by this mechanism is a mediator in
immediate (type I) allergic reactions, such as hay fever
and acute urticaria.

 Chemical and mechanical mast cell injury
causes degranulation and histamine
release.
 Drugs such as morphine and
tubocurarine, can displace histamine
from its bound form within cells.
 This type of release does not require
energy and is not associated with mast
cell injury or degranulation.
 Loss of granules from the mast cell also
releases histamine.

 contraction of smooth muscle.
 stimulation of secretions.
 dilation and increased permeability of
the capillaries.
 stimulation of sensory nerve endings.

 Symptoms associated with allergy and
anaphylactic shock result from the
release of certain mediators from their
storage sites.
 Difference between these two situations
results from differences in the sites from
which mediators are released and in their
rates of release.

 Itching, Urticaria
 Flushing
 Hypotension
 Tachycardia
 Bronchospasm
 Angioedema
 Wakefullness
 Increased acidity (Gastric acid secretion)

These compounds do not influence the formation or
release of histamine; rather, they block the receptor-
mediated response of a target tissue.
The H1-receptor blockers can be divided into:
1: first-generation drugs
2: second-generation drugs

 widely used
 effective
 inexpensive
 penetrate the CNS
 cause sedation
 Produces side effect

Allergic rhinitis and common cold
Allergic dermatitis, itching, Urticaria
Wasp string/bite: Pain and itching decreases
Allergic conjunctivitis
Motion sickness: Dimenhydrinate, promethazine
Morning sickness: Promethazine
Vertigo: cinnarizine
Appetite stimulant: Cypropatidine

Absorption:
Oral, parenteral routes
Distribution:
Throughout body.. Enter Brain
Newer compounds penetrate poorly
Metabolism:
Metabolized by Liver
Excretion:
Excreted in Urine

 Specific for H1 receptors.
 Do not penetrate the blood-brain
barrier.
 Show less CNS toxicity than the
first-generation drugs.

 Block the actions of histamine at all H2 receptors.
 Chief clinical use is to inhibit gastric acid secretion.
 Effective against nocturnal acid secretion.
 Competitively blocking the binding of histamine to H2
receptors, these agents reduce the intracellular
concentrations of cAMP and, thereby, secretion of
gastric acid.
 Drugs
Cimetidine
Ranitidine
Famotidine
Nizatidine

 Act selectively on H2 receptors in the stomach,
blood vessels, and other sites.
 No effect on H1 receptors.
 Competitive antagonists of histamine.
 Fully reversible.
 Completely inhibit gastric acid secretion
induced by histamine or gastrin.

 Peptic ulcers
 Acute stress ulcers
 Gastroesophageal reflux disease

Cimetidine:
Given orally, distribute widely throughout the body.
Excreted mainly in the urine.
Ranitidine:
Five- to ten-fold more potent.
Longer acting.
Minimal side effects.
Famotidine:
Similar to ranitidine.
20 to 50 times more potent than cimetidine.
Nizatidine:
Similar to ranitidine in its pharmacologic action and potency.
Eliminated by the kidney.

 Reduced gastric acid production
 Headache
 Dizziness
 Diarrhea
 Muscular pain

DRUGS BRANDS RELATIVE
POTENCY
DAILY DOSE
Cimetidine Tagamet 1X 400 mg Bid
Ranitidine Zantac 4-10X 150 mg Bid
Famotidine Pepcid 20-50X 20 mg Bid
Nizatidine Axid 4-10X 150 mg Bid

H3-selective ligands may be of value in sleep
disorders, obesity, and cognitive and
psychiatric disorders.
Tiprolisant, an inverse H3-receptor agonist, has
been shown to reduce sleep cycles in mutant
mice and in humans with narcolepsy.
Not clinically important.
Other drugs
Thioperamide
Clobenpropit

 Chronic inflammatory conditions such as
asthma.
 No selective H4 ligand is available for use in
humans.
 Useful in pruritus.
 Not yet clinically important
 Drug: Thioperamide

 The anti-inflammatory activity of 2nd
generation antihistamines about which little
is known, will continue to be researched and
possibly lead to an effective alternative to
corticosteroids in the treatments od allergic
conditions.
 The action of H4 receptor will also continue to
be researched and will possibly lead to
effective treatment of autoimmune diseases.
 Creating antihistamines with higher
selectivity and less adverse side effects will
continue to be a goal.

 Basic and Clinical Pharmacology 11th
Edition Katzung.
 Lippincott's Illustrated Reviews
Pharmacology 4th Edition.
 Google.com
 Google images.

Histamines

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