Histamine role
Plays an important role in:
-allergic reaction
-gastric acid secretion
Histamine function
-in vascular system: dilates small vessels and increases vascular permeability
-in bronchi: produces constriction of smooth muscle
-in stomach: stimulates secretion of acid
-in CNS: neurotransmitter
Histamine distribution
-highest in skin, GI, lung
-amount is proportional to mast cell content (except in CNS)
-stored in granules
-present in all tissue; lowest in plasma
,Synthesis and storage of histamine
-in periphery, it is synthesized and stored in 3 types of cells: mast cells and basophils
-mast cells: present in the skin, and other soft tissues
-basophils: present in blood
-In CNS, histamine is produced by neurons with cell bodies in the post.
hypothalamus, and with axonal projections to the frontal and temporal cortices and
other brain regions
Histamine release
-produced by an allergic and nonallergic mechanism
Allergic mechanism of histamine release
-requires a prior exposure; can not occur during initial allergen exposure
-causes antibodies to be made on the outside of mast cells and basophils, when re-
exposed to the allergen, it becomes bound to the antibodies
Nonallergic release of histamine
Several agents (certain drugs, radiocontrast media, plasma expanders) can act
directly on mast cells to trigger histamine release.
-With these agents, no prior sensitization is needed.
,-Cell injury can also cause direct release.
Effects of H1 stimulation
-vasodilation: artioles and venules; prominent in skin and face; total peripheral
resistance declines and BP drops
-increase capillary permeability: escape of fluid and protein into interstitial space
produces edema; BP may fall
-bronchoconstriction: antihistamines are of no use for treating an asthma attack
-CNS effects: role in cognition, memory and sleep/wake cycle
-other effects: activation on sensory nerves produces itching and pain; also
promotes secretion of mucus
Effects of H2 stimulation
-secretion of gastric acid
Mild allergy symptoms
-rhinitis
-itching
-localized edema
-caused by histamine acting at H1 receptors
-these reactions are generally responsive to antihistamines
, Severe allergic reactions (anaphylaxis)
-anaphylactic shock: bronchoconstriction, hypotension, edema of the glottis
-histamine has a minor role; antihistamines are of little help
-epi is the drug of choice
Types of antihistamines
-H1 antagonist: mild allergy disorders
-H2 antagonist: treatment of gastric and duodenal ulcers; not allergies
Subgroups of H1 antagonists
First generation: highly sedating
Second generation
MOA for antihistamines (H1)
-bind selectively to H1 histamine receptors; block histamine at the site
-do not block histamine release from mast cells or basophils
-can bind to histaminic receptors, and a few will bind to non-histaminic receptors
(block mucarnic receptors)