Histamine Flashcards
Histamine location
Many tissues, mainly in mast cells.
Highest amounts found in lungs, skin, nasal and gastrointestinal mucosa.
Mast Cells
Have high affinity IgE binding sites on their plasma membranes.
Also target parasites
Histamine synthesis and storage
Histamine is formed by decarboxulation of the amino acid histidine.
Histamine is stored in granules.
Release of Histamine
Released with several other chemical mediators.
Histamine can be released by trauma, allergies (Antibodies), anaphylaxis, cold, bacterial toxins, bee sting, venoms, and drugs.
Histamine release from mast cells-Cytolytic release
The plasm membrane is damaged.
Not energy dependent, no calcium is required.
Leakage of cytoplasmic contents
Inducers- phenothiazines and narcotic analgesics
Histamine release from mast cells- noncytolytic release
Requires energy (ATP) and calcium, and occurs by exocytotic release from granules. IgE antibodies binding to antigen-histamine release
Release of Histamine
Certain substances and drugs stimulate histamine release from mast cells without prior sensitization.
Mass cells degranulation protein (from bee venom)
Radiocontrast media (imaging uses)
d-tubocurare, succinylcholine, morphine, codeine, doxorubicin, promate.
Vancomycin causes red man syndrome
Red man syndrome
Caused vancomycin
Involves flushing, pruritis, chest pain, muscle spasm, and hypotension during infusion. Pretreatment with IV antihistamines attenuates the sx of red-man syndrome
Drugs that block the release of histamine from mast cells
Cromolyn and nedocromil- inhalation of a poweder.
Stablizes mast cells preventing noncytolytic degranulation.
Decreases sx of allergic rhinitis. Prophylactiv use to block asthmatic rxns but not useful in managing an acute asthmatic attack.
Poorly absorbed- few adverse effects
Effective only is used BEFORE a challenge
Four types of histamine receptors
H1 receptors- phospholipase C mechanism (respiratory and allergic reactions)
H2 receptors- adenylyl cyclase mechanism parietal cell acid secretion.
H3 receptors- on neurons and inhibit the release of histamine (feedback inhibition)
H4 receptors- proinflammatory activity
Histamines role in allergy and anaphylaxis- Stimulation of secretions
Stimulation of secretions
H1 increases mucus in nasal cavity and bronchi resulting in respiratory sx.
H2 stimulates gastric acid secretions
Histamines role in allergy and anaphylaxis- Constriction of smooth muscle
H1 constricts bronchi and intestines (cramps, diarrhea)
Histamines role in allergy and anaphylaxis- stimulation of sensory nerve endings
itching and pain caused by H1
Histamines role in allergy and anaphylaxis- dilation of smooth muscle in blood vessels
H1 decreased blood pressure (vasodilator)
H1 increases nitric oxide (vasodilator)
Histamines role in allergy and anaphylaxis- stimulating heart rate and contractility
H1&H2
Histamine directly increased HR and contractility by increasing the influx of calcium.
Histamine indirectly increases HR and contractility by baroreceptor-mediated increase in sympathetic tone in response to histamine induced vasodilation
Histamines role in allergy and anaphylaxis- Release of catecholamines
NE and epinephrine from the adrenal gland
Histamines role in allergy and anaphylaxis- Dilation and increased permeability of capillaries
Caused by H1 and H2 and gives red appearance
Histamine causes endothelial cells to contract and expose permeable basement membrane.
Leakage of proteins and fluid into surrounding tissues resulting from the permeable basement membrane.
Gaps b/w the endothelial cells also permit passage of blood cells that are recruited to tissue during mast-cell response “bulk flow”
Challenge with an allergen (bug bit, histamine, allergy test)- if positive skin test- “triple response of lewis”