Mediates smooth muscle contraction (bronchi, gut, large blood vessels); relaxes small arterioles and reduces peripheral resistance and blood pressure.
G protein linked to the H1 receptor?
Mechanism of action of the H1 receptor?
Acts through Gq protiein and activated phospholipase C enzyme= initiation of cellular events. Vasodilation achieved through endothelial H1 receptors which activate N2O synthase and release of endothelium derived N2O.
H2 receptor function?
Stimulates gastric acid secretion
H2 receptor is linked to which G protein?
Mechanism of action of H2 receptor?
Acts through Gs protein coupled with adenylyl cyclase enzyme activation, increases synthesis of cAMP which is linked to activation of intracellular protein kinase A = activates parietal cell proton pump to stimulate gastric acid secretion.
H3 receptor function?
Modulates neurotransmitter release in the CNS (inhibition of adenylyl cyclcase through Gi); localized on nerve terminals in the CNS.
H4 receptor effect:
Involved in inflammation involving eosinophils and other inflammatory cell types.
Autacoids, what are they and what is their stimulus?
Biologic factors that are synthesized in the body and play a role in physiologic or pathophysiologic responses to injury.
Autacoid- action, duration of action & metabolism
Generally act locally (termed local hormones) Have brief duration and undergo rapid degradation.
Two places histamines can be found?
Mast cell pool & non-mast cell pool
Mast cell pools are found
Everywhere in the body (mainly in CT)
Describe the synthesis of Histamine in the Mast Cell Pool:
Histamine is synthesized slowly and stored in secretory granules
Where can we find the Histamine that participates in inflammatory responses, allergies, shock, adverse drug reactions, hypersensitivity reactions, and cellular injury?
Mast Cell Pool
Describe synthesis and release of Histamine in the Non-Mast Cell Pool:
synthesized and released continuously
Describe turn-over rate of Histamine in the Non-Mast Cell Pool:
Turn over rate is rapid.
Describe absorption of histamine through oral route
Describe absorption of histamine via parenteral route
histamine is completely absorbed
Describe metabolism of histamine
Undergoes rapid metabolism and distribution in various tissues: Involved methylation and oxidation. Histamine is acted upon by enzyme histamine N-methyltransferase to form methyl histamine - which is acted on by MAO. Minor pathway involves breakdown of histamine by histaminase to form imidazoleacetic acid.
Describe the various roles of histamine
: (1) Anaphylaxis, Allergy, (2) Gastric Secretion, (3) NT: emetic response (4) Relaxation of small arterioles & increased vascular permeability (5) Mediator of several pathological states (ruminal bloat)
How is the allergy reaction influencing the body?
Induces vasodilation, itching, smooth muscle contraction, and edema. (Humans = flushing of skin, burning, itching.)
In what way does Histamine influence the neurons?
stimulates itchy sensation & pain. Release in CNS is involved in the emetic response to vestibular stimulation.
Histamine is involved in which pathological states?
ruminant bloating, GI disorders; laminitis, azoturia, retained placenta, pneumonia, gut edema of pigs.
Pharmacological effects of Histamine:
Given IV produces smooth muscle contraction, hypotension, increased gastric secretion, dermal reactions.
Histamine effects in the CVS of rabbits:
In rabbits it acts as a pressor agent - constriction of arteries is prominent.
Inhibitors of Histamine release (from mast cells) ?
Chromolyn Sodium: Inhibits release of histamine and autocoids from mast cells. Mechanism: Facilitates opening of Cl ion channel - hyperpolarizes the cell. (Does not inhibit H1 and H2 receptors.)
Chromolyn sodium pharmacological uses?
Prophylactic purposes: Used in pulomnary and nasal allergic reactions. (Mainly used in horses where it is administered by nebulization and delivered with a face mask. A 4% eye drop for allergic conjunctivitis. )
Treatment of allergic patients, allergic drug reactions, anaphylaxis. Treatment of pruritis assoc. with atopic dermatitis. Synergistic effect of antihistamine with corticosteroids / fatty acids. Treatment of respiratory disorders (Cetrizine.)
Moist eczema, actute eczematous otitis, insect stings, laminitis, paroxysmal myoglobinuria or azoturia, periodic ophthalmia can be treated w?
Therapeutic uses of anti-histamines in bovines?
Bloat, acetonemia, acute septic and gangernous mastitis, septic metritis, and retained placenta, pregnancy toxemia.