Autocoids Flashcards
HIstamine
H1-Gq → PLC → IP3/DAG & Ca2+
Present on endothelium, smooth muscle and nerve endings
H2-Gs → Adenylyl cyclase → ↑ cAMP
Gastric mucosa, cardiac muscle cells and some immune cells
H3-Reduces NT release from histaminergic and other neurons
H4-Chemotactic for EOS and mast cells; found on leukocytes in BM and blood
Inflammation and allergies
EFFECTS: -CVS: Vasodilation via H1 & H2 ↑ contractility and HR via H2 ↑ capillary permeability → edema via H1 especially at the post capillary venules → urticaria
-Triple Response: Intradermal injection causes a localized red spot, flare, and wheal
-GIT: H1 mediated contraction
Bronchiolar: H1 mediated bronchoconstriction [esp. in asthmatics]
- Nervous: stimulates nerve endings causing pain and itching [H1]
- Secretory tissue: H2 mediated gastric acid secretion
- Clinical Use: Pulmonary Function Testing → aerosol used to test nonspecific bronchial hyperreactivity
ADVERSE:
Anaphylaxis
Dose related toxicity: flushing, hypotension, tachycardia, HA, wheals, bronchoconstriction, GI upset
DO NOT give to asthmatics or pt’s with peptic ulcer disease/GI bleed
STORAGE AND RELEASE
-Immunologic [Type 1 HS]:
Ag binds IgE on surface of mast cells and basophils → Ca 2+ mediated degranulation → release of histamine, ATP and other mediators
Chemical and Mechanical:
Amines [morphine and tubocurarine displace bound histamine from heparin complex in nrg independent fashion
