Inflammation Terlecky1 Flashcards
What enzyme is responsible for histamine formation?
histidine decarboxylase
What cofactor does the enzyme histidine decarboxylase require?
pyridoxal phosphate (activated vitamin B6)
Histamine promotes WHAT?
*Vasodilation, smooth muscle contraction, increased vascular permeability, gastric secretion.
also, platelet aggregation, complement activation, mucous secretion, chemotactic attractant for inflame cells
How does histamine exist in the blood?
complexed with heparin and proteoglycans in metachromatic secretory granules in basophils. slow turn over.
What enzymes degrade histamine?
histamine n-methyltransferase (withMOA) converts to MIAA
or directly to imidazole acetic acid by diamine oxidase (histaminase)
The release of histamine is energy dependent… what mediates this?
ATP and Ca+2!
What does cromolyn sodium do?
blocks the influx of divalent ions (and so, histamine release). prophylactic tx of asthma
What do compound 48/80 and polymixin B do?
Ionophores! soooo influx of ca andrelease of histamine
Where do we find H1 receptors?
Smooth muscle of gut and bronchi, endothelium, brain.
How do H1 receptors elicit their effects?
second messengers IP3, DAG, Ca2+, NFB
where do we find h2 receptors?
Gastric mucosa (parietal cells), cardiac muscle cells, mast cells, brain.
H2 post receptor mechanism?
cAMP production
What are the cardiovascular effects of histamine?
Increased HR (via H2) decreased blood pressure (due to vasodilator effects H1)
How does histamine cause itching?
H1 receptor mediated stimulation of sensory nerve endings
What is an example of a physiological antagonist to histamine?
epinephrine! important for cases of systemic anaphylaxis
How do inverse agonists work?
Block histamine receptors!
What is the difference between first generation antihistamines and second gen anti histamines?
Sedative effects!!! 2nd gen do not have access to CNS
What are examples of first generation antihistamines(h1 blocker)?
diphenhydramine and chlorpheniramine
(dimenhydrinate, hydroxyzine, meclizine, promethazine)
used to reduce symptoms of allergy, allergic rhinitis, uticaria