Lec 1 - Histamine Flashcards
inflammatory histamine is synthesized in mast cells and ____
basophils
histamine is complexed in storage granules with sulfated polysaccharides, such as _____, chondroitin sulfate, and _____
heparin sulfate, proteases
non-mast cell histamine is found in some areas of the _____; it is also seen in the __ of the stomach
brain;
fundus
histamine is released when antigens bind Ig___ on mast cells. the Ig molecule is bound to ____ receptors.
E;
FcER1
histamine is also released with ___ or mechanical stress, cytotoxic agents such as ____. and various drugs such as high dose _____
thermal, venoms;
morphine
clustering of FcER1 receptors causes an influx of ____ into the cell, triggering release of histamine. what drug prevents histamine release?
Calcium;
cromylyn sodium
The H1 receptor is G ___ Coupled. binding causes an increase in what 2 signalling molecules?
q;
IP3 and DAG
H1: an increase in IP3/DAG causes an increase in _____. this increase causes smooth muscle _____.
calcium;
contraction
binding of H1 receptors also causes an increase in ____. This causes vasodilation due to effect on ____ Cells
NO;
endothelial
histamine constricts veins *
H1 receptors are mainly found in what 2 organ systems?
cardiovascular;
respiratory
____ receptors are responsible for stimulation of sensory nerves, causing sneezing and ____
H1; itching
binding of _____ causes endothelial cells to contract, causing a ____ in vascular permeability and ___
H1;
increase;
edema
binding of ____ in the lungs causes bronchoconstriction
H1 receptors
____ receptors are linked to relaxation of vascular smooth muscle and gastric secretion
H2
H2 receptors are G ___ coupled. binding causes an increase in what signalling molecule?
s, cAMP
H3 receptors are located mainly in the ____. They are linked to inhibition of _____ release via a decrease in ____ influx
CNS;
NT, Ca
H4 receptors are located on ______. they are linked to histamine-induced _____
mast cells, basophils, eiosinophils;
chemotaxis
H2 receptors moderate an increase in ____ and _____ in the heart. This is due to increase in cAMP whic binds ____ and thus causes an increase in ____ entry
rate, force of contraction;
PKA; Calcium
which H receptor is responsible for acid release in the stomach
H2
on the skin, histamine causes ___ and ____ in response to insect bites
flare, edema
H1 antagonists are predominantly ____ _____
inverse agonists
3 H1 antagonists ending in “mine”;
2 ending in “zine”
bromphenira-. diphenhydra-, pyrila-;
hydroxy-, prometha- (also meclizine)
cyproheptadine also mentioned in notes
1st generation antagonists (especially ____ and _____) have what side effect?
diphenhydramine, promethazine;
sedation
_____ has potent anti-motion sickness and anti-emetic effects
promethazine
first gen H1 blockers are more ____ soluble than 2nd gen. they thus cross the BBB _____ easily
lipid;
more
H1 antagonists have anti ____, _____, and ____ effects as well
muscarinic, cholinergic, sertonergic
phenothiazine and promethazine can also cause ____ side effects
extrapyramidal (dystonia, akathisia)
2nd gen H1 antagonists include these 4:
loratadine, desloratadine, fexofenadine, cetirizine
in addition to decreased lipid solubility, why don’t 2nd gen H1 blockers enter the CNS?
efflux via P-glycoprotein transporter
_____ is a physiologic antagonists to histamine
epinephrine
