Histamine/PG Flashcards
- endogenous substances in the body (histamine, serotonin, peptides, prostaglandins, leukotrienes)
- short duration of action and act near site of synthesis/release
- high levels cause undesirable effects
autacoids
- in basophils/mast cells: high levels in potential sites of injury, nose/mouth/feet, blood vessels
- in brain : neurotransmitter function
- ECL cells in stomach: activate acid production
histamine
immunologic histamine release - allergens cross link ______ on the cell surface eliciting granulation
-releases histamine causes type ____ allergic reaction (hay fever, acute urticaria)
IgE
type 1
in CV system, H1 receptor mediated response is vasodilation mediated by increase in _______ release, reflex tachycardia, and increased _______ of post capillary vessels
NO
permeability
effect of H1 on bronchiolar smooth muscle?
bronchoconstriction
effect of H1 on GI smooth muscle?
contraction, high doses produce diarrhea
- rapidly absorbed when taken orally
- distribute to most tissues
- 1st gen last 4-6 hrs, 2nd gen last 12-24 hours
- used for allergic reactions (not bronchial asthma)
- motion sickness, sedative effects
antihistamines
- have local anesthetic action (Na channel blockers)
- diphenhydramine and promethazine more potent than procaine
- also antiparkinsonian, anticholinergic, adrenregic blocking, serotonin blocking
H1 antagonists
- sedation
- antimuscarinic - urinary retention, blurred vision
- CYP450 inhibition (ketoconazole)
H1 antagonist toxicity
- at higher doses get cAMP dependent vasodilation and direct cardiac stimulation
- increased contractility and pacemaker
- antagonists have little effect on cardiac function
H2 mediated response
-stimulate parietal cells to secrete gastric acid
H2 receptor mediated response
- ranitidine, cimetidine, nizatidine, famotidine
- reduce gastric acid secretion - peptic ulcer, GERD
- effective doses don’t impact intestinal secretion, other H2 peripheral effects (HR)
H2 antagonists
-nervous system: presynaptic receptor activation modulates nuerotransmitter release
H3 mediated response
- family of oxygenation products of polyunsaturated LCFAs
- highly potent molecules, very short half life
eicosanoids
- converts arachidonic acid to prostaglandins
- constitutively expressed, widely distributed, has housekeeping functions
COX-1
- converts AA to prostaglandins
- inducible, production of inflammatory molecules, expressed in vascular endothelium (PGI2)
- renal isozyme essential for normal function
COX-2
all eicosanoid receptors are _______
G-protein coupled
TXA2 and PGF in vascular smooth muscle?
vasoconstrictor
PGE2 and PGI2 in vascular smooth muscle?
vasodilation
prostaglandin effects on GI smooth muscle?
longitudinal muscle contraction, relaxation of circular muscle, colicky cramps
PGE2 and PGI2 on airway?
relaxation
TXA2 and PGF on airway?
contraction
TXA2 effect on platelets?
aggregation
PGE1 and PGI2 effects on platelets?
inhibit aggregation
