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
major prostaglandin products of renal cortex?
PGE2 and PGI2
prostaglandin effects on kidney?
vasodilation
COX-1 in kidney promote salt _______ in the collecting ducts
-COX-2: increase medullary blood flow and _______ tubular sodium reabsorption
excretion
inhibit
______ enhances penile erection by relaxing smooth muscles in corpus cavernosum
PGE1
PGF and low concentration PGE2 in uterus?
contraction
high PGE2 in uterus?
relaxation
-oral PGE1 that induces first and second trimester abortion
misoprostol
PGE2 given vaginally for abortion, stimulates contraction of uterus, controlled release for induction of labor
dinoprostone
PGF2-alpha control of post partum hemorrhage
carboprost
- increase edema and vascular permeability
- modulation of lymphocyte function
- PGD2 released from mast cells, recruit eosinophils
PGE2 and PGI2
PGE1, relaxes smooth muscle
-used for ductus arteriosus, neonates awaiting cardiac surgery, erectile dysfunction
alprostadil
- treatment of NSAID induced ulcer
- combined with mifepristone to terminate early pregnancy
misoprostol
used to induce labor
PGE2, PGF2a
treatment of open angle glaucoma, PGF2a
latanoprost
inhibitor of platelets and vasodilator, treat pulmonary hypotension
prostacyclin (PGI2)
- treat pulm HTN
- requires constant IV infusion, 3-5 min half life
epoprostenol
inhaled treatment for pulm HTN
iloprost
SQ injection or IV for pulm HTN
treprostinil
- potent chemoattractants
- proinflammatory mediators of asthma and IBD
- cardiac depression
leukotrienes
5-LOX enzyme inhibitor
zileuton
leukotriene receptor antagonist
montelukast