NSAID 1 Flashcards
what are the 2 forms ox cyclo-oxygenase enzymes
COX1 and COX2
what is COX1
the constitutive form
what is COX2
the inducible form
which COX is the constitutive form
COX1
which COX is the inducible form
COX2
what are eicosanoids derived from
arachidonic acid
what are eicosanoids
large group of lipid compounds with diverse biological properties
what is the structure of arachidonic acid
C20 fatty acid with 4 unsaturated C-C bonds
where is arachidonic acid found
in most cell membranes
what happens during inflammation (what is released and how)
arachidonic acid liberation by phospholipase A2 and phospholipase C
what does phospholipase A2 do to arachidonic acid
snips it off from the phospholipid
what does phospholipase C do to arachidonic acid
snips it off from the phospholipid along with an IP/IP2/IP3 pathway (Gq)
what is the main pathway to get arachidonic acid
through phospholipid A2
what pathway to get arachidonic acid do muscarinic agonists use
the phospholipase C and IP3 pathway
what are the 4 oxidation pathways that stem from arachidonic acid
COX
lipoxygenase
P450 enzymes
isoprostane
what are the products made from the COX pathway
prostaglandins
thromboxane
prostacyclin
what are the products made from the lipooxygenase pathway
leukotrienes
what are prostaglandins involved in (3 things)
inflammation, prevention of peptic ulcers, uterine contraction
are prostaglandins vasoconstrictors or vasodilators
either or
what kind of blood flow are prostaglandins important for
regulation of renal blood flow
what do prostaglandins to do CNS temperature
cause fever
which COX product produces fever
prostaglandins
how do prostaglandins do its effects
via G protein coupled receptors
whats the starting point in the COX pathway
arachidonic acid
whats the starting point in the lipooxygenase pathway
arachidonic acid
do prostaglandins have a white or black cowboy hat
both
does prostacyclin have a white or black cowboy hat
white
does thromboxane have a white or black cowboy hat
black
what does prostacyclin do (3)
vasodilator
inhibits platelet aggregation
relaxes bronchiole smooth muscle
what is the short-form of writing prostacyclin
PGI2
where is prostacyclin synthesized
in the endothelium
what does thromboxane do (3)
vasoconstriction
platelet aggregation
constrict bronchiole smooth muscle
what is the short-form of writing thromboxane
TXA2
which COX product inhibits platelet aggregation
prostacyclin
which COX product causes platelet aggregation
thromboxane
which 2 COX products seem to have opposite effects
prostacyclin and thromboxane
which COX product always causes vasodilation
prostacyclin
which COX product always causes vasoconstriction
thromboxane
which COX product always causes relaxation of bronchiole smooth muscle
prostacyclin
which COX product always causes constriction of bronchiole smooth muscle
thromboxane
what is the main product in the lipoxygenase pathway
leukotrienes
where are leukotrienes produced
in inflammatory cells (basophils, mast cells, eosinophils, macrophages)
what is the leukotriene pathway of interest (2 disease states)
asthma and anaphylactic shock
what are the 2 substances of anaphylactic shock and what are they called
LTC4 and LTD4, the “slow reacting substance” of anaphylactic shock
what is the mechanism of action of montelukast
leukotriene antagonist for asthma
what concentrations does the platelet activating factor have effect
very low, <10^-10 M
what is platelet activating factor involved in (1 word)
inflammation (various aspects)
what does platelet activating factor do to lungs
causes constriction of bronchiole smooth muscle
where is platelet activating factor from and how
released from activated inflammatory cells by phospholipase A2
what is the mechanism of action of glucocorticoids (2 things)
inhibit phospholipase A2 by upregulating expression of lipocortin
how are glucocorticoids connected to platelet activating factor
lots of their anti-inflammatory effects may be mediated via inhibition of synthesis of platelet activating factor
how is platelet activating factor involved in asthma
constricts bronchiole smooth muscle
why is platelet activating factor an example of “lipid remodeling”
because in the structure of platelet activating factor, arachidonic acid is replaced by an acetyl group
what are the 4 steps in platelet activating factor synthesis
phosphatidyl choline –> phospholipase A2 –> arachidonic acid –> PAF
what are the cardinal signs of the inflammatory response
- redness (rubor)
- swelling (tumor)
- heat (calor)
- pain (dolor)
- loss of function
what is the inflammatory response (broad, why does it happen)
powerful response to protect from invading pathogens
what are the 3 phases of the inflammatory response
- acute inflammation
- immune response
- chronic inflammation
what is released in acute inflammation (1 word for the general class)
autocoids
what are 5 things being released in acute inflammation
(all autocoids) histamine serotonin bradykinin prostaglandins leukotrienes
what are 4 things that happen in acute inflammation
- vasodilation
- vascular permeability
- chemotaxis
- pain
what is chemotaxis
white blood cells leaving vessel to site of injury
what is the innate immune response
activation of immunologically competent cells
what does the innate immune response help activate
the adaptive immune response (more specific, antibodies)
why can the innate immune response be beneficial
if invading organisms can be phagocytosed or neutralized
how can the innate immune response become harmful
if it leads to chronic inflammation
what does acute inflammation lead to
innate immune response
what are the 2 main mediators of chronic inflammation
interleukins and tumor necrosis factor alpha
what can interleukins and tumor necrosis factor alpha initiate
chronic conditions such as rheumatoid arthritis
what happens to cells with chronic inflammation
cell damage
what do leukocytes do in chronic inflammation
release lysosomal enzymes
what do lysosomal enzymes do
cause the release of arachidonic acid
what causes the release of lysosomal enzymes in chronic inflammation
leukotrienes
what facilitates the release of lysosomal enzymes in chronic inflammation
mediators like bradykinin that stimulate phospholipase A2
what does bradykinin stimulate the release of in chronic inflammation
phospholipase A2
what are 3 cells that are normally present in tissue that cause the inflammatory response
vascular endothelial cells mast cells (histamine) tissue macrophages
what are 2 cells that gain access from blood that cause the inflammatory response
platelets (thrombocytes)
leucocytes (WBC)
where do corticosteroids affect the inflammatory response compared to NSAIDS +where do they effect
much higher (block phospholipids–> arachidonic acid)
which COX is the constitutive prostaglandin synthesis
COX1
which COX is the inducible prostaglandin synthesis
COX2
which COX does mucous gut secretion
COX1
which COX does platelet aggregation
COX1
what does COX1 do to platelets
aggregation
which COX does inflammation
COX2
which COX does pain
COX2
which COX has a white hat
COX1
which COX has a black hat
COX2
