What are eicosanoids? (molecule type, examples)
class of lipids include prostaglandins, throboxanes, leukotrienes
What is the COX2 seletive NSAID I should know? Benefits/side effects?
celecoxib. theoretically would decrease GI discomfort. sides: inhibit PG production in kidney: hypertension and edema: increased MIs. give at low dose for short periods.
Misoprostol: uses? class/type?
PGE1 analogue/PGE agonist prevents NSAID induced gastric ulcers. also, therapeutic abortion.
What do NSAIDS treat? What are the two types of NSAIDS? MoA?
treat inflammation ,fever, and pain. traditional NSAIDS block all COX enzymes. Newer enzymes are somewhat selective for COX2. All except aspirin are competitive inhibitors. Inhibit PG and TX synthesis.
Where do the cardiovascular benefits of aspirin come from?
aspirin is an irreversible non-selective COX inhibitor. COX in platelets is especially sensitive, since platelets can't regenerate COX.
What is the most common precursor of eicosanoids? (in humans) Why are eicosanoids hard to study?
arachidonic acid they are hard to study because the reaction to eicosanoids varies widely from tissue to tissue and from species to species.
What are the leukotriene inhibitor classes and uses?
reduce bronchoconstriction of asthma and allergens Classes are 5-lipoxygenase inhibitors to prevent LT synthesis and LT receptor inhibitors
What are the four traditional NSAID I need to know? Any exceptions in usage/MoA>
aspirin (irreversible inhibitor, not competitive), ibuprofen, naproxen (alleve), and acetominophen (does not have anti-inflammatory benefits).
What kinds of effects to eicosanoids usually have?
local effects: many enzymes degrade them, and active eicosanoids usually not found in systemic circulation. and they work in conjunction with other processes: sensitizing or antagonizing agents.
Describe, very basically, eicosanoid biosynthesis.
derived from arachodonic acid, which is usually trapped in the plasma membrane. synthesis depends on the release of arachodonic acid from the plasma membrane, usually related to stimuli that lead to an increase in intracellular calcium. Increased calcium causes the translocation of cytosolic PLA2 to the plasma membrane, where PLA2 can free arachidonic acid. This arachidonic acid is metabolized to various eicosanoids.
What is lipocortin?
a protein that inhibits PLA2 and thus inhibits the synthesis of eicosanoids (no arachodonic acid release from the plasma membrane). Incudeable by glucocordicoids and partially explains their anti-inflammatory action.
What are COX enzymes (function, pharm significance)
enzymes that make prostaglandins and thromboxanes from free arachidonic acid. This is the enzyme that is inhibited by NSAIDs.
What are the 2 forms of COX?
COX1: constitutively expressed. helps with cytoprotetction and gastric endothelium protection. COX2: induced by stimuli and palys a role in inflammation and cancer.
How are leukotrienes made from free arachidonic acid?
lipoxygenases form HPETEs from arachidonic acid. HPETEs rapidly metabolized to active leukotrienes.
Eicosanoid receptors: types? effects?
all are membmrane boud G protein coupled receptors. diversity of responses: LARGE number of receptors and a diverse number of signaling cascades.
What are the effects of eicosanoids on platelets? Which eicosanoids are important, source, and what are their effects?
TXA2. contributes to increased platelet aggregation and blood clotting at injury sites, as well as in pathologies like CVA and MI. PGI2 inhibits platelet aggregation and disaggregates preformed clumps. PGI2 synthesized by endothelial cells to counteract effects of TXA2.
What is a use for PGF agonists?
What are the effects of eicosanoids on vascular tone? Which eiconosoids, source, effects, triggers
only local effects. PGI2 made by COX is released by endothelial cells. relaxes blood vessels. sheer stress triggers the release of PGI2.
What eicosanoids play a role in the lungs? triggers?
leukotrienes. generally released in response to inflammatory agents. cause bronchoconstriction and leukocyte invasion.
What is the role of eicosanoids in the inflammatory response?
In general, prostaglandins and leukotrienes are potent mediators of the immune response and acute inflammatory response. increase local blood flow, increase vascular permeability, and promote leukocyte infiltration.
What is the role of eicosanoids in the kidneys, and what is the significance of this?
long term use of all COX inhibitors limited by effects on the kidney: hypertension, edema, CHF. In part because eicosanoids play a role in renal blood flow and salt excretion.
Role of eicosanoids in the uterus.
nonpregnant: PGFs contract and PGEs relax. Pregnant uterus: muscle contraction.
What are the effects of eicosanoids on the stomac?
PGs inhibit gastric acid secretion
Effects of eicosanoids on the nervous system.
Pain- PGE2 and PGI2 and LTB4 increase sensitivity to nociceptors. and, fever mediated by PGE2 in the hypothalamus.
What are the effects of eicosanoids on the eye?
PGF2 increases outflow of aqueous humor: decr. intraoculuar pressure.