Eicosanoids are metabolites of __________ _______ that can be synthesized and released from nearly ___ cells to affect a broad range of biological.
Autocoids are ________ which are biologically active compounds that are _______ synthesized and released. they act _________. they have a short _____-_____ and duration of action.
eicosanoids rapidly locally half-life
biologically active eicosanoids include:
PG, TX, LT
Actions of Eicosanoids
inflammation pain fever GI tract bronchial smooth muscle platelet aggregation uterus cardiovascular others
Indirect inhibitors of eicosanoids:
glucocorticoids fx cox1/2, lipocortin, Hcz
glucocorticoids prototypes
hydrocortisone/cortisol, prednisone, decxamethasone
glucocorticoids act by modifying gene expression. T/F?True False
true
glucocorticoids cellular actions:
upregulate lipocortin down-regulate cox1/2
glucocorticoids clinical uses
anti-inflammatory replacement therapy
glucocorticoids side fx
long term= cushings syndrome
NSAID prototypes
aspirin Sulindac Indomethacin Ketorolac Ibuprofen Naproxem
NSAID mechanism
directly inhibit Cox-1 and Cox-2
which NSAIDS are irreversible
which NSAIDS are reversible
indomethacin ibuprofen acetaminophen
reversibly binding NSAIDS are generally _______ acting.
short
are reversible NSAIDS useful as blocker of clot formation?
NO, only irreversible are
Stephens johnson syndrome can occur with?
acetic acids
what are the NSAID Acetic Acids and Pyrroles?
Indomethacin, Sulindac, Ketorolac
What are the NSAID PROprinoic acids?
IB, Naproxem
are proprinoic acids reversible binders of cox1/2?
YES
Are NSAID propinoic acids useful in blocking clot formation?
NO
Acetaminophen is believed to act by inhibiting _____, CNS specific.
COX 1
Acetaminophen fx:
weak inhibition of prostanoid synthesis blocks prostanoid effects on T and pain in CNS
Is Acetaminophen useful as an anti-inflammatory?
NO
Acetaminophen has the risk of __________, but not ________ or _________ like most NSAIDS.
hepatotoxicity GI fx blockade of plt aggregation
What are the NSAID Selective COX-2 inhibitors?
rofecoxib (vioxx) celecoxib (celebrex) valdecoxib (bextra) Etoricoxib (arcoxia)
what is the cox 2 hypothesis?
cox 2 more specific to inflammatory response
what is the NSAID Selective COX-2 inhibitor mechanism of action?
REVERSIBLE direct binding of Cox-2. also binds cox 1 but is 30x more selective for cox 2
What is the advantage of using NSAID Selective COX-2 inhibitors?
REDUCED neg GI fx
Celebrex is ____x more selective for Cox-2
7.6
VIOXX is ____x more selective for Cox-2
35
BEXTRA is ____x more selective for Cox-2
30
ARCOXIA is ____x more selective for Cox-2
106
Cox-2 selective inhibitors cause 2-3 fold increase in risk for
heart attack
which Cox-2 selective inhibitor is on market now?
CELEBREX
COX-2 is being studied to treat
cancer and alzhiemers
5'-Lipoxygenase inhibitor prototypes
Zileuton (Zyflo)
5'-Lipoxygenase inhibitor prototypes are useful in tx of astham and anaphylaxis. Explain why:
Leukotrienes are the most powerful constrictors of bronchial smooth muscle, and this inhibits the enzyme that makes leukotrienes.
5'-Lipoxygenase inhibitor use:
long-term asthma management
5'-Lipoxygenase inhibitor prototypes side fx
gastric indigestion short-acting-4x daily (compliance)
the future of eicosanoid therapy is to target:
individual receptors
Receptor AGONIST prototypes:
Misoprostol (cytotec) Dinoprstone/PGE2 (prostin E2) Carboprost (Hemabate)
Misoprostol is a ______ ________. it's cellular action is mimic actions of _____.
Clinical uses of Misoprostol (receptor agonist)
used w/ NSAID combo prevents negative GI fx of NSAIDS uterine stimulant
side fx of Misoprostol (receptor agonist)
DINOPROSTONE, CARBOPROST TROMETHAMINE, LATANOPROST mechanism, and cellular action. (receptor agonist)
FP receptor agonist, EP receptor agonist mimics cellular action is PGE2, PGF2a
DINOPROSTONE, CARBOPROST TROMETHAMINE, LATANOPROST clinical uses: (receptor agonist)
labor induction refractory postpartum hemorrhage induced abortion anti-glaucomal EYE drop (xalatan)
DINOPROSTONE, CARBOPROST TROMETHAMINE, LATANOPROST side fx: (receptor agaonist)
diarrhea/ vomitting uterine hypertonus
(receptor agonist) EPOPROSTEROL/prostacyclin mechanism of action and cellular action:
IP2 receptor agonist mimics action of PGI2
(receptor agonist) EPOPROSTEROL/prostacyclin uses:
serious pulmonary HTN
(receptor agonist) EPOPROSTEROL/prostacyclin side fx:
diarrhea, ^ HR, headache, nausea, flushing
Leukotriene receptor ANTAGONISTS prototypes:
Monteleukast (singulair) Zafirlukast (Accolate)
Leukotriene receptor ANTAGONISTS mech of action and cell action
CLT1-R receptor antagonist blocks actions of LTD4
Leukotriene receptor ANTAGONISTS clinical uses and side fx:
chronic management of asthma mild-GI, headahce, heartburn, allergic rx
