Eicosanoids Flashcards
How is eicosanoids produced and released? and what do they make?
Membrane phospholipids—(phospholipase A2)—>arachidonic acid
—-(lipooxygenase)—>leukotriene
or —(COX)—>prostaglandins or thromboxane A2
What condition does leukotrienes have a major role in?
Asthma (drug looking to stop the action or production of leukotrienes to treat asthma)
Which COX is constitutive and inducible? and what drugs inhibit them?
COX1—>constitutive
COX2—>inducible during inflammation
NISAIDs block both COX1/2
“-coxib” drug blocks ONLY COX2
What is glucocorticoid’s role in eicosanoids production?
It inhibits phospholipase A2 and COX2
How might NISAIDs exacerbate asthma?
Blocking COX activity—->increase leukotriene production—>exacerbate asthma
What is PGs role in PDA/renal vasculature/stomach/uterus?
PDA—>maintain PDA
Renal vasculature—>vessel dilate afferent arteriole
Stomach—>decrease acid production
Uterus—>contraction
What are the roles of LTA4/C4/D4?
Anaphylaxis and bronchoconstriction
What drug inhibit lipooxygenase? and what is it used for?
Zileuton/asthma
What drugs block LT receptor? and what are they used for?
“-lukasts”—>for asthma
Where is COX1/2 expressed?
COX1—>everywhere
COX2—->brain/kidney/site of inflammation
What are the PGE1 analogs?
Misoprostol—>NSAIDs inducer ulcer
Alprostadil—>keep PDA open/male impotence (alternative to the”-fils”)
What is dinoprostone/carboprost/latanoprost used for?
Dinoprostone—>PGE2 analog—>uterus contraction—>induce labor
Carboprost—>PGF2alpha analog—>uterus contraction—>abortion
Latanoprost—>increase drainage—>glaucoma
What is a PGI2 analog and what is it used for? what other drugs can be used for the same condition?
Epoprostenol—>vasodilator/inhibit platelet aggregation–>used for pul HTN
Pul HTN—>bosentan/sildenafil
Why do we use baby aspirin after MI?
Aspirin stop TXA2 production—>inhibit platelet aggregation
What are the effects of NSAIDs? and what is the prototype?
Analgesic/antipyretic/anti inflammatory/antiplatelet
Aspirin
How is aspirin irreversibly inhibit COX?
Covalent bond via acetylation of serine hydroxyl group near active site
How is aspirin dose dependent?
Low dose—>antiplatelet (81mg)
Moderate dose—>analgesia and antipyresis (650mg)
High dose—>anti inflammatory (up to 4000mg)
What is the side effect with low to moderate dose of aspirin and what other drugs have the same effect? what about high dose?
Hyperuricemia—>same with loop and thiazide—>gout
High dose side effect—>uricosuria/respiratory alkalosis
What do you see with aspirin overdose?
Hearing problem—>first sign
Inhibit respiration—>respiratory acidosis—>respiratory failure
Inhibit Krebs cycle—>shut down ATP production—>metabolic acidosis
Hyperthermia and hypokalemia
What is Reye syndrome and when do you see it?
Kids with viral illness taking aspirin—> vomiting/fever/lethargy
What is the drug interaction with aspirin?
Ethanol increase risk of GI bleed with aspirin
How do we manage aspirin overdose?
Right after ingestion—>gastric lavage or activated charcoal
Hours after ingestion—>alkalinize urine/dialysis
What are some other NSAIDs besides aspirin? and do they cause acid base imbalance and hyperuricemia like aspirin?
Ibuprofen/naproxen/indomethacin/ketorolac (pain management)/sulindac
Nah
Which NSAIDs is the strongest and weakest analgesic?
Ketorolac
Aspirin
Which NSAIDs have side effect of bone marrow suppression? and which with Stevens-Jonhson syndrome?
Indomethacin
Sulindac
What are the benefits and adverse effects of Celecoxib?
Benefit—>no effect on COX1—>less GI side effect
Adverse effect—>pro thrombotic—>MI and stroke
All NSAIDs increase risk for MI and stroke, except ?
Aspirin
How is acetaminophen difference from aspirin?
Acetaminophen has only analgesic and antipyretic effect/work via CNS/no peripheral effect
What does acetaminophen overdose cause? and how does it happen?
Hepatotoxicity
Acetaminophen is degraded through glucuronidation (major pathway) and P450 (minor)
Acetaminophen—(P450)—>NAPQI (toxic to the liver)
How does N-acetylcysteine work as an antidote for acetaminophen? and when do you have to give this drug?
It supply SH group to inactivate NAPQI
Within the first 12 hours
P450 inducer or inhibitor would worsen the toxicity of acetaminophen?
Inducer like alcohol
