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
