Pharm Chapter 42- Eicosanoids Flashcards
What are contraindications for aspirin
Aspirin hypersensitivity, aspirin-triggered asthma, children and teenagers with chicken pox or flu-like symptoms, due to risk of Reye’s syndrome
What affect does aspirin have with acetazolamine
Increases its concentration, which leads to CNS toxicity
What drug may inhibit the antiplatelet effect of aspirin
Ibuprofen
Compare naproxen to aspirin
Naproxen has a longer half life, is 20X more potent, and causes fewer Gi adverse effects than aspirin
How long can ketorolac be used
3-5 days max post-surgery
What COX-1/COX-2 inhibitor has the greatest selectivity for COX-2
Nabumetone
What is the leading cause of hepatic failure
Acetaminophen overdose
What are the common adverse effects of acetaminophen
Hepatotoxicity, nephrotoxicity (rare), rash, hypothermia
What is the only FDA approved COX-2 inhibitor
Celecoxib
What effect does celecoxib have on ACE inhibitors
Decreases ACE inhibitor efficacy
What is the clinical application of alprostadil
Maintenance of patent ductus arteriosus, ED
What are the contraindications for alprostadil
Sickle cell anemia or trait leukemia, myeloma, neonatal respiratory distress syndrome, anatomic deformation (of penis, penile implant, Peyronie’s disease)
What is the major contraindication for misoprostol
Pregnancy
What is carboprost used for
Abortion in second trimester, postpartum hemorrhage
What are common adverse effects of carboprost
Dystopia, pulmonary edema, GI disturbance with prevalent diarrhea, headache, paresthesia, fever, breast tenderness
What are contraindications for carboprost
Acute pelvic inflammatory disease. Cardiac, pulmonary, renal or hepatic disease
What is the use of letanoprost, bimatoprost, and Travis roar
Ocular hypertension, open-angle glaucoma
What are common side effects of latanoprost, bimatoprost, and travoprost
Macular retinal edema, blurred vision, hyperpigmentation of eyelid, iris pigmentation
What is the major use of epoprostenol
Pulmonary hypertension
What are the contraindications for epoprostenol
Heart failure with severe left ventricular dysfunction. Chronic use in patients developing pulmonary edema
What is the major clinical application of zileuton
Asthma
What are common side effects of zileuton
Increased liver enzymes, urticaria, abdominal discomfort, dizziness, insomnia
What are contraindications for use of zileuton
Active liver disease, elevated liver enzymes
What are the clinical applications for montelukast and zafirlukast
Chronic asthma, perennial allergic rhinitis (montelukast), and seasonal allergic rhinitis (montelukast)
What are substances that are rapidly synthesized in response to specific stimuli, act quickly in the immediate environment, and remain active for only a short time before degradation
Autacoids
What is the common precursor to the majority of eicosanoids
Arachidonic acid
What is the precursor for arachidonic acid
Linoleic acid
What enzyme facilitates the rate limiting step of eicosanoid formation
Phospholipase A2
What does the Cyclooxygenase pathway lead to the formation of
Prostaglandins, prostacylin, thromboxane
What does the lipoxygenase pathway lead to the formation of
Leukotrienes and lipoxins
What is the tissue location for COX1 and COX2
COX1 is ubiquitous expression; COX1 is in inflamed and activated tissues
What tissues expression PGD2
Mast cells, neurons
What tissues expression PGE2
Many tissues, including macrophages and mast cells
What tissues express PGF2alpha
Vascular smooth muscle, uterine smooth muscle
What are the functions of PGD2
Bronchoconstriction (asthma), sleep control functions, Alzheimer’s
What are the functions of PGE2
Potentiation of responses to painful stimuli, vasodilation, bronchoconstriction, cytoprotective, inflammatory cell activation, fever, mucous production, possibly erectile function
What are the functions of PGF2alpha
Vascular tone, reproductive physiology, bronchoconstriction
What series of prostaglandins is the most biologically prevalent
PG2
What is the chief eicosanoid product of platelets
TXA2
What is the primary eicosanoid product of the vascular endothelium
PGI2
What is the physiological antagonist to TXA2
PGI2
What are the immediate products of lipoxygenase reactions
HPETEs
What is the direct precursor to LTA4
5-HPETE
What is the precursor to all bioactive leukotrienes
LTA4
What helps 5-LOX translocate to the nuclear membrane
FLAP
Where is LTA4 converted to LTB4
In neutrophils and erythrocytes
Where does LTA4 conversion to LTC4 occur
Mast cells, basophils, eosinophils, and macrophages
What lipoxygenase is most present in the brain
12-LOX
What are the 2 GPCRs that LTB4 acts via
BLT1 and BLT2
What do LTC4 and LTD4 cause
Vasoconstriction, bronchospasm, and increased vascular permeability
What are the actions of resolvin E1
Regulates neutrophil infiltration, DC. Function and IL-21 production. Promotes resolution, reduces colitis, and protects from osteoclasts-mediated bone destruction
What is the function of resolvin E2
Regulates neutrophil infiltration
What are the functions of protectin D1
Regulates neutrophil and T cell infiltration, regulates TNF and interferon production, promotes resolution, reduces peritonitis and airway inflammation, protects brain from ischemia/reperfusion injury may mitigates kidney ischemia injury
What is the function of maresin 1
Regulates neutrophil infiltration and promotes resolution
What eicosanoids are involved with pain and hyperalgesia
PGE2, PGI2, LTB4
What eicosanoids are involved with local heat and systemic fever
PGE2, PGI2, and LXA4
What eicosanoids areinvolved in increased vascular permeability
LTC4, LTD4, LTE4
What eicosanoids are involved in chemotaxis leukocyte adhesion
LTB4, HETE, LXA4, LXB4
What does PGE2 inhibit the function of (what cells)
B and T lymphocytes and NK cells
What eicosanoids attract eosinophils to asthmatic pathways
LTD4 and LTE4
What do human colorectal adenomas and carcinomas express an abundant amount of
COX2
What does inhibition of phospholipase A2 prevent
The release of arachidonic acid from cellular phospholipids (rate limiting step)
Describe reye’’s syndrome
Condition characterized. By hepatic encephalopathy and liver steatosis in young children
What is ridogrel a receptor antagonist to
TXA2
What do dazoxiben and pirmagrel inhibit
Thromboxane synthase
What synthesis does adenosine inhibit
LTB4
