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PGs

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zijimubo1's version from 2016-12-16 13:53

Section 1

Question Answer
alprostadil (2)1) maintains patency of ductus arteriosus in cases of CHD. IV administered; PGE1
2) ED for patients on nitrates
epoprostenolPrimary pulmonary hypertension; continuously IV infusion
latanoprostEye topical; open-angle glaucoma - increases uveoscleral outflow of aqueous humor. Increases melanization of lashes and irises. PGF2a analog
treprostinilPrimary pulmonary hypertension; longer half life than EPOPROSTENOL; given subcutaneously
misoprostol (2)1) Synthetic PGE analog; tablets; minimize risk of GI bleeding and ulceration in high risk patients taking NSAIDS

2) expel blastocyst; abortion
carboprostPGF2a, im injection; produce uterine contractions to induce abortion; less common - arrythmias
dinoporstone (3)PGE2, vaginal suppository;
1) produce uterine contractions to induce abortion
2) control postpartum hemorrhage
3) prepare cervix for dilation (cervical rippening)
zafirlukast2qd, slow 3 days effective; asthma and airway inflammation
montelukastasthma; children > 1, adults
zileutonAsthma - 4qd, rapid 2 hours. Selective for 5-lipoxygenase. Ulcerative colitis, RA
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Section 2

Question Answer
What are the eicosanoids (3)?prostaglandins, leukotrienes, thromboxanes
How are eicosanoids made?By PLA2, derivatives of Arachidonic acid; oxygenated products of polyunsaturated long fatty acids.
What is the rate limiting step in PG and LT synthesis?Phospholipase A2
Arachidonic acid metabolism products are stored or synthesized by demand?synthesized by demand
AA 5-lipoxygenase pathway gives rise to:leukotrienes
AA cyclooxygenase pathway makes:prostaglandins and thromboxane
Cycloxygenase catalyzes first two steps in conversion of AA into PGs and TXA2. What inhibits cycloxygenase?NSAIDS
COX1 Cell type expression?Expressed constitutively in most cells in body.
COX2 Cell type expression?Induced in momocytes, fibroblast, etc. during INFLAMMATION. Shunts AA down cycloxygenase pathway when induced.
5-lipoxygenase Cell type expression?WBCs.
List steps of 5-lipoxygenase pathway.AA >> HPETE >> HETE + LTs
What inhibits PLA2?glucocorticoids
memorize

Section 3

Question Answer
Name 3 important leukotrienesLTB4, LTC4, LTD4
Name the SRS-A leukotrienes. Slow Reacting Substance of Anaphylaxis. LTC4 , LTD4
What is the significance of SRS-A LTs?They are potent BRONCHOCONSTRICTERS that mediate asthma and anaphylaxis
What is significant of LTB4?It is a potent NEUTROPHIL ATTRACTOR
Name 4 important products of cycloxygenase pathwayPGE2, PGF2a, PGI2, TXA2
MOA of Cycloxygenase productsProstaglandins are GPCR.
PGs 2nd messengers and their actions (2)1) IP3/DAG/Ca2+ - smooth muscle contraction; aggregation of platelets. 2) Gs/Adenylyl Cyclase/Cyclic AMP production - mediates muscle relaxation; inhibits platelet aggregation.
Explain the role of PGs as hormonesPGs are LOCAL hormones that act at or near site of synthesis. PGs and LTs act as paracrine and autocrine hormones.
memorize

Section 4

Question Answer
COX1 importance (2)1) Protects stomach by releasing mucus. 2) TXA2 synthesis
COX 2 importance (2)PG production acts on local arteries to increase perfusion: 1) Protects kidney blood flow 2) Protects cardiac blood flow.
What is the function of LTs?Inc. blood vessel permeability, allowing plasma fluid to pass the extra-vascular space, swelling inflamed tissue.
Difference between 5-lipoxygenase and cycloxygenase.5-lipoxygenase not stored in tissues or widely distributed. Found in neutrophils, eosinophils, monocytes, macrophages, and mast cells.
How are PGE2 and PGF2alpha degraded? (2)1) Intramolecular - NON-enzymatic rapid; molecules unstable and rearrange spontaneously. Enzymatically - 15-OH dehydrogenase and 13-reducatse enzyme. 2) B- or w- oxidation - slowl shorten side chains
How is TXA2 and PGI2 degraded?nonezymatic; rapid
Explain Dietary AA AA derived from linoleic acid(C18:2). Omega-3 fatty acids found in fish incorporates (C20:5) and (C22:5) into AA in membranes. Metabolism of longer fatty acids results in POORER receptor agonists.
Effects of Omega-3Reduced potency of TXA2, thus reduces risk of strokes and MI. BUT increase risk of hemorrhagic stroke.
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Section 5

Question Answer
Inc platelet aggregationTXA2
Vasoconstrictor (inc BP)TXA2
Dec platelet aggregationPGI2
Vasodilator, BronchodilatorPGE2, PGI2
BronchoconstrictorPGF2a, TXA2
Kidney from COX2, Natriuresis, diuresis, renin releasePGE2, PGI2
Dec gastric acid, pepsin, secretion; Inc MucusPGE2, PGI2
Inc GI motilityPGE2, PGF2a
Uterine contractionsPGE2, PGF2a
Sensitive to algesic agentsPGE2, PGI2
Inc Body TempPGE2, PGF2a, PGI2
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