4. Prostaglandins and Leukotrienes

Question 1 What are eicosanoids?

A class of lipids that includes prostaglandins, thromboxanes, and leukotrienes.

Question 2 From what type of acids are eicosanoids derived?

Eicosanoic acids, especially arachidonic acid.

Question 3 What is the full chemical description of arachidonic acid given in the lecture?

All-cis-5,8,11,14-eicosatetraenoic acid.

Question 4 Why are eicosanoids described as hormone-like but distinct from classical hormones?

They act locally near their site of origin and are rapidly catabolized.

Question 5 What term is used for eicosanoids because of their local action?

Locally acting hormones.

Question 6 Who coined the term prostaglandins according to the lecture?

Ulf von Euler.

Question 7 In what year were prostaglandins discovered according to the lecture?

1935.

Question 8 What effects did seminal vesicle extracts produce in the discovery of prostaglandins?

They lowered blood pressure and contracted uterine tissue.

Question 9 In which mammalian cells are eicosanoids stated to be absent?

Red blood cells.

Question 10 Which eicosanoid family is especially associated with platelets?

Thromboxanes.

Question 11 Which eicosanoid family is especially associated with leukocytes?

Leukotrienes.

Question 12 How do eicosanoids generally act physiologically?

As local paracrine mediators.

Question 13 Are eicosanoids transported through the circulation to distant targets?

No.

Question 14 Are eicosanoids stored in cells for later release?

No; they are synthesized on demand.

Question 15 How long-lived are eicosanoids according to the lecture?

Very short-lived, generally less than 1 minute.

Question 16 At approximately what concentration range do eicosanoids act?

Nanomolar concentrations.

Question 17 What are the two major structural divisions of eicosanoids in the lecture?

Cyclic prostaglandin-related compounds and linear leukotrienes/tetraenes.

Question 18 What structural feature characterizes cyclic prostaglandins?

A cyclopentane ring.

Question 19 Which compounds are included under the cyclic group?

Prostaglandins, prostacyclins, and thromboxanes.

Question 20 Which compounds are linear?

Leukotrienes and tetraenes.

Question 21 Through what overall biochemical cascade are these compounds derived?

The arachidonic acid cascade.

Question 22 Why do different prostaglandins have different biological activities?

They differ in substitutions on the cyclopentane ring.

Question 23 What determines the letter classification PGA, PGB, PGC, PGD, PGE, PGF, PGG, and PGH?

The ring pattern.

Question 24 What does the subscript number in PGE1 or PGE2 represent?

The number of double bonds in the side chain.

Question 25 What is the key precursor of eicosanoids?

Arachidonic acid.

Question 26 Where is arachidonic acid stored before eicosanoid synthesis?

In membrane phospholipids, such as phosphoinositol.

Question 27 Which enzyme liberates arachidonic acid from membrane phospholipids?

Phospholipase A2 (PLA2).

Question 28 What is identified as the rate-limiting step in eicosanoid biosynthesis?

PLA2-mediated liberation of arachidonic acid.

Question 29 What drug class inhibits PLA2 according to the lecture?

Glucocorticoids.

Question 30 What are the two major arachidonic acid pathways?

The cyclooxygenase (COX) pathway and lipoxygenase (LOX) pathway.

Question 31 What products arise from the COX pathway?

Prostaglandins and thromboxanes.

Question 32 What products arise from the LOX pathway?

Leukotrienes.

Question 33 What does cyclooxygenase do to arachidonic acid?

Adds oxygen to form PGG2, which is then reduced to PGH2.

Question 34 What intermediate is formed from arachidonic acid before PGH2?

PGG2.

Question 35 What are the two major cyclooxygenase isoenzymes?

COX-1 and COX-2.

Question 36 How is COX-1 characterized?

Constitutive.

Question 37 Where is COX-1 especially expressed according to the lecture?

Gastric mucosa, kidney, platelets, and endothelium.

Question 38 How is COX-2 characterized?

Inducible.

Question 39 In what cells is COX-2 induced during inflammation?

Macrophages and monocytes.

Question 40 Which common drug class inhibits both COX-1 and COX-2?

NSAIDs.

Question 41 Name NSAIDs listed as COX inhibitors in the lecture.

Ibuprofen, naproxen, aspirin, and indomethacin.

Question 42 Name COX-2-selective inhibitors listed in the lecture.

Celecoxib and rofecoxib.

Question 43 What advantage is attributed to COX-2-selective inhibitors in the lecture?

Less gastrointestinal damage and prevention of NSAID-associated ulcers.

Question 44 What does lipoxygenase convert arachidonic acid into?

HPETEs and then HETEs.

Question 45 Which lipoxygenase specifically produces leukotrienes?

5-lipoxygenase.

Question 46 What can LTA4 become by hydrolysis?

LTB4.

Question 47 What can LTA4 become by glutathione conjugation?

LTC4.

Question 48 What leukotrienes can be formed after LTC4?

LTD4, LTE4, and LTF4.

Question 49 What broad processes are prostaglandins associated with?

Inflammation, pain, fever, cardiovascular disease, asthma, glaucoma, and preterm labor.

Question 50 What local effects of prostaglandins are listed?

Vasodilation, ovulation, uterine contraction, and immune modulation.

Question 51 How do prostaglandins affect gastric secretion according to the lecture?

They inhibit gastric secretion and provide gastric protection.

Question 52 Why can NSAID use promote peptic ulcers?

COX inhibition decreases protective prostaglandin synthesis.

Question 53 What effect can prostaglandins have on bone in rheumatoid arthritis?

They can stimulate bone resorption.

Question 54 What are the major vascular effects of thromboxanes?

Potent vasoconstriction.

Question 55 What effect do thromboxanes have on platelets?

They stimulate platelet aggregation and clot formation.

Question 56 Where are thromboxanes synthesized?

Platelets.

Question 57 Where is prostacyclin PGI2 produced?

Vessel walls or endothelium.

Question 58 What does PGI2 do to platelet aggregation?

It inhibits platelet aggregation.

Question 59 What does PGI2 do to clotting?

It inhibits clotting.

Question 60 What opposing eicosanoid activity does PGI2 balance?

Thromboxane activity.

Question 61 What broad inflammatory signs are associated with leukotrienes?

Redness, heat, pain, and swelling.

Question 62 What major airway effect do leukotrienes produce?

Bronchoconstriction.

Question 63 In which conditions is leukotriene-induced bronchoconstriction especially important?

Asthma and anaphylaxis.

Question 64 What is the main function of LTB4 emphasized in the lecture?

Chemotaxis of neutrophils.

Question 65 What effect does LTB4 have on T cells?

It promotes T-cell proliferation.

Question 66 Which leukotrienes make up the slow-reacting substance of anaphylaxis?

LTC4, LTD4, and LTE4.

Question 67 What does SRS-A stand for?

Slow-reacting substance of anaphylaxis.

Question 68 How do steroids such as hydrocortisone and prednisone affect eicosanoid synthesis?

They block PLA2 and prevent arachidonic acid release.

Question 69 How do NSAIDs affect eicosanoid synthesis?

They inhibit COX and decrease prostaglandin synthesis.

Question 70 How do COX-2 inhibitors differ from nonselective NSAIDs in the lecture?

They target inflammation more selectively with less GI damage.

Question 71 Which leukotriene-targeting drugs are listed for asthma treatment?

Montelukast and zileuton.

Question 72 Where is PGD2 synthesized according to the lecture table?

Mast cells.

Question 73 What is the biologic activity of PGD2 in the lecture table?

Inhibition of platelet aggregation.

Question 74 Where is PGE2 synthesized according to the table?

Kidney, spleen, and heart.

Question 75 What biologic activities are listed for PGE2?

Vasodilation and uterine contraction.

Question 76 Where is PGF2α synthesized according to the table?

Kidney, spleen, and heart.

Question 77 What biologic activities are listed for PGF2α?

Vasoconstriction and bronchoconstriction.

Question 78 What is PGH2 a precursor for?

Thromboxanes such as TXA2 and TXB2.

Question 79 Where is PGI2 synthesized?

Endothelium.

Question 80 What aggregation effects are listed for PGI2?

It inhibits platelet and leukocyte aggregation.

Question 81 Where is TXA2 synthesized?

Platelets.

Question 82 What are the main actions of TXA2?

Platelet aggregation and vasoconstriction.

Question 83 Where is TXB2 synthesized?

Platelets.

Question 84 What action is listed for TXB2?

Vasoconstriction.

Question 85 Which cells synthesize LTB4 according to the table?

Neutrophils, mast cells, and monocytes.

Question 86 What functions are listed for LTB4?

Chemotaxis, leukocyte aggregation, and T-cell proliferation.

Question 87 Which cells synthesize LTC4 according to the table?

Macrophages and monocytes.

Question 88 What functions are listed for LTC4?

SRS-A activity and bronchoconstriction.

Question 89 Which cells synthesize LTD4 according to the table?

Macrophages and monocytes.

Question 90 What special role is given to LTD4 in SRS-A?

It is described as the main SRS-A component.

Question 91 What major action accompanies LTD4 activity?

Bronchoconstriction.

Question 92 Which cells synthesize LTE4 according to the table?

Mast cells and basophils.

Question 93 What actions are listed for LTE4?

SRS-A activity, vasoconstriction, and bronchoconstriction.

Question 94 What are the major physiologic roles of eicosanoids summarized in the lecture?

Inflammation, immunity, hemostasis, and smooth muscle tone.

Question 95 What major drug groups target eicosanoid pathways?

Steroids, NSAIDs, COX-2 inhibitors, and leukotriene blockers.

Question 96 A patient takes a glucocorticoid. What early step of eicosanoid synthesis is inhibited?

PLA2-mediated arachidonic acid release.

Question 97 A patient takes aspirin. Which pathway is directly inhibited?

The COX pathway.

Question 98 A patient takes zileuton. Which eicosanoid branch is being targeted?

The leukotriene-producing LOX pathway.

Question 99 A patient takes montelukast for asthma. Which mediator family is being opposed?

Leukotrienes.

Question 100 Which eicosanoid promotes platelet aggregation while another opposes it?

TXA2 promotes platelet aggregation, whereas PGI2 inhibits it.