Eicosanoid Pharmacology

Question 1

Be able to draw out the eicosanoid pathway along with drugs blocking each step.

Answer 1

Question 2

Which COX has constitutive action and which is inducible?

Answer 2

COX1 constitutive action
COX 2 inducible

Question 3

LTB4 action?

Answer 3

inflammatory mediator > neutrophil and chemoattractant; activates PMNs; inc free radical formation > cell damage

Question 4

LTA4, LTC4, and LTD4 effects?

Answer 4

cause anaphylaxis and bronchoconstriction (role in asthma)

Question 5

Where is COX 1 primarily found in the body?

Answer 5

most tissues, including platelets and stomach where acts to synthesize thromboxane and cytoprotective prostaglandins, respectively

Question 6

Where is COX 2 primarily found in the body?

Answer 6

the brain and kidney and at sites of inlammation

Question 7

What are some PGE1 drugs?

Answer 7

misoprostol, alprostadil

Question 8

Indication of alprostadil?

Answer 8

maintains patency ductus arteriosus

vasodilation; used in male impotence

Question 9

In what conditions are misoprostol and alprostadil contraindicated in?

Answer 9

contraindicated in pregnancy, unless used as abortifacient

Question 10

Name a PGE2 analog drug that is used for cervical ripening and as an abortifacient?

Answer 10

dinoprostone

Question 11

Name a PGF2a drug/s?

Answer 11

carboprost
latanoprost

Question 12

Carboprost indication?

Answer 12

abortifacient

Question 13

MOA PGF2a drugs?

Answer 13

uterine and bronchiolar smooth muscle contraction

Question 14

PGI2 analog drug name?

Answer 14

PGI2 (prostacyclin)

epoprostenol

Question 15

Indication for epoprostenol?

Answer 15

pulmonary HTN

Question 16

PGE2 and PGF2 stimulation have what effects on the body?

Answer 16

both inc. in primary dysmenorrhea

Question 17

What is the function of TXA2?

Answer 17

platelet aggregator

Question 18

TXA2 is coupled to what pathway. Explain how this may lead to its effects?

Answer 18

IP3 DAG

activation of TxA2 receptors> stimulation of phospholipase C > PIP2 hydrolysis > inc IP3 > mobilization of bound Ca2+ > free Ca2 > plt. aggregation

Question 19

Describe how activation of PGI2 receptors affect platelets and the pathway taken.

Answer 19

activation of PGI2 receptors> stimulation of adenylyl cyclase > inc. cAMP > inc. activity of internal Ca2+ “pumps” > dec free Ca2+ > plt stabilization

Question 20

Does aspirin cause irreversible or reversible inhibition of COX?

Answer 20

irreversible

Question 21

In low doses what is the main benefit of aspirin use?

Answer 21

anti platelet aggregation

Question 22

In moderate doses what is the main benefit of aspirin use?

Answer 22

analgesia and antipyresis

Question 23

At high doses what is the major benefit to using aspirin?

Answer 23

anti-inflammatory effects

Question 24

List some S/E of aspirin use? (List 5)

Answer 24

• Gi irritation: gastritis, ulcers, bleeding
• salicylism: tinnitus, vertigo, dec. hearing - often first signs of toxicity
• bronchoconstriction: exacerbation of asthma
• hypersensitivity, especially the “triad” of asthma, nasal polyps, rhinitis
• Reye syndrome: encephalopathy
• inc. bleeding time (antiplatelet)
• chronic use: associated with renal dysfunction

Question 25

What are some drug interactions to be aware of when using aspirin?

Answer 25

ethanol (inc. GI bleeding,) warfarin (^ effects), and uricosurics (dec effects)

Question 26

What are some reversible inhibitors of COX 1 and COX 2 with analgesic, antipyretic, and anti-inflammatory action?

Answer 26

Ibuprofen, Naproxen, Indomethacin, Ketorlac, Sulindac

Question 27

NSAIDs (other than aspirin) are associated with an increased risk of what adverse events?

Answer 27

adverse CVS thrombotic events such as MI and stroke

Question 28

Which NSAID has the most analgesic effect?

Answer 28

ketorlac

Question 29

How can NSAIDs affect the renal system?

Answer 29

chronic use may cause nephritis, nephritic syndrome, acute failure (via dec. formation of PGE2 and PGI2, which normally maintain GFR and RBF) does not occur with sulindac

Question 30

Sulindac toxicities?

Answer 30

SJS, hematotoxicity

Question 31

Indomethacin toxicity?

Answer 31

thrombocytopenia, agranulocytosis, and > CNS effects

Question 32

What is the primary difference between Celecoxib and the other antiinflammatory agents?

Answer 32

Selective COX 2 inhibitor less GI toxicity less antiplatelet action

Question 33

Acetaminophen MOA?

Answer 33

inhibition of COX but not in peripheral tissues

Question 34

Describe the properties of acetaminophen compared to ASA?

Answer 34

equivalent analgesic and antipyretic activity but lacks significant antiinflammatory effects no antiplatelet action not implicated in Reye syndrome No effect on uric acid not bronchospastic (safe in NSAID hypersensitivity and asthmatics GI distress is minimal

Question 35

When should you preferably take NAC after toxic doses of Tylenol?

Answer 35

within first 12 hours

Question 36

Does indomethacin close or maintain patency of ductus arteriosus?

Answer 36

it closes it