Eicosanoid Pharmacology Flashcards
Be able to draw out the eicosanoid pathway along with drugs blocking each step.
Which COX has constitutive action and which is inducible?
COX1 constitutive action
COX 2 inducible
LTB4 action?
inflammatory mediator > neutrophil and chemoattractant; activates PMNs; inc free radical formation > cell damage
LTA4, LTC4, and LTD4 effects?
cause anaphylaxis and bronchoconstriction (role in asthma)
Where is COX 1 primarily found in the body?
most tissues, including platelets and stomach where acts to synthesize thromboxane and cytoprotective prostaglandins, respectively
Where is COX 2 primarily found in the body?
the brain and kidney and at sites of inlammation
What are some PGE1 drugs?
misoprostol, alprostadil
Indication of alprostadil?
maintains patency ductus arteriosus
vasodilation; used in male impotence
In what conditions are misoprostol and alprostadil contraindicated in?
contraindicated in pregnancy, unless used as abortifacient
Name a PGE2 analog drug that is used for cervical ripening and as an abortifacient?
dinoprostone
Name a PGF2a drug/s?
carboprost
latanoprost
Carboprost indication?
abortifacient
MOA PGF2a drugs?
uterine and bronchiolar smooth muscle contraction
PGI2 analog drug name?
PGI2 (prostacyclin)
epoprostenol
Indication for epoprostenol?
pulmonary HTN
PGE2 and PGF2 stimulation have what effects on the body?
both inc. in primary dysmenorrhea
What is the function of TXA2?
platelet aggregator
TXA2 is coupled to what pathway. Explain how this may lead to its effects?
IP3 DAG
activation of TxA2 receptors> stimulation of phospholipase C > PIP2 hydrolysis > inc IP3 > mobilization of bound Ca2+ > free Ca2 > plt. aggregation
Describe how activation of PGI2 receptors affect platelets and the pathway taken.
activation of PGI2 receptors> stimulation of adenylyl cyclase > inc. cAMP > inc. activity of internal Ca2+ “pumps” > dec free Ca2+ > plt stabilization
Does aspirin cause irreversible or reversible inhibition of COX?
irreversible
In low doses what is the main benefit of aspirin use?
anti platelet aggregation
In moderate doses what is the main benefit of aspirin use?
analgesia and antipyresis
At high doses what is the major benefit to using aspirin?
anti-inflammatory effects
List some S/E of aspirin use? (List 5)
- 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
What are some drug interactions to be aware of when using aspirin?
ethanol (inc. GI bleeding,) warfarin (^ effects), and uricosurics (dec effects)
What are some reversible inhibitors of COX 1 and COX 2 with analgesic, antipyretic, and anti-inflammatory action?
Ibuprofen, Naproxen, Indomethacin, Ketorlac, Sulindac
NSAIDs (other than aspirin) are associated with an increased risk of what adverse events?
adverse CVS thrombotic events such as MI and stroke
Which NSAID has the most analgesic effect?
ketorlac
How can NSAIDs affect the renal system?
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
Sulindac toxicities?
SJS, hematotoxicity
Indomethacin toxicity?
thrombocytopenia, agranulocytosis, and > CNS effects
What is the primary difference between Celecoxib and the other antiinflammatory agents?
Selective COX 2 inhibitor
less GI toxicity
less antiplatelet action
Acetaminophen MOA?
inhibition of COX but not in peripheral tissues
Describe the properties of acetaminophen compared to ASA?
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
When should you preferably take NAC after toxic doses of Tylenol?
within first 12 hours
Does indomethacin close or maintain patency of ductus arteriosus?
it closes it
