Term
| How is Arachidonic acid processed to achieve various biological activities? |
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Definition
AA is available in diet and mostly during essential FA synthesis
1) Esterified, phospholipid form is cleaved and freed by PLA and then acted upon by either Cyclooxygenase, 12'-lipoxygenase or 5'-lipoxygenase
2) COX1 (constitutive) or COX2 (induced) oxygenate and cyclize AA into unstable endoperoxide intermediates which become Prostacyclin (dilation), Thromboxane (clotting) and Prostaglandins.
PGG2 makes PGH2, which makes short lived prostaglandins and thromboxane.
3) Lipoxygenase acts on AA to form 5'-hydroxyperoxyeicosatetranenoic acid (5-HPETE)
5'-HPETE then forms leukotriene B4 (L-B4), thioether leuokotrienes (LTC), or slow reacting substance of anaphylaxis or luekotrienes (C4, D4)
LTs are metabolized by omega oxidation and peroxidative inactivation (short-lived) |
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Term
| How are Leukotrienes metabolized? |
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Definition
| Short-lived and metabolized by omega oxidation and peroxidative inactivation. |
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Term
Why would you prescribe Celecoxib?
What about Zileutin or Zafirlukast? |
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Definition
1) COX-II inhibitor (like recalled Vioxx) that is successful at treating pain with a minimum of GI side effects (prostaglandin-mediated enteric protection)
2) Use them in Asthma treatment (increase dilation)
Zileutin= inhibits 5'LOX, preventing 5HPETE production
Zafirlukast= Leukotriene antagonist, leaving LTB4 (PMN chemotaxis) |
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Term
| What is the common structure of most Eicosanoid receptors? |
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Definition
| G-coupled 7 transmembrane receptors. |
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Term
| What are the effects of Prostaglandins, thromboxane and leukotrienes on Smooth muscle? |
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Definition
1) Vessels
TXA2 is vasoconstrictor
Leukotrienes C4, D4 and E4 are vasoconstrictors
PGI2 is a vasodilator
2) Uterus- PGE ad PGF contract pregnant uterus
3) Lungs- PGE2, PGI2 are bronchodilators
PGF2 and TXA and leukotrienes are bronchoconstrictors |
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Term
| What are the effects of Prostaglandins, thromboxane and leukotrienes on Blood element? |
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Definition
1) TXA2 is platelet aggregator
PGI2 is antiaggregant
LTB4 is important for PMN chemotaxis. |
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Term
| What are the effects of Prostaglandins, thromboxane and leukotrienes on the Kidney and urine formation? |
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Definition
Can be synthesized and delivered to kidney
1) PG maintains renal blood flow and GFR, leads to EPO release, has natriuretic tubular action, antagonizes vasopressin (water-diuretic), and stabilizes corticomedullary solute.
PGE2 and PGI2 cause renal vasodilation, natruresis, diuressis and renin release
LTs are vasoactive, affect renal permeability, cell growth and renal cellular volume. |
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Term
| What are the effects of Prostaglandins, thromboxane and leukotrienes on the CNS? |
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Definition
1) PGs produced by vasculature, choroid plexus and neurons
They cause sedation, inhibition of locomotor function, maintenance of body temperature, water balance, and food intake and gonadotropic secretion.
** may modulate adrenergic function and AA release from CNS tissue**
2) Leukotrienes synthesized in low levels and affect vasculature the most. |
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Term
| What is the affect of PGE2 and PGI2 on pain? |
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Definition
| increase pain sensation by sensitizing afferent nerve fibers. |
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Term
| Which eicosanoid is required for maintenance of ductus arteriosus patency |
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Definition
| PGE2 keeps it open prenatally and then fades after birth. |
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Term
| How does leukotriene signaling relate to inflammation? |
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Definition
LTB4 (chemotaxis, aggregation, degranulation of leukocytes)
C, D, E4= vasoconstriction and leakage from venules. |
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Term
| How is GI mucus secretion and acid secretion inhibition achieved? |
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Definition
PGE2 and PGI2 (-) acid secretion and (+) mucus secretion
THIS IS WHY YOU WANT COX-2 INHIBITOR |
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Term
| Which Eicosanoids are responsible for Redness, Heat, Pain and Edema in inflammation? |
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Definition
Redness= Vasodilation- PGE2 and PGI2
Heat= PGE2 and hypothalmic regulation
Edema= Dilation by PGE2, and LTC/D4 edematogenic action
Pain= PGE2 sensitizes afferent sensory nerves (histamine, bradykin) |
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Term
| Which Eicosanoids are responsible for the 3 P's of CV system? |
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Definition
Platelets= TXA2 vs. PGI2 (aggreg vs. disaggreg)
Patency- TXA2 vs. PGI2 (constrict vs. dilate)
Permeability- LT4's edematogenic |
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Term
| How are PGE2 and PGF2 alpha used in Gynecology? |
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Definition
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Term
| Why might you use PGE1 in CV disease? |
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Definition
| If it involves a ductus=dependent CV malformation, PGE1 (alprostadil) will maintain patency until surgery. |
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Term
| What are the few accepted uses of exogenous prostaglandins? |
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Definition
1) CV for relief of peripheral vascular disease, hypertension and extracorporeal circulation
2) Inhibit tumor metastasis and growth |
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Term
| Why might you prescribe Misoprostol |
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Definition
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Term
| What are the basic functions of Antipyretics? |
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Definition
| Reduce elevated body temperature but DO NOT lower normal body temperature |
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Term
| What are the basic functions of Analgesics? |
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Definition
| Reduce mild-moderate pain from integumental (blood vessel; muscle; head) structures, but DO NOT affect severe pain from visceral organs or cause addiction. |
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Term
| What are the basic functions of Anti-inflammatory drugs? |
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Definition
Reduce: redness, edema, pain and heat
DO NOT affect cellular accumulation or proliferation. |
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Term
| What are the different anti-inflammatory effects of NSAIDS due to? |
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Definition
Differential COX-1 and COX-II targetting
Potent= indomethacin, aspirin
Moderate- Meclofenamate
None- Acetaminophen |
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Term
| How might NSAID use affect Lipoxygenase activity? |
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Definition
INDIRECTLY!
It can stabilize membranes, inhibiting PLA2 and preventing AA mobilization. |
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Term
| What are the 3 main mechanisms of action of NSAIDS |
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Definition
1) COX inhibition
2) Affect enzymes in macromolecular biosynthesis
3) Act as oxygen free radical scavenger that interferes with hydrophobic mediators |
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Term
Which NSAID has a reversible, non-competitive action?
What about competitive? |
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Definition
1) Acetometaphen
2) Ibuprofen and Piroxicam |
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Term
| What are some important adverse effects of NSAID use? |
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Definition
1) GI- ulceration/vomiting/nausea
2) Antiplatelet- bleeding
3) Renal- nephritis and necrosis
4) Allergic- Anaphylactoid
5) Uterine- delayed parturition and premature ductal closure
6) CNS- Reye's syndrome (encephalopathy secondary to viral treatment)
7) Salicylism: Tinnitus
8) Hepatic injury secondary to high dose aspirin usage |
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Term
| What is Salycylism? What are its metabolic effects? |
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Definition
Too much aspirin use can cause Tinnitus, dizziness and nausea, as well as metabolic effects in severe cases.
Salicylates uncouple OXFOS in skeletal muscle, which can cause respiratory alkalosis (compensated va renal bicarbonate excretion)
If doses are too high, respiration decreases and CO2 increases are retained, leading to uncompensated respiratory acidosis (toxicity). |
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Term
| What is "Aspirin intolerance"? |
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Definition
| Anaphylactoid-like (not IGE-mediated), that includes urticaria, rhinitis, nasal polyps and bronchoconstriction. |
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Term
How does Acetaminophen work?
What are important side-effects? |
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Definition
Analgesic and Antipyretic ONLY- reversible, noncompetitive COX (weak against 1 and 2, but good against 3 in brain) inhibition
DOES NOT cause stomach ulceration or platelet inhibition
Can cause fulminant hepatic failure from toxic doses |
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Term
| What is the deal with COX-II inhibitors? |
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Definition
COX-II is the inducible COX which is responsible for the inflammatory response, leading to PGE2, PGI2, TXA2 release.
COX-II NSAIDS are developed to treat inflammation without GI side-effects of other NSAIDS
BUT, VIOXX causes heart issues (Celeconib recently made) |
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