Leukotrienes

Prostaglandins

Cytokines

Platelet Activating Factor

Serotonin

Reactive oxygen species, lysozomal enzymes

Eicosanoid Synthesis

1. Arachidonic acid made by phospholipase A2
2. Phospholipase A2 gets further modified
   1. COX I & II- prostaglandins, thromboxane - affected by NSAIDS
   2. Lipoxygenase - leukotrienes, HPETE, HETE. Zileuton inhibits lipoxygenase. Montelukast, zafirlukast inhibit downstream enzymes

Eicosanoid Effects,

Other targeted organs

Effects:

PGE and prostacyclin: arteriolar dilation

PGF, TXA: Venule constriction

PGE, PGI: Pain sensitization

Increase vascular permeability, chemotaxis of leukocytes

OTHER ORGANS: Vasculature, GI tract, Kidney

Action: PGE₁ analog

use: Prevention of NSAID-induced ulcers, therapeutic abortion

Action: Block COX I and II, etodolac somewhat more selective for II, celecoxib selective for II

Use:

Analgesia,

antipyresis (via PGE₂ block),

anti-inflammatory

1. GI: Irritation, damage, ulcer -Cox 1- reduce w/omeprazole, misoprostol
2. Kidney: Reduce renal blood flow, salt/water retention - bad for ppl w/CHF, kidney disease, hyperkalemia, on ACEi or diuretics
3. Bleeding - COX1, TXA₂
4. Clotting - COX2
5. Uterine - cox1 - inhibition of uterine contraction and cervical dilation in preg

1. Indomethacin: used to treat gout & induce patent ductus arteriosis closing.  Most toxic.
2. Ketorolac: Propensity toward GI + Renal problems, short-term use only. BUT more specific for COXII

1. Zero-order in high concentratin
2. Antiplatelet, due to its being non-reversible inhibition of COX
3. Causes Reye syndrome in kids w/virus
4. More toxic in overdose: Salicylism: tinnitus, dizzyness, hyperventilation,metabolic acidosis 

Acetaminophen

Action, use, tox

Action: unknown...cox III?

Use: Analgesic, antipyretic

Tox: Overdose: irreversible hepatic necrosis. Treat with acetylcysteine. Ethanol induces enzyme that promotes this.

H_1:

vasodilation, itch, and pain.

capillary dilation and permeability (edema), constriction of bronchiolar smooth muscle, and activation of peripheral nociceptive receptors.

H₂: acid secretion

Bind to glucocorticoid response element and:

1. Inhibit phospholipase A, COX
2. Inhibit inflammatory mediators and cytokines
3. Decrease IL2, platelet activating factor
4. Induce apoptosis in rapidly-dividing lymphocytes

Duration of Action: cortisone<prednisone<triamcinolone<dexamethasone

Cortisone + Prednisone retain mineralocorticoid activtiy

Triamcinolone and Dexamethasone good as topicals

Prednisone good for systemic use

Beclomethasone, flunisolide, triamcinolone used for asthma