Autocoids

Eicosanoids (20 C molecules from AA) are hormones, short half-lives, require continuous synthesis, paracrine, autocrine, mediate local or

corrdinated responses and include Prostaglandins (uterine contractions), Prostacyclines, Thromboxanes, Leukotrienes (millisec half-life)

Bind G-protein receptors activating PLA2, PLC, DAG

Ariachidonic acid converted to PGH2 via Cyclooxygenase, PGH2 converted to prostacyclines and thromboxanes, alternatively AA converted to

prostaglandins and leukotrienes by Lipoxygenase

PGE2 and PGI2 (E-I-E-I-O) generally open, bind EP3 receptor in parietal cells HCl secretion (inhibit cAMP) and in gastric epithelial cells to

HCO3 secretion (Misoprotstol-15-deoxy-16-hydroxy-16-methyl-PE GE1 used to activate EP3 receptors when chronic NSAIDs given)

Prostaglandins generally CO, PGE2 induced by IL-1 COX2 in hypothalamus, PGE2 and PGI2 vasodilate (hypotensive), PGD2 vasodilates at

low conc. and vasoconstricts at high conc. (and in pulmonary circulation), TXA2 potent vasoconstrictor, LTC4 and LTD4 are hypotensive

and decrease cardiac contractility

NSAIDs have anti-inflammatory, antipyretic, analgesic, platelet, GI, renal, and cardiovascular effects

COX1 generally expressed in GI tract, COX2 generally expressed in inflammatory tissues (monocytes)

Drug / Class/MOA / Uses / Side effects/toxicity / Miscellaneous

Glucocorticoids

/ steroid, inhibit PLA2 (lipocortin) and COX synthesis / anti-inflammatory / immunosuppressive, hypertension, fluid retention, CNS excitability, moods / include cortisol, prednisone, dexamethasone, cortisone
Salicylates / O2 consumption, uncouple OxPhos, aerobic gluc. metab. / analgesic, antipyretic / hematocrit and CO, plasma volume, respiratory alkalosis (OD), hyperglycemia, glucocorticoids / bleeding time, gluc. stores, serum triglyc., CONTRAINDICATED in hemophilia, Vit. K deficiency, hepatic damage, hypoprothombinemia
Aspirin / salicylate, irreversible COX inhibitor / analgesia, anti-inflammatory, antipyresis, plt. agg. / tinnitis, deafness, vertigo, Rye’s syndrome (kids w. virus), OD result in hyperventilation, resp. alkalosis, shock, coma, organ failure, death / short half-life (15 min), COX1 sel?, CONTRAINDICATED in peptic ulcers, kids with viruses, trt. OD with vomiting/lavage, HCO3, fluids + electrolytes
Acetaminophen / analgesic, antipyretic / OD cause hepatic necrosis (trt. with NAC) / NO anti-inflammatory or effects on plt., uric acid resorp., acid/base
Indomethacin / Acetic Acid (sal) / gout / high toxicity / COX1 sel?
Sulindac / “ / gastric distress / less potent than indomethacin
Etolodac / “ / limited toxicity / some COX2 selectivity
Fenamates / fenamate / not widely used / diarrhea, more toxic than NSAIDs / ex. Mefenamic + Meclofenamic acid
Tolmetin / sim. to aspirin / better tolerated than aspirin
Ketorolac / analgesic / allergic conjunctivitis, ocular inflammation, SHORT term use only
Diclofenac / nonselective NSAID / LONG term treatment of RA, osteoarthritis, ankylosing spondylitis
Drug / Class/MOA / Uses / Side effects/toxicity / Miscellaneous
Ibuprofen / Propionic acid / anti-inflammatory, antipyretic, analgesic / joint swelling and morning stiffness in RA, better tolerance than aspirin
Naproxen / “ / “ / CNS and GI sim. to indomethacin / longer half-life (14 hrs)
Dazoxiben / inhibit lipoxygenase
Pirmagrel
Celexocib / sel. COX2 inhibitor / long half-life (11 hrs)
Rofecoxib / “ / long half-life (17 hrs)
Piroxicam / sel. COX1 inhibitor? / long half-life (57 hrs)