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Promotes inflammation and sensitize receptors to painful stimuli (PGE2 and PGI2)Protection of the gastric mucosa (PGE2 and PGI2)Reduces secretion of gastric acidIncreases secretion of bicarbonate and cytoprotective mucusMaintenance of submucosal blood flowStimulates platelet aggregation with synthesis of TXA2Vasodilation with synthesis of prostacyclinPromotes vasodilation and maintain renal blood flow in the kidney (PGE2, and PGI2)Mediates fever and contributes to perception of pain in the brainPromotes contraction of uterus at termCOX-1: Housekeeping.Protects gastric mucosa, supports renal function, and promotes platelet aggregationInhibition of COX-1 can cause harmful effects:Gastric erosion and ulcerationBleeding tendenciesRenal impairmentBeneficial Effect from inhibition:Protection against MI and strokeCOX-2: Produced mainly at sites of tissue injuryMediates inflammation and sensitizes receptors to painful stimuliFound in brain to mediate fever and perception of pain, kidneys to support renalfunction, blood vessels to promote vasodilation, and colon where it can contribute to
colon cancerInhibition of COX-2 can provide the following benefits:Suppress inflammationAlleviates painReduces feverProtection against colorectal cancersInhibition of COX-2 has the following adverse effects:Renal impairmentPromotion of MI and strokeDrug Class: First-Generation Nonsteroidal Anti inflammatory Drugs (NSAIDs) Page number: p. 605Prototype drug: Aspirin (ASA)Other Drugs in class:Indications for use: Mild to moderate pain (joint, muscle, and HA pain), reduces fever, protectsagainst thrombotic disorders, drug of choice for rheumatoid arthritis and other inflammatoryconditions, dysmenorrheaMechanism of Action:IRREVERSIBLE nonselective inhibitor of cyclooxygenase (Inhibition of COX2= reduction ofinflammation, pain, and fever and inhibition of COX1= protection against MI and ischemicstroke.Duration of action depends on how quickly specific tissues can synthesize new molecules ofCOX1 and COX2Relieves pain through actions in the periphery by inhibiting COX2 which suppressesprostanoid production and also works in the CNS for pain relief.Inhibiting prostaglandin synthesis in uterine smooth muscle alleviates dysmenorrheaSuppresses platelet aggregation by causing irreversible inhibition of COX1, the enzyme thatmakes TXA2. Recommended daily for ischemic stroke, TIA, primary prevention of MI, acuteMI, previous MI, chronic stable angina, unstable angina, and angioplasty or otherrevascularization proceduresProtects against colorectal cancer by inhibiting COX2Pharmacokinetics:Absorption: Small Intestine. If given rectally, absorbed slowly and blood levels are lower.Half-life: 15-20 mins d/t rapid conversion to salicylic acidDistribution: All body tissues and fluids including breast milk, fetal tissues, and CNSExcretion of salicylic acid depends on urinary pH. The higher the pH, the increased rate ofexcretionAdverse Reactions:Common: Gastric distress, heartburn, and nauseaOccult GI Bleeding, gastric ulceration, perforation, and bleeding. Ulcers result from: