pharm

• epigastric distress, nausea/vomiting
• gastric ulseration, GI hemorrhage, erosive gastritis
• low dose of aspirin for CV benefits associated with 2- to 4- increases in upper GI
• none acetylated salicylates > less effect on cytoprotective PGs in GI

• antiplatelet effect = inc. risk of bleeding
• dec. plasma iron
• dec. life or RBC

patients at risk of GI bleeding, ethanol use, platelet bleeding disorder, post surgery

patients with already present congestive heart failure or renal disease = dec. renal function + salt and water retention caused by salicylates > inc. in blood volume can be up to 20%

non-cardiogenic: older patients who ingest salicylates regularly > cardiogenic pulmonary edema 

cardiogenic: compromised cardiac function (e.g. congestive heart failure) > and pulmonary edema

oxid. phosphorylation uncoupling > inc. production of CO₂ > inc. respiration (mainly by an increase in depth with only a slight increase in rate) > P_co2 dec., >  blood alkalosis > renal acidosis.

oxid. phosphorylation uncoupling (large aspirin doses) > depletion of glycogen = heat = and dec. aerobic metabolism

direct effect on respiratory center in the medulla (at higher conc.)

at therapeutic doses

plasma alkalosis = renal acidosis > renal excretion of bicarbonate > Na+ and K+ excretion > dec. plasma bicarbonate  > blood pH returns to normal > homeostasis

at low doses > inhibit urate excretion > inhibit uricosuric agents (e.g. probenecid)

at intermediate doses > no effect

at high doses > inc. urate excretion > renal calculi

note: avoid treatment for gout

rare

• prolonged and excessive ingestion of analgesic mixtures containing salicylates in
• combination with acetaminophen or other analgesic-antipyretic compounds can produce
• papillary necrosis and interstitial nephritis

• in patients with prolonged use
• onset is slow and damage is reversible with cessation of aspirin

fatal disease: acute onset of encephalopathy, liver dysfunction, and fatty infiltration of the liver and other viscera

likely mechanism: epidemiological evidence suggests an association between aspirin use and Reye’s syndrome 

aspirin is contraindicated in children < 16yo who have or are recovering from chickenpox or flu-like symptoms

aspirin-induced anaphylactoid reactions are not immunological

incidence of hypersensitivity estimated at 10-25% in patients with asthma, nasal polyps, chronic urticaria

1% in healthy individuals. Aspirin intolerance is a contraindication to the use of any other NSAIDs 

aspirin induced airway hyperreactivity in asthmatics, leading to bronchoconstriction, ocular and nasal congestion

• aspirin triad:
• 
•  
• possible mechanism: inhibition of COX pathways shunts AA to LOX, resulting in increased formation of leukotrienes > cross-reactivity with NSAIDs