• most are organic acids
• most are well absorbed
• renally excreted

• analgesia, antipyretic (low dose)
• antiinflammatory
  • musculoskeletal disorders- RA or OA
  • symptomatic relief
  • kids with RA (aspirin, naproxen, tometin)
• closure of patent ductus arteriosus- indomethacin
• chemopreventative in cancer

• CV
• allergy
• analgesic nephropathy
• gastric and duodenal ulceration (less GI problems than aspirin)
• CNS
• hemorrhage risk
• prolong gestation of labor

• PGI2 is protective for vessel endothelium (synthesized by COX2)
• inhibition of prostacyclin synthesis without inh. thromboxoane synthesis, you could promote increased platelet aggregation of endothelium that is detrimental
• increase potential for MI and stroke (esp. COX2 agents)

• closure of patent ductus
• cause more GI distress
• take at night to prevent morning stiffness

• prodrug (must be metabolized to active metabolite which is 500x more active than prodrug)

• OTC: 200 mg tablets
• short half life (2 hrs)
• adverse effects
  • GI effects
  • ocular disturbances- blurred vision, toxic amblyopia

• dosage- 200 mg tablets
• longer half life (14 hrs)
• adverse effects
  • GI effects
  • CNS side effects- drowsiness, headache, fatigue, depression
  • dermatologic problems- rash, pruritis

• indication- antiinflammatory for rheumatoid arthritis
• PK
  • absorbed completely (food delays absorption)
  • LONG half life (50 hrs)
  • eliminated by metabolism
• adverse effects (some discontinue to side effects)

• mechanism- preferentially inhibit COX2 (not absolute)
• PK
  • half life 11 hrs
  • metabolized by CYP's (sign. drug interaction with lithium and fluconazole)
• no established clinical efficacy superior to nonselective inhibitors
• adverse effects: increased risk of-
  • thrombosis
  • HTN
  • atherogenesis
  • esp. with more highly selective COX2 drugs, but seen at lower levels
  • CI: CV, cerebrovascular disease
• use lowest possible dose for shrotest time: not a first choice drug

• analgesic and antipyretic activity
  • NO antiinflammatory activity
• no effect on CV or resp. systems
• no GI effects
• no acid base changes, no uricosuric effects
• no effects on platelets or coagulation

Preferred drug for lowering fever in children

• well absorbed
• metabolized to glucuronic acid and sulfate conjugates
  • small portion metabolized to reactive metabolite: NAPQI
    • normally- react with glutathione and renders harmless
    • process is CYP dependent
    • large doses- deplete GSH and liver toxicity ensues

• single doses of 10-15 g give serious hepatotoxicity
• 20-25 g are potentially fatal
• symptoms- nausea, abdominal pain, anorexia
• induction of CYP increases risk of toxicity
• plasma transaminases elevated 12-36 hrs after ingestion
• clinical indication of hepatic damage 2-4 days
  • liver enzymes peak 72-96 hrs after drug

• nomograms used to predict effects
• activated charcoal to reduce absorption
• N acetylcysteine (mucomyst)
  • indicated for those at risk of injury
  • detoxify NAPQI
  • loading doses given followed by maintenance dose
• aggressive supportive care
• renal failure also possible

• indication- acetomenaphin toxicity (provide enough sulfahydryl groups for the NAPQI to react with)
• adverse reactions
  • rash
  • nausea
  • vomitting
  • diarrhea
  • rare anaphyllactoid rxn

• occasional rashes and other allergic rxns
  • patients hypersensitive to NSAIDs and aspirin are rarely sensitive to acetominophen
• renal tubular necrosis
• hypoglycemic coma

• mechanism
  • inhibits DHFR
  • leads to inhibit DNA syntehsis
  • inhibits immune cell proliferation
  • inhibits disease progression
• indication- RA at low doses to inh. immune system, cancer chemotherapeutic agents

• major mediator of inflammation and immune cell stimulation
• these agents also modify disease process