TABLE 322 Comparison of Pharmacologic Agents

Analgesics are the drugs most often associated with adverse drug events, with similar rates for overmedication as for undermedication despite the likely reporting bias for overmedication. Sedatives are the next most likely category of medication to cause adverse reactions.9

NONOPIOID AGENTS Acetaminophen (paracetamol in some countries) is an effective analgesic, adequate for mild to moderate pain. Its efficacy is significantly enhanced when it is combined with codeine. Acetaminophen does not affect platelet aggregation, nor is it anti-inflammatory. Acetaminophen may be hepatotoxic above 140 mg/kg per day in the setting of normal hepatorenal function.

NSAIDs are a class of drugs including aspirin, naproxen, indomethacin, ibuprofen, and ketorolac (standard doses are shown in T§bl§..,3.2-3). In therapeutic doses these agents decrease levels of inflammatory mediators generated at the site of tissue injury. They do not cause sedation or respiratory depression or interfere with bowel or bladder function.10 Even when insufficient alone, NSAIDs have significant opioid dose-sparing effects. There are oral, rectal, intravenous, and topical preparations. The NSAID ketorolac is approved by the U.S. Food and Drug Administration for parenteral use. Topical NSAIDs, effective in acute musculoskeletal injuries, are associated with the lowest side-effect profile.11 They are available in Australia and the United Kingdom but currently not in the United States. Adverse effects of NSAIDs include platelet dysfunction, impaired coagulation, and gastrointestinal irritation and bleeding; hence they should be used with care in patients with thrombocytopenia or coagulopathies and in those at risk for bleeding or gastric ulceration. Acute renal failure has been reported and may be precipitated in patients who are volume depleted or have lost more than 10 percent of their blood volume, have preexisting renal or cardiac disease, or are taking loop diuretics. Ibuprofen is safer than ketorolac in this respect.12

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