Acetaminophen Acetaminophen is a common choice for treating fevers as well as easing pain. Its mechanism of action in analgesia is unclear, but it is thought to reduce the synthesis of prostaglandins in the central nervous system. Acetaminophen does not exhibit anti- inflammatory effects in the peripheral nervous system and is typically reserved for pain without inflammation. Even though it is commonly used, there is only limited evidence of its efficacy in treating chronic pain. However, it is known to provide analgesic effects for some patients, and it is reasonable to consider using acetaminophen as an adjunct for mild to moderate musculoskeletal pain. 128,129 Typical doses of acetaminophen are 325-650mg every 4 to 6 hours, or 1000mg up to three times daily. Acetaminophen is associated with hepatotoxicity when taken in high doses, particularly in cases of acute or chronic overdose; therefore, the maximum daily dose should be limited. There is some debate over the maximum daily dose of acetaminophen. The Food and Drug Administration recommends a maximum dose of 4 grams per day. However, when used long term, many experts recommend a maximum of 3000mg per day, and even lowering this to 2000mg per day in older patients, patients who have or are at risk of liver disease such as those with alcohol use disorder or malnourishment, and patients with organ dysfunction. 129,130 While acetaminophen does not appear to interact with platelet function or increase the risk of bleeding, it is known to interact with warfarin and may require more frequent INR monitoring. It also interacts with isoniazid and other agents that induce the CYP450 enzyme system. 130 Acetaminophen is found in a number of prescription and over-the-counter products. Patients should be counseled to be aware of the acetaminophen content of other products they are taking and to avoid exceeding their daily limit. 130 Nonselective Non-steroidal anti-inflammatory agents (NSAIDs) Nonselective non-steroidal anti-inflammatory agents (NSAIDs) decrease pain and inflammation by blocking cyclooxygenase (COX), thereby decreasing the production of prostaglandins. There are two isoforms of cyclooxygenase, COX-1 and COX-2. COX-2 is upregulated in inflammatory states and is involved in the production of prostaglandins; COX-1 is found in most tissues and regulates normal cellular processes such as gastric protection, platelet aggregation, kidney function, and vascular homeostasis. Nonselective NSAIDs block both COX-1 and COX-2, leading to anti- inflammatory effects as well as adverse reactions. 111,131 NSAIDs are a mainstay of treatment in musculoskeletal pain with an inflammatory component, such as menstrual cramps or muscle sprains. More than 17 million Americans use NSAIDs on a daily basis, making them one of the most commonly used classes of medications in the world. 130 However, the efficacy of these medications in pain without ongoing inflammation, such as low back pain, is low. 111,129
Examples of nonselective NSAIDs and their typical dosages used for analgesia include: 111 ● Naproxen, 250-550mg every 12 hours ● Ibuprofen, 400mg every 4 to 6 hours ● Ketoprofen, 50mg every 6 hours or 75mg every 8 hours ● Flurbiprofen, 50 to 100mg every 6 to 12 hours ● Etodolac, immediate release 200 to 400mg every 6 to 8 hours, or extended-release 400 to 1000mg daily ● Indomethacin, immediate release 25 to 50mg every 8 to 12 hours, or controlled release 75mg once or twice daily ● Sulindac, 150 to 200mg every 12 hours ● Meloxicam, 7.5 to 15mg once daily ● Piroxicam, 10 to 20mg once daily A variety of side effects are associated with NSAIDs; ● Oxaprozin, 1200mg once daily ● Diclofenac, 50mg every 8 hours the risk of developing side effects is increased with high, frequent dosing or longer durations. Gastrointestinal effects, such as dyspepsia, peptic ulcer disease, and bleeding, are more likely in patients over 60, those with a prior history of a gastrointestinal event, those taking high doses of NSAIDs, or those taking glucocorticoids, antiplatelet drugs, or anticoagulants. Gastrointestinal effects may be reduced by taking the drug with food, milk, or antacids. Adverse effects on the kidneys can include worsening of underlying hypertension, electrolyte and fluid abnormalities, and an increased risk of acute renal failure and renal cell cancer. Patients with existing glomerular disease, hypercalcemia, renal insufficiency, or volume depletion conditions are at an increased risk of developing acute renal failure. 111,130 Both chronic and short-term use of NSAIDs is associated with an increased risk of myocardial infarction or stroke. In addition, NSAIDs can exacerbate heart failure through sodium and water retention and increases in blood pressure. This risk can be minimized by using the lowest effective dose for the shortest duration possible. Hepatic enzymes can be elevated by NSAIDs, but liver failure is rare. Other rare side effects include anaphylaxis, pulmonary effects such as bronchospasm or pulmonary infiltrates, neutropenia, tinnitus, and life-threatening rashes such as Stevens-Johnson syndrome. 111,130 NSAIDs have antiplatelet effects that can be beneficial in some patients, such as using aspirin for cardiac prophylaxis in patients with coronary heart disease. However, these effects can create issues in patients with preexisting platelet deficits or when considering surgery. For most NSAIDs, platelet function normalizes within 3 days of discontinuation, suggesting that NSAIDs should generally be discontinued at least 3 days prior to surgery. The antiplatelet effects of NSAIDs can be exacerbated when combined with other antiplatelet agents or anticoagulants, increasing the risk of bleeding. Therefore, NSAIDs should be avoided if possible in patients taking blood thinning agents. Certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) also appear to
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Book Code: CA23CME
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