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Okeliten.orgAspirin vs tramadol

Oral Analgesics for Acute Nonspecific Pain


3.20.2018 | Dylan Leapman
Aspirin vs tramadol
Oral Analgesics for Acute Nonspecific Pain

No ceiling dose; greater analgesia can be obtained by increasing the dosage with no limit except those imposed by side effects.

400 mg ibuprofen safest inexpensive choice; decreases some adverse GI events with misoprostol 800 mg, H 2 blockers, and PPI.

B 6. Acetaminophen in doses up to 1,000 mg is the initial choice for most mild to moderate acute pain.

B. COX-2 inhibitors provide analgesia equal to NSAIDs at greater cost and may be reserved for patients who have a history of GI bleeding and have failed treatment with acetaminophen.

See page 835 for more information. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, opinion, or case series.

One RCT 32 found that dosages of 10 mg per day or less produce fewer endoscopically detected ulcers than naproxen (500 mg twice per day). COX-2 inhibitors are associated with significantly greater numbers of thrombotic cardiovascular events, which offset the increased number of serious GI adverse effects observed with NSAIDs. Higher-dosage valdecoxib (20 mg per day) produced numbers of endoscopic ulcers similar to naproxen. 35. 30 This cardiothrombotic risk led to the recent much-publicized recall of rofecoxib from the U.S. 31 Fewer safety data exist for the newest COX-2 inhibitor, valdecoxib. 34 Initiation of COX-2 inhibitors in elderly patients with hypertension may be associated with significant edema and increased blood pressure. 29 Rofecoxib, in particular, demonstrated a 3.9-fold increase in the incidence of serious thromboembolic adverse events compared with placebo after 18 months of use. In another trial, 33 valdecoxib (10 mg and 20 mg per day) produced fewer endoscopic ulcers than high-dose NSAIDs (800 mg of ibuprofen three times per day or 75 mg of diclofenac twice per day). This is seen particularly with rofecoxib. As with traditional NSAIDs, COX-2 inhibitors may impair renal function and have no benefit over NSAIDs in this area. Despite trials showing decreased endoscopic ulcers, no data have shown a decrease in meaningful or serious adverse effects with valdecoxib versus other NSAIDs. market.

Minimal 6, 8.

A. The first-line NSAID for safety, efficacy, and cost is ibuprofen in doses of 400 mg.

For moderate to severe pain, consider narcotic acetaminophen or narcotic ibuprofen combination. B 36 through 38.

GI, plaet function inhibition, renal dysfunction.

Renal dysfunction; hypertension; thrombotic events.

Codeine, a prodrug, depends on P450 metabolism to morphine for its analgesic effect. A meta-analysis 39 of codeine in a dose of 60 mg for acute pain from surgery and dental extraction trials showed poor efficacy with an NNT of 16.7 (95 percent CI, 11 to 48). This may explain why the literature has shown it to be a relatively poor analgesic. In patients deficient in cytochrome P450 (up to 10 percent of white persons), the drug lacks efficacy.

GI, plaet function inhibition, renal dysfunction.

Acetaminophen Good Minimal. Information from references 6 through 8, 10, 12 through 14, 18 through 20, 22 through 31, and 34 through 41.

NSAIDs = nonsteroidal anti-inflammatory drugs; GI = gastrointestinal; H 2 = histamine 2 ; PPI = proton pump inhibitor; COX = cyclooxygenase.

Once or twice per day, only advantage over most traditional NSAIDs for acute pain.

12 Ibuprofen has shown similar effectiveness to a combination of acetaminophen, codeine, and caffeine for postpartum perineal pain with fewer side effects. For dysmenorrhea, acetaminophen was no better than placebo. In a meta-analysis 12 of randomized controlled trials (RCTs) of analgesics for dysmenorrhea, ibuprofen (Motrin) and naproxen (Aleve, Naprosyn) were equally effective, and both were better than acetaminophen and aspirin. 13. Strong evidence supports the use of nonprescription NSAIDs for dysmenorrhea and acute postpartum pain. Only naproxen had side effects worse than those of placebo.

15 to 20 mg per kg every four to six hours; daily maximum of 4 g.

Based on a cost-effectiveness analysis, researchers concluded that misoprostol should be used only in high-risk patients. 14 Higher prescription doses of naproxen and ibuprofen are associated with increased GI side effects similar to other prescription NSAIDs. 21. Side effects may limit the use of NSAIDs. The most serious side effects include gastrointestinal (GI) bleeding and perforation, renal dysfunction, and plaet dysfunction. 15 Epidemiologic data also support the use of 400 mg of ibuprofen first when choosing an NSAID. 18 Only misoprostol (800 mg per day) has been shown to reduce the risk of other serious upper GI injury (i.e., perforation and/or bleeding). 17 Histamine 2 blockers, misoprostol (Cytotec), and proton pump inhibitors have been shown to reduce the risk of duodenal ulcers with daily NSAID use. Ibuprofen provides an excellent GI safety profile that is not significantly different from placebo in dosages of 800 to 1,200 mg per day. 16 Data from studies of subacute and chronic pain (osteoarthritis of the hip) therapy suggest that higher doses may provide better analgesia, but have more adverse effects. 19, 20 The NNT with misoprostol to prevent one serious GI side effect is 264 patients.

NSAID = nonsteroidal anti-inflammatory drug; COX = cyclooxygenase; GI = gastrointestinal.

A. The first-line NSAID for safety, efficacy, and cost is ibuprofen in doses of 400 mg.

A. Tramadol, propoxyphene, and codeine provide inferior analgesia to other recommended agents.

Cyclooxygenase-2 inhibitors provide equivalent efficacy to traditional NSAIDs but lack a demonstrable safety advantage for the treatment of acute pain. For more severe acute pain, the evidence supports the addition of oral narcotic medications such as hydrocodone, morphine, or oxycodone. The safest NSAID is ibuprofen in doses of 400 mg. Physicians most often recommend or prescribe oral medication for relief of acute pain. Higher doses may offer somewhat greater analgesia but with more adverse effects. Although they may be more expensive, these alternatives may be chosen for their more convenient dosing. This review of the available evidence supports the use of acetaminophen in doses up to 1,000 mg as the initial choice for mild to moderate acute pain. In some cases, modest improvements in analgesic efficacy can be achieved by adding or changing to a nonsteroidal anti-inflammatory drug (NSAID). Specific oral analgesics that have shown poor efficacy and side effects include codeine, propoxyphene, and tramadol. Other NSAIDs have failed to demonstrate consistently greater efficacy or safety than ibuprofen.

An RCT 43 comparing single doses of tramadol and hydrocodone-acetaminophen in 68 patients with soft-tissue pain found significantly lower pain scores in patients receiving hydrocodoneacetaminophen, even using an inadequate dose of 5 mg of hydrocodone with 500 mg of acetaminophen. 44. Tramadol also has proved ineffective for postoperative orthopedic pain. Tramadol, a unique analgesic possessing both opiate and noradrenergic qualities, has been promoted as having improved safety and a decreased abuse potential.

This review focuses on the most commonly used oral analgesics for acute pain available in the United States: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, tramadol (Ultram), and opiates.

22 through 24, 26 to 28.

Sedation, nausea, vomiting, constipation.

SACHS, M.D., M.P.H., University of California, Los Angeles, Emergency Medicine Center, Los Angeles, California. CAROLYN J.

Sedation, nausea, vomiting, constipation.

Hydrocodone (Vicodin; combined with acetaminophen or ibuprofen) Good 2.40 to 8.00.

No evidence that any one NSAID is more effective than another 10, 12 – 14, 18 – 20 Selective COX-2 inhibitors Excellent.

Once or twice per day, only advantage over most traditional NSAIDs for acute pain.

For moderate to severe pain, consider narcotic acetaminophen or narcotic ibuprofen combination. B 36 through 38.

NSAIDs are excellent analgesics with no clinically important difference in efficacy among specific drugs. Higher doses of NSAIDs may be used for anti-inflammatory effects. However, this review focuses only on doses used for analgesia. 10 They are superior to acetaminophen for some types of pain, and in many acute pain settings they provide analgesia equal to usual starting doses of narcotics. 11 However, unlike narcotics that lack a ceiling dose, NSAIDs have a maximum dose above which no additional analgesia is obtained.

15 to 20 mg per kg every four to six hours; daily maximum of 4 g.

No ceiling dose; greater analgesia can be obtained by increasing the dosage with no limit except those imposed by side effects.

Acetaminophen in doses up to 1,000 mg is the initial choice for most mild to moderate acute pain. B 6.

Expensive 22 – 31, 34, 35 Opioids Excellent.

View/Print Table Recommended Acetaminophen Fair $ 0.40 4,000 mg. Information from references 6 through 8, 10, 12 through 14, 18 through 20, 22 through 31, and 34 through 41.

NSAID = nonsteroidal anti-inflammatory drug; COX = cyclooxygenase; GI = gastrointestinal.

Recommended: oxycodone, hydrocodone 36 – 38 Not recommended for acute pain: codeine, propoxyphene, pentazocine 39 – 41.

2 Acute pain generally does not involve the long-term, daily use of analgesics. 1 Unfortunay, considerable confusion exists about the efficacy and safety of commonly used analgesics. This review provides a survey of the best available evidence regarding oral analgesia for acute pain, which is defined as pain associated with new tissue injury that typically lasts less than one month, but at times for as long as six months. Approximay one half of the population reports pain or discomfort that persists continuously or intermittently for longer than three months. View/Print Table. An even greater number of persons are likely to have acute pain at any one time.

Recommended: oxycodone, hydrocodone 36 – 38 Not recommended for acute pain: codeine, propoxyphene, pentazocine 39 – 41.

Symptoms reported with overdose in one case series 45 were the following: lethargy, 26 (30 percent); nausea, 12 (14 percent); tachycardia, 11 (13 percent); agitation, nine (10 percent); seizures, seven (8 percent); coma and hypertension, four each (5 percent); and respiratory depression, two (2 percent). Tramadol can cause serious neurotoxicity in quantities just five times the usual dose. Because of its inferior efficacy and no clear benefit regarding safety compared with other alternatives, tramadol should not be a first-line oral analgesic.

NSAIDs = nonsteroidal anti-inflammatory drugs; GI = gastrointestinal; H 2 = histamine 2 ; PPI = proton pump inhibitor; COX = cyclooxygenase.

28 Comparative trials have confirmed that COX-2 inhibitors are no more or less effective than NSAIDs. A meta-analysis of the oldest COX-2 inhibitor, celecoxib, showed fair to good efficacy for postoperative pain with an NNT of 4.5 (95 percent CI, 3.3 to 7.2) compared with placebo. Valdecoxib (20 mg and 40 mg) has been effective for acute postoperative pain of wisdom tooth extraction with an NNT of 1.6 to 1.7. Traditional NSAIDs inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. Theoretically, these medications could provide analgesia equal to that of traditional NSAIDs without many of the side effects. 22 In several RCTs, 23 – 26 rofecoxib has shown good analgesic efficacy for some acute pain conditions (e.g., joint replacement surgery, dysmenorrhea), but not for others (e.g., tonsillectomy, prostate biopsy). In recent years, three new oral prescription medications (celecoxib, rofecoxib, and valdecoxib ) have been marketed in the United States; they selectively inhibit COX-2 enzymes without inhibiting COX-1 enzymes. Most of the analgesic effects of NSAIDs have been attributed to their COX-2 inhibition, while their undesirable side effects have been attributed to their inhibition of COX-1 enzymes. 27 Valdecoxib also has demonstrated analgesia superior to that of placebo in postoperative knee surgery.

Tramadol, propoxyphene, and codeine provide inferior analgesia to other recommended agents. A.

400 mg ibuprofen safest inexpensive choice; decreases some adverse GI events with misoprostol 800 mg, H 2 blockers, and PPI.

Direct comparative studies between acetaminophen (1,000-mg dose) and NSAIDs show that NSAIDs are more effective than acetaminophen in some situations (e.g., dental and menstrual pain), but provide equivalent analgesia in others (e.g., orthopedic surgery and tension headache). 7, 8.

It also has a worse safety profile than acetaminophen. Aspirin is an effective analgesic for acute pain, but it has not proved more effective than equal doses of acetaminophen. 9.

Figure 1 summarizes this approach. They may be a choice for some patients in whom acetaminophen has been ineffective and NSAIDs are contraindicated because of previous episodes of GI bleeding. Overall points regarding drug classes are listed in Table 1, 6 – 8, 10, 12 – 14, 18 – 20, 22 – 31, 34 – 41 and more specific prescribing information is given in Table 2. 6, 8, 12, 22, 27, 28, 37 – 39, 41, 43, 44, 46, 47 When efficacy, side effects, and cost are balanced, the evidence supports a treatment algorithm for oral acute pain therapy that begins with acetaminophen or ibuprofen for mild to moderate pain and progresses to the use of narcotics (i.e., hydrocodone or oxycodone) in combination with acetaminophen or ibuprofen for severe pain. COX-2 inhibitors provide analgesia equal to traditional NSAIDs for many painful conditions, but lack a better safety profile in acute pain treatment and are significantly more expensive. View/Print Table Acetaminophen Good Minimal.

In a meta-analysis of 40 trials involving 4,171 patients comparing acetaminophen with placebo for postoperative pain, acetaminophen in a dose of 1,000 mg had an NNT of 4.6 (95 percent confidence interval, 3.8 to 5.4) for at least 50 percent pain relief versus placebo. 6. Acetaminophen is a unique analgesic without a clearly defined mechanism. Lower doses were less effective.

Tolerance and physical dependence can occur with chronic use of all opioids, but these are not generally a concern in the treatment of acute pain. No evidence supports the use of agonist/antagonist medications (e.g., pentazocine, butorphanol ) to decrease opioid side effects. One randomized, single-dose postoperative study 42 reported a 20 percent rate of dysphoria with pentazocine and butorphanol versus a 3 percent rate with other opioids. At therapeutically equivalent doses, different narcotics are likely to produce similar levels of side effects such as constipation, respiratory and cardiovascular depression, nausea, and pruritus. While clinical trials have failed to show that any one narcotic has fewer side effects than another in the population as a whole, persons vary greatly with regard to their tolerance for narcotic side effects. In fact, the literature suggests that these medications produce more side effects than more effective narcotics.

The narcotic combination offered little benefit over acetaminophen alone. 41 Thus, propoxyphene provides minimal if any additional analgesia to acetaminophen alone and is associated with significant adverse effects. As with codeine, propoxyphene has poor efficacy and significant side effects. Adverse effects of propoxyphene were similar to those reported in trials of codeine. Another systematic review 41 found that the NNT for a single 65-mg dose of propoxyphene to achieve at least 50 percent pain relief was 7.7 (95 percent CI, 4.6 to 22) when compared with placebo. It cannot be recommended for routine use. A meta-analysis 40 of 26 trials involving 2,231 patients compared the combination of acetaminophen and propoxyphene with acetaminophen alone or placebo. For the combination of propoxyphene and acetaminophen (650 mg), the NNT was 4.4 (95 percent CI, 3.5 to 5.6) when compared with placebo, similar to the NNT for acetaminophen alone.

COX-2 inhibitors provide analgesia equal to NSAIDs at greater cost and may be reserved for patients who have a history of GI bleeding and have failed treatment with acetaminophen. B.

39 through 41, 43, 44.

Expensive 22 – 31, 34, 35 Opioids Excellent.

See page 835 for more information. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, opinion, or case series.

39 through 41, 43, 44.

37 Single-dose oral oxycodone, with or without acetaminophen, appears to be comparable in efficacy to intramuscular morphine and NSAIDs. Opiates are potent and appropriate analgesics for moderate to severe acute pain. Hydrocodone generally is considered the most potent oral narcotic analgesic that does not require specialized prescribing documentation. Another trial 37 found that the combination of 7.5 mg of hydrocodone and 750 mg of acetaminophen was highly effective for the relief of acute pain. Side effects are similar to other narcotics. The results of one RCT 36 found that hydrocodone in a dose of 15 mg with 400 mg of ibuprofen is significantly better than 400 mg of ibuprofen alone for postoperative pain. No substantial evidence supports the notion that any other narcotic has greater efficacy or fewer side effects than morphine (Duramorph). Although use of oral morphine plays a role in the treatment of chronic pain, oral narcotic treatment of acute pain most often involves codeine, propoxyphene (Darvon), hydrocodone (Vicodin), and oxycodone (Roxicodone). However, no literature compares hydrocodone with other oral narcotics. Regular oral morphine takes one hour to work while sustained-release formulations may take two to four hours. 38.

Ibuprofen (Motrin; 400 mg initially) Good 0.24 2,400 mg Minimal 12 Naproxen (Aleve) Good 0.24 1,376 mg Minimal 12.

Underused for acute pain 6 – 8 NSAIDs Excellent.

No evidence that any one NSAID is more effective than another 10, 12 – 14, 18 – 20 Selective COX-2 inhibitors Excellent.

Underused for acute pain 6 – 8 NSAIDs Excellent.

22 through 24, 26 to 28.

Renal dysfunction; hypertension; thrombotic events.

2005 Mar 1;71(5):913-918. Am Fam Physician.

For example, when acetaminophen is said to have an NNT of four compared with placebo, it means that for every four patients who take acetaminophen instead of placebo, at least one patient will experience a 50 percent decrease in pain. It refers to the number of patients who have to use the treatment for one patient to benefit. 3 Other measures of pain relief include average decreases on visual analog scales and functional outcome measures. Much of the literature on oral analgesics defines the efficacy of a specific analgesic as the proportion of patients who need to take that analgesic to experience at least a 50 percent reduction in pain compared with placebo. The lower the NNT, the greater the likelihood that a given patient will achieve a 50 percent reduction in pain. 4, 5. For meaningful analgesia of acute pain, patients must report at least a 13-mm difference between analgesic choices. The concept of number needed to treat (NNT) is a particularly helpful way to convey this outcome. A visual analog scale is a 100-mm line with no pain at one end and severe pain at the other. The other three patients may have a significant decrease in pain (e.g., 40 or 30 percent), but this is not reflected in the NNT.

Aspirin vs tramadol