Intranasal ketorolac: for short-term pain management

Ketorolac is a member of the pyrrolo-pyrrole group of NSAIDs, and has been available in several formulations for some time, for the treatment of pain. Intranasal ketorolac has recently become available. Intranasal ketorolac was effective in providing short-term relief from postoperative pain in four well designed, phase II or III trials. In the two phase III trials, a single intranasal dose of ketorolac 31.5?mg, with or without backup analgesia, was associated with significantly higher 6-hour summed post-treatment pain intensity difference scores (primary endpoint) than placebo in adult patients with acute pain following major surgery, including abdominal and orthopaedic surgery. Intranasal ketorolac 31.5?mg up to three or four times daily for ≤5 days also had an opioid-sparing effect in these trials, with significantly less morphine used among ketorolac than among placebo recipients over the first 48 hours of treatment. Moreover, a greater proportion of ketorolac recipients experienced analgesia onset within 1 and 1.5 hours but not 2 hours than placebo recipients, indicating a more rapid onset with intranasal ketorolac. In adult patients with acute pain following major surgery, intranasal ketorolac 31.5?mg three or four times daily for ≤5 days was generally well tolerated. Most adverse events in clinical trials were considered to be of mild severity and transient in nature, with those in the phase III trials generally being characteristic of common events following major abdominal surgery and morphine administration.     

Minimising the adverse effects of ketorolac.

Gastrointestinal bleeding and perforation, platelet inhibition with altered haemostasis, and renal impairment are among the list of adverse effects associated with the administration of ketorolac. The incidence of serious adverse events has declined since dosage guidelines were revised. Most of the published literature suggests that the overall risk of gastrointestinal or operative site bleeding related to ketorolac therapy is only slightly higher than with opioids. The risk for adverse events, however, increases with high doses, with prolonged therapy (>5 days) or in vulnerable patients (e.g. the elderly). Acute renal failure has been reported after ketorolac treatment but is usually reversible after discontinuation of the drug. As with other nonsteroidal anti-inflammatory drugs (NSAIDs), ketorolac may trigger allergic or hypersensitivity reactions. Careful patient selection is essential if use of ketorolac is considered. Contraindications to ketorolac use include a history of, or current risk of, gastrointestinal bleeding, risk of renal failure, compromised haemostasis, hypersensitivity to aspirin (acetylsalicylic acid) or other NSAIDs, labour, delivery and nursing. Ketorolac should be prescribed at the lowest dosage necessary to control pain; the duration of therapy should also be limited to as few days as possible. Practitioners should be familiar with, and follow, label warnings and dosage guidelines.     

地佐辛与酮咯酸氨丁三醇在颈髓过伸伤的镇痛效果比较

目的 回顾性分析比较地佐辛与酮咯酸氨丁三醇在颈髓过伸伤中不同疼痛程度的患者的镇痛效果,指导合理选择镇痛药物. 方法 回顾性分析2012年12月至2015年12月解放军第98医院80例颈髓过伸伤出现痛觉过敏患者的病历资料,以长海痛尺评分评定患者疼痛程度,长海痛尺评分≥3分为用药指征,随机分为观察组和对照组,观察组给于地佐辛7.5mg肌注,对照组给于酮咯酸氨丁三醇60mg肌注,比较2组对于不同疼痛程度患者用药后疼痛评分情况,3分以下为有效,≥3分为无效镇痛,并观察2组用药后发生的不良反应情况. 结果 从镇痛有效率比较,2组用药30min后,中重度疼痛,观察组有效率100.0%,对照组有效率94.7%,差异无统计学意义(P>0.05),均为有效镇痛.剧烈以上疼痛,观察组镇痛有效率95.0%,对照组有效率仅为42.9%,差异有统计学意义(P<0.01),地佐辛镇痛效果优于酮咯酸氨丁三醇.从镇痛前后疼痛评分比较,2组在中重度疼痛镇痛后评分差异无统计学意义(P>0.05);观察组与对照组剧烈以上疼痛镇痛后评分分别为(1.32±0.99)、(3.40±2.20),差异有统计学意义(P<0.05).观察组药品不良反应发生率(20.0%)高于对照组(7.5%),差异有统计学意义(P<0.05). 结论 在颈髓过伸伤的镇痛治疗中,中重度疼痛可选择地佐辛或酮咯酸氨丁三醇,剧烈以上疼痛地佐辛镇痛效果明显优于酮咯酸氨丁三醇,但地佐辛不良反应率较高,因此临床用药上建议根据疼痛评分来合理选择镇痛药.     

The role of COX-2 in acute pain and the use of selective COX-2 inhibitors for acute pain relief

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain. Cyclooxygenase (COX) enzyme is of particular interest because it is the major target of NSAIDs. Although NSAIDs are remarkably effective in the management of pain and inflammation, their use is limited by several adverse effects including gastrointestinal bleeding and ulceration, impaired renal function, and inhibition of platelet aggregation. Discovery of a second cyclooxygenase, COX-2, led to the hypothesis that NSAID side effects could be decreased, as the inhibition of COX-2 is more directly implicated in ameliorating inflammation while the inhibition of COX-1 is related to adverse effects in the GI tract. This stimulated the development of selective COX-2 inhibitors (coxibs) that are better tolerated than nonselective NSAIDs but comparable in analgesic efficacy. This article provides an overview on the therapeutic use of selective COX-2 inhibitors for relief of acute pain, largely based on clinical trials in patients undergoing the surgical removal of impacted third molars, with focus on analgesic efficacy and the potential safety associated with their use compared to dual COX-1/COX-2 inhibitors.     

Comparison of intramuscular ketorolac tromethamine and morphine sulfate for analgesia of pain after major surgery

Ketorolac tromethamine is a new injectable nonnarcotic analgesic. In a parallel, double-blind study, the analgesic efficacies of single intramuscular doses of ketorolac 10, 30 and 90 mg were compared with those of morphine sulfate 6 and 12 mg. Two hundred forty-one patients were categorized according to type of surgical procedure and severity of pain. Pain intensity and pain relief were assessed for 6 hours by scoring standard verbal and visual analog scales. Patients receiving ketorolac 10, 30 or 90 mg or morphine (MS) 12 mg all had significantly better pain relief in almost all measurements performed than those receiving MS 6 mg (p less than 0.05). Ketorolac 10 and 30 mg were as effective as morphine 12 mg during the entire 6-hour observation period, and ketorolac 90 mg was more effective than morphine 12 mg during the entire 6 hours. Patients with pain related to major surgery (e.g., cholecystectomy and abdominal hysterectomy) were better able to distinguish analgesic potency of morphine than those having less traumatic procedures (e.g., tendon and ligament repairs).     

A double-blind study with placebo control of intramuscular ketorolac tromethamine in the treatment of cancer pain

The analgesic efficacy of ketorolac tromethamine was compared to placebo in 126 patients suffering moderate or severe chronic pain due to cancer in a double-blind parallel randomized study. Ketorolac was administered intramuscularly in doses of 10, 30 or 90 mg. Pain intensity and pain relief were assessed for 6 hours by scoring standard verbal scales and an overall assessment of the medication was given by the patients and the observer on completion of the study. Each dose of ketorolac was statistically superior to placebo for the sum of pain intensity difference (SPID) but no difference was seen between the three ketorolac regimens. When the ketorolac groups are combined, there was a significantly better pain relief as compared to placebo. The global evaluation scores were also statistically superior in the ketorolac groups combined than in the placebo group. A total of 15 patients reported minor adverse events, 10 being after ketorolac doses. This study shows that single intramuscular doses of ketorolac of 10 mg and above are effective in the relief of cancer pain, and are associated with a low incidence of side-effects.     

Ketorolac, an injectable nonnarcotic analgesic

Clinical studies of the injectable nonsteroidal anti-inflammatory agent (NSAIA) ketorolac tromethamine are reviewed, and the chemistry, pharmacology, pharmacokinetics, drug interactions, and adverse effects of ketorolac are described. Ketorolac exhibits anti-inflammatory, analgesic, and antipyretic activity. Although the exact mechanisms of action have not been determined, its effects appear to be associated principally with the inhibition of prostaglandin synthesis. After oral, i.m., or i.v. administration, ketorolac and its metabolites are excreted mainly in urine. Ketorolac tromethamine has been used for the symptomatic relief of moderate to severe postoperative pain, including that associated with abdominal, gynecologic, oral, orthopedic, or urologic surgery. Ketorolac has also been used for the relief of acute renal colic, pain associated with trauma, and visceral pain associated with cancer. When administered i.m., ketorolac produced analgesia comparable to that of i.m. doses of meperidine, pentazocine, or morphine. The most common adverse effects associated with short-term administration are nervous system and gastrointestinal effects; these are usually mild and occur in about 39% of patients. Unlike opiate analgesics, ketorolac does not appear to cause tolerance or physical dependence in patients receiving long-term therapy. Ketorolac tromethamine has been administered concomitantly with morphine or meperidine without apparent adverse interaction. For short-term pain management, an initial i.m. ketorolac tromethamine loading dose of 30 or 60 mg is recommended. Ketorolac tromethamine appears to be as effective as morphine or meperidine for short-term management of moderate to severe postoperative pain. It lacks the respiratory depressant effects of opiate analgesics but shares the toxic potentials of other NSAIAs.     

酮咯酸氨丁三醇在预防鼻窦手术术后疼痛中的应用

目的:探讨酮咯酸氨丁三醇对鼻内镜下鼻窦手术术后早期疼痛的预防效果及安全性。方法:取60例择期行鼻内镜下鼻窦手术成年患者,随机分为酮咯酸组和芬太尼组,均采取全凭静脉麻醉,于雷米芬太尼停止泵入前15min分别静脉予以酮咯酸氨丁三醇30mg或芬太尼50μg,观察术后疼痛及出血情况。结果:两组患者术后疼痛(30min 3.2±1.3vs 3.4±1.5,60min 2.0±1.1vs2.8±2)及出血情况(鼻出血VAS评分6.6±3.1VS 5.1±3.1,痰中带血VAS评分3.1±1.8vs 3.4±1.8,更换敷料VAS评分5.2±3.5vs 4.3±3.4)差异均无统计学意义。结论:手术结束前静脉给予酮咯酸氨丁三醇可以较好的替代麻醉性镇痛药用于预防鼻内镜下鼻窦手术的成年患者术后镇痛而不增加术后出血风险。     

Pharmacological treatments for persistent non-malignant pain in older persons

Persistent non-malignant pain is common, often neglected and under-treated among older persons. Some older adults do not complain because they consider chronic pain to be a characteristic of normal aging. Physicians have concerns regarding adverse effects of pharmacological treatment. The model of the World Health Organization for treatment of cancer pain is generally accepted and also recommended for persistent non-cancer pain. Furthermore, non-pharmacological treatment should complement drug treatment whenever possible. An initial assessment and possible treatment of underlying causes of pain are pertinent. Modern pharmacological pain management is based on non-opioid and opioid analgesics. NSAIDs are among the most widely prescribed class of drugs in the world. The new cyclo-oxygenase-2 inhibitors such as celecoxib and rofecoxib offer an alternative for the treatment of mild-to-moderate pain in patients with a history of gastric ulcers or bleeding. Paracetamol (acetaminophen) is being used widely for the management of mild pain across all age groups as it has moderate adverse effects at therapeutic dosages. For moderate pain, a combination of non-opioid analgesics and opioid analgesics with moderate pain relief properties (e.g. oxycodone, codeine, tramadol and tilidine/naloxone) is recommended. For severe pain, a combination of non-opioid analgesics and opioid analgesics with strong pain relief properties (e.g. morphine, codeine) is recommended. The least toxic means of achieving systemic pain relief should be used. For continuous pain, sustained-release analgesic preparations are recommended. Drugs should be given on a fixed time schedule, and possible adverse effects and interactions should be carefully monitored. Adjuvant drugs, such as antidepressants or anticonvulsants, can be very effective especially in the treatment of certain types of pain, such as in diabetic neuropathy. Effective pain management should result in decreased pain, increased function and improvement in mood and sleep.     

Report of an anaphylactoid and an anaphylactic reaction to ketorolac in two pediatric surgical patients

Ketorolac is a potent analgesic drug that has been restricted in dosage and use because of its potential adverse effects. The diagnostic and ethical challenges of 2 children who had unpredictable adverse drug reactions to ketorolac are reported. Case 1: A 3-year-old boy received ketorolac 1 mg/kg for prevention of postoperative pain at the end of an orthopedic surgical procedure. Ten minutes later, he had bilateral palpebral edema, erythema in thorax, hypotension, and tachycardia. The adverse event was classified as a mixed reaction probably related to ketorolac. Case 2: A 7-year-old girl, who had previously received ketorolac in 2 different surgical procedures, underwent a third orthopedic surgery. She received ketorolac 1 mg/kg as pre-emptive analgesia at 1.5 hours of anesthetic time (approximately 1 hour of surgical time). The patient developed palpebral edema 5 minutes later in addition to erythema in thorax, hypotension, tachycardia, tachypnea, oxygen desaturation, and wheezing. The adverse event was classified as a systemic reaction probably related to ketorolac. The 2 patients were successfully treated with symptomatic therapy. Although rare in its frequency, ketorolac administration may be associated to anaphylactic and anaphylactoid reactions in children with or without history of previous exposure. Because ketorolac is off-licensed for pediatric patients, it should be administered only after the risks and benefits have been discussed with the child's parents in the preanesthetic consultation.     

Analgesia in PACU: nonsteroidal anti-inflammatory drugs

Control and abolition of pain during and after surgical procedures is crucial point in the practice of anaesthesiology. In the last years the concept of multimodal analgesia (the use of different analgesic and techniques to relieve pain), has developed and non-steroidal anti-inflammatory drugs (NSAIDs) have a major role in it, because they have an opioid sparing effect. Moreover, they are very effective on somatic and breakthrough pain. NSAIDs can be divided functionally in four classes: salicylates, acetaminophen, non-specific inhibitors (i.e. ibuprofen, ketorolac, etc.) and cyclooxygenase2-inhibitors (coxibs). The target of action of these drugs is the different isozymes of the Prostaglandin G/H synthase, called Cyclooxygenases (COX). At least three different types of COX have been identified, which are probably organ specific. These isozymes play a crucial role in the developing of the inflammatory cascade, and in the genesis of various pain mediators released from tissue injury. Their most important side effects affect mainly gastrointestinal system, the kidney and the coagulation system. Less important are the effects on the liver and the immunologic system (asthma). The analgesic nephropathy and the coagulopathy must be taken into account in the surgical patient, for the possibility of increase perioperative morbidity. Very recently the newest class of coxibs, although they reduce g.i. bleeding and coagulopathy, have proved to increase the risk of cardiovascular accidents both in long term therapy than postoperatively in cardiac surgical patients. Many data are needed, but in patients at high risk of cardiac disease other NSAIDs should be considered.     

Postoperative pain control in children: a guide to drug choice

Postoperative pain in children can usually be well controlled with a combination of analgesics, including acetaminophen (paracetamol), NSAIDs, opioids, and local/regional anesthesia. Recent research has shown that the dosage of acetaminophen required to provide analgesia is higher than the traditional dosages used for the regulation of elevated body temperature. Rectal administration of acetaminophen gives a lower and more variable bioavailability compared with oral administration. There is growing experience with the use of NSAIDs in children and several studies have demonstrated the relatively strong analgesic potential of these drugs. Titration of opioids to analgesic effect, and the use of nurse- and patient-controlled continuous opioid infusions in children have gained widespread use and, with proper education and supervision, are considered excellent methods of pain control. Local peripheral and central blocks decrease the need for anesthetics during surgery and provide effective postoperative pain relief.     

Lornoxicam,a new potent NSAID with an improved tolerability profile

Lornoxicam is a member of the oxicam group of nonsteroidal antiinflammatory drugs (NSAIDs). Oxicams have potent antiinflammatory and analgesic effects, but their use is associated with a high risk of gastrointestinal adverse effects. Lornoxicam has been shown to be at least as effective as comparative NSAIDs and more effective than 10 mg morphine when used at doses > or = 8 mg to control pain after oral surgery. In addition, oral doses of lornoxicam of 16-24 mg daily have been more effective than tramadol 300 mg daily in pain following knee surgery. Lornoxicam combines the high therapeutic potency of oxicams with an improved gastrointestinal toxicity profile as compared to naproxen, for example. This is probably due to the short half-life of lornoxicam as compared to the other oxicams. The clinical trials published so far, mostly comparative, clearly do- cument the efficacy of lornoxicam as a potent analgesic with excellent antiinflammatory properties in a range of painful and/or inflammatory conditions, including postoperative pain and rheumatoid arthritis.     

Parecoxib: new preparation. A NSAID for postoperative pain: no proven advantage

(1) Parecoxib is the second nonsteroidal antiinflammatory drug, after ketoprofen, to be marketed in France for the treatment of postoperative pain. (2) Another injectable NSAID, ketorolac, was marketed briefly in the 1990s. It was shown to be no more effective than ketoprofen, but was withdrawn from the French market because it provoked bleeding. (3) The clinical evaluation dossier on parecoxib contains no data from comparative trials with ketoprofen. The three trials versus ketorolac failed to show that parecoxib was more effective. (4) The two trials comparing parecoxib with morphine are biased by the use of a too low dose of morphine (4 mg). Four trials show that adding parecoxib reduces morphine requirements in patients injecting the opiate on demand. There is no evidence that this reduction translates into a lower risk of adverse reactions to opiates. (5) Parecoxib is marketed as "Cox-2-specific inhibitor", but follow-up is too short to show whether this property avoids the severe adverse effects seen with other NSAIDs, such as renal failure, gastrointestinal haemorrhage, and delayed wound healing. Parecoxib, like its principal metabolite valdecoxib, can cause severe hypersensitivity reactions. (6) Parecoxib is 10 times more expensive than injectable ketoprofen in France. (7) In practice, ketoprofen is still the best choice for parenteral NSAID-based pain relief in the postoperative setting.     

Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential

Ketorolac is a non-steroidal agent with potent analgesic and moderate anti-inflammatory activity. It is administered as the tromethamine salt orally, intramuscularly, intravenously, and as a topical ophthalmic solution. Clinical studies indicate single-dose efficacy greater than that of morphine, pethidine (meperidine) and pentazocine in moderate to severe postoperative pain, with some evidence of a more favourable adverse effect profile than morphine or pethidine. In single-dose studies ketorolac has also compared favourably with aspirin, paracetamol (acetaminophen) and a few other non-steroidal anti-inflammatory drugs. If further investigation confirms the initially favourable findings regarding efficacy and tolerability, ketorolac will be a useful alternative to opioid agents in postsurgical pain. It may well also find use in acute musculoskeletal pain, where it appears at least as effective as other agents with which it has been compared. From the limited clinical data available, ketorolac also seems promising in the treatment of ocular inflammatory conditions. Additional multiple-dose studies are required to evaluate fully the potential of ketorolac in the management of chronic pain states where it has shown superior efficacy to aspirin. In summary, ketorolac offers promise as an alternative to opioid and to other nonsteroidal analgesics in ameliorating moderate to severe postsurgical pain, and with wider clinical experience may find a place in the treatment of acute musculoskeletal and other pain states, and ocular inflammatory conditions.     

A double-blind single dose comparison of intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic

The efficacy of a single dose of intramuscular ketorolac 10 mg or 90 mg was compared with pethidine 100 mg in a randomized double-blind study in 121 patients reporting at least moderate pain due to renal colic. Pain was assessed before drug administration, and then at 1 hour and 12 hours after the dose. Sedation was also assessed at these times, and additionally at the 12 hour assessment the time of the next analgesic dose was recorded. At 1 hour after dosing, pain scores had decreased in all groups; the largest decrease was seen in the ketorolac 90 mg group. The difference in the decrease was significant between the two ketorolac groups, but the differences between ketorolac and pethidine were not significant. Fewer patients in the ketorolac 90 mg group (17%) required a further dose of analgesic within 10 hours than in either the ketorolac 10 mg group (39%) or the pethidine 100 mg group (47%). The difference between ketorolac 90 mg and pethidine 100 mg was statistically significant. At both assessment times the proportion of patients with no sedation was higher in the two ketorolac groups than in the pethidine group. The overall incidence of adverse events was low with all drugs, notably so for the occurrence of vomiting after ketorolac. The results of the study show that intramuscular ketorolac is efficacious in the treatment of renal colic.     

Ketorolac, a new non-opioid analgesic: a single-blind trial versus buprenorphine in pain after orthopaedic surgery

A randomized single-blind, double-observer trial was performed to evaluate the efficacy of a new non-steroidal anti-inflammatory analgesic drug, ketorolac, in the treatment of post-orthopaedic surgery pain. Sixty patients with moderate to severe pain were studied; 30 patients were treated with ketorolac at a dose of 30 mg intramuscularly up to 4-times a day, whilst the other 30 patients received 0.3 mg buprenorphine intramuscularly up to 4-times a day. A significant reduction in the severity of the pain was recorded in both groups. Throughout the study, comparable efficacy was found between the two therapies although buprenorphine showed greater efficacy during the first 8 hours. Interestingly, the withdrawals due to adverse events were significantly less in the ketorolac group (p less than 0.001). This study, therefore, suggests that ketorolac may be a useful and more acceptable alternative to buprenorphine in the treatment of post-orthopaedic surgery pain.     

酮咯酸氨丁三醇联合盐酸哌替啶治疗肾绞痛的临床观察

目的:观察酮咯酸氨丁三醇联合盐酸哌替啶治疗肾绞痛的临床疗效。方法:将我院2008年5月-2010年5月收治的中、重度疼痛的肾绞痛患者120例随机均分为3组,均采取肌肉注射药物进行镇痛治疗。其中,Ⅰ组应用酮咯酸氨丁三醇60mg;Ⅱ组应用盐酸哌替啶100mg;Ⅲ组应用酮咯酸氨丁三醇30mg+盐酸哌替啶50mg。记录用药前以及用药后3h内(0、0.5、1、1.5、2、2.5、3h)的疼痛强度、疼痛强度差、疼痛缓解度以判断镇痛效果,并观察各组治疗中的不良反应情况。结果:用药后,3组均在0.5h起效,在中度疼痛的镇痛方面,Ⅲ组在用药3h内的所有观察点均优于Ⅰ、Ⅱ组(P<0.05),在2h时差异最为显著(P<0.01);在重度疼痛的镇痛方面,Ⅲ组在用药1.5、2、2.5、3h时效果优于Ⅰ、Ⅱ组(P<0.05);Ⅲ组的中度以上疼痛缓解程度除0.5h外,其余各点与Ⅰ、Ⅱ组比较,差异均有统计学意义(P<0.05)。Ⅲ组不良反应的发生率小于其他2组(P<0.05)。结论:酮咯酸氨丁三醇联合盐酸哌替啶治疗肾绞痛效果显著,同时可减少盐酸哌替啶的使用量,并可延长镇痛时间,且安全性较好。     

Weak opiate analgesics: modest practical merits

(1) The first-line drugs for mild to moderate pain are non opiate analgesics, namely paracetamol and nonsteroidal antiinflammatory drugs (NSAIDs). (2) Codeine, dextropropoxyphene and tramadol are weak opiates; they are often used with paracetamol in fixed-dose combinations, in order to reinforce the analgesic effect of paracetamol. (3) These analgesic combinations have only been evaluated in a few situations associated with chronic and acute pain. And the endpoints used in clinical trials are designed more to show statistically significant differences than clear clinical differences. (4) In acute pain, available meta-analyses confirm that the first-line drug is paracetamol, or, if necessary, ibuprofen, a NSAID. (5) The paracetamol + codeine combination slightly increases the analgesic effect of paracetamol, but causes more adverse effects. Combinations of paracetamol + dextropropoxyphene and paracetamol + tramadol are even less useful. (6) The few available clinical trials fail to demonstrate that combining paracetamol with a NSAID is any more effective than either drug given alone, while adverse effects are increased. (7) Paracetamol is also the first-line treatment for chronic non cancer pain, such as low back pain or pain due to osteoarthritis of the hip. NSAIDs have no advantages over paracetamol in these settings. We found no trials of paracetamol + NSAID combinations. Combinations of paracetamol and weak opiates have been inadequately studied in this situation, and are only second-line options.     

Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain

Chronic pain is a debilitating condition that is associated with many common diseases; this places a major burden on the healthcare system. There are currently numerous analgesic agents available for the treatment of chronic pain. In general, the oral non-opioid analgesic, paracetamol, is recommended for the initial treatment of mild to moderate pain. Therapeutic doses of paracetamol do not appear to result in hepatotoxicity, although overdose may lead to acute liver failure. Current data suggest that paracetamol has acceptable gastrointestinal tolerability. Another class of non-opioid analgesic with confirmed efficacy for the treatment of chronic mild to moderate pain are non-steroidal anti-inflammatory drugs (NSAIDs), although this efficacy is offset by the potential of adverse gastrointestinal events. In particular, non-selective NSAIDs, also known as cyclooxygenase (COX) inhibitors, carry an increased risk of serious upper gastrointestinal complications, including ulcers, perforation and bleeding. The introduction of COX-2 inhibitors provided a NSAID-based option with improved gastrointestinal safety, but increased risk of cardiovascular effects. Opioids are powerful analgesic agents used to treat moderate to severe chronic pain. However, treatment with opioids is associated with a number of common adverse effects, including constipation, nausea or vomiting, pruritus, somnolence or cognitive impairment, dry mouth, tolerance or dependence and urinary retention. Although there are multiple strategies in place to manage adverse events that arise from both non-opioid and opioid analgesic therapy, a better understanding of the mechanisms involved in the development of specific drug-related adverse effects is required along with proper prescribing practices and adequate physician/patient education. Balanced against the adverse effects of pain management medications, there is a need to be mindful of the widespread, often serious, adverse consequences of poorly managed pain itself.