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PubMed2004

A reassessment of trends in the medical use and abuse of opioid analgesics and implications for diversion control: 1997-2002.

This study updates a previous analysis of trends in medical use and abuse of opioid analgesics, and provides data from 1997 through 2002. Two research questions were evaluated: 1) What are the trends in the medical use and abuse of frequently prescribed opioid analgesics used to treat severe pain, including fentanyl, hydromorphone, meperidine, morphine, and oxycodone? 2) What is the abuse trend for opioid analgesics as a class compared to trends in the abuse of other drug classes? Results demonstrated marked increases in medical use and abuse of four of the five studied opioid analgesics. In 2002, opioid analgesics accounted for 9.85% of all drug abuse, up from 5.75% in 1997. Increase in medical use of opioids is a general indicator of progress in providing pain relief. Increases in abuse of opioids is a growing public health problem and should be addressed by identifying the causes and sources of diversion, without interfering with legitimate medical practice and patient care.

Analgesics, Opioid↗

PubMed2004

Opioids in renal failure and dialysis patients.

This article reviews the literature pertaining to the metabolism of several of the commonly used opioids, and the known activity of their metabolites. The effect of renal failure on the pharmacokinetics of these drugs and metabolites is then reviewed. Finally, the effect of renal dialysis on opioid drugs and metabolites is reviewed. Based on the review, it is recommended that morphine and codeine are avoided in renal failure/dialysis patients; hydromorphone or oxycodone are used with caution and close monitoring; and that methadone and fentanyl/sufentanil appear to be safe to use. Note is made that the "safe" drugs in renal failure are also the least dialyzable.

Analgesics, Opioid↗

PubMed2006

The validity and utility of the BPI interference measures for evaluating the impact of osteoarthritic pain.

The psychometric properties of the Brief Pain Inventory (BPI), a widely used measure of pain and its impact on functioning, were assessed using data from two clinical trials of controlled-release oxycodone in osteoarthritis (OA) patients. Specifically, the pain-related functional interference subscale and the sleep item from that subscale were examined. In Study 1 (n = 133), "night awakenings with pain" was positively correlated with the BPI interference score and sleep item and both correlated negatively with "quality of sleep." In Study 2 (n = 107), pain experienced "at night while in bed" correlated higher with sleep interference than with the BPI interference subscale. Intraclass correlations denoted adequate test-retest reliability; moderate-to-large Guyatt's statistics provided evidence of responsiveness. These analyses address a gap in the literature regarding the psychometric properties of the BPI interference measures in noncancer pain patients, confirming their reliability, validity, and responsiveness as potential endpoints in trials of pain medications involving patients with OA.

Aged↗

PubMed2006

Drug utilization review on a tertiary palliative care unit.

Drugs are indispensable for the management of symptoms in palliative care patients, and account for a significant proportion of expenditures on a Tertiary Palliative Care Unit (TPCU). Drug expenditures for Edmonton's TPCU increased by 40% in 2002 compared to 2001. Fifty-five percent of the increase was attributable to injectable fentanyl, oral and injectable ondansetron, and total parenteral nutrition (TPN). As there was no increase in the unit cost of these drugs between 2001 and 2002, the increased expenditures reflected increased utilization. The hypothesis of this study was that the increased utilization of these drugs reflected appropriate prescribing. The objective was to compare the indications for prescribing these drugs in 2002 against evidence- and consensus-based criteria. Patients who received these drugs while admitted to the TPCU from January 1 to December 31, 2002 were identified through the pharmacy database. Evidence- and consensus-based criteria for drug utilization were developed. Prescribing indications were retrospectively compared against the criteria. Drug prescriptions were categorized as follows: (1) meeting criteria, (2) not meeting criteria, or (3) uncertain. The drugs under study were prescribed during 48 out of 234 admissions to the TPCU in 2002. Prescriptions for fentanyl met criteria in 26 of 29 cases. Indications were unsuccessful therapy with morphine, hydromorphone, and oxycodone (20), requirement for rapid titration from fentanyl patch (5), renal failure (2), and sublingual administration for breakthrough pain (1). Prescriptions for ondansetron met criteria in 19 of 21 cases. Indications were nausea refractory to metoclopramide and dexamethasone (13), and nausea related to radiotherapy or chemotherapy (6). Prescriptions for TPN met criteria for initiation in only one of five cases. However, in all cases, TPN had been started prior to admission. In cases where death was considered imminent, TPN was continued pending consultation with the patient and family regarding discontinuation. These data indicate that the increased prescribing of fentanyl and ondansetron on the TPCU satisfied evidence- and consensus-based criteria in most cases, apparently justifying the associated increase in drug expenditures. This type of analysis may be useful whenever increased drug utilization requires review. A cost effectiveness analysis would be the next step in evaluating the costs vs. the benefits. The issue of discontinuing TPN in palliative care patients requires further investigation.

Adult↗

PubMed2004

Oral dextromethorphan reduces perioperative analgesic administration in children undergoing tympanomastoid surgery.

OBJECTIVE: To determine whether oral dextromethorphan (1 mg/kg) given one hour prior to surgery decreases opioid administration in the perioperative period in children undergoing tympanomastoid surgery. METHODS: This was a prospective randomized double-blinded and placebo-controlled study in which 20 male and 18 female children (age 11.5 +/- 3.5 years) were enrolled. Nineteen children received dextromethorphan (DM), while the other 19 received placebos. Postoperative pain was assessed using a visual analogue scale and a pain score of > or =5 was treated with intravenous morphine sulfate. Patients were discharged home on oral oxycodone. RESULTS: The total doses of fentanyl administered during surgery were higher in the placebo group compared to the DM group (4.1 +/- 2 vs 2.6 +/- 1.4 microg/kg, P = 0.02) and the total doses of intravenous morphine administered in the postoperative period were also higher in the placebo group compared to the DM group (150 +/- 80 vs 73 +/- 56 microg/kg, P = 0.004). The placebo group had a higher pain score at the time of admission to the Day Surgery Unit (DSU) and a higher maximum pain score, compared to the DM group, during their combined stay in the Post-Anesthesia Care Unit and DSU (7.3 +/- 1.5 vs 3.1 +/- 2.6, P = 0.001). CONCLUSIONS: Premedication with DM reduces the need for opioid administration in the perioperative period in children undergoing tympanomastoid surgery. EBM RATING: A.

Administration, Oral↗

PubMed2004

Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs. 2000.

The treatment of pain has received increasing attention over the past decade promoted by national guidelines, the 'pain as the 5th vital sign' campaign and direct-to-consumer advertising. We examined national trends in office visits and analgesic treatment for musculoskeletal pain in the office setting, comparing data from 1980 and 2000. We analysed the National Ambulatory Medical Care Survey (NAMCS)--a nationally representative survey of visits to office-based physicians--using data from 1980-81 (n=89,000 visits) and 1999-2000 (n=45,000 visits). During this time, NSAID prescriptions increased for both acute (19 vs. 33%, RR=1.74; 95% CI, 1.52-1.95) and chronic (25 vs. 29%, RR=1.16; 95% CI, 0.97-1.35) musculoskeletal pain visits. In 2000, one-third of the NSAID prescriptions were for COX II agents. Opioids increased for acute pain (8 vs. 11%, RR=1.38; 95% CI, 0.92-1.83) and doubled for chronic pain (8 vs. 16%, RR=2.0; 95% CI, 1.52-2.48). The use of more potent opioids (hydrocodone, oxycodone, morphine) for chronic musculoskeletal pain increased from 2 to 9% of visits (RR=4.5; 95% CI, 2.18-6.87). This corresponds to 5.9 million visits where potent opioids were prescribed in 2000--an increase of 4.6 million visits from 1980 (assuming the total number of outpatient visits was constant at the 2000 level). In spite of the increased attention to pain treatment, there has not been an increase in office visits for musculoskeletal pain complaints. The threshold for prescribing NSAIDS and opioids, however, has dropped.

Adolescent↗

PubMed2005

A preclinical comparison between different opioids: antinociceptive versus adverse effects.

Reduced side-effect liability of opioids may enhance the patient's quality of life and decrease the incidence of opioid-insensitive pain. Literature offers few comparative data between different opioids at equianalgesic doses. Therefore morphine, fentanyl, buprenorphine, codeine, hydrocodone and oxycodone were compared for analgesic properties and side-effect profiles in rats. Analgesic efficacy was analysed using a tail withdrawal test for acute thermal nociception, a formalin test for chemically induced inflammatory pain and a von Frey test for mechanical hypersensitivity. For side-effect profiling inhibition of gastrointestinal activity was evaluated in a charcoal and ricinus oil test, arterial PCO(2) was determined for measuring respiratory depression, the discriminative stimulus properties linked to the narcotic cue were assessed using a drug discrimination learning test, and motor coordination was tested through rotarod performance. ED(50)'s for the occurrence of side-effects were compared to ED(50)'s in behavioural pain tests. Fentanyl had a strong analgesic potency and, compared to other opioids, an acceptable side-effect profiling at analgesic ED(50)'s. Also consistent was the ceiling effect of buprenorphine implying an increased safety margin for side-effects, but a decreased analgesic efficacy. Differences between opioids as observed in this study can have important indications for their use in acute as well as in the onset of chronic treatments.

Analgesics↗

PubMed2026

Comparative effectiveness and safety of pharmacological interventions for sleep outcomes in chronic non-cancer pain: a systematic review and network meta-analysis.

Sleep disturbances are highly prevalent among individuals with chronic non-cancer pain and are associated with worse pain severity and poorer prognosis. The comparative trade-offs between the effectiveness and safety of available pharmacotherapies for sleep outcomes in this population remain poorly defined. Ninety-eight RCTs involving 28,920 participants (mean age 53.2 years, 71.2% female) were included. Moderate-certainty evidence demonstrated that melatonin significantly improved sleep quality compared with placebo (standardized mean difference [SMD] = -0.60, 95%CI: -0.98, -0.22). Ten agents (e.g., amitriptyline, oxycodone, gabapentin, pregabalin, duloxetine) also showed statistically significant improvements in subjective sleep quality (SMD = -0.24 to -1.07), but most effects were supported by low-certainty evidence and were accompanied by an increased risk of adverse events (odds ratio [OR] = 1.90 to 37.00). Conversely, melatonin was not associated with an increased risk (OR = 0.88, 95%CI: 0.19, 3.94). Our findings indicate that melatonin shows promise as a safe, adjunctive option for improving sleep quality in this population, but larger, condition-specific trials are warranted to confirm these effects. Other pharmacological agents are limited by lower-certainty and unfavorable safety profiles. These results should be interpreted cautiously given limited direct comparisons, heterogeneous chronic pain populations, the high proportion of trials at high risk of bias, and the predominance of subjective sleep outcomes.

Humans↗

PubMed1999

Effects of selected antihypertensives and analgesics on hepatic porphyrin accumulation: implications for clinical porphyria.

When patients with acute porphyrias are treated with antihypertensives and analgesics, they could be placed at increased risk of developing porphyric attacks, since little is known about the potential for many of these drugs to induce these attacks. We used primary chick embryo liver cells, which maintain intact heme synthesis and regulation, to study the effects of antihypertensives and analgesics on porphyrin accumulation. Cells were treated with desferrioxamine to block heme synthesis partially, simulating conditions encountered in porphyric patients. Typically, cells were treated for 20 hr with the test drugs (3.16 to 1000 microM), along with desferrioxamine. Porphyrins were measured spectrofluorometrically, as uro-, copro,- and protoporphyrin. The evaluated drugs included six antihypertensives (two calcium channel blockers, an angiotensin receptor antagonist, and three inhibitors of angiotensin converting enzyme) and eight analgesics. Of the calcium channel blockers tested, nifedipine greatly increased porphyrin accumulation, whereas diltiazem caused only a slight increase. Losartan (an angiotensin receptor antagonist), captopril, or lisinopril (two angiotensin converting enzyme inhibitors) produced only small increases in porphyrin accumulation. In contrast, enalapril (another angiotensin converting enzyme inhibitor) substantially increased porphyrin accumulation when given in high concentrations. Among the analgesics tested, fentanyl and tramadol produced the highest porphyrin accumulations. Nalbuphine, hydrocodone, oxycodone, and dezocine were moderately or weakly porphyrogenic, whereas buprenorphine and morphine did not increase porphyrin accumulation. These studies suggest that patients with acute porphyrias may be at greater risk for developing porphyric attacks when treated with nifedipine (compared with diltiazem), enalapril (compared with captopril or lisinopril), and tramadol (compared with the other analgesics).

Analgesics↗

PubMed2003

The toxicity of opiates and their metabolites in HepG2 cells.

The toxicity of codeine (C), codeinone (CO), morphine (M), oxycodone (OC), pholcodine (P) and pholcodine-N-oxide (P-NOX) was assessed in HepG2 cells by determining cell viability via the measurement of lactate dehydrogenase (LDH) leakage through the membrane, depletion of reduced glutathione (GSH) and measurement of total protein content. Incubation of C, M, OC, P or P-NOX with HepG2 cells resulted in no significant loss of cell viability, depletion of GSH or decreased total protein content. In contrast, with CO there was a marked depletion of GSH with significant differences from control cells (P<0.05) being detected after as little as 5 min. This effect preceded the loss of cell viability and the decrease in total protein content. To identify the cause of GSH depletion during incubations with CO, the incubation solutions were analysed by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Analysis showed that a codeinone-glutathione conjugate (CO-SG) had been formed. This adduct was synthesised and characterised by LC/MS/MS and by nuclear magnetic resonance spectroscopy (NMR). CO-SG was quantified in the incubation solutions using the synthesised standard substance. Results obtained in this study support the hypothesis that the toxicity of CO may be partly due to GSH depletion. The absence of LDH leakage and GSH depletion in the incubations containing C or OC suggests, that the presence of both a double bond at Delta 7 and an adjoining keto-group in the 6-position are necessary to elicit the toxicity of M analogues with regard to GSH depletion.

Carcinoma, Hepatocellular↗

PubMed2002

A randomized controlled trial of early oral analgesia in gynecologic oncology patients undergoing intra-abdominal surgery.

OBJECTIVE: To evaluate the safety and efficacy of early oral analgesia after intra-abdominal surgery in gynecologic oncology patients. METHODS: Over a 2.5-year period, 227 gynecologic oncology patients undergoing intra-abdominal surgery were enrolled in a randomized controlled trial of early oral versus traditional parenteral analgesia. All patients initially received parenteral morphine via a patient-controlled analgesia (PCA) pump with a basal dose of 0.5 mg/h and a PCA dose of 1 mg with a 10-minute lockout. On the first postoperative day, all patients began a clear liquid diet, which was advanced as tolerated. Patients allocated to early oral analgesia were switched from parenteral to oral morphine. They received a scheduled dose of 20 mg every 4 hours with an additional dose of 10 mg every 2 hours as needed for breakthrough pain. Patients allocated to traditional parenteral analgesia continued to receive parenteral morphine via a PCA pump with basal and PCA doses. On the second postoperative day, the scheduled oral and basal parenteral doses were discontinued. The oral and parenteral PCA doses were continued until 24 hours before discharge, at which time the patient was switched to oxycodone 5 mg/acetaminophen 325 mg. RESULTS: There were no significant differences among the groups in any demographic or clinical indices, including age, case distribution, surgery length, blood loss, time to return of bowel function, length of hospital stay, pain, sedation, and satisfaction scores, and incidence of nausea, vomiting, or major postoperative complications. CONCLUSIONS: Early oral analgesia in gynecologic oncology patients undergoing intra-abdominal surgery is safe and efficacious.

Abdomen↗

PubMed2000

Weak analgesics and nonsteroidal anti-inflammatory agents in the management of children with acute pain.

The PSIs include acetaminophen, NSAIDs, and salicylates. They can be used alone for the treatment of mild pain or as an adjunct to opioid analgesia. In children, most experience is with acetaminophen and ibuprofen. For the treatment of mild to moderate pain, these agents can be administered as needed or at fixed intervals. The latter dosing scheme may provide a more consistent serum level, thereby improving analgesia. The major advantages of acetaminophen are its availability as a suppository for PR administration and its lack of effects on renal and GI function, adverse effects that may be seen with the NSAIDs. Many of the effects on platelet functioning, RBF, and the GI tract may be eliminated with the introduction of NSAIDs that selectively inhibit COX II without effects on COX I, the enzyme present in the GI tract, renal system, and platelets. Future evaluations with these agents in the pediatric population are needed. For more severe pain, the NSAID salicylate or acetaminophen can be combined with a weak opioid, such as codeine, oxycodone, or hydrocodone. When using oral analgesics, factors that may interfere with effective analgesia include a child's refusal to take the medication, ineffective doses and dosing regimens, decreased bioavailability following PO administration, inability to tolerate PO medications because of nausea or vomiting, altered GI motility, and a delayed onset caused by slow absorption. With such caveats in mind, the PO route provides an effective and cost-effective means for many patients. It should be considered as the primary route for pediatric patients in the treatment of mild to moderate pain, even in the hospital setting.

Acute Disease↗

PubMed2003

Prospective comparison of short-term convalescence: laparoscopic radical prostatectomy versus open radical retropubic prostatectomy.

OBJECTIVES: To evaluate and compare prospectively the convalescence of patients after laparoscopic radical prostatectomy (LRP) and open radical retropubic prostatectomy (RRP) in a standardized clinical care pathway at a single institution by two surgeons of equal experience and training. METHODS: The study included all 60 patients undergoing LRP and RRP by two fellowship-trained surgeons in their first year of practice. The postoperative care of these patients was uniform and standardized. The medical records were reviewed and convalescence data obtained by an independent urologist and physician's assistant. RESULTS: Of the 60 patients, 24 underwent RRP and 36 underwent attempted LRP; 3 patients were converted from LRP to RRP. The differences in mean age, preoperative prostate-specific antigen level, Gleason score, in-hospital morphine equivalent requirement, time to oral intake, and hospital stay were not statistically significant between the LRP and RRP groups. The operating room time was significantly longer (5.8 +/- 1.2 hours versus 2.8 +/- 0.55 hours, P <0.0001) and the estimated blood loss was significantly lower in the LRP group (533 +/- 212 mL versus 1473 +/- 768 mL, P <0.0001) than in the RRP group. Pain medication use at home was significantly less in the LRP group (9 +/- 13 versus 17 +/- 15 oxycodone tablets, P <0.04), as was the time to complete convalescence (30 +/- 18 days versus 47 +/- 21 days, P <0.002). CONCLUSIONS: Although LRP took almost twice as long to complete as RRP in our initial clinical experience, the patients had a similar hospital course. LRP patients required less pain medication after discharge and had a shorter time to complete recovery than did RRP patients. Additional studies are needed to address long-term cancer control, potency, and continence outcomes to determine the precise role of LRP in the treatment of men with clinically localized prostate cancer.

Convalescence↗

PubMed2003

Valdecoxib: a review.

BACKGROUND: Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, naproxen, and related agents are nonselective inhibitors of both cyclooxygenase-1 (COX-1) and COX-2, which catalyze prostaglandin synthesis. This inhibition accounts not only for the analgesic, anti-inflammatory, and antipyretic effects of these agents, but also for side effects such as gastric mucosal damage and renal toxicity. Substantial evidence suggests that sparing COX-1 is advantageous for gastric safety. OBJECTIVE: This article reviews available information on the new COX-2-selective inhibitor valdecoxib, including its clinical pharmacology, pharmacokinetics, adverse effects, potential drug interactions, and contraindications and warnings. Results of clinical trials of efficacy and tolerability are summarized. METHODS: Articles for inclusion in this review were identified through searches of PubMed and MEDLINE (1966-December 2002) and International Pharmaceutical Abstracts (1970-December 2002). Search terms included valdecoxib, Bextra, COX-2-selective inhibitors, coxibs, and selective cyclooxygenase inhibitors. The reference lists of identified articles were reviewed for additional publications. Product information was also obtained from the manufacturer of valdecoxib. RESULTS: Fourteen clinical studies involving > 4000 patients have been conducted. Valdecoxib was significantly more effective than placebo in the treatment of adult rheumatoid arthritis, osteoarthritis, pain associated with primary dysmenorrhea, and postoperative pain. Valdecoxib was comparable to naproxen for the treatment of rheumatoid arthritis in 1 study and equivalent to naproxen for the treatment of osteoarthritis in other studies. Three studies found valdecoxib comparable to naproxen sodium for the relief of moderate to severe pain due to primary dysmenorrhea, and others found valdecoxib comparable to oxycodone plus acetaminophen and significantly more effective than rofecoxib for the relief of pain associated with dental surgery (P < 0.05). Four safety studies and 2 reviews of clinical trials documented lower rates of endoscopic gastroduodenal ulcer formation with valdecoxib compared with ibuprofen, naproxen, and diclofenac (P < 0.001 to P < 0.05). Valdecoxib did not inhibit platelet function (bleeding time and platelet aggregation) in healthy adults or in the elderly. Due to the risk of potentially serious skin and allergic reactions, patients who are allergic to sulfa-containing drugs should not take valdecoxib. The drug should be discontinued immediately if rash develops. CONCLUSIONS: In clinical trials, valdecoxib was effective for the treatment of osteoarthritis, rheumatoid arthritis, and moderate to severe pain associated with primary dysmenorrhea. As with the other COX-2-selective inhibitors (celecoxib and rofecoxib), valdecoxib appears to produce less gastrointestinal toxicity than conventional nonselective NSAIDs, although some of the relevant clinical studies have been published only as abstracts. Use of valdecoxib should be reserved for patients at risk for NSAID-induced gastrointestinal problems.

Adult↗

PubMed1997

Obstructive sleep apnea surgery: risk management and complications.

BACKGROUND: Hypoxemia, hypertension, airway obstruction, and death have been associated with surgery for obstructive sleep apnea syndrome (OSAS). Patient analysis was undertaken to identify potential factors that could affect risk-management outcome. METHODS: One hundred eighty-two consecutively treated patients with OSAS undergoing 210 procedures were evaluated. Fifty-four factors were analyzed. RESULTS: Group characteristics included a mean age of 48.2 years, a mean respiratory disturbance index of 42.3, and a mean low oxyhemoglobin desaturation (LSAT) of 77.5%. Surgery included a combination of uvulopalatopharyngoplasty (162 patients; 77%) and maxillofacial procedures (173 patients; 82%). Patients with a respiratory disturbance index greater than 40 and an LSAT less than 80% (117 patients; 64%) were maintained on nasal continuous positive airway pressure. Thirty-nine patients (18.6% had difficult intubations. There was a positive correlation (p > 0.001) of difficult intubations, neck circumference (> 45.6 cm) and skeletal deficiency (Sella-Nasion-Point B < 75 degrees). All tubes were removed with the patient awake in the operating room with two transient episodes of airway obstruction. One hundred forty-eight of the patients (70.5%) required postoperative intravenous antihypertensive medications. Patients with a preoperative history of hypertension had a significantly increased risk (p > 0.01) of requiring intraoperative and postoperative intravenous antihypertensive medications. The mean hospital stay was 2.2 days (SD +/- 0.9). Analgesia was achieved with intravenous morphine sulfate or meperidine HCl (intensive care unit) and oral oxycodone (non-intensive care unit). There were no significant oxyhemoglobin desaturations, irrespective of severity of OSAS or obesity (mean LSAT day 1, 94.8% (SD +/- 2.4); mean LSAT day 2, 95.5% (SD +/- 1.6)). Complications included postoperative bleeding (n = 4), infection (n = 5), seroma (n = 3), arrhythmia (n = 4), angina (n = 1), and loss of skeletal fixation (n = 1). CONCLUSION: Intraoperative airway risks can be reduced by use of fiberoptic intubation in patients with increased neck circumference and skeletal deficiency. Patients with OSAS are at a significantly increased risk for hypertension. Nasal continuous positive airway pressure eliminated the postoperative risk of hypoxemia, which allowed the use of adequate parenteral or oral analgesics.

Female↗

PubMed1999

Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action.

Tricyclic antidepressants and carbamazepine have become the mainstay in the treatment of neuropathic pain. Within the last decade, controlled trials have shown that numerous other drugs relieve such pain. We identified all placebo-controlled trials and calculated numbers needed to treat (NNT) to obtain one patient with more than 50% pain relief in order to compare the efficacy with the current treatments, and to search for relations between mechanism of pain and drug action. In diabetic neuropathy, NNT was 1.4 in a study with optimal doses of the tricyclic antidepressant imipramine as compared to 2.4 in other studies on tricyclics. The NNT was 6.7 for selective serotonin reuptake inhibitors, 3.3 for carbamazepine, 10.0 for mexiletine, 3.7 for gabapentin, 1.9 for dextromethorphan, 3.4 for tramadol and levodopa and 5.9 for capsaicin. In postherpetic neuralgia, the NNT was 2.3 for tricyclics, 3.2 for gabapentin, 2.5 for oxycodone and 5.3 for capsaicin, whereas dextromethorphan was inactive. In peripheral nerve injury, NNT was 2.5 for tricyclics and 3.5 for capsaicin. In central pain, NNT was 2.5 for tricyclics and 3. 4 for carbamazepine, whereas selective serotonin reuptake inhibitors, mexiletine and dextromethorphan were inactive. There were no clear relations between mechanism of action of the drugs and the effect in distinct pain conditions or for single drug classes and different pain conditions. It is concluded that tricyclic antidepressants in optimal doses appear to be the most efficient treatment of neuropathic pain, but some of the other treatments may be important due to their better tolerability. Relations between drug and pain mechanisms may be elucidated by studies focusing on specific neuropathic pain phenomena such as pain paroxysms and touch-evoked pain.

Analgesics↗

PubMed1997

Opioids in headache treatment. Is there a role?

There may be a population of patients subject to frequent headache and in whom optimal analgesic effect is obtained only by frequent but controlled use of opiate drugs and in whom adverse drug effects are minimal. It is emphasized again that the reality is that there are currently a large amount of opioids being prescribed for headache patients because of patients' demands. One of the major considerations for physicians prescribing such treatment is familiarity with the legal guidelines. The federal law requires physicians to register if they are to maintain or detoxify with opioids addicts defined as "any individual who habitually uses any narcotic drug so as to endanger the public morals, health, safety, or welfare, or is so far addicted to the use of narcotic drugs as to have lost the power of self-control with reference to his addiction." A subsequent regulation, however, stated that the law was not intended to impose any limitation on prescription of narcotics for intractable pain. There are also many different state regulations covering, for example, limitations on amounts to be prescribed and reporting of patients who are habitual narcotic users. Obviously, headache patients who request liberal amounts of opioids must be screened. There has been considerable recent effort to provide guidelines regarding which patients with nonmalignant pain might be poor candidates for opioid treatment by reason of both probable treatment failure and risk of drug overuse. Many of these guidelines are not relevant to headache patients in whom pain is rarely continuous and rarely demands scheduled analgesia, as is often the case with pain of other types. There is general agreement that any previous history of any type of substance abuse is an important indicator of danger of recurrence of such behavior. Evaluation of psychological state and personality structure is of great importance. The more evidence of emotional disturbance, the greater the danger both of poor results and of drug abuse. In the chronic daily headache population, treatment failure has been found to correlate with abnormalities on the Minnesota Multiphasic Personality Inventory (MMPI). It is possible that formal psychological testing prior to the prescription of opioid drugs will prove of value in identifying those headache patients at greatest risk for drug abuse. The importance of making opioid treatment part of a multifaceted pain program has been emphasized. Portenoy emphasizes the need for (1) careful discussion with the patient (and often family) of the potential side effects of the drugs, and (2) scrupulous monitoring of adherence to the appropriate dosage and maintenance of prescription by a single physician. The more psychological disturbance evidenced by the patient, the more the risk with failure of drug treatment and of drug abuse. Finally, the analgesic needs of the patient with frequent migraine are different from those of the patient with tension-type headache. Migraine infrequently occurs more than two or three times a week for any period and usually responds to ergotamine, dihydroergotamine, sumatriptan, or a phenothiazine. Addition of codeine or oxycodone for the occasional intractable attack may be needed. When demands in a migraine patient for opioids in amounts greater than 10 to 15 tablets per month occur, there is obvious cause for concern. The opioid agonist-antagonist butorphanol, now available in nasal inhalation form, is alleged to have low abuse potential because it tends to produce dysphoria (an unpleasant emotional state) rather than the euphoria of other opioids. It is therefore unscheduled. The drug, however, does have abuse potential, and the limits needed to be placed on its use are still uncertain. Markley recently recommended a restriction to not more than two bottles (30 treatments) per month. The population with frequent tension-type headaches presents the major problem. Large numbers of these patients use drugs--often in combination

Analgesics, Opioid↗

PubMed2001

Equianalgesic dose ratios for opioids. a critical review and proposals for long-term dosing.

Clinicians involved in the opioid pharmacotherapy of cancer-related pain should be acquainted with a variety of opioids and be skilled in the selection of doses when the type of opioid or route of administration needs changing. The optimal dose should avoid under-dosing or overdosing, both associated with negative outcomes for the patient. Although equianalgesic dose tables are generally used to determine the new doses in these circumstances, the evidence to support the ratios indicated in these tables largely refers to the context of single dose administration. The applicability of these ratios to the setting of chronic opioid administration has been questioned. A systematic search of published literature from 1966 to September 1999 was conducted to critically appraise the emerging evidence on equianalgesic dose ratios derived from studies of chronic opioid administration. There were six major findings: 1) there exists a general paucity of data related to long-term dosing and studies are heterogeneous in nature; 2) the ratios exhibit extremely wide ranges; 3) methadone is more potent than previously appreciated; 4) the ratios related to methadone are highly correlated with the dose of the previous opioid; 5) the ratio may change according to the direction the opioid switch; and 6) discrepancies exist with respect to both oxycodone and fentanyl. Overall, these findings have important clinical implications for clinicians and warrant consideration in the potential revision of current tables. The complexity of the clinical context in which many switches occur must be recognized and also appreciated in the design of future studies.

Analgesics, Opioid↗