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New directions in pain management.

Pain medicine is one of the most rapidly developing medical specialties of today. While there are many modalities that can be used in managing the patient in pain, drug treatment remains, for the most part, the cornerstone of treatment. Opioids retain their position as the foundation of most analgesic strategies, although they tend to be used nowadays in combination with adjuvant analgesics such as paracetamol and nonsteroidal antiinflammatory drugs. The range of available opioids has also been expanded with drugs such as hydromorphone and oxycodone, originally developed almost a century ago. This expanded choice has resulted in the concept of opioid rotation in chronic pain states, an approach that is aimed at maintaining pain control while minimizing adverse effects. Nonsteroidal antiinflammatory drugs continue to play an important role, especially as adjuvants, and the development of drugs such as celecoxib and refecoxib, highly specific for the inhibition of cyclooxygenase 2 pathway has been a further advance. The treatment of neuropathic pain continues to be a challenge to the clinician. While this has traditionally been treated with drugs from the anticonvulsant, antiarrhythmic and anti-depressant groups, results from these treatments have often been less than satisfactory. This has led to the development of completely new drug classes that modulate neuronal transmission in pain pathways, some of which are derived from exotic animal sources, such as the conotoxins from the marine snail family and epibatidine from a species of frog. The role of cannabinoids remains controversial.

Analgesics, Opioid↗

Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects.

BACKGROUND: Chronic noncancer pain (CNCP) is a major health problem, for which opioids provide one treatment option. However, evidence is needed about side effects, efficacy, and risk of misuse or addiction. METHODS: This meta-analysis was carried out with these objectives: to compare the efficacy of opioids for CNCP with other drugs and placebo; to identify types of CNCP that respond better to opioids; and to determine the most common side effects of opioids. We searched MEDLINE, EMBASE, CENTRAL (up to May 2005) and reference lists for randomized controlled trials of any opioid administered by oral or transdermal routes or rectal suppositories for CNCP (defined as pain for longer than 6 mo). Extracted outcomes included pain, function or side effects. Methodological quality was assessed with the Jadad instrument; analyses were conducted with Revman 4.2.7. RESULTS: Included were 41 randomized trials involving 6019 patients: 80% of the patients had nociceptive pain (osteoarthritis, rheumatoid arthritis or back pain); 12%, neuropathic pain (postherpetic neuralgia, diabetic neuropathy or phantom limb pain); 7%, fibromyalgia; and 1%, mixed pain. The methodological quality of 87% of the studies was high. The opioids studied were classified as weak (tramadol, propoxyphene, codeine) or strong (morphine, oxycodone). Average duration of treatment was 5 (range 1-16) weeks. Dropout rates averaged 33% in the opioid groups and 38% in the placebo groups. Opioids were more effective than placebo for both pain and functional outcomes in patients with nociceptive or neuropathic pain or fibromyalgia. Strong, but not weak, opioids were significantly superior to naproxen and nortriptyline, and only for pain relief. Among the side effects of opioids, only constipation and nausea were clinically and statistically significant. INTERPRETATION: Weak and strong opioids outperformed placebo for pain and function in all types of CNCP. Other drugs produced better functional outcomes than opioids, whereas for pain relief they were outperformed only by strong opioids. Despite the relative shortness of the trials, more than one-third of the participants abandoned treatment.

Analgesics, Opioid↗

Avinza - 24-h sustained-release oral morphine therapy.

Avinza is a once-daily, extended-release oral morphine preparation. It has a pharmacokinetic profile that exhibits less peak-to-trough fluctuations in plasma concentration whilst providing analgesia statistically identical to that produced by MS Contin (controlled-release morphine sulfate), Oxycontin (oxycodone HCl controlled-release) and six doses of oral morphine sulfate administered every 4 h. Avinza improves quality of sleep by several measures but interestingly gives the best sleep improvement when given in the morning rather than at night. It causes the same side effects of other opioids: constipation, nausea, vomiting, somnolence and mood swings. Doses of 30 - 60 mg/day have been shown to be well tolerated by patients with osteoarthritis (even in the elderly), who have failed other medications.

Administration, Oral↗

Warfarin and royal jelly interaction.

An 87-year-old African-American man came to the internal medicine clinic for a routine anticoagulation management visit. He had no complaints. His medical history was significant for stage IV-A follicular non-Hodgkin's lymphoma, atrial fibrillation, and hypertension. His long-term drug therapy consisted of warfarin, felodopine, lisinopril-hydrochlorothiazide, controlled-release diltiazem, potassium chloride, and oxycodone. He reported adherence with his prescribed drugs and denied taking any over-the-counter or herbal products. Overall, the patient's drug therapy had been consistent during the preceding 3 months, no significant changes had occurred in his clinical status, and no significant changes had been noted in his diet; his international normalized ratio (INR) had ranged from 1.9-2.4 (therapeutic range 2-3). He denied tobacco use, alcohol consumption, and recent travel. Four weeks later, the patient came to the emergency department with hematuria. He denied dysuria, taking more than the prescribed amount of warfarin, any changes in his diet, taking any over-the-counter or herbal products, and any other bleeding. On admission to the hospital, his INR was 6.88, which increased to 7.29 during his hospital stay. On further investigation, the patient admitted that he had started taking an herbal supplement, royal jelly, 1 week earlier. When asked specifically about the ingredients in the supplement, he stated that royal jelly was the only component. Relative to the patient's denial of any other changes in his condition or drug regimen, the most probable explanation for his elevated INR and subsequent bleeding is a possible interaction between royal jelly and warfarin. To our knowledge, no case reports concerning royal jelly and warfarin taken concomitantly have been reported. Clinicians should be proactive and repeatedly provide education regarding the potential dangers of dietary supplements taken with conventional drugs.

Aged, 80 and over↗

Trust violated: analgesics for addicts.

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Addiction among cancer patients on strong analgesics is a rare but difficult management challenge. The case is presented of a 28-year-old woman with breast cancer and painful bone metastases, suffering with dysfunctional social chaos and addicted to Percocet (oxycodone and acetaminophen). Having broken the trust of her health care team, trust was rebuilt by incorporating the substance abuse clinic and enforcing a contractual agreement. With open and honest support, the team was able to both care for and empower the patient. Issues of trust, liability, opioid tolerance, and barriers to optimal analgesia for cancer pain are discussed.

Adult↗

Identifying drugs needing pharmacogenetic monitoring in a Korean hospital.

PURPOSE: A decision matrix for identifying drugs for which pharmacogenetic drug monitoring (PDM) provides the greatest benefit in a Korean setting is described. SUMMARY: We developed a decision matrix including the ethnic frequency of clinically relevant polymorphic cytochrome P-450 (CYP) enzymes, and the metabolic profiles and adverse drug reactions of drugs. Using the developed decision matrix based on the population allele frequencies of CYP enzymes, we identified potential candidates for PDM among the most commonly used drugs at Seoul National University Hospital (SNUH). Collectively, 17 of these drugs were largely metabolized by at least one polymorphic CYP enzyme. Pharmacogenetic information was used to identify CYP2C9, CYP2C19, and CYP2D6 as the major CYP enzymes of clinical importance for pharmacologic effect and safety in Koreans. The frequencies of poor and intermediate metabolizers among Koreans were 0% and 2.3-12% for CYP2C9, 12% and 42% for CYP2C19, and 0.44% and 28% for CYP2D6, respectively. The frequency of ultrarapid metabolizers of CYP2D6 was 2.28%. The decision matrix and pharmacogenetic information were used to identify seven drugs for PDM: warfarin, glimepiride, diazepam, amitriptyline, nortriptyline, codeine, and oxycodone. This approach can be applied to other institutional hospitals or other ethnic populations and would be helpful for advancing pharmacy practice. Further work is required to assess the practical and potential clinical relevance of pharmacogenetic variations on drugs of interest before the implementation of PDM. CONCLUSION: A decision matrix helped identify drugs for which PDM provides the greatest potential benefit at one Korean hospital.

Alleles↗

Tolerability of treatments for postherpetic neuralgia.

Herpes zoster occurs in up to 20% of people infected with varicella-zoster virus, due to reactivation of the virus from latently infected sensory ganglia. Although pain is a typical feature of acute zoster, pain persisting for more than a month after resolution of the rash is less common and is termed postherpetic neuralgia (PHN). The pain associated with PHN is neuropathic in origin and is notoriously difficult to treat. The incidence of herpes zoster and its associated complications both increase with age, so PHN should be seen more commonly in an aging population. Vaccination with live, attenuated varicella vaccine is safe and efficacious, particularly in children. It decreases the incidence of acute varicella and subsequent herpes zoster. Aciclovir is well tolerated, with renal toxicity only at high intravenous doses. Treatment of acute varicella with aciclovir attenuates acute illness but does not prevent herpes zoster. Treatment of herpes zoster with aciclovir or its derivatives minimises symptoms and may reduce the rate of PHN. Foscarnet is an alternative for an aciclovir-resistant virus but its use is limited by renal and CNS toxicity. Corticosteroids reduce acute pain in herpes zoster but do not affect the incidence of PHN. Their use in some patients may be limited by adverse effects such as gastritis and impaired glucose tolerance. Treatment of established PHN is difficult and may require a holistic approach. Tricyclic antidepressants and gabapentin are the systemic agents with the most proven benefit, although opioids such as oxycodone and NMDA receptor antagonists such as ketamine may be useful in some people. Adverse effects from tricyclic antidepressants are common but usually mild, while gabapentin is generally well tolerated. Although effective, the relatively common adverse effects of opioids and ketamine limit their usefulness in treating PHN. Topical treatment with 5% lidocaine patch or capsaicin is of benefit in some patients and is generally well tolerated. Intrathecal methyl prednisolone may be considered for intractable pain but efficacy and safety have not been confirmed.

Amines↗

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.

Aged↗

Suprofen. A review of its pharmacodynamic and pharmacokinetic properties, and analgesic efficacy.

Suprofen (sutoprofen) is a non-steroidal anti-inflammatory analgesic, closely related structurally to drugs such as ibuprofen, ketoprofen and naproxen. In patients with acute pain, single oral doses of suprofen are at least as effective as: usual therapeutic doses of aspirin; codeine alone or combined with aspirin; dextropropoxyphene alone or in various combinations; oxycodone combined with aspirin; dipyrone; pentazocine; paracetamol (acetaminophen); diflunisal; ibuprofen; indomethacin; or mefenamic acid. In chronic pain due to osteoarthritis, suprofen is as effective as usual dosages of aspirin or dextropropoxyphene during long term therapy, and as effective as diclofenac, ibuprofen, indomethacin and naproxen during short term treatment. As with other non-steroidal anti-inflammatory drugs, gastrointestinal complaints are the most frequently reported side effects, although discontinuation due to gastrointestinal effects may be necessary less frequently with suprofen than with aspirin, dextropropoxyphene or combinations of the two. Suprofen appears to be a useful alternative to mild analgesics, analgesic combinations or the older more established non-steroidal anti-inflammatory drugs in the treatment of patients with acute or chronic pain. However, further definition of its efficacy and tolerability is required, especially in comparison with newer non-steroidal anti-inflammatory analgesics.

Acute Disease↗

Strategies for the treatment of cancer pain in the new millennium.

As was the case in the era before us, in the new millennium we will continue to see an abundance of patients experiencing cancer-related pain for different reasons. Although much needless pain and suffering still affects many of those with cancer, we are presented with a medical dichotomy. With the analgesic drugs available today, and the relatively simple and effective guidelines to treat cancer pain published and disseminated by the World Health Organization, why do people with cancer continue to experience pain? As we search for the answer, the horizon may hold promising new drugs, 'old drugs' with new interest and applications, and new strategies for the field of pain therapy. Possibilities include the isolation and development of analgesics or analgesic combinations that may minimise the adverse effects which are often associated with the current therapeutic class of opioid analgesics. In addition, current research points to promising results identifying the N-methyl D-aspartate non-opioid receptor as a likely component of neuropathic pain. Drugs such as gabapentin, the mechanism of action of which is not well known, have found favour within the clinical community for their analgesic properties and good tolerability. Methadone, in a phase of resurgence, has garnered the attention of the clinical community because of its unique receptor activity and pharmacoeconomic benefits. A number of clinical studies have demonstrated that methadone has a valuable role in treating cancer pain. Perhaps, an unbalanced focus on the risks of inappropriate use, rather than the benefits, should not compromise or distract from the use of methadone as an alternative to morphine. Studies are on going to assess the potential role of methadone in treating neuropathic pain. Drugs such as cannabinoids, although currently applicable for patients with anorexia, nausea and/or vomiting, may offer benefits to patients experiencing pain. Other opportunities exist with such compounds as alpha2-adrenergic agonists, nicotine, lidocaine and ketamine. New strategies such as the switching opioids and/or their route of administration may offer improved analgesia with fewer adverse effects, thus providing therapeutic alternatives for the clinical community. In addition, there is interest in the co-administration of opioids that act on different receptors. For instance, oxycodone appears to be a kappa opioid receptor agonist and may offer enhanced analgesia when combined with morphine.

Analgesics, Opioid↗

Valdecoxib.

In ten large, well-controlled, randomised trials (n = 203 to 1089), valdecoxib, a selective inhibitor of cyclo-oxygenase-2, was significantly more effective than placebo in the treatment of osteoarthritis, rheumatoid arthritis and pain associated with primary dysmenorrhoea, and for postsurgical analgesia. Valdecoxib 1.25 to 10mg twice daily and valdecoxib 10mg once daily were more effective than placebo for the relief of pain in patients with osteoarthritis of the knee, and dosages above 5mg twice daily were similar in efficacy to naproxen 500mg twice daily. Similarly, valdecoxib 5 and 10 mg/day were as effective for osteoarthritis of the hip as naproxen 500mg twice daily. In patients with rheumatoid arthritis, valdecoxib 10, 20 or 40 mg/day was significantly more effective than placebo, and similar in efficacy to naproxen 500mg twice daily; there were no significant differences in efficacy between the three dosages of valdecoxib. Valdecoxib 20 or 40mg administered 1 to 3 hours before and 12, 24 and 36 hours after hip arthroplasty provided significantly better analgesia than placebo, and significantly reduced the amount of morphine taken by patients. Single doses of valdecoxib 10 to 80mg administered before foot or oral surgery provided significantly better analgesia than placebo; when administered after oral surgery, valdecoxib 20 or 40mg provided greater sustained analgesia than oxycodone 10mg/paracetamol 1000mg or rofecoxib 50mg. In contrast to three nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), valdecoxib 40mg twice daily did not cause significant changes in platelet function and bleeding times. Chronic users of NSAIDs who were switched to valdecoxib 10 or 20 mg/day for 12 weeks experienced significantly fewer gastroduodenal erosions or ulcers than patients receiving ibuprofen 2400 mg/day or diclofenac 150 mg/day for 12 weeks. Valdecoxib was generally well tolerated in clinical trials, with a similar incidence of adverse events to placebo.

Arthritis↗

Letrozole: a review of its use in postmenopausal women with breast cancer.

Letrozole (Femara), a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer. In early-stage disease, extending adjuvant endocrine therapy with letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free survival; compared with placebo there was a 43% relative reduction in disease recurrences or new contralateral breast tumours at a median follow-up of 2.4 years. The results of 4 months' neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated primary disease favour letrozole. In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment; time to disease progression was significantly longer (9.4 vs 6.0 months, p < 0.0001) and objective response rate was significantly greater with letrozole, but median overall survival was similar between groups. For second-line therapy of advanced breast cancer that had progressed on antiestrogen therapy, letrozole showed efficacy equivalent to that of anastrozole and similar to or better than that of megestrol acetate. Letrozole is generally well tolerated and has a similar tolerability profile to tamoxifen; the most common treatment-related adverse events were hot flushes, nausea and hair thinning. In patients with tumours that had progressed on antiestrogen therapy, letrozole was tolerated as least as well as, or better than, anastrozole or megestrol acetate. In the trial of extended adjuvant therapy, adverse events reported more frequently with letrozole than placebo were hot flushes, arthralgia, myalgia and arthritis. The long-term effects of letrozole on bone mineral density or lipid profile have not been determined and these parameters may require monitoring. In several pharmacoeconomic modelling studies from various public healthcare system perspectives, letrozole was considered a cost effective choice for first-line (vs tamoxifen) or second-line (vs megestrol acetate) treatment for advanced breast cancer in postmenopausal women. In conclusion, letrozole 2.5 mg/day is effective in the treatment of postmenopausal women with early-stage or advanced breast cancer. The efficacy, cost effectiveness and favourable tolerability profile of letrozole are reflected in current treatment guidelines recommending the drug as first-line therapy for advanced breast cancer. Letrozole is superior to tamoxifen for first-line treatment and is at least as effective as standard second-line treatments in disease that has progressed on antiestrogen therapy. For early-stage disease, letrozole is superior to tamoxifen in the neoadjuvant setting, and prolongs disease-free survival when administered after the standard 5-year period of adjuvant tamoxifen therapy.

Antineoplastic Agents↗

Transurethral microwave thermotherapy of the prostate without intravenous sedation: results of a single United States center using both low- and high-energy protocols. TJUH TUMT Study Group.

PURPOSE: Previous studies have indicated that high-energy transurethral microwave thermotherapy (TUMT) requires intravenous (IV) sedation and/or narcotics for patient tolerance. This study was performed to determine tolerability, patient acceptance, and efficacy of TUMT using both low- and high-energy protocols in a single United States university setting. MATERIALS AND METHODS: Between August 11, 1997 and October 28, 1999, 210 men (mean age 64.9 +/- 9.1 years) presenting with symptomatic benign prostatic hyperplasia (BPH) received treatment with a Prostatron TUMT using either the low-energy Prostasoft 2.O or high-energy Prostasoft 2.5 software. Each patient had digital rectal examination and prostate-specific antigen level consistent with BPH, American Urological Association symptom score > or = 15, and Qmax <15 mL/s. Each patient received TUMT with only ibuprofen 400 mg by mouth (PO), lorazepam 1.0 mg PO, and ketorolac 30 mg intramuscularly (IM) prior to TUMT. A few patients who were concerned about limited pain threshold received oxycodone 5 mg/acetaminophen 325 mg PO. Of 210 patients treated, 12-month efficacy data were available for analysis in 80 patients. RESULTS: Forty-eight men (mean age 65 +/- 9.2 years) received low-energy 2.0 software TUMT, and 32 men (mean age 65.1 +/- 9.2 years) were treated with high-energy 2.5 software. Mean prostatic volume was 44.3 +/- 23.9 mL and 60.7 +/- 26.4 mL for the 2.0 and 2.5 groups, respectively. Mean energy delivered was 108.8 +/- 50.4 kJ and 173.1 +/- 41.1 kJ for the 2.0 and 2.5 treatment groups, respectively. International Prostate Symptom Score decreased from 23 pre-TUMT to 8 post-TUMT and 21 pre-TUMT to 10 post-TUMT at 12 months in the 2.0 and 2.5 groups, respectively. Mean peak flow rate improved 31.9% from 9.1 mL/s pre-TUMT to 12.0 mL/s post-TUMT and 45.8% from 9.6 mL/s pre-TUMT to 14.0 mL/s post-TUMT at 12 months in the 2.0 and 2.5 groups, respectively. All but two patients tolerated treatment without IV sedation. One patient experienced intolerable rectal spasm, and treatment was terminated in another patient because of poorly controlled hypertension. CONCLUSIONS: Patients can be treated safely with TUMT using either low or high energy, with almost universal patient tolerance and without the need for IV sedation or narcotics, if they premedicated effectively using a PO/IM regimen. Patients experience significant relief of symptoms whether low- or high-energy TUMT is used; however, high-energy TUMT improves flow rate to a greater extent than does low-energy therapy.

Aged↗

Gateways to clinical trials.

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Aciclovir, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alteplase, amifostine hydrate, antithymocyte globulin (equine), aspirin, atorvastatin calcium, azathioprine; Bacillus Calmette-Guérin, basiliximab, bicalutamide, bimatoprost, BMS-214662, brimonidine tartrate, buprenorphine hydrochloride; Cabergoline, carbamazepine, carboplatin, ciclosporine, cisplatin, cyclophosphamide; Daclizumab, desmopressin acetate, dihydroergotamine mesylate, dorzolamide hydrochloride, doxorubicin, dutasteride; Everolimus; Fluocinolone acetonide, frovatriptan, FTY-720, fulvestrant; Gabapentin, galantamine hydrobromide, ganciclovir, gemcitabine, glatiramer acetate; Hydrocodone bitartrate; Interferon beta, interferon beta-1a, interferon beta-1b, ipratropium bromide; Ketotifen; Lamivudine, latanoprost, levodopa, lidocaine hydrochloride, lonafarnib; Metformin hydrochloride, methylprednisolone, metoclopramide hydrochloride, mirtazapine, mitoxantrone hydrochloride, modafinil, muromonab-CD3, mycophenolate mofetil; NS-2330; Olopatadine hydrochloride, omalizumab, oxcarbazepine, oxycodone hydrochloride; Paclitaxel, paracetamol, piribedil, pramipexole hydrochloride, pravastatin sodium, prednisone; Quetiapine fumarate; Raloxifene hydrochloride, rituximab, rizatriptan sulfate, Ro-63-8695, ropinirole hydrochloride, rosiglitazone maleate; Simvastatin, siplizumab, sirolimus; Tacrolimus, tegaserod maleate, timolol maleate, tiotropium bromide, tipifarnib, tizanidine hydrochloride, tolterodine tartrate, topiramate, travoprost; Unoprostone isopropyl ester; Valganciclovir hydrochloride, visilizumab; Zidovudine.

Drug Therapy↗

Current concepts in acute pain management.

Analgesics most commonly prescribed in dentistry for acute pain relief include the nonsteroidal anti-inflammatory drug, acetaminophen, and various opioid-containing analgesic combinations. The NSAIDs and presumably acetaminophen act by inhibiting cyclooxgenase enzymes responsible for the formation of prostaglandins that promote pain and inflammation. Opioids such as codeine, hydrocodone, and oxycodone stimulate endogenous opioid receptors to bring about analgesic and other effects. Numerous clinical studies have confirmed that moderate to severe pain of dental origin is best managed through the use of ibuprofen or another NSAID whose maximum analgesic effect is at least equal to that of standard doses of acetaminophen-opioid combinations. If an NSAID cannot be prescribed because of patient intolerance, analgesic preparations that combine effective doses of an orally active opioid with 600 to 1,000 mg of acetaminophen are preferred in the healthy adult. On occasion, prescribing both an NSAID and an acetaminophen-opioid combination may be helpful in patients not responding to a single product. In all cases, however, the primary analgesic should be taken on a fixed schedule, not on a "prn" (or as needed) basis, which only guarantees the patient will experience pain.

Acute Disease↗

Misuse of prescribed controlled substances defined by urinalysis.

The use of controlled substances to treat pain is associated with the need to monitor carefully patients for signs of addictive behaviors that may lead to the misuse or abuse of medications. At the West Virginia Pain Treatment Center in Morgantown, a narcotic protocol is employed which consists of a narcotic contract, consent, psychological evaluation, and random urinalysis to ensure the safe and proper use of controlled substances. This study reports the findings of a retrospective study of 186 patients at the center from Jan. 1, 2001 to Dec. 31, 2001, which revealed that there were 355 infractions of the narcotic contract. Products containing hydrocodone were found to be most frequently misused (20.3%), followed by oxycodone products (19.7%). Patients prescribed controlled substances should be repeatedly evaluated for medication misuse and the presence of addictive behaviors.

Female↗

Intramuscularly administered dexmedetomidine attenuates hemodynamic and stress hormone responses to gynecologic laparoscopy.

The hemodynamic and endocrine effects of three different doses of dexmedetomidine (0.6, 1.2, and 2.4 micrograms/kg), oxycodone (0.13 mg/kg), and saline solution, injected intramuscularly 45-60 min before induction of general anesthesia, were compared in a double-blind, randomized study involving 100 women undergoing gynecologic diagnostic laparoscopy. Anesthesia was induced with thiopental (4.5 mg/kg) and maintained with 0.3% end-tidal isoflurane and 70% nitrous oxide in oxygen. Arterial blood pressure and heart rate increased after endotracheal intubation and during laparoscopy in all groups, but the maximal mean arterial pressure after tracheal intubation was lower in the dexmedetomidine 2.4-micrograms/kg group (104 mm Hg [SD 19]) than in the saline solution group (130 mm Hg [SD 12]). Dexmedetomidine (2.4 and 1.2 micrograms/kg) attenuated the maximal heart rate after intubation (84 [SD 11] and 101 beats/min [SD 15], respectively) compared with saline solution (116 beats/min [SD 19]). On the other hand, 40% of the patients in the dexmedetomidine 2.4-micrograms/kg group received atropine in the postanesthesia care unit for bradycardia (heart rate < or = 40 beats/min). Preoperative anxiety and sedation before and after preanesthetic medication were evaluated by the patients with the aid of a profile of mood-state questionnaire; only dexmedetomidine 2.4 micrograms/kg produced significant anxiolysis and sedation. Plasma concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylglycol, cortisol, and beta-endorphin increased less in the dexmedetomidine 2.4-micrograms/kg group in response to tracheal intubation and surgery than in the saline solution group.

Adrenergic alpha-Agonists↗

Racial differences in health care utilization among patients with osteoarthritis.

OBJECTIVE: Research has identified racial variations in certain aspects of osteoarthritis (OA) related medical care. We compared health services utilization between African American and white veteran outpatients with OA. METHODS: Subjects were 1612 white and 861 African American patients receiving medical care for OA at the Durham VAMC, Durham, NC, USA. Two major components of OA related medical care were examined during a one-year period: physician visits and use of analgesic and antiinflammatory medications. RESULTS: There were no racial differences in overall frequency of OA related physician visits or visits to rheumatologists. About 86% of both African American and white patients were prescribed some analgesic or antiinflammatory medication. There were, however, racial differences in the use of specific drug classes. African Americans were more likely to be prescribed nonselective nonsteroidal antiinflammatory drugs (69% vs 60%), but less likely to be prescribed COX-2 inhibitors (4% vs 7%) and narcotic analgesics (33% vs 40%) than whites (all p < 0.05). African Americans also had a shorter annual mean days' supply for several common medications, including acetaminophen, acetaminophen combined with codeine, and acetaminophen combined with oxycodone (all p < 0.05). CONCLUSION: African Americans and white veterans with OA did not differ substantially in their use of physician services. However, within this equal access health care system that requires minimal co-payments for medications, there were racial differences in prescription medication use. These differences may have implications for both quality of pain relief and risk of side effects.

Black or African American↗