Robert Taylor

Extended-release formulations of tramadol in the treatment of chronic pain

Introduction: Tramadol is a centrally acting analgesic available throughout the world. Its dual opioid and non-opioid mechanisms of action, favorable efficacy and safety clinical profiles and non-controlled regulatory status in most markets contribute to its widespread use. A drawback of the immediate-release formulation of tramadol (four-times-a-day dosing) might be addressed by an extended-release formulation. Extended-release formulations also can offer advantages in the management of chronic pain: convenience, reduced pill burden (possibly leading to improved compliance) and the attenuation of peaks and troughs in serum concentration (possibly leading to reduced adverse effects). Areas covered: The authors review tramadols mechanisms of action and the clinical literature regarding the use of tramadol extended-release formulations for the management of conditions involving chronic pain, such as neuropathic pain syndromes, osteoarthritis and cancer pain. Expert opinion: Based on the literature cited, extended-release formulations of tramadol seem to offer a rational and important addition to the analgesic armamentarium. As is true for all such options, the benefits and risks must be assessed for each patient.

Pain after earthquake

IntroductionOn 6 April 2009, at 03:32 local time, an Mw 6.3 earthquake hit the Abruzzi region of central Italy causing widespread damage in the City of L Aquila and its nearby villages. The earthquake caused 308 casualties and over 1,500 injuries, displaced more than 25,000 people and induced significant damage to more than 10,000 buildings in the LAquila region.ObjectivesThis observational retrospective study evaluated the prevalence and drug treatment of pain in the five weeks following the LAquila earthquake (April 6, 2009).Methods958 triage documents were analysed for patients pain severity, pain type, and treatment efficacy.ResultsA third of pain patients reported pain with a prevalence of 34.6%. More than half of pain patients reported severe pain (58.8%). Analgesic agents were limited to available drugs: anti-inflammatory agents, paracetamol, and weak opioids. Reduction in verbal numerical pain scores within the first 24 hours after treatment was achieved with the medications at hand. Pain prevalence and characterization exhibited a biphasic pattern with acute pain syndromes owing to trauma occurring in the first 15 days after the earthquake; traumatic pain then decreased and re-surged at around week five, owing to rebuilding efforts. In the second through fourth week, reports of pain occurred mainly owing to relapses of chronic conditions.ConclusionsThis study indicates that pain is prevalent during natural disasters, may exhibit a discernible pattern over the weeks following the event, and current drug treatments in this region may be adequate for emergency situations.

Perspectives on transdermal scopolamine for the treatment of postoperative nausea and vomiting

Transdermal scopolamine, a patch system that delivers 1.5 mg of scopolamine gradually over 72 hours following an initial bolus, was approved in the United States in 2001 for the prevention of postoperative nausea and vomiting (PONV) in adults. Scopolamine (hyoscine) is a selective competitive anatagonist of muscarinic cholinergic receptors. Low serum concentrations of scopolamine produce an antiemetic effect. Transdermal scopolamine is effective in preventing PONV versus placebo [relative risk (RR)=0.77, 95% confidence interval (CI), 0.61-0.98, P = 0.03] and a significantly reduced risk for postoperative nausea (RR=0.59, 95% CI, 0.48-0.73, P < 0.001), postoperative vomiting (RR=0.68, 95% CI, 0.61-0.76, P < 0.001), and PONV (RR 0.73, 95% CI, 0.60-0.88, P = 001) in the first 24 hours after the start of anesthesia.

Mitigating the risk of opioid abuse through a balanced undergraduate pain medicine curriculum.

Chronic pain is highly prevalent in the United States and Canada, occurring in an estimated 30% of the adult population. Despite its high prevalence, US and Canadian medical schools provide very little training in pain management, including training in the safe and effective use of potent analgesics, most notably opioids. In 2005, the International Association for the Study of Pain published recommendations for a core undergraduate pain management curriculum, and several universities have implemented pilot programs based on this curriculum. However, when outcomes have been formally assessed, these initiatives have resulted in only modest improvements in physician knowledge about chronic pain and its treatment. This article discusses strategies to improve undergraduate pain management curricula and proposes areas in which those efforts can be augmented. Emphasis is placed on opioids, which have great potency as analgesics but also substantial risks in terms of adverse events and the risk of abuse and addiction. The authors conclude that the most important element of an undergraduate pain curriculum is clinical experience under mentors who are capable of reinforcing didactic learning by modeling best practices.

Opioid antagonists for pain

Introduction: Opioid receptor antagonists are well known for their ability to attenuate or reverse the effects of opioid agonists. This property has made them useful in mitigating opioid side effects, overdose and abuse. Paradoxically, opioid antagonists have been reported to produce analgesia or enhance analgesia of opioid agonists. The authors review the current state of the clinical use of opioid antagonists as analgesics. Areas covered: Published clinical trials, case reports and other sources were reviewed to determine the effectiveness and safety of opioid antagonists for use in relieving pain. The results are summarized. Postulated mechanisms for how opioid antagonists might exert an analgesic effect are also briefly summarized. Expert opinion: Since the comprehensive review by Leavitt in 2009, few new studies on the use of opioid antagonists for pain have been published. The few clinical trials generally consist of small populations. However, there does appear to be a trend of effectiveness of low doses (higher doses antagonize opioid agonist effects). How opioid antagonists can elicit an analgesic effect is still unclear, but a number of possibilities have been suggested. Although the data do not yet support recommendation of widespread application of this off-label use of opioid antagonists, further study appears worthwhile.

Perspectives on the Role of Fospropofol in the Monitored Anesthesia Care Setting

Monitored anesthesia care (MAC) is a safe, effective, and appropriate form of anesthesia for many minor surgical procedures. The proliferation of outpatient procedures has heightened interest in MAC sedation agents. Among the most commonly used MAC sedation agents today are benzodiazepines, including midazolam, and propofol. Recently approved in the United States is fospropofol, a prodrug of propofol which hydrolyzes in the body by alkaline phosphatase to liberate propofol. Propofol liberated from fospropofol has unique pharmacological properties, but recently retracted pharmacokinetic (PK) and pharmacodynamic (PD) evaluations make it difficult to formulate clear conclusions with respect to fospropofols PK/PD properties. In safety and efficacy clinical studies, fospropofol demonstrated dose-dependent sedation with good rates of success at doses of 6.5u2009mg/kg along with good levels of patient and physician acceptance. Fospropofol has been associated with less pain at injection site than propofol. The most commonly reported side effects with fospropofol are paresthesia and pruritus. Fospropofol is a promising new sedation agent that appears to be well suited for MAC sedation, but further studies are needed to better understand its PK/PD properties as well its appropriate clinical role in outpatient procedures.

Ketorolac tromethamine - routes and clinical implications.

Opioids have long been used for analgesic purposes for a wide range of procedures. However, the binding of these drugs to opiate receptors has created various challenges to the clinician due to unfavorable side effect profiles and the potential for tolerance and abuse. In 1989, ketorolac became an approved nonsteroidal inflammatory drug (NSAID) for injectable use as an analgesic. Over the last 20 years, numerous studies have been conducted involving ketorolac. These studies have provided additional information about various routes of administration and their effect on the efficacy and the side effect profile of ketorolac. Moreover, ketorolac has been compared with several widely used analgesics. This review evaluates both the potential benefits and potential drawbacks of ketorolac generally, and specifically discusses routes of administration, including their advantages and disadvantages when compared to several traditional analgesics in both inpatient and outpatient settings.

Low Back Pain in a Natural Disaster

Low back pain is usually self‐limited. The transition from acute to chronic LBP is influenced by physical and psychological factors. Identification of all contributing factors, in a mass emergency setting, differentiating primary and secondary life‐threatening forms of LBP, is the best approach for success. Aims of the present report were to estimate the prevalence of LBP in population afferent to four advanced medical presidiums (AMPs) during postseismic emergency period and to evaluate frequency of use, types of pain killers administered to patients and short‐term efficacy of them.

Fixed-dose combinations for emerging treatment of pain

Introduction: Pain is a large and growing medical need that is not currently being fully met, primarily due to the shortcomings of existing analgesics (insufficient efficacy or limiting side-effects). Better outcomes might be achieved using a combination of analgesics. The ratio of the combinations matters and should therefore be evaluated using rigorous quantitative and well-documented analysis. Areas covered: Advances have been made in understanding the normal physiology of pain processing, including the pathways and neurotransmitters involved. Insight has also been gained about physiological processes that can lead to different ‘types of pain and the transition from acute to chronic pain conditions. This ‘multimechanistic nature of most pains is better matched using a ‘multimechanistic rather than ‘monomechanistic analgesic approach. Such an approach – and the experimental design and data analysis to assess optimal combinations – is described and discussed. Expert opinion: There are sound pharmacologic, as well as practical, reasons for using combinations of drugs to treat pain. Compared with single agents, they offer a potential better match to the underlying pain physiology and thus greater efficacy or reduced side effects. The optimal efficacy and side-effect ratio must be determined in a scientifically rigorous manner.

Prophylaxis of postoperative nausea and vomiting in adolescent patients: a review with emphasis on combination of fixed-dose ondansetron and transdermal scopolamine.

Postoperative nausea and vomiting (PONV) is a relatively common occurrence (20–30%) that delays discharge and, if persistent, can lead to serious complications. The incidence of PONV is a function of patient characteristics, the type and duration of surgery, the type of anesthesia, and the choice of pre-, intra-, and postoperative pharmacotherapy. There are no completely effective antiemetic agents for this condition, but recommendations for treatment strategies are separately available for pediatric and adult patients. Left unclear is whether adolescents should be guided by the pediatric or the adult recommendations. We review the developmental physiology of the relevant physiological factors (absorption, distribution, metabolism, and elimination). We also review the clinical evidence regarding the safety and efficacy of a fixed-dose combination of ondansetron (4u2009mg, i.v.) and transdermal scopolamine (1.5u2009mg).