Discover the most talked about and latest scientific content & concepts.

Journal: Journal of pain & palliative care pharmacotherapy


ABSTRACT Rheumatoid arthritis (RA) is a painful, debilitating disease characterized by inflammation of the joints, with the proliferation of the synovium and the progressive erosion of cartilage and bone. The treatment of RA is still unsatisfactory, but a number of powerful disease-modifying antirheumatic drugs have become available, such as methotrexate (MTX). Even in the current era of biological targeted therapies, MTX remains the initial preferred antirheumatic drug and is considered to be the gold standard for treatment of RA. The combination of its perceived efficacy, acceptable safety profile, and low cost, as well as decades of clinical experience, makes MTX the cornerstone of treatment for RA and the anchor drug in combination with various biological agents. In this review, the authors aim to summarize the research done in the field of drug delivery systems of MTX according to its routes of administration for treatment of RA. The last part of the review addresses combination therapy with MTX and future direction in the drug delivery of MTX. This review also provides the reader with a general overview of RA and its therapeutic strategies with respect of MTX, which may bring uniformity in medical practice for effective management of RA.

Concepts: Pharmacology, Medicine, Rheumatoid arthritis, Therapy, Osteoarthritis, Drugs, Methotrexate, Disease-modifying antirheumatic drug


ABSTRACT Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a “main stream” pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. In a single-dose, open-label study, patients inhaled a single 15.1 ± 0.1 mg dose of cannabis using the Syqe Inhaler device. Blood samples for Δ(9)-tetrahydrocannabinol (THC) and 11-hydroxy-Δ(9)-THC were taken at baseline and up to 120 minutes. Pain intensity (0-10 VAS), adverse events, and satisfaction score were monitored following the inhalation. A uniform pharmacokinetic profile was exhibited across all participants (Δ(9)-THC plasma Cmax ± SD was 38 ± 10 ng/mL, Tmax ± SD was 3 ± 1 minutes, AUC0→infinity ± SD was 607 ± 200 ng·min/mL). Higher plasma Cmax increase per mg Δ(9)-THC administered (12.3 ng/mL/mg THC) and lower interindividual variability of Cmax (25.3%), compared with reported alternative modes of THC delivery, were measured. A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ(9)-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs.

Concepts: Pharmacology, Medicine, Distribution, Tetrahydrocannabinol, Pharmacokinetics, Cannabis, Neuropathic pain, Medical cannabis


Harmful and nonmedical use of prescription opioids has increased precipitously in the United States and some other countries in recent years, but not everywhere around the world. Addressing this problem requires attention to scientific data and to objective and balanced consideration of factors driving the problems. Unfortunately, the situation has been blurred by some politicians, health professionals, and the media by their using inadequate concepts, misrepresenting and exaggerating facts, and demonizing pain patients. In this article, we analyze what has occurred and present what we believe to be a balanced view of the problems. We advocate comprehensive drug control policies implemented in a way to reduce harmful use and diversion problems balancing the public health benefits and risks of opioid medications. We make recommendations for responsible prescribing, including implementing the World Health Organization (WHO) policy guidelines and similar United Nations Office of Drug Control (UNODC), which we believe can contribute measurably to the prevention of diversion of prescription opioids while ensuring patient access to the most appropriate medicines. Measures to reduce the risks of nonmedical use of opioid medicines should be based to the greatest extent possible on accurate evaluation of the mechanisms leading to such use, including diversion activities.

Concepts: Pharmacology, Public health, United States, Drug, Opioid, Pharmaceutical drug, Implementation, World Health Organization


ABSTRACT Management of postoperative pain remains an important clinical problem throughout the world. Using the PAIN-OUT acute pain registry database to examine perioperative pain management in orthopedic surgery patients, we compared patient-reported outcomes (PROs) in a pooled sample obtained from four American hospitals (N = 473) with PROs in a pooled sample of 20 European institutions (N = 8799). Most American hospitals consistently assess acute pain in surgical patients due to Joint Commission accreditation guidelines. Therefore, we hypothesized that this practice would create a climate of clinical staff sensitivity to patients' pain and a greater readiness to intervene when pain is higher than one would find in Europe as a whole. American institutions might then provide better control of postoperative pain after orthopedic surgery than European institutions. Because of the large sample sizes, our analyses focused on effect size rather than statistical significance. Evaluation of the pain PROs revealed that European patients reported much lower Worst Pain on the first day after orthopedic surgery than American patients. The mean Worst Pain (± SD) for Europeans was 5.4 (2.5) but for Americans the mean was 7.4 (2.7), p < .0001, a large effect size. Europeans also reported significantly less emotional discomfort, less interference of pain with activity and lower Least Pain. Nonetheless, 98.3% of American patients received opioids on the ward on the first postoperative day compared to 70.2% of European patients, and 41.1% received regional analgesia on the ward while 15.9% of European patients received regional analgesia (both small effect sizes). Overall, the results are clear in demonstrating much better pain control in the ensemble of European countries as compared to the United States.

Concepts: United States, Statistical significance, Opioid, Pain, Effect size, Suffering, Pain management, Statistical power


Interstitial cystitis (IC) is a chronic pain disorder of the bladder that is often underdiagnosed and mistreated. The difficulties in diagnosis stem from numerous theories regarding pathophysiology and etiology, including the breakdown of the glycosaminoglycan (GAG) layer, altered permeability of the urothelium, uroinflammation, and neural up-regulation. Dysfunction of the bladder increases the struggle for proper treatment and continues to prove difficult for health care providers to correctly diagnose and manage IC. If diagnosed and/or managed inappropriately, IC may contribute to increased symptom burden and decreased quality of life with respect to activities of daily living. When evaluating a patient’s clinical presentation in combination with predefined risk factors, a health care provider can better establish a true diagnosis of IC, which, in turn, leads to better management of IC-associated symptoms. This review will help health care providers better understand the disease process by discussing pathophysiology, pain pathways, and common symptoms of IC, with the goal of better aiding them in the proper diagnosis and treatment of patients with IC.


Delirium is a neuropsychiatric syndrome that can occur in hospitalized patients, including in palliative care settings. The aim of this study is to describe patterns of delirium in patients receiving dexamethasone at the request of an inpatient palliative consultation team by using a modified chart abstraction tool. This retrospective study analyzed patterns of delirium development in adult hospitalized patients receiving opioids for cancer-related pain and initiated on dexamethasone with recommendation from the palliative care team. Primary end point described patterns of delirium, and the study secondarily analyzed source delirium documentation, Glasgow Coma Scale score, Richmond Agitation-Sedation Scale score, and Eastern Cooperative Oncology Group Performance pre- and post-dexamethasone administration. A total 59 patients were included in this retrospective chart review. There was no difference in delirium rate during the pre- and post-dexamethasone periods (n = 35 and 31, respectively; P = .62). There also were no significant differences in mental status, agitation, or functional status before or after dexamethasone, although data were limited by electronic health record incompleteness. Evidence of delirium was most commonly documented in physician notes (n = 58, 71%). The findings showed that incidence and severity of delirium were not impacted after patients were started on dexamethasone as recommended by an inpatient palliative team, although data were limited.


The central principle of “balance” represents the dual obligation of governments to establish a system of control that ensures the adequate availability of controlled substances for medical and scientific purposes while simultaneously preventing their nonmedical use, diversion, and trafficking, two primary goals of the international control system. On the one hand, although strong opioids, including morphine, are absolutely necessary for the relief of severe pain, legitimate access to opioids for pain treatment and palliative care is lacking in the majority of the world’s countries. On the other hand, in a few high-income countries with higher consumption of prescription opioids, diversion and nonmedical use are increasingly prevalent. This report presents examples of unbalanced systems and a joint statement from global and regional palliative care organizations to promote development of balanced systems for optimal public health outcomes. Although nonmedical use of controlled substances poses a risk to society, the system of control is not intended to be a barrier to their availability for medical and scientific purposes, nor to interfere in their legitimate medical use for patient care. As representatives of palliative care organizations, we urge heads of state to act and to take measures to ensure and restore balanced systems in their countries and call on public health leaders and regulators to work together.


The inappropriate use of opioids in the United States has increased markedly and has resulted in a tragic loss of lives. To combat this problem, prescription drug monitoring programs (PDMPs) have been instituted in most states. Use of the programs is voluntary for prescribers in some states, whereas in other states it is mandatory. The current study used a self-report survey instrument that was administered to 223 participant physicians. The goal of the study was to compare awareness and use of the PDMP in a state that mandates use (Ohio) with one that does not (North Carolina). Although awareness was not significantly different between respondents from the two states, self-reported use was significantly higher in the state mandating use (Ohio post-mandate vs. Ohio pre-mandate: 64% vs. 51%; χ2 = 15.66, P < .0001; and Ohio post-mandate vs. North Carolina: 64% vs. 42%; χ2 = 12.76, P < .0001). Based on these results, mandating use may be an effective method to increase PDMP utilization.


The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti-inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 µg/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects.


Topical analgesics are effective and alternative means to systemic therapy, often minimizing the adverse drug effects and complications of systemic analgesic use. Despite the number of available topical analgesics, there is little direction provided in practice guidelines on their appropriate use and little is known about patterns of their prescribing. To begin understanding these knowledge gaps, we sought provider perspectives on topical analgesic use at a large academic medical center. This electronic survey seeks to explore the perceptions and prescription patterns of topical analgesics among prescribers in a large academic medical center, where the availability of topical analgesics varies. Among topical analgesics, lidocaine (78%) is prescribed more frequently than nonsteroidal anti-inflammatory drugs (NSAIDs; 41%) or morphine (3%). Formulations and indications of use varied between faculty physicians and nonfaculty providers. Reasons for prescribing were largely based on anecdotal experience. Based on the survey results, it is clear that more topical agents are needed to manage pain; however, so too is guidance on appropriate prescribing.