Stefan Wirz

A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation.

Background: Opioid‐induced constipation can have a major negative impact on patients’ quality of life. This randomised, double‐blinded study evaluated the analgesic efficacy of prolonged‐release (PR) oral oxycodone when co‐administered with PR oral naloxone, and its impact on opioid‐induced constipation in patients with severe chronic pain. Another objective was to identify the optimal dose ratio of oxycodone and naloxone.

Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain

Background and objectives:  Opioid‐induced constipation can have a major negative impact on patients’ quality of life. This randomised clinical trial evaluated patient assessment of the efficacy and tolerability of oral prolonged‐release (PR) oxycodone when co‐administered with oral naloxone PR.

Gastrointestinal symptoms under opioid therapy: A prospective comparison of oral sustained-release hydromorphone, transdermal fentanyl, and transdermal buprenorphine

Introduction: The purpose of this trial was to evaluate the effect of long‐term treatment with oral sustained‐release hydromorphone, transdermal fentanyl, and transdermal buprenorphine on nausea, emesis and constipation.

Management of constipation in palliative care patients undergoing opioid therapy: is polyethylene glycol an option?

This study assessed the efficacy of laxative use for treatment of constipation in patients receiving opioid therapy, with special attention to polyethylene glycol 3350/electrolyte solution (PEG-ES). Computerized data from 206 patients were analyzed using descriptive statistics. Subgroups were analyzed using confirmatory statistics. Constipation occurred in 42.7 percent of patients. Laxatives were administered to 74.3 percent of these patients using a standardized step scheme, with good results in 78.4 percent. As a therapy for constipation, the combined administration of PEG-ES, sodium picosulphate, and liquid paraffin proved most effective, although statistical analysis yielded no significance. Early use of PEG-ES using a step scheme holds promise for treatment of opioid-related constipation in palliative care patients, although further investigation is warranted.

Managing cancer pain and symptoms of outpatients by rotation to sustained-release hydromorphone: a prospective clinical trial

PurposeIn this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromorphone for controlling pain and symptoms in outpatients with cancer pain. MethodsBefore and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical Rating Scales (NRS)], or as categorical parameters, and analyzed by descriptive and confirmatory statistics (ANOVA, Wilcoxon, χ2). ResultsRotation was successful in 64% of patients experiencing pain (60%), and gastrointestinal (32%) and central (26%) symptoms under oral morphine (38%), transdermal fentanyl (22%), tramadol (20%), oxycodone (12%), or sublingual buprenorphine (8%). NRS of pain (4.1 to 3.2; P=0.015), gastrointestinal symptoms, especially defecation rates (P=0.04), and incidence of insomnia improved after an increase in morphine-equivalent doses from 108.9 to 137.6 mg/d without modifying concomitant analgesics or coanalgesics. ConclusionsSwitching the opioid to oral hydromorphone may be a helpful technique to alleviate pain and several symptoms, but it is still not clear to what extent the underlying mechanisms, such as the technique of rotation itself, better dose adjustment, or using a different opioid have an impact.

Review Article: Chronobiology: influence of circadian rhythms on the therapy of severe pain:

Modern pain therapy widely follows the WHO (World Health Organization) guidelines using a three-step ‘ladder’ for pain relief. This escalating step scheme includes the administration in the order nonopioids, mild opioids and strong opioids, and adjuvants at any step. Analgesics should be given ‘by the clock’ rather than ‘on demand’. However, the chronobiological parameters circadian pain rhythm, circadian efficacy of analgesics, and individual circadian need for analgesics are to be considered. The results of a multitude of studies in chronobiology are not consistent. Therefore, further studies with standardized protocols are needed that allow to assign more consistent rhythms to diseases, pain causes, and analgesic efficacy of opioids. In many cases, each patient perceives pain and its intensity individually during the time of day. By administration of analgesics over a constant or continuous dosage time fluctuations in pain perception and the outcomes of many studies in chronobiology are ignored that prove the influence of biological rhythms on the pharmacokinetic and pharmacodynamic aspects of analgesics. As different types of pain show different rhythms (highest pain intensities arising at different times of the day) analgesics should be dosed flexibly. It is also very important that drug therapy can be adjusted individually to the pain rhythm of the patient as well as to the type and cause of pain. In severe pain, therapy should be particularly careful. A flexible dosage depending on pain intensity and rapid dose adjustment are essentials of a modern pain therapy. Therefore, opioids that are flexible to use are better suited to treat the individual pain of the patient than rigid modified release oral or transdermal systems. J Oncol Pharm Practice (2010) 16: 81—87.

Sudden sensorineural hearing loss after heroin injection

Sudden sensorineural hearing loss is a symptom of cochlear injury. Potential aetiologies are vascular diseases, viral infections, allergic reactions, autoimmune disorders, and traumatic rupture of the intralabyrinthe membrane. Unlike in unilateral cases bilateral sensorineural hearing loss is often associated with specific disease entities. We report a case of sudden bilateral deafness after intravenous heroin abuse. The putative pathophysiological mechanisms are discussed.

Perioperative Glycine Treatment Attenuates Ischemia/reperfusion Injury and Ameliorates Smooth Muscle Dysfunction in Intestinal Transplantation

Background. Ischemia/reperfusion evokes a functionally relevant inflammatory response within the muscularis propria of small bowel grafts by activation of resident macrophages and leukocyte recruitment. We hypothesized that immunomodulatory perioperative treatment with glycine attenuates the proinflammatory cascade and improves smooth muscle dysfunction of small bowel grafts. Methods. Orthotopic SBTx was performed in Lewis rats. Glycine (1 mg/g body weight) was infused (0.1 mL/g/hr) for 2 hr before harvest as preconditioning in the donor, and for 2 hr from the onset of reperfusion in the recipient. Transplanted vehicle (isotonic saline)-treated animals and naive animals served as controls. Rats were sacrificed after 3 hr and 24 hr. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry. Mediator mRNA expression was determined by real-time-PCR. Jejunal circular smooth muscle contractility was assessed in a standard organ bath. Results. Compared with vehicle controls, glycine-treated graft muscularis expressed a significant alleviation in mRNA peak expression for IL-6, IL-1&bgr;, ICAM-1, MCP-1, TNF&agr;, COX-2, and iNOS. Also glycine-treated grafts exhibited significantly less infiltration with ED-1-positive macrophages and MPO-positive neutrophils as well as reduced apoptosis. Concurrent to these results, vehicle controls showed an 80% decrease in smooth muscle contractility, whereas glycine-treated animals exhibited only a 40% decrease in contractile activity compared with controls. Conclusions. The data indicate that perioperative glycine treatment reduces the molecular and cellular inflammatory response within the grafts and improves smooth muscle dysfunction after transplantation. Therefore, the glycine-activated chloride channel on resident and infiltrating leukocytes could be a promising pharmacologic target to attenuate ischemia/reperfusion injury after ITx.

Management of Chronic Orofacial Pain: A Survey of General Dentists in German University Hospitals

AIM This survey assessed procedures performed by general dentists in German university hospitals treating patients with chronic orofacial pain (COP). METHODS A standardized questionnaire was sent to dentists at all 42 German universities. Doctors were asked to describe demographics, diagnoses, etiologies, diagnostic, and treatment procedures for their patients seen over a 3-month period. RESULTS A total of 34,242 patients from 19 responding university hospitals were enrolled. COP of greater than 6 months duration was identified in 1,767 patients (5.2%), of whom 64% were female, 76% were between 20 and 59 years old, 66.3% frequently changed doctors, and 29.5% demonstrated psychological comorbidities. The most common causes of COP were temporomandibular disorders, atypical odontalgia, and atypical facial pain accounting for 83.4% of the sample, with purported etiologies of surgery or trauma (52.4%), musculoskeletal disorders (24.2%), prosthetics (11.4%), or psychosomatic causes (11.7%). A secondary pain syndrome was found in 25% of patients. Before admission to the universities, 59.4% of patients reported inadequate pain control. Following admission, the number of patients receiving specialized therapies significantly increased from 40.6% to 88.2% (chi(2) test; P < 0.001), and improved pain was reported in 71.4% of patients. Multimodal therapy included treatment of malocclusion (47.1%), surgery (37.7%), analgesics (27.5%), and physiotherapy (22%). Specialized pain assessment (26.5%) or visual analog scales (16.9%) were applied irregularly and pain therapists were rarely consulted (8.9%). Despite the high psychological comorbidity (29.5%), psychological treatments were obtained for only 11%. CONCLUSIONS The prevalence of COP is 5% in German University dental practices, where current guidelines of COP treatment are followed incompletely, and patients with psychological disorders are usually not treated. Interdisciplinary practice principles should be encouraged.

The effects of morphine on human 5-HT3A receptors.

5-HT3 receptors are ligand-gated ion channels that are involved in the modulation of emesis and pain. In this study, we investigated whether the opioid analgesic, morphine, exerts specific effects on human 5-HT3 receptors. Whole-cell patches from HEK-293 cells stably transfected with the human 5-HT3A receptor cDNA were used to determine the effects of morphine on the 5-HT-induced currents using the patch clamp technique. At negative membrane potentials, 5-HT induced inward currents in a concentration-dependent manner. The 5-HT3 receptor antagonist, ondansetron, (0.3 nM) reversibly inhibited the 5-HT-induced signals. Morphine reversibly suppressed 5-HT-induced peak currents as a function of concentration (IC50 = 1.1 μM, Hill coefficient = 1.2). The block by morphine decreased with increasing 5-HT concentrations, suggesting a competitive effect. In addition, the activation, as well as the inactivation, kinetics of the currents were significantly slowed in the presence of morphine. The morphine antagonist, naloxone, also inhibited 5-HT-induced currents (e.g., at 3 μM by 17%). The effects of morphine and naloxone were not additive. The potency of morphine and the competitivity of the blocking effect points to a specific mechanism at a receptor site rather than an unspecific membrane effect.