Nabilone. A preliminary review of its pharmacological properties and therapeutic use

Nabilone is a new orally active cannabinoid for the treatment of severe gastrointestinal toxicity associated with cancer chemotherapy. The pharmacological profile of nabilone suggests that it acts primarily by preventing emesis controlled by the medulla oblongata, although its secondary mild anxiolytic activity may contribute to the overall efficacy. Nabilone 2mg twice daily starting 12 hours prior to, and continued for the duration of, chemotherapy produces significant reduction in the severity and duration of nausea and the frequency of vomiting in about 50 to 70% of patients with severe symptoms refractory to conventional therapy. Nabilone has proven to be more effective in controlling symptoms and preferred by more patients than prochlorperazine 10mg 2 to 4 times daily in a limited number of studies, despite a higher incidence of side effects. Comparative trials against other new antiemetic agents, such as high dose metoclopramide, and use of nabilone in combination with other antiemetics remain to be undertaken. The incidence of side effects is high with nabilone; drowsiness, dizziness and/or vertigo occur in 60 to 70% of patients, but rarely lead to drug withdrawal, although more troublesome effects, such as postural hypotension, ataxia, vision disturbance and toxic psychoses, may cause discontinuation of therapy. Thus, nabilone offers an effective alternative to the treatment options available in a difficult therapeutic area - those patients with severe gastrointestinal side effects from cancer chemotherapy who are refractory to conventional therapy.     

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials

Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required.     

Analgesic and antihyperalgesic effects of nabilone on experimental heat pain

ABSTRACT

Objective: In this study, we explored the analgesic and antihyperalgesic properties of a synthetic cannabinoid (nabilone) on experimental heat pain in men and women, as well as its effects on descending pain inhibitory systems.

Research design and methods: A double-blind, placebo controlled, crossover study of nabilone single doses of 0.5 and 1?mg was conducted. Excitatory systems were elicited using a temporal summation test (tonic heat pain evoked by a Peltier thermode) administered before and after activation of descending inhibitory control (triggered using a counter-irritation procedure). These tests were given before and after drug treatment. Primary outcome measures included average heat pain, temporal summa­tion of heat pain, and drug-induced changes in the strength of descending analgesia. Possible adverse reactions were monitored throughout treatment. Seven men (mean age = 22.5 years, SD = ± 1.5) and 10 women (mean age = 23.2 years, SD = ± 2.8) completed this study.

Results: Nabilone (1?mg and 0.5?mg) did not reduce the global pain intensity experienced during tonic heat pain (all values of p > 0.18). It also failed to potentiate the strength of descending inhibitory responses (all values of p > 43). Nevertheless, at the highest dose (1?mg), and only for women, nabilone significantly (?p = 0.003) dampened the temporal summation experienced during the last portion of the tonic heat pulse test (i.e., the period of time during which temporal summation is greatest). This antihyperalgesic effect was not observed for men (at either 0.5?mg or 1?mg dose), suggesting that the anti­hyperalgesic properties of cannabinoids are greater for women than for men. Adverse reactions encountered were generally mild and did not provoke the cessation of testing.

Conclusions: Nabilone failed to produce analgesic effects and it did not interact with descending pain inhibitory systems. However, we found that a single 1?mg dose of nabilone reduced temporal summation for women but not men. Although a titration regime and a larger sample of subjects might have provided more robust effects, these preliminary results suggest that nabilone appears effective at relieving hyperalgesic responses in women. Possible neurobiological mechanisms and clinical implications are further discussed.     

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence?

Background Introduction of the monoclonal antibody rituximab to chemotherapy regimens has substantially improved disease-free and overall survival in patients with non-Hodgkin lymphomas (NHL). The short-term safety of this drug has been widely reported, but there are few data on long-term safety, which suggests that these patients require prolonged follow-up. Aim of the review To review the literature on follow-up models, with a focus on the safety of rituximab therapy for diffuse large B-cell lymphoma and follicular lymphoma. Method The Cochrane Library, Embassy, Lilacs, Medline, and Scirus databases were searched for systematic reviews and randomized controlled trials. Furthermore, textbooks and journals on pharmaceutical care and institutional websites were searched for patient management recommendations. The outcomes were follow-up models and grade 3, 4, and 5 adverse reactions. Results Five systematic reviews and eight clinical trials or updates describing patient follow-up or reporting adverse reactions were identified. Only one systematic review and seven clinical trials reported follow-up routines for patients receiving rituximab, including information on staging, frequency of reassessment, and laboratory tests, as well as pre-infusion care and management of acute or delayed adverse reactions. Five systematic reviews and four clinical trials reported data on statistically significant adverse reactions (fever, leukopenia, infection). Four guidelines or institutional protocols for treatment and follow-up were identified, as well as seven studies describing experiences in the implementation of pharmaceutical care for oncology patients, but none were specifically focused on follow-up of patients receiving rituximab for NHL. Conclusion Although some systematic reviews and clinical trials contain guidance on follow-up of patients receiving rituximab for NHL, there are no validated strategies for systematic follow-up of these patients with a focus on safety. As there are few data on long-term safety profile of these novel treatments, monitoring strategies should be developed and implemented to ensure safe and optimized use of drugs recently added to the therapeutic arsenal of clinical oncology.     

Dexibuprofen: pharmacology, therapeutic uses and safety

Dexibuprofen is the single pharmacologically effective enantiomer of rac-ibuprofen. Racibuprofen and dexibuprofen differ in their physico-chemical properties, in terms of their pharmacological properties and their metabolic profiles. Several clinical trials and post-marketing surveillance studies were performed to broaden the findings on dexibuprofen. In the last 5 years 4836 patients have been exposed to dexibuprofen in clinical trials and PMS trials. Only in 3.7% of patients adverse drug reactions have been reported and 3 serious adverse drug reactions (0.06%) were observed. In the dose ratio of 1 : 0.5 (rac-ibuprofen vs. dexibuprofen) at least equivalent efficacy was proven in acute mild to severe somatic and visceral pain models. Dexibuprofen has proven at least comparable efficacy to diclofenac, naproxen and celecoxib and has shown a favourable tolerability. The results suggest that dexibuprofen processed in a special crystal form is a safe and effective treatment for different pain conditions.     

Dexibuprofen: pharmacology, therapeutic uses and safety

Dexibuprofen is the single pharmacologically effective enantiomer of rac-ibuprofen. Racibuprofen and dexibuprofen differ in their physico-chemical properties, in terms of their pharmacological properties and their metabolic profiles. Several clinical trials and post-marketing surveillance studies were performed to broaden the findings on dexibuprofen. In the last 5 years 4836 patients have been exposed to dexibuprofen in clinical trials and PMS trials. Only in 3.7% of patients adverse drug reactions have been reported and 3 serious adverse drug reactions (0.06%) were observed. In the dose ratio of 1 : 0.5 (rac-ibuprofen vs. dexibuprofen) at least equivalent efficacy was proven in acute mild to severe somatic and visceral pain models. Dexibuprofen has proven at least comparable efficacy to diclofenac, naproxen and celecoxib and has shown a favourable tolerability. The results suggest that dexibuprofen processed in a special crystal form is a safe and effective treatment for different pain conditions.     

1985年～1997年氟喹诺酮类药物致不良反应病例统计分析

目的;正确评价氟喹诺酮类药物在临床的应用情况,为临床提供一定的数据资料,指导合理用药。方法：本文收集了１９８５年～１９９７年国内文献报道的２３７例氟喹诺酮类药物的不良反应病例,并进行统计分析。结果：归纳总结出氟喹诺酮类药物的不良反应发生的一般规律和有关特征。结论：氟喹诺酮类药物在临床应用时特别是用于儿童患者,应严格掌握适应证,避免滥用。     

Parecoxib: new preparation. A NSAID for postoperative pain: no proven advantage

(1) Parecoxib is the second nonsteroidal antiinflammatory drug, after ketoprofen, to be marketed in France for the treatment of postoperative pain. (2) Another injectable NSAID, ketorolac, was marketed briefly in the 1990s. It was shown to be no more effective than ketoprofen, but was withdrawn from the French market because it provoked bleeding. (3) The clinical evaluation dossier on parecoxib contains no data from comparative trials with ketoprofen. The three trials versus ketorolac failed to show that parecoxib was more effective. (4) The two trials comparing parecoxib with morphine are biased by the use of a too low dose of morphine (4 mg). Four trials show that adding parecoxib reduces morphine requirements in patients injecting the opiate on demand. There is no evidence that this reduction translates into a lower risk of adverse reactions to opiates. (5) Parecoxib is marketed as "Cox-2-specific inhibitor", but follow-up is too short to show whether this property avoids the severe adverse effects seen with other NSAIDs, such as renal failure, gastrointestinal haemorrhage, and delayed wound healing. Parecoxib, like its principal metabolite valdecoxib, can cause severe hypersensitivity reactions. (6) Parecoxib is 10 times more expensive than injectable ketoprofen in France. (7) In practice, ketoprofen is still the best choice for parenteral NSAID-based pain relief in the postoperative setting.     

Lack of effect of central nervous system-active doses of nabilone on capsaicin-induced pain and hyperalgesia

相似文献   

Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat.

1. The antiinflammatory activity of synthetic cannabinoid nabilone in the rat model of carrageenan-induced acute hindpaw inflammation was compared with that of the endocannabinoid palmitoylethanolamide and the nonsteroidal antiinflammatory drug indomethacin. 2. Preliminary experiments in rats used a tetrad of behavioural tests, specific for tetrahydrocannabinol-type activity in the CNS. These showed that the oral dose of nabilone 2.5 mg kg(-1) had no cannabinoid psychoactivity. 3. Intraplantar injection of carrageenan (1% w v(-1)) elicited a time-dependent increase in paw volume and thermal hyperalgesia. 4. Nabilone (0.75, 1.5, 2.5 mg kg(-1), p.o.), given 1 h before carrageenan, reduced the development of oedema and the associated hyperalgesia in a dose-related manner. Nabilone 2.5 mg kg(-1), palmitoylethanolamide 10 mg kg(-1) and indomethacin 5 mg kg(-1), given p.o. 1 h before carrageenan, also reduced the inflammatory parameters in a time-dependent manner. 5. The selective CB(2) cannabinoid receptor antagonist [N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3 carboxamide] (SR 144528), 3 mg kg(-1) p.o. 1 h before nabilone and palmitoylethanolamide, prevented the anti-oedema and antihyperalgesic effects of the two cannabinoid agonists 3 h after carrageenan. 6. Our findings show the antiinflammatory effect of nabilone and confirm that of palmitoylethanolamide indicating that these actions are mediated by an uncharacterized CB(2)-like cannabinoid receptor.     

临床药师在神经病理性癌痛患者镇痛治疗中的作用

目的：优化癌痛药物治疗,促进癌痛患者合理用药。方法：临床药师参与癌痛患者治疗方案的制定,结合患者癌痛特点,充分考虑其不良反应,建议医师调整相关治疗药物。结果：临床药师在本病例中凭借自身的专业知识,从混合性疼痛的滴定及不良反应方面,积极配合医师,为患者提供了合理的用药方案。经治疗后,患者的疼痛控制良好,不良反应得以缓解。结论：抗肿瘤专业临床药师参与临床实践,可从药学的角度发挥优势,优化治疗方案,预防不良反应的发生。     

Adverse drug reactions in special populations – the elderly

The International Conference on Harmonization considers older people a ‘special population’, as they differ from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions (ADRs). Medical practice is often based on single disease guidelines derived from clinical trials that have not included frail older people or those with multiple morbidities. This presents a challenge caring for older people, as drug doses in trials may not be achievable in real world patients and risks of ADRs are underestimated in clinical trial populations. The majority of ADRs in older people are Type A, potentially avoidable and associated with commonly prescribed medications. Several ADRs are particularly associated with major adverse consequences in the elderly and their reduction is therefore a clinical priority. Falls are strongly associated with benzodiazepines, neuroleptics, antidepressants and antihypertensives. There is good evidence for medication review as part of a multifactorial intervention to reduce falls risk in community dwelling elderly. Multiple medications also contribute to delirium, another multifactorial syndrome resulting in excess mortality particularly in frail older people. Clostridium difficile associated with use of broad spectrum antibiotics mainly affects frail older people and results in prolonged hospital stay with substantial morbidity and mortality. Antipsychotics increase the risk of stroke by more than three-fold in patients with dementia. Inappropriate prescribing can be reduced by adherence to prescribing guidelines, suitable monitoring and regular medication review. Given the heterogeneity within the older population, providing individualized care is pivotal to preventing ADRs.     

Ziconotide infusion for severe chronic pain: case series of patients with neuropathic pain

Ziconotide intrathecal infusion was recently approved by the United States Food and Drug Administration for the treatment of intractable severe chronic pain. Patients with neuropathic pain make up a significant population among those who experience chronic pain for which there are less than optimal pharmacotherapeutic options. Published clinical trials provide a global view of ziconotide efficacy and safety. A subset of patients in clinical trials obtained complete pain relief, a remarkable finding given the history of drug treatment for neuropathic pain. To provide more information regarding those who respond to ziconotide therapy, we discuss three patients with neuropathic pain who received ziconotide infusion. Two patients with longstanding neuropathic pain, one with complex regional pain syndrome (formerly known as reflex sympathetic dystrophy) of the leg and one with lumbar radiculitis, achieved temporary but complete pain relief from single 5- and 10-microg epidural test doses. In the third case, a patient with longstanding bilateral leg and foot neuropathic pain from acquired immunodeficiency syndrome and antiretroviral drug therapy achieved considerable pain relief from a long-term continuous intrathecal infusion. The patients who received a single dose had mild central nervous system adverse effects such as sedation, somnolence, nausea, headache, and lightheadedness. The patient who received the intrathecal infusion experienced mild-to-severe adverse effects depending on the rate of infusion; these effects included sedation, confusion, memory impairment, slurred speech, and double vision. This patient could sense impending adverse effects and made rate adjustments or suspended infusion to avert untoward symptoms. In all three cases, patients achieved considerable pain relief that was long-lasting and persisted well after dose administration or suspension of infusion.     

临床思维指导下的癌痛药物治疗

目的:探索癌痛用药的规范,以避免镇痛药物的滥用。方法:以药物治疗的临床思维为指导,从疾病(癌痛的病因、评估、分度)、患者(一般情况、疾病史、手术史、用药史)、药物(治疗药物的分类、药效学、药动学、剂型与给药方式、剂量、不良反应、相互作用)3个方面综合分析具体病例的临床资料。结果与结论:在临床思维指导下,可以科学、合理地进行癌痛药物治疗。     

Treating pain in multiple sclerosis

INTRODUCTION: Multiple sclerosis (MS) is an inflammatory, demyelinating, central nervous system disease that frequently causes pain. AREAS COVERED: This article reviews the current literature and describes the therapeutic options for treating MS-related pain. The reader will be provided with current, evidence-based knowledge about the treatment of MS-related pain, and the review will take a practical approach to the various drugs for treating pain, including starting dose, titration and side effects. EXPERT OPINION: Only cannabinoids have been assessed in randomized, controlled trials. Because of the concern regarding the risk of abuse and psychiatric adverse events, published guidelines as well as expert recommendations suggest using them as second-line therapy only. Hence, current treatment should be based on the general principles for treating peripheral neuropathic pain, taking into account drug-induced adverse effects.     

A study of the safety of tenoxicam in general practice

An open, noncomparative study was undertaken to examine the safety of tenoxicam, a new nonsteroidal antiinflammatory drug (NSAID) in general practice. One thousand two hundred and sixty-seven patients with rheumatic conditions were recruited by 392 general practitioners throughout New Zealand. Forty-three point six percent of patients recruited were over 65 years of age, 62.5% had some form of concomitant disease and 76.3% of patients were already receiving NSAIDs. Three hundred and four (23.9%) patients experienced adverse drug reactions, the commonest being gastrointestinal (11.4%), central and peripheral nervous system disorders (2.8%) and skin reactions (2.5%). The profile of adverse drug reactions in those more than 65 was similar to those in patients under 65 years. Of the reactions reported, 14.7% were considered severe. Three peptic ulcers were reported. There were no unexpected adverse drug reactions. Eight hundred and forty-nine patients completed 6 months treatment. Subjective assessments of overall efficacy, pain at night, pain on movement and stiffness made before treatment and at 1, 3 and 6 months posttreatment showed that tenoxicam significantly improved all parameters. The clinical response was maintained throughout the 6 month study period and was not different in patients less than or greater than 65 years.     

Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.)

Objective: This paper provides a systematic review of adverse drug reactions (ADRs) associated with the use of extracts of the herb St. John's wort (Hypericum perforatum L.) for the treatment of mild to moderate depression. Methods: Searches of four computerized literature databases were performed for records of (ADRs). Manufacturers of hypericum products, the international drug monitoring centre of the World Health Organization (WHO) and the national drug safety monitoring bodies of Germany and the United Kingdom were also contacted for information. Results: Information on (ADRs) originates from case reports, clinical trials, post-marketing surveillance and drug monitoring studies. Collectively, the data suggest that hypericum is well tolerated, with an incidence of adverse reactions similar to that of placebo. The most common adverse effects are gastrointestinal symptoms, dizziness/confusion and tiredness/sedation. A potential serious adverse effect is photosensitivity, but this appears to occur extremely rarely. Conclusions: Hypericum has an encouraging safety profile. However, as most of the current data originate from short-term investigations, more long-term studies are desirable. Received: 2 February 1998 / Accepted in revised form: 8 June 1998     

某院2009例药品不良反应报告回顾性分析

目的：分析我院2009例药品不良反应（ADR）报告的发生特点,提取并发现风险信号,为优化药品安全性监测模式,促进临床合理用药提供参考。方法：以《WHO不良反应术语集》、《药品不良反应报告和监测管理办法》、《药品不良反应因果关系评价表》等为标准,采用回顾性调查研究方法,对2009例有效ADR报告中患者年龄、给药途径、严重ADR涉及药物种类、ADR累及器官/系统、监测上报人员类型等数据进行分类汇总和统计分析。结果：2009例有效ADR报告中,60岁以上患者ADR的发生比例为34.15%,14岁及以下患者ADR的发生比例为7.22%;静脉滴注给药途径ADR的发生例数最高,肌肉注射给药途径ADR的发生例数最低。ADR涉及药物品种主要为心血管系统药物、抗微生物药物和抗肿瘤药物;ADR临床表现以全身性损害最为常见,其次分别是皮肤及其附件损害和中枢及外周神经系统损害;ADR报表上报人员以医师为主,占比为87.11%,药师上报例数最低,占比为0.99%;严重ADR主要涉及抗肿瘤药物、诊断用药（造影剂）和抗微生物药物。结论：在ADR日常监测过程中,抗感染药物、心血管药物及抗肿瘤药物是ADR监测重点药物类别,60岁以上和14岁及以下的患者是ADR监测重点人群,静脉滴注给药途径是ADR监测重点给药途径,皮肤及其附件病变是提示ADR发生的重要信号。临床ADR监测应重点关注上述影响因素,结合患者具体情况,实施个体化给药,进一步提高临床合理用药水平,确保患者用药安全。     

Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders

BackgroundTranscranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects.ObjectiveWe convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson’s disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction.MethodsExperts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies.ResultsAlthough most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson’s disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy).ConclusionAll recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.     

Effects of the synthetic cannabinoid nabilone on spatial learning and hippocampal neurotransmission

Cannabinoids, the active components of marijuana, affect memory and hippocampal neurotransmission. It has been claimed that nabilone, a synthetic cannabinoid endowed with antiemetic properties, has a peculiar profile of actions. We studied the effects of the drug on spatial learning and in vitro hippocampal CA1 electrophysiology in the rat. Nabilone (0.1, 0.5, and 1.0 mg/kg ip) does not impair place learning in a water maze task, whereas Delta(8)-tetrahydrocannabinol (Delta(8)-THC) disrupts this function. At concentrations ranging from 1 nM to 10 microM nabilone does not influence basal glutamatergic neurotransmission, which is decreased by Delta(8)-THC. Although cannabinoids have been consistently reported to affect synaptic plasticity, nabilone 1 microM does not change paired-pulse facilitation, long-term potentiation and the magnitude of long-term depression. However, the time course of the latter phenomenon is significantly changed by the drug, the depression being lower than in control experiments from 7 to 35 min postinduction. Altogether, our data indicate that there might be differences in the effects of agonists for central cannabinoid receptors, which could help to understand the pharmacology of this class of molecules. The results also suggest that amnesia induced by cannabinoids be possibly related to their effects on hippocampal neurotransmission. The study supports the use of nabilone in conditions the course of which is complicated by cognitive impairment.