Prurito en pacientes en diálisis. Revisión de la literatura y nuevas perspectivas

Uremic pruritus (UP) is one of the most uncomfortable symptoms for patients in dialysis. UP has a great impact on dialysis patients’ quality of life and has a great prevalence between those (28–70%). Physiopathology of UP is unknown and usually is unnoticed for most nephrologists (in more than 65% of centers is underdiagnosed). This lack of awareness drives to the unsuccessful treatment of this symptom. Moreover, the fact that most studies have been carried out on small populations and the difficulty assessing UP complicates a correct therapeutical approach. For this reason, we have designed treatment algorithms based on the efficacy of the drugs but also its safeness to avoid adverse effects.     

Gabapentin as an Adjuvant Therapy for Prevention of Acute Phantom-Limb Pain in Pediatric Patients Undergoing Amputation for Malignant Bone Tumors: A Prospective Double-Blind Randomized Controlled Trial

Context

Gabapentin is reported to have an analgesic effect of reducing phantom-limb pain (PLP) in adult patients. There is no study on preoperative use of gabapentin in pediatric population in terms of PLP prevention.

加巴喷丁治疗血液透析患者顽固性尿毒症皮肤瘙痒的临床研究

目的 观察加巴喷丁（gabapentin）治疗顽固性尿毒症性皮肤瘙痒的有效性和安全性。 方法 采用随机对照研究,选择顽固性皮肤瘙痒的维持性血液透析（MHD）患者,随机分为试验组25例和对照组24例。试验组患者每周3次透析后晚间口服加巴喷丁100~300 mg;对照组每天口服氯雷他定10 mg。12周后根据视觉模拟评分、瘙痒VAG评分和改良Duo氏瘙痒评分进行疗效评价,同时观察不良反应。 结果 试验组患者经治疗后皮肤瘙痒症状明显改善,瘙痒分布范围减小,发作频率降低,睡眠明显改善,VAS评分（1.46±1.38比8.71±1.17,P < 0.01）、VAG评分（2.92±1.63比8.29±0.68,P < 0.01）和改良Duo氏瘙痒评分（11.33±3.99比30.75±4.87,P < 0.01）均较治疗前显著下降。对照组患者经治疗后瘙痒症状部分缓解,但疗效与试验组差异有统计学意义（P < 0.01）。服用加巴喷丁患者中,36%出现嗜睡、头晕,而症状均在1周内减轻或消失,没有患者因此中断治疗;未观察到严重不良反应。 结论 短期服用加巴喷丁能够安全和有效地治疗部分MHD患者的顽固性皮肤瘙痒。长期疗效及安全性仍需大样本和长期研究。     

口服加巴喷丁对胫骨内固定术后患者镇痛的效果

目的 探讨胫骨内固定术口服加巴喷丁的术后镇痛效果.方法 椎管内麻醉下行胫骨内固定患者48例,随机分为口服加巴喷丁的观察组和口服安慰剂的对照组.记录两组患者术后各时点VAS评分、术后至初次使用哌替啶时间和第1个24 h总用量.结果 术后不同时点观察组的VAS评分均低于对照组（P＜0.05）;观察组初次使用哌替啶时间长于对照组,而第1个24 h哌替啶总用量少于对照组（P＜0.05）.结论 椎管内麻醉下胫骨内固定术后立即口服加巴喷丁具有镇痛效果.     

Isobolographic analysis of interaction between drugs with nonparallel dose–response relationship curves: a practical application

The objective of this study was to characterize the anticonvulsant and acute adverse-effect potentials of topiramate (TPM) and gabapentin (GBP)—two second-generation antiepileptic drugs administered alone and in combination in the maximal electroshock (MES)-induced seizures and chimney test in mice. The anticonvulsant and acute adverse effects of the combination of TPM with GBP at the fixed ratio of 1:1 were determined using the type I isobolographic analysis for nonparallel dose–response relationship curves (DRRCs). To ascertain any pharmacokinetic contribution to the observed interaction between TPM and GBP, total brain concentrations of both drugs were determined. The isobolographic analysis of interaction for TPM and GBP, whose DRRCs were not parallel in both MES and chimney tests, was accompanied with a presentation of all required calculations allowing the determination of lower and upper lines of additivity. The isobolographic analysis revealed that TPM combined with GBP at the fixed-ratio combination of 1:1 interacted supraadditively (synergistically) in terms of suppression of MES-induced seizures, and simultaneously, the combination produced additive interaction with respect to motor coordination impairment (adverse effects) in the chimney test. The evaluation of pharmacokinetic characteristics of interaction for the combination of TPM with GBP revealed that neither TPM nor GBP affected their total brain concentrations in experimental animals, and thus, the observed interaction in the MES test was pharmacodynamic in nature. In conclusion, the combination of TPM with GBP, because of supraadditivity in the MES test and additivity in terms of motor coordination impairment in the chimney test as well as lack of pharmacokinetic interactions between drugs, fulfilled the criterion of a favorable combination, worthy of recommendation in further clinical practice.     

新型抗癫痫药物的严重不良反应及其防范

目的：综合5种新型抗癫痫药物在国外文献中报道的严重不良反应（Serious adverse reactions,SARs）,提出相应的防范措施。方法：检索1990～2009年MEDLINE／PUBMED数据库中有关新型抗癫痫药物不良反应的文献,从中筛选出5种新型抗癫痫药物SARs的英文文献共132篇,将其SARs的临床表现、发生率、机制、危险因素、预防措施进行总结和分析。结果：加巴喷丁（GBP）可引起行为异常、认知障碍、诱发肌阵挛发作;拉莫三嗪（LTG）可引起严重皮疹、肝肾功能衰竭、弥散血管内凝血、致畸;左乙拉西坦（LEV）可引起抑郁、行为异常、自杀倾向;托吡酯（TPM）可引起抑郁、认知障碍、急性闭角性青光眼、肾结石;奥卡西平（OXC）可引起低钠血症、血管神经性水肿、加重肌阵挛发作等。若能个体化选用抗癫痫新药,并采取合理的预防措施,可以避免或降低用药风险。结论：已在我国上市的新型抗癫痫药物均有SARs,这些不良反应导致了患者的生活质量下降,甚至危及生命,因此,临床医师在选用药物、监护治疗时必须熟悉与警惕这些新药的SARs,制定防范措施。     

Differential pharmacological modulation of the spontaneous stimulus-independent activity in the rat spinal cord following peripheral nerve injury

Peripheral nerve injury is a significant clinical problem that is often difficult to treat. The major clinical symptoms are numbness, tactile and cooling allodynia, hyperalgesias as well as ongoing pain. In animal models of neuropathy, abnormal responses to applied (or evoked) stimuli can be gauged, but spontaneous pain, a major clinical issue, has proved very difficult to assess. In neuropathic animals, spinal neuronal hyperexcitability indicative of peripheral and central changes with high levels of spontaneous neuronal firing has been reported. This latter stimulus-independent firing of sensory neurones may be a measure related to ongoing pain. Two weeks after L5/6 spinal nerve ligation, deep dorsal horn neurones were recorded in halothane-anesthetized rats. The majority of neurones in neuropathic rats showed increased levels of spontaneous firing with irregular firing patterns. We examined and compared the effects of 5 centrally acting pharmacological agents: morphine (i.t. or i.v.), gabapentin, ketamine, memantine and mepyramine on stimulus-independent neuronal firing. This ongoing activity showed high sensitivity to gabapentin (s.c.) and morphine (i.t.) administration, being significantly reduced in a dose-dependent manner. Morphine administered via the systemic route produced modest but non-significant reductions of spontaneous activity. The two NMDA receptor antagonists, ketamine and memantine, and the histamine H1 receptor antagonist, mepyramine, produced minor effects at doses known to be effective on stimulus evoked measures of deep dorsal horn neurones. This may form an electrophysiological basis for the efficacy of gabapentin and spinal morphine on ongoing pain in patients with peripheral neuropathy.     

A double-blind evaluation of gabapentin on alcohol effects and drinking in a clinical laboratory paradigm

INTRODUCTION: There has been increasing interest in the use of anticonvulsant agents in the treatment of alcoholism. Anticonvulsant agents have mostly been evaluated as an alternative to benzodiazepines in the treatment of alcohol withdrawal. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol (i.e., interactions that could increase psychomotor deficits, cognitive impairment, and increase intoxication). This is particularly important in the treatment of alcohol withdrawal and relapse prevention in outpatients. Unfortunately, these untoward clinical interactions between anticonvulsants and alcohol in alcoholic patients have not been thoroughly assessed. The current clinical laboratory study was conducted to evaluate the safety and tolerability of the anticonvulsant gabapentin in alcoholic subjects. In addition, the ability of gabapentin to reduce alcohol craving and consumption was evaluated. METHODS: Thirty-five non-treatment-seeking alcoholic subjects were enrolled in a subacute human laboratory study and received double-blind treatment with up to 1,200 mg of gabapentin (n=18) or placebo (n=17) for 8 days. The safety and tolerability of gabapentin were monitored in the natural environment during the first 5 days of medication treatment and during a free-choice limited access consumption paradigm following an initial drink of alcohol in a bar-lab setting on Day 7. RESULTS: There was no overall effect of gabapentin on drinking or craving; however, it was tolerated (e.g., mood and sedation) as well as placebo over 5 days of natural drinking. During the bar-lab drinking session, there were no differences in subjective high or intoxication between subjects treated with gabapentin or placebo. DISCUSSION: This study provides initial evidence that the anticonvulsant gabapentin is safe if used in conjunction with alcohol consumption in alcoholic individuals. Further study is needed with this and other lab models to determine the utility and safety of gabapentin in the treatment of alcoholism.     

Gabapentin zur Schmerztherapie

Zusammenfassung Gabapentin, welches seit einigen Jahren als Zusatzmedikament für die Therapie fokaler Anf?lle zugelassen ist, wird vermehrt in der Behandlung neuropathischer Schmerzen eingesetzt. Eine Verringerung glutamaterger Transmission, eine Verst?rkung der GABAergen Transmission und eine Bindung an spannungsabh?ngige Kalziumkan?le werden als Mechanismen der schmerzlindernden Wirkung von Gabapentin diskutiert. Experimentelle Untersuchungen belegen die Wirkung von Gabapentin beim neuropathischen Schmerz. Der Wirkort liegt vermutlich im Dorsalhorn des Rückenmarkes. Für die diabetische Polyneuropathie, die postherpetische Neuralgie und die Migr?neprophylaxe weisen plazebokontrollierte Studien eine Wirksamkeit von Gabapentin nach. Für die Trigeminusneuralgie und die sympathische Reflexdystrophie wird eine schmerzlindernde Wirkung bisher nur durch Fallberichte gestützt. Die effektive Dosis liegt zwischen 1200 und 3600 mg/Tag. Als h?ufigste Nebenwirkungen werden Schwindel, Ataxie und Müdigkeit genannt. Um den endgültigen Stellenwert von Gabapentin in der Schmerztherapie abzusch?tzen, muss auf die Ergebnisse kontrollierter Studien gewartet werden, die Gabapentin mit der jeweiligen Referenzsubstanz vergleichen.