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1.
Cochrane Database Syst Rev ; 1: CD006282, 2020 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-32006461

RESUMEN

BACKGROUND: Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination with a (point) mutation in the second SMN1 allele. This results in degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the ability to walk without support and have a shortened life expectancy, whereas children with SMA type III develop the ability to walk and have a normal life expectancy. This is an update of a review first published in 2009 and previously updated in 2011. OBJECTIVES: To evaluate if drug treatment is able to slow or arrest the disease progression of SMA types II and III, and to assess if such therapy can be given safely. SEARCH METHODS: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and ISI Web of Science conference proceedings in October 2018. In October 2018, we also searched two trials registries to identify unpublished trials. SELECTION CRITERIA: We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a homozygous deletion or hemizygous deletion in combination with a point mutation in the second allele of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis. The primary outcome measure was change in disability score within one year after the onset of treatment. Secondary outcome measures within one year after the onset of treatment were change in muscle strength, ability to stand or walk, change in quality of life, time from the start of treatment until death or full-time ventilation and adverse events attributable to treatment during the trial period. Treatment strategies involving SMN1-replacement with viral vectors are out of the scope of this review, but a summary is given in Appendix 1. Drug treatment for SMA type I is the topic of a separate Cochrane Review. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: The review authors found 10 randomised, placebo-controlled trials of treatments for SMA types II and III for inclusion in this review, with 717 participants. We added four of the trials at this update. The trials investigated creatine (55 participants), gabapentin (84 participants), hydroxyurea (57 participants), nusinersen (126 participants), olesoxime (165 participants), phenylbutyrate (107 participants), somatotropin (20 participants), thyrotropin-releasing hormone (TRH) (nine participants), valproic acid (33 participants), and combination therapy with valproic acid and acetyl-L-carnitine (ALC) (61 participants). Treatment duration was from three to 24 months. None of the studies investigated the same treatment and none was completely free of bias. All studies had adequate blinding, sequence generation and reporting of primary outcomes. Based on moderate-certainty evidence, intrathecal nusinersen improved motor function (disability) in children with SMA type II, with a 3.7-point improvement in the nusinersen group on the Hammersmith Functional Motor Scale Expanded (HFMSE; range of possible scores 0 to 66), compared to a 1.9-point decline on the HFMSE in the sham procedure group (P < 0.01; n = 126). On all motor function scales used, higher scores indicate better function. Based on moderate-certainty evidence from two studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: creatine (median change 1 higher, 95% confidence interval (CI) -1 to 2; on the Gross Motor Function Measure (GMFM), scale 0 to 264; n = 40); and combination therapy with valproic acid and carnitine (mean difference (MD) 0.64, 95% CI -1.1 to 2.38; on the Modified Hammersmith Functional Motor Scale (MHFMS), scale 0 to 40; n = 61). Based on low-certainty evidence from other single studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: gabapentin (median change 0 in the gabapentin group and -2 in the placebo group on the SMA Functional Rating Scale (SMAFRS), scale 0 to 50; n = 66); hydroxyurea (MD -1.88, 95% CI -3.89 to 0.13 on the GMFM, scale 0 to 264; n = 57), phenylbutyrate (MD -0.13, 95% CI -0.84 to 0.58 on the Hammersmith Functional Motor Scale (HFMS) scale 0 to 40; n = 90) and monotherapy of valproic acid (MD 0.06, 95% CI -1.32 to 1.44 on SMAFRS, scale 0 to 50; n = 31). Very low-certainty evidence suggested that the following interventions had little or no effect on motor function: olesoxime (MD 2, 95% -0.25 to 4.25 on the Motor Function Measure (MFM) D1 + D2, scale 0 to 75; n = 160) and somatotropin (median change at 3 months 0.25 higher, 95% CI -1 to 2.5 on the HFMSE, scale 0 to 66; n = 19). One small TRH trial did not report effects on motor function and the certainty of evidence for other outcomes from this trial were low or very low. Results of nine completed trials investigating 4-aminopyridine, acetyl-L-carnitine, CK-2127107, hydroxyurea, pyridostigmine, riluzole, RO6885247/RG7800, salbutamol and valproic acid were awaited and not available for analysis at the time of writing. Various trials and studies investigating treatment strategies other than nusinersen (e.g. SMN2-augmentation by small molecules), are currently ongoing. AUTHORS' CONCLUSIONS: Nusinersen improves motor function in SMA type II, based on moderate-certainty evidence. Creatine, gabapentin, hydroxyurea, phenylbutyrate, valproic acid and the combination of valproic acid and ALC probably have no clinically important effect on motor function in SMA types II or III (or both) based on low-certainty evidence, and olesoxime and somatropin may also have little to no clinically important effect but evidence was of very low-certainty. One trial of TRH did not measure motor function.


Asunto(s)
Fármacos Neuroprotectores/uso terapéutico , Atrofias Musculares Espinales de la Infancia/tratamiento farmacológico , Adolescente , Aminas/uso terapéutico , Niño , Preescolar , Creatina/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Humanos , Hidroxiurea/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Hormona Liberadora de Tirotropina/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico
3.
Sci Rep ; 9(1): 7681, 2019 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-31118458

RESUMEN

This 4-year randomized controlled trial (RCT) aimed at investigating whether routine home use of both a SnCl2/AmF/NaF-containing mouth rinse and toothpaste has a preventive effect on oral health. Fifty-four test subjects were examined in biannual intervals. The primary endpoint "dental erosion" was determined by the Basic Erosive Wear Examination (BEWE). The secondary endpoints were "saliva pH", "dentin hypersensitivity" generated by Visual Analogue Scale (VAS), and "discoloration" measured by the Lobene Stain Index (LSI). A mixed model for repeated measures (MMRM) was used to analyze the primary endpoint "dental erosion". Primary analysis showed a significant intervention effect of the SnCl2/AmF/NaF-containing test product (p1 = 0.0242). This result was confirmed by two additional MMRM-based sensitivity analyses. Comparison of all models showed "dental erosion" values of the intervention group  below values of the control group. Discoloration of the teeth was significantly higher in the intervention than in the control group at all time points. Saliva pH and dentin hypersensitivity were not significantly different between groups over four years. In summary, this RCT is the first to indicate a possible preventive effect of SnCl2/AmF/NaF-containing oral hygiene products on dental erosion over a follow-up period of four years.


Asunto(s)
Aminas/uso terapéutico , Dentífricos/administración & dosificación , Sensibilidad de la Dentina/prevención & control , Antisépticos Bucales/administración & dosificación , Fluoruros de Estaño/uso terapéutico , Erosión de los Dientes/prevención & control , Adulto , Aminas/administración & dosificación , Femenino , Fluoruración , Estudios de Seguimiento , Humanos , Concentración de Iones de Hidrógeno , Masculino , Proyectos Piloto , Saliva/química , Fluoruros de Estaño/administración & dosificación , Blanqueamiento de Dientes , Escala Visual Analógica , Adulto Joven
4.
Oxid Med Cell Longev ; 2019: 3738980, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31015889

RESUMEN

Nanotechnology-based drug delivery systems for cancer therapy are the topic of interest for many researchers and scientists. Graphene oxide (GO) and its derivates are among the most extensively studied delivery systems of this type. The increased surface area, elevated loading capacity, and aptitude for surface functionalization together with the ability to induce reactive oxygen species make GO a promising tool for the development of novel anticancer therapies. Moreover, GO nanoparticles not only function as effective drug carriers but also have the potential to exert their own inhibitory effects on tumour cells. Recent results show that the functionalization of GO with different functional groups, namely, with amine groups, leads to increased reactivity of the nanoparticles. The last steers different hypotheses for the mechanisms through which this functionalization of GO could potentially lead to improved anticancer capacity. In this research, we have evaluated the potential of amine-functionalized graphene oxide nanoparticles (GO-NH2) as new molecules for colorectal cancer therapy. For the purpose, we have assessed the impact of aminated graphene oxide (GO) sheets on the viability of colon cancer cells, their potential to generate ROS, and their potential to influence cellular proliferation and survival. In order to elucidate their mechanism of action on the cellular systems, we have probed their genotoxic and cytostatic properties and compared them to pristine GO. Our results revealed that both GO samples (pristine and aminated) were composed of few-layer sheets with different particle sizes, zeta potential, and surface characteristics. Furthermore, we have detected increased cyto- and genotoxicity of the aminated GO nanoparticles following 24-hour exposure on Colon 26 cells. The last leads us to conclude that exposure of cancer cells to GO, namely, aminated GO, can significantly contribute to cancer cell killing by enhancing the cytotoxicity effect exerted through the induction of ROS, subsequent DNA damage, and apoptosis.


Asunto(s)
Aminas/uso terapéutico , Neoplasias Colorrectales/terapia , Grafito/uso terapéutico , Animales , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Forma de la Célula , Supervivencia Celular , Neoplasias Colorrectales/patología , Daño del ADN , Ratones , Nanopartículas/química , Nanopartículas/ultraestructura , Especies Reactivas de Oxígeno/metabolismo
5.
Medicine (Baltimore) ; 97(38): e11581, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30235654

RESUMEN

BACKGROUND: The purpose of this meta-analysis from randomized controlled trials (RCTs) was to determine the efficacy and safety of the preoperative use of gabapentin for the treatment of acute and chronic postoperative pain following breast cancer surgery. METHODS: In November 2017, a systematic computer-based search was conducted in PubMed, Embase, Web of Science, Cochrane Library, and Google databases. RCTs comparing gabapentin with placebo in patients undergoing breast cancer surgery were retrieved. The primary endpoint was the visual analog scale (VAS) after surgery and 24 hours after surgery and total morphine consumption. The secondary outcomes were incidence of chronic pain and complications (the incidence of nausea). Software Stata 12.0 was used for meta-analysis. RESULTS: Finally, 9 RCTs were included in the meta-analysis. Results indicated that gabapentin was associated with reduced pain scores after surgery and 24 hours after surgery. Meanwhile, oral gabapentin was associated with a reduction of the total morphine consumption after breast cancer surgery. Similarly, gabapentin was associated with a reduction in the incidence of chronic pain and the incidence of nausea. CONCLUSIONS: Preoperative use of gabapentin was able to reduce acute and chronic postoperative pain, total morphine consumption and the occurrence of nausea following breast cancer surgery. Further studies should determine the optimal dose of gabapentin for pain control after breast cancer surgery.


Asunto(s)
Aminas/uso terapéutico , Neoplasias de la Mama/cirugía , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Mastectomía/efectos adversos , Morfina/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Ácido gamma-Aminobutírico/uso terapéutico , Aminas/administración & dosificación , Dolor Crónico/complicaciones , Dolor Crónico/epidemiología , Ácidos Ciclohexanocarboxílicos/administración & dosificación , Femenino , Gabapentina , Humanos , Morfina/administración & dosificación , Dimensión del Dolor , Dolor Postoperatorio/prevención & control , Cuidados Preoperatorios/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido gamma-Aminobutírico/administración & dosificación
6.
Artículo en Inglés | MEDLINE | ID: mdl-30191088

RESUMEN

Background: Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by exocrine gland and extraglandular symptoms. We present a case report of pSS with an initial presentation of athetoid movements. Case Report: A 74-year-old female presented with a 2-month history of slow undulating movements in her trunk and thighs that eventually spread to her neck and lower extremities. She also reported dry eyes, dry mouth, as well as pain in her shoulders and thighs. Her proinflammatory markers and rheumatologic profile were positive. Her salivary gland biopsy revealed a Focus score > 2. Brain magnetic resonance imaging was normal. A diagnosis of pSS was made. The patient's symptoms improved with hydroxychloroquine, pilocarpine, gabapentin, and clonazepam. Discussion: Clinicians should consider and screen for primary autoimmune disorders as a cause of subacute athetoid movements in elderly patients. Although aggressive treatment has been recommended, treatment should be tailored to each patient's specific needs.


Asunto(s)
Atetosis/complicaciones , Trastornos del Movimiento/complicaciones , Síndrome de Sjögren/etiología , Anciano , Aminas/uso terapéutico , Anticonvulsivantes/uso terapéutico , Atetosis/tratamiento farmacológico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Femenino , Gabapentina , Humanos , Hidroxicloroquina/uso terapéutico , Trastornos del Movimiento/tratamiento farmacológico , Agonistas Muscarínicos/uso terapéutico , Pilocarpina/uso terapéutico , Síndrome de Sjögren/tratamiento farmacológico , Ácido gamma-Aminobutírico/uso terapéutico
8.
J Stroke Cerebrovasc Dis ; 27(10): 2768-2769, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30064867

RESUMEN

Paroxysmal sympathetic hyperactivity is a condition involving a sudden increase in body temperature, heart rate, blood pressure, respiratory rate, sweating, and posturing followed by severe brain injury. Most of the reported preceding disorders involve head trauma, followed by anoxic brain injury, and stroke. Here, we report an extremely rare case of 17-year-old man diagnosed with hemorrhagic arteriovenous malformation, underwent emergent surgery, was on prolonged sedation due to postoperative complications, and subsequently developed paroxysmal sympathetic hyperactivity. We recommend monitoring for paroxysmal sympathetic hyperactivity occurrence with severe brain injury patients, even when sedating.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Lesiones Encefálicas/etiología , Hemorragia Cerebral/cirugía , Malformaciones Arteriovenosas Intracraneales/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Sistema Nervioso Simpático/fisiopatología , Adolescente , Antagonistas Adrenérgicos beta/uso terapéutico , Aminas/uso terapéutico , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/terapia , Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/fisiopatología , Lesiones Encefálicas/terapia , Angiografía Cerebral/métodos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/etiología , Angiografía por Tomografía Computarizada , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Gabapentina , Humanos , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Masculino , Propranolol/uso terapéutico , Sistema Nervioso Simpático/efectos de los fármacos , Resultado del Tratamiento , Ácido gamma-Aminobutírico/uso terapéutico
9.
Anesthesiol Clin ; 36(3): 361-373, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30092934

RESUMEN

Pain control after orthopedic surgery is challenging. A multimodal approach provides superior analgesia with fewer side effects compared with opioids alone. This approach is particularly useful in light of the current opioid epidemic in the United States. Several new nonopioid agents have emerged into the market in recent years. New agents included in this review are intravenous acetaminophen, intranasal ketorolac, and newer nonsteroidal anti-inflammatory drugs, and the established medications ketamine and gabapentinoids. This article evaluates the evidence supporting these drugs in a multimodal context, including a brief discussion of cost.


Asunto(s)
Analgesia/métodos , Procedimientos Ortopédicos/métodos , Dolor Postoperatorio/tratamiento farmacológico , Acetaminofén/uso terapéutico , Aminas/uso terapéutico , Celecoxib/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Gabapentina , Humanos , Ibuprofeno/uso terapéutico , Ketamina/uso terapéutico , Ketorolaco/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico
10.
Drugs Aging ; 35(8): 699-705, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30073604

RESUMEN

The improved detection and successful treatment of breast cancer, resulting in better survival rates, has led to an increasing number of women living with the effects of treatment modalities and their long-term consequences. Menopausal symptoms following breast cancer can occur at an earlier age, be more severe and significantly influence a woman's overall wellbeing, in particular, sexual function, quality of life and adherence to treatment. There is a dearth of good quality evidence on the safest and most effective treatment options available for these women, and this article aims to summarize the current available treatments. Pertinent to these women is general advice, such as avoidance of triggers, and lifestyle modifications. Following which, non-pharmacological interventions, including cognitive behavior therapy (CBT), hypnosis, acupuncture, stellate ganglion nerve block and complementary agents, are discussed. Pharmacological therapies and their safety profile in these high-risk women are then examined; namely, menopausal hormone therapy, progestogens, antidepressants (selective serotonin reuptake inhibitors and selective noradrenaline reuptake inhibitors), gabapentin, clonidine and intra-vaginal dehydroepiandrosterone (DHEA). Finally, neurokinin 3 receptor antagonists, promising new agents for the treatment of troublesome menopausal vasomotor symptoms, are discussed.


Asunto(s)
Neoplasias de la Mama/terapia , Estilo de Vida , Menopausia , Aminas/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Femenino , Gabapentina , Humanos , Calidad de Vida , Ácido gamma-Aminobutírico/uso terapéutico
11.
Cochrane Database Syst Rev ; 6: CD009567, 2018 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-29959871

RESUMEN

BACKGROUND: Acute high altitude illness is defined as a group of cerebral and pulmonary syndromes that can occur during travel to high altitudes. It is more common above 2500 metres, but can be seen at lower elevations, especially in susceptible people. Acute high altitude illness includes a wide spectrum of syndromes defined under the terms 'acute mountain sickness' (AMS), 'high altitude cerebral oedema' and 'high altitude pulmonary oedema'. There are several interventions available to treat this condition, both pharmacological and non-pharmacological; however, there is a great uncertainty regarding their benefits and harms. OBJECTIVES: To assess the clinical effectiveness, and safety of interventions (non-pharmacological and pharmacological), as monotherapy or in any combination, for treating acute high altitude illness. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science, CINAHL, Wanfang database and the World Health Organization International Clinical Trials Registry Platform for ongoing studies on 10 August 2017. We did not apply any language restriction. SELECTION CRITERIA: We included randomized controlled trials evaluating the effects of pharmacological and non-pharmacological interventions for individuals suffering from acute high altitude illness: acute mountain sickness, high altitude pulmonary oedema or high altitude cerebral oedema. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of study reports, the risk of bias for each and performed the data extraction. We resolved disagreements through discussion with a third author. We assessed the quality of evidence with GRADE. MAIN RESULTS: We included 13 studies enrolling a total of 468 participants. We identified two ongoing studies. All studies included adults, and two studies included both teenagers and adults. The 13 studies took place in high altitude areas, mostly in the European Alps. Twelve studies included participants with acute mountain sickness, and one study included participants with high altitude pulmonary oedema. Follow-up was usually less than one day. We downgraded the quality of the evidence in most cases due to risk of bias and imprecision. We report results for the main comparisons as follows.Non-pharmacological interventions (3 studies, 124 participants)All-cause mortality and complete relief of AMS symptoms were not reported in the three included trials. One study in 64 participants found that a simulated descent of 193 millibars versus 20 millibars may reduce the average of symptoms to 2.5 vs 3.1 units after 12 hours of treatment (clinical score ranged from 0 to 11 ‒ worse; reduction of 0.6 points on average with the intervention; low quality of evidence). In addition, no complications were found with use of hyperbaric chambers versus supplementary oxygen (one study; 29 participants; low-quality evidence).Pharmacological interventions (11 trials, 375 participants)All-cause mortality was not reported in the 11 included trials. One trial found a greater proportion of participants with complete relief of AMS symptoms after 12 and 16 hours when dexamethasone was administered in comparison with placebo (47.1% versus 0%, respectively; one study; 35 participants; low quality of evidence). Likewise, when acetazolamide was compared with placebo, the effects on symptom severity was uncertain (standardized mean difference (SMD) -1.15, 95% CI -2.56 to 0.27; 2 studies, 25 participants; low-quality evidence). One trial of dexamethasone in comparison with placebo in 35 participants found a reduction in symptom severity (difference on change in the AMS score: 3.7 units reported by authors; moderate quality of evidence). The effects from two additional trials comparing gabapentin with placebo and magnesium with placebo on symptom severity at the end of treatment were uncertain. For gabapentin versus placebo: mean visual analogue scale (VAS) score of 2.92 versus 4.75, respectively; 24 participants; low quality of evidence. For magnesium versus placebo: mean scores of 9 and 10.3 units, respectively; 25 participants; low quality of evidence). The trials did not find adverse events from either treatment (low quality of evidence). One trial comparing magnesium sulphate versus placebo found that flushing was a frequent event in the magnesium sulphate arm (percentage of flushing: 75% versus 7.7%, respectively; one study; 25 participants; low quality of evidence). AUTHORS' CONCLUSIONS: There is limited available evidence to determine the effects of non-pharmacological and pharmacological interventions in treating acute high altitude illness. Low-quality evidence suggests that dexamethasone and acetazolamide might reduce AMS score compared to placebo. However, the clinical benefits and harms related to these potential interventions remain unclear. Overall, the evidence is of limited practical significance in the clinical field. High-quality research in this field is needed, since most trials were poorly conducted and reported.


Asunto(s)
Mal de Altura/terapia , Acetazolamida/uso terapéutico , Enfermedad Aguda , Adolescente , Adulto , Aminas/uso terapéutico , Anticonvulsivantes/uso terapéutico , Presión Atmosférica , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Dexametasona/uso terapéutico , Gabapentina , Glucocorticoides/uso terapéutico , Humanos , Hipertensión Pulmonar/terapia , Magnesio/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Ácido gamma-Aminobutírico/uso terapéutico
12.
Psychiatr Danub ; 30(2): 142-149, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29930223

RESUMEN

The gabapentinoids gabapentin and pregabalin have been related to addiction citing pharmacovigilance data, some case presentations and increasing reports mainly from methadone maintenance treatment programs or emergency medicine. Most of these reports were based on patients with another current or previous substance use disorder (SUD). According to the ICD-10 dependence criteria, physical dependence (withdrawal symptoms, tolerance) was reported most frequently alongside regular use of gabapentinoids. Far less patients showed key symptoms of behavioral dependence (craving, loss of control, or addictive behavior). Through a literature review, we found 2 and 13 case reports about gabapentionoid-seeking behavior or craving for gabapentin and pregabalin, respectively. Those patients without a history of another SUD, but being behaviorally dependent on gabapentinoids, deemed more appropriate to reflect the true addictive power of these drugs. We found solely 4 such cases, all referring to pregabalin and none for gabapentin. Taking into account that gabapentinoids have become widely distributed and easily obtainable via the internet or black-markets, one would expect many more of these cases, if gabapentinoids had considerable addictive power. Moreover, we are not aware of any patient who sought detoxification treatment owing to the misuse of gabapentinoids. Unlike for traditional psychoactive drugs, there is only very scarce evidence for gabapentinoids to be misused in a long-term manner and to be rewarding and reinforcing in animal experiments. Further, we assessed the hazardous potential of gabapentin and pregabalin in relation to that of traditional substances of abuse. Altogether, we support the view that gabapentinoids are quite rarely addictive in the general population. In patients with a history of SUD, however, gabapentinoids (notably pregabalin) should avoided or, if thought to be beneficial, administered with caution by using a strict prescription and therapy monitoring.


Asunto(s)
Aminas , Ácidos Ciclohexanocarboxílicos , Pregabalina , Trastornos Relacionados con Sustancias/diagnóstico , Ácido gamma-Aminobutírico , Adulto , Aminas/efectos adversos , Aminas/uso terapéutico , Animales , Comorbilidad , Ansia , Ácidos Ciclohexanocarboxílicos/efectos adversos , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Gabapentina , Humanos , Masculino , Metadona/efectos adversos , Metadona/uso terapéutico , Narcóticos , Tratamiento de Sustitución de Opiáceos , Pregabalina/efectos adversos , Pregabalina/uso terapéutico , Recompensa , Síndrome de Abstinencia a Sustancias/diagnóstico , Síndrome de Abstinencia a Sustancias/etiología , Trastornos Relacionados con Sustancias/psicología , Ácido gamma-Aminobutírico/efectos adversos , Ácido gamma-Aminobutírico/uso terapéutico
13.
Cochrane Database Syst Rev ; 6: CD007522, 2018 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-29929212

RESUMEN

BACKGROUND: Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium. OBJECTIVES: To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal. SEARCH METHODS: We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials. SELECTION CRITERIA: Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1 study, very low-quality evidence); clonidine versus clonidine plus amantadine (RR 1.03, 95% CI 0.86 to 1.24; 69 participants, 1 study); clonidine versus buprenorphine in an inpatient setting (RR 1.04, 95% CI 0.90 to 1.20; 1 study, 35 participants, very low-quality evidence); methadone versus tramadol (RR 0.95, 95% CI 0.65 to 1.37; 1 study, 72 participants, very low-quality evidence); methadone versus methadone plus gabapentin (RR 1.17, 95% CI 0.96 to 1.43; 1 study, 40 participants, low-quality evidence), and tincture of opium versus methadone (1 study, 74 participants, low-quality evidence).Comparing different pharmacological treatments with each other, adding amantadine to clonidine decreased withdrawal scores rated at day 3 (mean difference (MD) -3.56, 95% CI -5.97 to -1.15; 1 study, 60 participants, very low-quality evidence). Comparing clonidine with buprenorphine in an inpatient setting, we found no difference in withdrawal symptoms rated by a physician (MD -1.40, 95% CI -2.93 to 0.13; 1 study, 34 participants, very low-quality evidence), and results in favour of buprenorpine when rated by participants (MD -11.80, 95% CI -15.56 to -8.04). Buprenorphine was superior to clonidine in controlling severe withdrawal symptoms in an outpatient setting (RR 0.35, 95% CI 0.19 to 0.64; 1 study, 76 participants). We found no difference in the comparison of methadone versus tramadol (MD 0.04, 95% CI -2.68 to 2.76; 1 study, 72 participants) and in the comparison of methadone versus methadone plus gabapentin (MD -2.20, 95% CI -6.72 to 2.32; 1 study, 40 participants).Comparing clonidine versus buprenorphine in an outpatient setting, more adverse effects were reported in the clonidine group (1 study, 76 participants). Higher numbers of participants in the clonidine group experienced hypotension at days 5 to 8, headache at days 1 to 8, sedation at days 5 to 8, dizziness and dry mouth at days 1 to 10, and nausea at days 1 to 9. Sweating was reported in a significantly higher number of participants in the buprenorphine group at days 1 to 10. We found no difference between groups for all the other comparisons considering this outcome.Comparing different dosages of the same pharmacological detoxification treatment, a high dose of clonidine (1 to 1.2 mg/day) did not differ from a low dose of clonidine (0.5 to 0.6 mg/day) in completion of treatment in an inpatient setting (RR 1.00, 95% CI 0.84 to 1.19; 1 study, 68 participants), however a higher number of participants with hypotension was reported in the high-dose group (RR 3.25, 95% CI 1.77 to 5.98). Gradual reduction of methadone was associated with more adverse effects than abrupt withdrawal of methadone (RR 2.25, 95% CI 1.02 to 4.94; 1 study, 20 participants, very low-quality evidence). AUTHORS' CONCLUSIONS: Results did not support using any specific pharmacological approach for the management of opium withdrawal due to generally very low-quality evidence and small or no differences between treatments. However, it seems that opium withdrawal symptoms are significant, especially at days 2 to 4 after discontinuation of opium. All of the assessed medications might be useful in alleviating symptoms. Those who receive clonidine might experience hypotension.


Asunto(s)
Trastornos Relacionados con Opioides/tratamiento farmacológico , Opio/efectos adversos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Amantadina/uso terapéutico , Aminas/uso terapéutico , Baclofeno/uso terapéutico , Buprenorfina/efectos adversos , Buprenorfina/uso terapéutico , Clonidina/efectos adversos , Clonidina/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Gabapentina , Humanos , Metadona/uso terapéutico , Opio/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tramadol/uso terapéutico , Ácido gamma-Aminobutírico/uso terapéutico
14.
Dermatol Clin ; 36(3): 245-258, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29929596

RESUMEN

Pruritus is a common symptom in cutaneous T-cell lymphoma (CTCL) and critically affects the quality of life of patients. Understanding the pruritogenesis has led to development of new therapeutic agents with promising outcomes in management of this recalcitrant symptom. Clinical assessments are warranted to aid in evaluation of treatment response or disease recurrence. Severe pruritus scores may require further investigation of emotional distress for a better patient approach. Dermatologists play a key role in the treatment of CTCL-pruritus by guiding the patient in the importance of preserving the integrity of the skin barrier.


Asunto(s)
Antipruriginosos/uso terapéutico , Linfoma Cutáneo de Células T/complicaciones , Prurito/tratamiento farmacológico , Prurito/fisiopatología , Corticoesteroides/uso terapéutico , Aminas/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Emolientes/uso terapéutico , Gabapentina , Antagonistas de los Receptores Histamínicos/uso terapéutico , Humanos , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Antagonistas del Receptor de Neuroquinina-1/uso terapéutico , Prurito/etiología , Inhibidores de la Captación de Serotonina/uso terapéutico , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Escala Visual Analógica , Ácido gamma-Aminobutírico/uso terapéutico
15.
Dermatol Clin ; 36(3): 277-292, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29929599

RESUMEN

End-stage renal disease chronic itch is a frequent symptom that bothers patients with advanced stages of chronic kidney disease. The pathogenesis of the chronic itch symptom is complex and not yet fully understood and includes many metabolic, immunologic, and neurogenic factors. A significant burden of the disease results in decreased quality of life with sleep impairment, depressive symptoms, and increased mortality of affected individuals. No treatment of choice is available; topical therapy (emollients), phototherapy (UV-B), and systemic therapy (antiepileptics, opioid agonists, and antagonists) provide significant relief in varying percentages of patients.


Asunto(s)
Antipruriginosos/uso terapéutico , Fallo Renal Crónico/complicaciones , Prurito/etiología , Prurito/terapia , Terapia Ultravioleta , Aminas/uso terapéutico , Analgésicos Opioides/uso terapéutico , Anticonvulsivantes/uso terapéutico , Enfermedad Crónica , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Emolientes/uso terapéutico , Gabapentina , Humanos , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Nalbufina/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Pregabalina/uso terapéutico , Prurito/fisiopatología , Calidad de Vida , Diálisis Renal , Índice de Severidad de la Enfermedad , Ácido gamma-Aminobutírico/uso terapéutico
17.
Eur J Pharmacol ; 833: 44-49, 2018 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-29842875

RESUMEN

The antipruritic activity of gabapentin, an anticonvulsant, was studied in a mouse model of allergic itch. In mice sensitized by an extract of the salivary glands of the mosquito (ESGM), an intradermal injection of ESGM elicited scratching and increased peripheral nerve firing. Oral or intradermal administration of gabapentin at the ESGM injection site inhibited ESGM-induced scratching and peripheral nerve firing. However, gabapentin did not affect histamine-induced scratching. The distributions of immunoreactivity to the voltage-dependent calcium channel α2δ-1 subunit, a site of gabapentin action, and the histamine H1 receptor differed in the mouse dorsal root ganglia. The α2δ-1 subunit was mainly found in neurons that were 15-20 µm in diameter, whereas the H1 receptor was mainly in 20-30 µm neurons. In addition, α2δ-1 subunit immunoreactivity co-localized with that of transient receptor potential vanilloid 1 (TRPV1). These results suggest that gabapentin regulates allergic itch by acting on the calcium channel α2δ-1 subunit in peripheral TRPV1-positive neurons.


Asunto(s)
Aminas , Antipruriginosos , Canales de Calcio/metabolismo , Culicidae/inmunología , Ácidos Ciclohexanocarboxílicos , Hipersensibilidad/tratamiento farmacológico , Prurito/tratamiento farmacológico , Saliva/inmunología , Ácido gamma-Aminobutírico , Aminas/farmacología , Aminas/uso terapéutico , Animales , Antipruriginosos/farmacología , Antipruriginosos/uso terapéutico , Ácidos Ciclohexanocarboxílicos/farmacología , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Gabapentina , Hipersensibilidad/metabolismo , Masculino , Ratones Endogámicos ICR , Neuronas/metabolismo , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/fisiología , Prurito/metabolismo , Receptores Histamínicos H1/metabolismo , Canales Catiónicos TRPV/metabolismo , Ácido gamma-Aminobutírico/farmacología , Ácido gamma-Aminobutírico/uso terapéutico
18.
Dis Colon Rectum ; 61(7): 824-829, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29771804

RESUMEN

BACKGROUND: Postoperative pain is a frequent cause for delayed discharge following outpatient procedures, including anorectal surgery. Both central and peripheral pain receptor sensitization are thought to contribute to postoperative pain. Blocking these receptors and preempting sensitization prevents hyperalgesia leading to lower pain medication requirements. Studies in the orthopedic, urologic, and gynecologic literature support this practice, but the use of preemptive analgesia in anorectal surgery is understudied. OBJECTIVE: This study aimed to evaluate the effectiveness of preemptive analgesia in decreasing postoperative pain. DESIGN: This is a randomized, double-blinded, placebo-controlled trial. SETTING: This study was conducted at the University of Vermont Medical Center, a tertiary care referral center in Burlington, Vermont. PATIENTS: Patients who were over 18 years of age, ASA Physical Status Classes I, II, or III, and undergoing surgery for anal fissure, fistula or condyloma or hemorrhoids were selected. INTERVENTIONS: Preoperative oral acetaminophen and gabapentin followed by intravenous ketamine and dexamethasone were given before incision compared with oral placebos. MAIN OUTCOME MEASURES: The primary outcomes measured were postoperative pain scores, percentage of patients utilizing breakthrough narcotics, and rates of side effects. RESULTS: Ninety patients were enrolled. Because of patient withdrawal, screen failures, and loss to follow-up, 61 patients were analyzed (30 in the preemptive analgesia group and 31 in the control group). Patients in the active group had significantly less pain in the postanesthesia care unit and at 8 hours postoperatively. Significantly fewer participants in the active group used narcotics in the postanesthesia care unit and at 8 hours postoperatively. Average pain scores were excellent for both groups. There was no difference in the number of medication-related side effects between the 2 groups. LIMITATIONS: This study was limited by the small sample size and excellent pain control in both groups. CONCLUSIONS: Preemptive analgesia is safe and results in decreased pain in the early postoperative period following anorectal surgery. It should be implemented by surgeons performing these procedures. See Video Abstract at http://links.lww.com/DCR/A588.


Asunto(s)
Acetaminofén/uso terapéutico , Aminas/uso terapéutico , Canal Anal/cirugía , Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Enfermedades del Ano/cirugía , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Dexametasona/uso terapéutico , Ketamina/uso terapéutico , Dolor Postoperatorio/prevención & control , Ácido gamma-Aminobutírico/uso terapéutico , Adulto , Procedimientos Quirúrgicos Ambulatorios , Analgésicos Opioides/uso terapéutico , Condiloma Acuminado/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo , Método Doble Ciego , Femenino , Fisura Anal/cirugía , Gabapentina , Hemorreoidectomía , Hemorroides/cirugía , Humanos , Hidromorfona/uso terapéutico , Ibuprofeno/uso terapéutico , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Dolor Postoperatorio/tratamiento farmacológico , Fístula Rectal/cirugía , Recto/cirugía
19.
Ginekol Pol ; 89(4): 200-4, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29781075

RESUMEN

OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) is a common chemotherapy side effect, but its prevention and treatment remains a challenge. Neurotoxicity may lead to dose limitation or even treatment discontinuation, and therefore potentially affect the efficacy of anticancer treatment and long term outcomes. The practice to administer gabapentin for neuropathy may be applicable, but is limited by insufficient studies. The aim of our study was to assess the presence of chemotherapy-induced peripheral neuropathy in ovarian cancer patients treated with first-line paclitaxel and carboplatin chemotherapy and evaluate the effectiveness of gabapentin in treatment of this condition. MATERIAL AND METHODS: 61 ovarian cancer patients treated with first line chemotherapy were included in the study. The first phase of the study was to assess neurological condition of each patient by: neuropathy symptoms scale, McGill's scale, neurological deficit and quality of life, during the chemotherapy. In the second phase of the study we evaluated the response to gabapentin treatment in a group of patients who developed neuropathy. RESULTS: 78.7% of the patients developed chemotherapy related neuropathy. During the course of chemotherapy these patients experienced significant exacerbation of neuropathy symptoms (p < 0.0001), neuropathic pain (p < 0.0001), neurologic deficit (p < 0.0012) and worsening of quality of life (p < 0.0002). Patients who were qualified to undergo the gabapentin treatment observed improvement in symptoms (p < 0.027), pain (p < 0.027) and neurologic deficit (p < 0.019). Quality of life did not change significantly after gabapentin treatment (p < 0.128). CONCLUSIONS: Chemotherapy substantially deteriorates the neurologic condition of the patients and the quality of life. Paclitaxel and carboplatin treated patients may benefit from gabapentin therapy in chemotherapy-induced peripheral neuropathy.


Asunto(s)
Aminas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/efectos adversos , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Ácido gamma-Aminobutírico/uso terapéutico , Adulto , Femenino , Gabapentina , Humanos , Persona de Mediana Edad
20.
Seizure ; 59: 28-33, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29730273

RESUMEN

PURPOSE: Hyponatremia induced by antiepileptic drugs is common, but detailed evidence is lacking. This can be problematic for the treating neurologist confronted with a patient with severe hyponatremia in need of an alternative drug. The objective of this study was to examine the association between individual antiepileptic drugs and hospitalization due to hyponatremia. METHODS: This was a register-based case-control study of patients in the general Swedish population. We included 14,359 individuals with a principal diagnosis of hyponatremia and 57,383 matched controls. The association between newly initiated (≤90 days) and ongoing antiepileptic treatment was investigated using multivariable logistic regression adjusting for concomitant drugs, medical conditions, previous hospitalizations and sociaoeconomic factors. RESULTS: For newly initiated antiepileptic drugs, adjusted ORs (95% CI) for hospitalization due to hyponatremia, compared to controls, were: carbamazepine 9.63 (6.18-15.33); phenytoin 4.83 (1.14-25.76); valproate 4.96 (2.44-10.66); lamotrigine 1.67 (0.70-4.08); levetiracetam 9.76 (4.02-27.59) and gabapentin 1.61 (1.08-2.38). Newly initiated oxcarbazepine treatment was only found in the hyponatremia group and not in controls. Adjusted ORs (CI) for individuals with ongoing treatment ranged from 7.97 (3.70-18.50) for oxcarbazepine to 0.83 (0.64-1.06) for gabapentin. CONCLUSION: There was a strong association between newly initiated treatment with carbamazepine, oxcarbazepine and levetiracetam, and hospitalization due to hyponatremia. The corresponding association for phenytoin and valproate was moderate. The risk for hyponatremia was lower during ongoing treatment. Lamotrigine and gabapentin had the lowest risk both during initiation and ongoing treatment and may be advantageous in patients at risk of developing hyponatremia.


Asunto(s)
Anticonvulsivantes/efectos adversos , Hospitalización , Hiponatremia/inducido químicamente , Hiponatremia/terapia , Anciano , Aminas/efectos adversos , Aminas/uso terapéutico , Anticonvulsivantes/uso terapéutico , Carbamazepina/efectos adversos , Carbamazepina/análogos & derivados , Carbamazepina/uso terapéutico , Estudios de Casos y Controles , Ácidos Ciclohexanocarboxílicos/efectos adversos , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Femenino , Gabapentina , Humanos , Lamotrigina , Levetiracetam , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Oxcarbazepina , Piracetam/efectos adversos , Piracetam/análogos & derivados , Piracetam/uso terapéutico , Sistema de Registros , Estudios Retrospectivos , Factores de Tiempo , Triazinas/efectos adversos , Triazinas/uso terapéutico , Ácido gamma-Aminobutírico/efectos adversos , Ácido gamma-Aminobutírico/uso terapéutico
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