ABSTRACT
Introducción: tramadol es un analgésico opioide usado frecuentemente para el manejo del dolor crónico no oncológico (DCNO). En Chile, es parte del arsenal farmacológico de los centros de atención primaria para el tratamiento de patologías como artrosis de cadera y rodilla. Es considerado seguro y efectivo, sin embargo, existen reportes de efectos adversos serios por polimorfismos hepáticos, interacciones farmacológicas, intoxicaciones, adicción y muerte. La dosis óptima de tramadol es paciente dependiente. Por esto, es necesario contar con orientaciones específicas para prescribir tramadol de manera segura y eficaz según las características de cada paciente. Materiales y métodos: se revisaron guías actualizadas, revisiones sistemáticas y guías de sociedades internacionales sobre el uso de opioides en DCNO y el uso de tramadol en patologías de DCNO como artrosis, lumbago crónico, dolor neuropático y fibromialgia. Resultados: tramadol no está indicado en el tratamiento de cuadros de dolor primario como fibromialgia y en DCNO secundario es un fármaco de segunda línea o no está recomendado. En dolor crónico neuropático (DCN) es segunda línea de tratamiento. En osteoartritis de cadera, rodilla y mano, se reporta efecto analgésico modesto. Sopesar riesgos versus beneficios en estos pacientes. En artritis reumatoide y lumbago crónico se desaconseja su uso. Conclusiones: tramadol es un medicamento seguro y efectivo si se indica, administra, supervisa y descontinúa adecuadamente. Sin embargo, puede asociarse a interacciones farmacológicas, efectos secundarios serios, conductas de abuso y usos ilícitos, por lo que es necesario conocer y manejar adecuadamente su farmacología e indicaciones.
Introduction: Tramadol is an opioid pain medicine commonly used for chronic non-cancer pain (CNCP) management. In Chile, it is part of the pharmacological arsenal available in primary care centers for treating specific CNCP pathologies, such as hip and knee arthrosis. Tramadol is considered a safe and effective drug. Nevertheless, there are reports of serious adverse effects of tramadol, such as poisoning, addiction, and death, probably caused by liver polymorphisms and drug interaction. The optimal dose of tramadol is patient-specific. Specific knowledge is needed to prescribe tramadol in a safe and effective way according to the patient's medical backward. Methods: We review updated guidelines, systematic reviews, and guidelines from international societies about the use of opioids and tramadol in CNCP pathologies such as osteoarthritis, chronic low back pain, neuropathic pain, and fibromyalgia. Results: Tramadol has no role in primary pain treatment, such as fibromyalgia, but is a second-line drug for chronic neuropathic pain (CNP) and some secondary pain syndromes. Tramadol has a modest analgesic effect in osteoarthritis patients. Clinicians should always weigh the risks and benefits before prescribing tramadol. Tramadol use is discouraged in rheumatoid arthritis and chronic lumbago. Conclusions: Tramadol is a safe and effective drug if correctly indicated, administered, supervised, and discontinued. However, it may be associated with pharmacological interactions, serious side effects, abuse behaviors, and illicit uses, and it is necessary that clinicians know and manage its pharmacology and indications appropriately.
ABSTRACT
Eighteen male cluster headache (CH) inpatients within a CH series participated in this research. Blood samples were drawn from patients at least 6-hour pain-free after the last acute CH episode and then shortly prior (SP), during, and soon after (SA) a new acute CH attack. Three healthy male, age-comparable drug-free volunteers served as controls; 5 samples were obtained from each of these individual over a 24-hour period. Individual patient's methionine-enkephalin (MET) plasma concentration showed significant changes, and in some subjects, dramatic changes, during the different phases of a single CH episode. Peptide levels followed a general pattern of higher plasma concentration SP to an acute CH attack, followed by decreased levels during the attack itself, and falling even further SA the acute episode. Consistently, 16 of the 18 patients tested showed pre-CH peptide levels significantly higher (arbitrarily the authors considered values 20% or more as "significant") than their own values obtained during the acute CH pain phase, with observed differences reaching 80% or more in 7 of these individuals. For about half of these patients, peptide concentration during the acute CH episode was significantly above the control's range (68.2-87.6 pg MET/mL; control's circulating MET concentration remaining essentially unchanged during a 24-hour period). MET levels were further decreased in essentially all of the post-CH samples, with values falling within (n = 6) or even further below than those in the control's range (n = 11). Neither age, time of CH occurrence, nor patient's use of a number of medications known for failing to influence plasma MET degradation kinetics seemed to significantly influence MET levels. These results might help in the biochemical characterization of the actual phases of a CH episode. Developing drugs modulating MET bioavailability could lead to novel antinociceptive agents useful for the treatment of CH's associated pain.
Subject(s)
Cluster Headache/blood , Enkephalin, Methionine/blood , Plasma/metabolism , Adult , Humans , Male , Middle Aged , Time FactorsABSTRACT
Results from a longitudinal study (blood drawn at days 29, 64, 89,124, 142, and 182 of the protocol) shows that the concentration of platelet-poor plasma (PPP) methionine(5)-enkephalin (MET) in healthy, drug-free, white male individuals (n = 5) remains within a relatively narrow range, well within the experimental error of the analytical procedures used. Interindividual differences fail to reach statistical significance [x ± SD and range (MET picograms per mL of PPP) of 91.2 ± 15.1, 67.1-113.5; 69.6 ± 7.5, 66.1-90.1; 76.6 ± 12.6, 58.5-93.1; 86.8 ± 10.9, 76.3-107.4; and 84.5 ± 11.4, 68.9-103.4; for subjects 1-5, respectively]. MET levels were similar to those recorded from single samples obtained from a group of 24 white male, age-comparable, drug-free healthy volunteers [x ± SD and range (picograms of MET per mL of PPP) of 83.3 ± 15.1 and 57.4-119.1]. The controls' range for all the subjects (n = 29) was 57.4-119.1 pgMET/mL PPP. Compared with the controls, individual patients with cluster headache (CH) show a much wider variation in PPP MET levels (blood drawn at different time intervals, at least 10 samples per patient, over a period of 221-298 days), with many (slightly over half) of single values below the controls range; no single MET level was above the controls range [x ± SD and range (picograms of MET per mL of PPP) of 56.4 ± 27.7, 6.1-100.5; 72.6 ± 20.5, 43.0-113.0; 46.0 ± 28.5, 10.0-92.6; 53.6 ± 27.5, 13.0-101.0; 52.0 ± 26.1, 17.5-83.6; 63.5 ± 22.3, 21.7-91.3 for individuals A-F, respectively]. Although interindividual differences within the patients' group were not statistically significant, their peptide levels were significantly lower than those of controls. Neither the presence of unspecified "headaches between clinic visits" and "daily headaches" (patients E and F, respectively), nor the use of a number of drugs known to lack inhibitory activity upon the aminopeptidase-MET degradation reaction, seemed to significantly influence MET concentration. The results could lead to a better understanding of the etiology of the pain associated with CH, with the relative changes in plasma peptide perhaps reflecting the patients' vulnerability to such a condition. Pharmacological modulation of MET function may prove useful in the treatment of CH-associated pain, whether the development of such drugs could find useful pharmacological applications remains to be explored.
