Uso de coadyuvantes en dolor postoperatorio / Use of adjuvants in postoperative pain

Resumen: Los analgésicos coadyuvantes son compuestos que tienen una baja potencia analgésica. Sin embargo, la sinergia con opioides incrementa su efecto y favorece una reducción en los eventos adversos de los narcóticos para el control del dolor postoperatorio. Las estrategias ahorradoras de opioides están relacionadas con el efecto de una variedad de receptores, de los cuales podemos nombrar: los antagonistas NMDA como la ketamina, magnesio y dextrometorfano, los agonistas α-2 como la clonidina y la dexmedetomidina, los inhibidores de la subunidad α-2δ de los canales de calcio como la pregabalina y la gabapentina, los bloqueadores de los canales de sodio como la lidocaína y, finalmente, los glucocorticoides. En esta revisión se describirán las características, indicaciones, dosis y niveles de evidencia del uso de los coadyuvantes de uso intravenoso y regional en el contexto perioperatorio. (visite http://www.painoutmexico.com para ver artículo completo y Tablas).

Abstract: The adjuvant analgesics are compounds that have a low analgesic potency. However, with these compounds, the adverse effects of opioids may be diminished for the control of postoperative pain. Opioid-sparing strategies are related to the effect on a variety of receptors, of which we should name: the NMDA antagonists such as ketamine, magnesium and dextromethorphan, the α-2 agonists such as clonidine and dexmedetomidine, subunit α-2δ of calcium channels inhibitors; such as pregabalin and gabapentin, sodium channels blockers such as lidocaine and finally glucocorticoids. In this review we describe the characteristics, indications, doses and levels of evidence of use of adjuvants in the perioperative context (visit http://www.painoutmexico.com to see the full article and Tables).

Eletrocardiografia em onças-pardas (Puma concolor) anestesiadas com sevoflurano ou isoflurano / Electrocardiography in pumas (puma concolor) anesthetized with sevoflurane or isoflurane

O objetivo deste trabalho foi descrever os achados eletrocardiográficos de 11 onças- pardas (Puma concolor). Os animais foram sedados com 0,15mg/kg de detomidina associado a 5mg/kg de cetamina e mantidos anestesiados com sevoflurano (GSEVO, n=6) ou isoflurano (GISO, n=5). A frequência cardíaca foi de 95 ± 13bpm. As alterações observadas nos animais no GSEVO foram: atrial standtill com condução ventricular, episódios isolados de contração ventricular prematura, bloqueio atrioventricular de primeiro grau, diminuição da amplitude do complexo QRS, onda S profunda e aumento da amplitude da onda T. No grupo GISO, observou-se bloqueio de ramo direito do feixe de His, bloqueio atrioventricular de primeiro grau e aumento da amplitude da onda T. Arritmias não puderam ser associadas ao uso dos anestésicos inalatórios devido à não sensibilização do miocárdio às catecolaminas. Achados como o BAV de primeiro grau pode ter ocorrido devido ao uso de agonistas alfa-2 adrenérgicos. Este estudo aumentou o conhecimento sobre as alterações eletrocardiográficas em onças-pardas anestesiadas, entretanto mais estudos são necessários para correlacionar estes achados ao uso de agentes anestésicos.(AU)

The aim of this study was to describe electrocardiographic findings in pumas (Puma concolor). The animals were sedated with 0.15mg/kg of detomidine plus 5mg/kg of ketamine and anesthetized with sevoflurane (GSEVO, n=6), or isoflurane (GISO, n=5). The heart rate was 95 ± 13bpm. The changes observed on GSEVO animals were: atrial standstill with ventricular conduction, isolated episodes of ventricular premature contraction, atrioventricular blockage of first degree, reduction of the amplitude of the QRS complexes, deep S wave, and increase of the amplitude of the T wave. In the GISO group a right bundle branch block of the His bundle, atrioventricular blockage of first degree and of the amplitude of the T wave. Arrhythmias couldn´t be related to the use of inhalant anesthesia due to the lack of myocardial awareness to catecholamines. Findings such as atrioventricular block in first degree may have occurred due to the use of alfa-2 adrenergic agonists. This study improved the knowledge about electrocardiographic alterations in anesthetized pumas, however further studies are required to correlate these findings to the use of anesthetic agents.(AU)

Evaluation of cardiopulmonary parameters and recovery from anesthesia in cougars (Puma concolor) anesthetized with detomidine/ketamine and isoflurane or sevoflurane / Avaliação de parâmetros cardiorrespiratórios e recuperação da anestesia em pumas (Puma concolor) anestesiados com detomidina/cetamina e isoflurano ou sevoflurano

The aim of this study was to assess the cardiopulmonary effects, the onset time after the administration of a detomidine/ketamine combination, and the recovery from anesthesia of cougars (Puma concolor) anesthetized with detomidine/ketamine and isoflurane or sevoflurane for abdominal ultrasound imaging. Fourteen animals were randomly allocated into two experimental groups: GISO (n=7) and GSEVO (n=7). Chemical restraint was performed using 0.15mg/kg detomidine combined with 5mg/kg ketamine intramuscularly; anesthesia induction was achieved using 2mg/kg propofol intravenously and maintenance with isoflurane (GISO) or sevoflurane (GSEVO). The following parameters were assessed: heart rate, respiratory rate, systolic and diastolic arterial blood pressure, mean arterial blood pressure, oxyhemoglobin saturation, rectal temperature, central venous pressure, and end-tidal carbon dioxide. The time to sternal recumbency (TSR) and time to standing position (TSP) were also determined. There was not statistically significant difference for the cardiopulmonary variables or TSP whereas TSR was significantly shorter in GSEVO. The time to onset of anesthesia was 11.1±1.2 minutes and 11.3±1.8 minutes for GISO and GSEVO, respectively. The anesthesia of cougars with detomidine/ketamine and isoflurane or sevoflurane was conducted with safety, cardiopulmonary stability, and increased time to sternal recumbency in the GISO group.

O objetivo do presente estudo foi avaliar os efeitos cardiorrespiratórios e a recuperação anestésica de onças-pardas (Puma concolor) submetidas à anestesia com detomidina/cetamina e isofluorano ou sevofluorano para avaliação ultrassonográfica abdominal. Para isso, foram utilizados 14 animais divididos aleatoriamente em dois grupos experimentais GISO (n=7) e GSEVO (n=7). Foram submetidos à contenção química com detomidina 0,15mg/kg associada à cetamina 5mg/kg pela via intramuscular, induzidos com propofol 2mg/kg pela via intravenosa e mantidos com isofluorano (GISO) ou sevofluorano. Foram avaliados os parâmetros: frequência cardíaca e respiratória, pressão arterial sistólica, média e diastólica saturação de oxihemoglobina, temperatura retal, pressão venosa central e fração expirada de dióxido de carbono. O tempo para adoção de decúbito esternal e posição quadrupedal também foram avaliados. Não houve diferença estatística para as variáveis cardiorrespiratórias e no tempo para adoção da posição quadrupedal. O tempo para adoção de decúbito esternal foi significativamente menor no GSEVO em relação ao GISO. Concluiu-se que a anestesia de onças pardas com detomidina/cetamina e isoflurano ou sevoflurano foi realizada de maneira segura, com estabilidade cardiorrespiratória e com aumento no tempo para adoção de decúbito esternal no GISO.

An Acute Therapeutic Evaluation of Three Regimens of Tiotropium and Formoterol in COPD Patients: A Randomized, Double-blind, Placebo-Controlled Clinical Study.

Aims: To evaluate therapeutic rationality of combining long-acting β2-agonists (formoterol) with duration of action of 12 hours and anticholinergics (tiotropium) with 24 hours as fixed dose inhaled combination (FDC) still widely prescribed in developing countries in COPD patients. Study Design: A randomized, double-blind, placebo-controlled, parallel design study. The three regimens that were used; tiotropium 18 μg once a day in the morning along with the formoterol matched placebo in the evening, the FDC of tiotropium 18 μg plus formoterol 12 μg once a day in the morning and formoterol matched placebo in the evening and the same FDC of the two drugs once a day in the morning and once a day formoterol 12 μg in the evening in patients of COPD without any co-morbidity. Place and Duration of Study: Tertiary care pulmonary medicine university teaching government hospital of Delhi, India; 1 year. Methodology: Sixty COPD patients (Male, Avg. age 56±11 years) divided into 3 groups of 20 each without any comorbidity were admitted in the hospital for 24 hours. The spirometry, perception of dyspnea on Borg's scale and vitals such as blood pressure (BP) and pulse rate (PR) were recorded at the following interval 30 minutes, 2 hours, 12 hours after the morning dose and 30 minutes and 12 hours after the evening dose. Results: Addition of formoterol in the evening along with the FDC in the morning enhanced the peak effects in percentage predicted FEV1 (82.55+/-12.639), FEV1/FVC (0.592±0.097) that remained till the next dose (24 hours) which was statistically (P=.05) superior to the tiotropium alone group (75.55+/-17.981) as well as FDC alone group (74.55+/-12.655). Conclusion: There is no advantage of FDC once a day over tiotropium alone. However addition of evening dose of formoterol has shown therapeutic superiority over once a day FDC of the two in COPD.

Status Asmaticus: lenda ou realidade? Como tratar melhor? / Status Asmathicus: legend or reality? How to treat better?

A história natural do status asmaticus é na maioria das vezes de resolução com mortalidade geral menor que 1%. Cerca de 80% dos pacientes com exacerbação de asma brônquica são liberados da emergência nas primeiras duas horas de tratamento. No entanto, nos pacientes com necessidade de ventilação mecânica a mortalidade pode chegar a 8%. O tratamento rápido e eficaz é essencial para o sucesso do tratamento e a prevenção de complicações. Neste artigo são abordadas as recomendações atuais do tratamento das exacerbações graves de asma brônquica nos setores de emergência e terapia intensiva...

The natural history of status asthmaticus is, most of the time, sorted out with overall mortality less than 1%. About 80% of patients with exacerbation of asthma emergency are released within the first two hours of treatment. However, in patients requiring mechanical ventilation mortality can reach 8%. The rapid and effective treatment is essential for the success of the treatment and the prevention of complications. This paper addresses the current recommendations the treatment of severe exacerbations of asthma in the emergency department and intensive care...

Seguridad de los beta 2 agonistas (B2A) en asma bronquial / Safety of beta-agonists in asthma

Los broncodilatadores beta 2 agonistas (B2A), forman parte muy importante en la farmacoterapia del asma bronquial, enfermedad que avanza en el mundo, de manera epidémica. Los B2A, son prescritos a millones de personas en el mundo, por consiguiente; los aspectos de seguridad son de interés público. Los broncodilatadores B2A de acción corta (Short-Acting B2 Agonists o SABA) como salbutamol inhalatorio, según las evidencias actuales, confirman su seguridad, en su uso como fármaco de rescate o a demanda. Los broncodilatadores B2A de acción prolongada (Long-Acting B2 Agonists o LABA), se utilizan asociados a corticoides inhalatorios, como medicamentos controladores de exacerbaciones de accesos asmáticos, por razones de seguridad los LABAs se usan asociados a corticoides inhalatorios...

Beta 2 agonist bronchodilators (B2A) are very important part in the pharmaco therapy of bronchial asthma, a disease that progresses in the world in an epidemic way. The B2A are prescribed to millions of people around the world, there fore the safety aspects is of public interest. Short-Acting B2 Agonists (SABAs), such as albuterol inhaler, according to current evidence, have confirmed their safety when used as a quick-relief or rescue medication. The long-acting B2 agonists (LABAs) are used associated with inhaled corticosteroids as controller drugs for asthma exacerbations, for safety reasons LABAs are used associated with inhaled corticoid...

Comparação da contenção farmacológica com cetamina e xilazina, administradas pela via intramuscular no membro torácico ou pélvico, em jacarés-do-papo-amarelo juvenis / Comparison of pharmacological restraint with ketamine and xylazine, administered intramuscularly in the forelimb or hindlimb, in broad-snouted caiman juveniles

Os répteis possuem um sistema porta-renal, o qual pode desviar parte do sangue proveniente das porções caudais do corpo aos rins antes que a mesma atinja a circulação sistêmica. Em vista disto, vem sendo aconselhada a administração de medicamentos injetáveis nos membros torácicos, para que se evite a filtração imediata pelo parênquima renal, causando redução do efeito esperado. O objetivo do presente estudo foi comparar aspectos qualitativos e quantitativos da associação de cetamina (30 mg/kg) e xilazina (1 mg/kg), injetada no membro torácico ou pélvico, em jacarés-do-papo-amarelo (Caiman latirostris) juvenis. Oito animais machos com peso médio (±DP) de 1,3 (±0,3) kg e, aproximadamente, dois anos de idade foram anestesiados em duas ocasiões distintas com intervalo de sete dias. Em cada ocasião, os animais receberam, de forma aleatória, a associação anestésica por via intramuscular em membro torácico (tratamento MT) ou pélvico (tratamento MP). Foram avaliados os intervalos de tempo entre a administração do tratamento e a perda do reflexo de endireitamento (período de indução), entre a perda e o retorno desse reflexo (duração do efeito clínico importante) e entre o retorno do reflexo de endireitamento e os primeiros movimentos de deambulação (duração do efeito residual), as frequências cardíaca e respiratória e as temperaturas ambiental e cloacal. Os escores de sedação/anestesia foram avaliados através de uma escala com variação de 0 (alerta/consciente) a 10 (anestesia profunda/sobredosagem). No tratamento MP, dois animais não apresentaram perda de reflexo de endireitamento. Considerando somente aqueles que apresentaram a perda desse reflexo, o tempo de indução (21±9 e 17±5 minutos) e a duração do efeito clínico importante (35±19 e 43±21 minutos) e residual (28±31 e 12±11 minutos) foram similares entre os tratamentos MT e MP (média±desvio padrão)...

Reptiles possess a renal portal system which can divert part of the blood from the caudal portions of the body to the kidney before it reaches the systemic circulation. In view of this, it has been recommended the administration of injectable medications in the forelimbs, in order to avoid immediate glomerular filtration, which might result in a reduction of the expected effect. The aim of this study was to compare qualitative and quantitative aspects of the pharmacological restraint provided by the combination of ketamine (30mg/kg) and xylazine (1mg/kg), injected into the forelimb or hindlimb, in broad-snouted caiman juveniles (Caiman latirostris). Eight male animals, with a mean weight (±SD) of 1.3 (±0.3) kg, and aged about 2 years old, were anesthetized on two separate occasions with an interval of 7 days. On each occasion, the animals were randomly assigned to receive the anesthetic combination intramuscularly into the forelimb (FL treatment) or hindlimb (HL treatment). The time intervals between administration of treatment and loss of the righting reflex (induction time), between the loss and return of this reflex (duration of important clinical effect), and between the return of the righting reflex and first movements of ambulation (duration of residual effect) were measured as well as heart and respiratory rates and cloacal and environmental temperatures. Sedation/anesthesia scores were evaluated using a scale ranging from 0 (alert/conscious) to 10 (deep anesthesia/overdose). In the HL treatment, loss of righting reflex was not observed in two animals. Considering only those animals whose loss of righting reflex was observed, the induction time (21±9 and 17±5 minutes), the duration of important clinical effect (35±19 and 43±21 minutes), and the duration of residual effect (28±31 and 12±11 minutes) were similar between the FL and HL treatments, respectively (mean±SD). Sedation/anesthesia scores were significantly higher than at baseline...

Effect of Protease Activated Receptor-2 Agonist on Intestinal SIgA in Rats with Acute Necrotizing Pancreatitis / 医药导报

Objective To discuss the effects of proteinase-activated receptor-2( PAR-2 )agonists on intestinal SIgA levels in rats with severe acute necrotizing pancreatitis( SAP). Methods This study established SAP rat model and observed the levels of TNF-α and IL-6 in intestinal mucosa,SIgA content in intestinal mucus and histopathological changes of intestinal mucosa 6,12,and 24 h after establishment of model. The univariate analysis was used to compare the difference among groups. Linear correlation analysis was used to compare correlation between inflammatory mediators( TNF-α,IL-6 )and SIgA content in intestinal mucus,as well as the histopathological scores of intestinal mucosa. Results The level of TNF-α and IL-6 in intestinal mucosa and histopathological scores of intestinal mucosa were all significantly increased but SIgA content was decreased in model group at each time point after establishment of model,as compared with the sham-operated group(P﹤0. 05). The level of TNF-α and IL-6 in intestinal mucosa and histopathological scores of intestinal mucosa were all significantly decreased while SIgA content in intestinal mucus increased in pretreatment group at each time point after establishment of model,as compared with the model group(P﹤0. 05). There was a positive relationship between inflammatory mediators(TNF-α,IL-6)in intestinal mucosa and histopathological scores of intestinal mucosa(P﹤0. 01). There was a negative relationship between inflammatory mediators(TNF-α,IL-6)and SIgA content in intestinal mucus(P﹤0. 05). Conclusion Intestinal mucosa immune barrier was impaired in the early stage of SAP in rats. PAR-2 agonist has therapeutic effects on intestinal mucosa immune barrier,which is related to the inhibition of excessive release of inflammatory mediators( TNF-α and IL-6)in rats with SAP.

Simultaneous Determination of Seven β2-Agonists in Livestock Manure by On-line Cleanup Liquid Chromatography-Tandem Mass Spectrometry / 分析化学

A new method using on-line cleanup technology combined with liquid chromatography tandem mass spectrometry ( UHPLC-MS/MS) was developed for the determination of seven kinds of β2-agonists residues, Formoterol, Salmeterol, Carbuterol, Clenisopenterol, Clenpenterol, Clencyclohexerol and Clenbuterol-hydroxymethyl in livestock manure. The sample was sufficiently extracted by acidic acetonitrile and diluted by 0. 2% formic acid. The extract was online purified on HyperSep Retain CX column where the sample matrix was washed away and the analytes were retained. The analytes were eluted into Hypersil Gold C18 column by 2% Ammonia-methanol solution. The seven β2-agonists were detected in selected reaction monitoring ( SRM) mode via positive electrospray ionization ( ESI+) by liquid chromatography-tandem mass spectrometry. The results showed good linearity correlation coefficients over 0 . 9928 for the seven kinds of β2-agonists in 0 . 5-100 μg/L concentration range. The LOD of seven kinds of β2-agonists in livestock mature is 1 μg/kg, while the LOQ is 5 μg/kg. When 5-50 μg/kg of the seven kinds ofβ2-agonists were added into the blank livestock manure, an average recovery of 67% -112% was obtained with the relative standard deviations of 2. 9%-10. 2%. The method is simple, rapid and has good reproducibility for quantitative and confirmatory analysis ofβ2-agonist residues.

Recent advance in inhaler medications for chronic obstructive pulmonary disease patients

Chronic obstructive pulmonary disease (COPD) is one of the highest ranking diseases with regard to prevalence and mortality in Korea and also worldwide. In the past decade, effective inhaler medications for COPD treatment have been developed or approved. These inhaler medications have been proven to have beneficial effects on symptoms, lung function, quality of life, exercise capacity, and exacerbation. The inhalers used widely are long-acting anticholinergics, long-acting beta2-agonists, and combined inhalers of a corticosteroid and long-acting beta2-agonist. These inhaler medications are more effective than oral medications and less likely to produce adverse events. However, the inhaler medications should be used appropriately to achieve the desired effect. For COPD patients with a forced expiratory volume in 1 second (FEV1) less than 80% of the predicted value, a long-acting anticholinergic or long-acting beta2-agonist is usually the medication of first choice. If a COPD patient with a FEV1 less than 60% of the predicted value suffers frequent exacerbations, a combined inhaler of corticosteroid and long-acting beta2-agonist is a good choice. To prescribe an inhaler medication for COPD patients, spirometry should be performed, not only to confirm the diagnosis but also to define severity. These effective inhaler medications should be used widely for COPD patients in Korea.

Potential Masking of Airway Eosinophilic Inflammation by Combination Therapy in Asthma

PURPOSE: Long-acting beta2 agonists (LABA) may mask ongoing bronchial inflammation, leaving asthmatic patients at greater risk of severe complications. The aim of this study was to compare the effect of combination therapy using low-dose inhaled corticosteroids (ICS) plus LABA on airway inflammation in asthma to the effect of medium-dose ICS alone. METHODS: Twenty-four patients with asthma not controlled by low-dose (400 microg per day) budesonide alone were enrolled in this prospective crossover study. Patients were randomized into 2 treatment phases: one receiving medium-dose (800 microg per day) budesonide (ICS phase), and the other receiving a combination therapy of low-dose budesonide/formoterol (360 microg/9 microg per day) delivered by a single inhaler (LABA phase). Each treatment phase lasted for 6 week, after which patients were crossed over. Asthma symptoms, lung function, and airway inflammation were compared between the 2 phases. RESULTS: Twenty-three patients completed the study; adequate sputum samples were collected from 17 patients. Asthma symptoms and lung function remained similar between the 2 phases. However, the mean sputum eosinophil percentage was higher in the LABA phase than in the ICS phase (5.07+/-3.82% vs. 1.02+/-1.70%; P or =3%) was more frequently observed in the LABA phase than in the ICS phase (six vs. two). CONCLUSION: Addition of LABA may mask airway eosinophilic inflammation in asthmatic patients whose symptoms are not controlled with low-dose ICS.

Rol de la dexmedetomidina en el tratamiento del dolor / Role of dexmedetomidine in the treatment of pain

La dexmedetomidina es un fármaco agonista de los receptores alfa-2 adrenérgicos, altamente selectivo, utilizado para sedación en unidades de cuidados críticos. Posee también, efectos analgésicos importantes que pueden atribuirle un rol en el manejo clínico del dolor. Diversas comunicaciones científicas han estudiado su utilidad en el manejo del dolor agudo, crónico y en cuidados paliativos, tanto en adultos como en niños. En este artículo de revisión se analiza la evidencia científica disponible hasta la fecha con el objeto de dilucidar cuál es el real aporte de este fármaco en el tratamiento de las diversas formas de dolor...

Dexmedetomidine is a highly selective alpha-2 adrenergic agonist commonly used in the critical care units for sedation therapy. It has analgesic effects that may be used in pain treatment. Many scientific reports have studied its utility in the management of acute and chronic pain and palliative care. In this review we analyze the scientific evidence in relation to the real role of dexmedetomidine in pain therapy...

Unusual cause of hypokalemia and paralysis in an elderly patient with Bronchial Asthma.

Asthma is a syndrome characterized by airflow obstruction that varies markedly, both spontaneously and with treatment. There are so many adverse effects of drugs which are used in the management of bronchial asthma in elderly. We report a case of sudden onset paralysis of both lower limbs after treatment of asthma with nebulized β2- agonists. The inappropriate and continuous use of such drugs may cause the hypokalaemic paralysis though lifesaving many times. Hypokalaemia is a common adverse effect of β2- agonists but hypokalaemic paralysis of both lower limbs is a rare entity.

Eficacia del indacaterol como broncodilatador en un grupo de pacientes asmáticos / Effectiveness of Indacaterol as bronchodilator in a group of asthmatic patients

La búsqueda de nuevas opciones terapéuticas para tratar las enfermedades obstructivas bronquiales representa un reto permanente y los broncodilatadores constituyen unos de los fármacos más empleados para la atención de estos pacientes. En los últimos años han ido ganando fuerza los broncodilatadores de acción prolongada, pero el mayor efecto alcanzado era 12 h, superado por un broncodilatador nuevo salido al mercado en el año 2011, denominado indacaterol, del grupo de los beta agonistas, se diferencia de estos por la duración de su efecto que llega a alcanzar 24 h. Se realizó un estudio prospectivo, a ciego, tipo ensayo clínico, aleatorizado, con 90 pacientes asmáticos, entre 18 y 59 años de edad, que acudieron al departamento de pruebas funcionales respiratorias para estudiarles la función pulmonar. Todos recibieron de manera aleatoria indacaterol, salbutamol o placebo, y se les repitió la espirometría a los 15 min y a las 24 h de aplicado cada medicamento. Se evidenció que la respuesta broncodilatadora obtenida en los que usaron indacaterol, a las 24 h, fue muy superior a la respuesta de los que usaron otros fármacos. Se muestra además un discreto aumento de la frecuencia cardiaca y de la tensión arterial en los que usaron indacaterol y salbutamol, principalmente a los 15 min de empleados dichos medicamentos, pero dentro de los límites considerados como normales. No se evidenciaron efectos adversos

The search for new therapeutic options to treat bronchial obstructive diseases represents a permanent challenge and bronchodilators constitute one of the most used drugs in the treatment of these patients. In recent years, long acting bronchodilators have grown importance, but the greatest effect has been 12 h, superseded by a new bronchodilator that came on to the market in the year 2011 named Indacaterol, which belongs to the group of ß2-agonists and differentiates from the rest for its effect on the duration which lasts 24 hours. A randomized, essay-type, blind, prospective study was performed in 90 asthmatic patients, ranging from 18 to 59 years of age that presented to the department of respiratory functional tests for a study of their pulmonary functions. All the patients randomly received Indacaterol, Salbutamol or Placebo and spirometry was repeated 15 minutes and 24 hours after treatment. It was evidenced that the bronchodilator response obtained at the 24 hours in those patients that used Indacaterol, was higher than the response in the patients that used other drugs. The patients that used Indacterol and Salbutamol also showed a discrete increase of the cardiac frequency and blood pressure, mainly 15 minutes after receiving such drugs, but this increase is considered within the normal limits. Adverse effects were not evidenced

Beta 2 agonistas en deportistas. ¿Una ayuda ergogénica? / Beta 2 agonists in athletes. An ergogenic aid?

El asma es una condición crónica de las vías aéreas con hiperreactividad bronquial y broncoconstricción. El ejercicio puede desencadenar los síntomas asmáticos, lo que se conoce como broncoespasmo inducido por el ejercicio (BIE). El asma es común en atletas olímpicos, por lo cual los deportistas utilizan los medicamentos β2 agonistas para prevenir y tratar los episodios de asma. Estos fármacos se suministran preferiblemente por inhalación. En el deporte, los β2 agonistas están restringidos por la regulación antidopaje, con base en que estos medicamentos tienen el potencial de mejorar el rendimiento físico, lo que puede resultar en una ventaja competitiva. Los β2 agonistas están prohibidos por la WADA (World Anti-doping Agency), con excepción del salbutamol (con suministro máximo permitido de 1.600 µg en 24 horas) y el salmeterol inhalado. Estos fármacos, administrados por vía oral, pueden tener efectos ergogénicos en los deportistas. Se ha documentado que administrado por esta vía el salbutamol puede mejorar el rendimiento en disciplinas de resistencia, aumentar la fuerza muscular y mejorar la potencia anaeróbica. Sin embargo, según la evidencia científica, los β2 agonistas inhalados no tienen un efecto relevante de aumento en el rendimiento en deportistas no asmáticos.

Asthma is a chronic disorder of the airways with bronchial hyperresponsiveness and bronchoconstriction. Exercise can trigger asthma symptoms; this condition is known as exerciseinduced bronchospasm (EIB). Asthma is common in Olympic athletes who therefore use β2 agonists to prevent and treat its episodes. These drugs are preferably supplied by inhalation. In sports, the use of β2 agonists is restricted by anti-doping regulation, arguing that these drugs have the potential to improve physical performance, which can result in a competitive advantage. β2 agonists are prohibited by the WADA (World Anti-Doping Agency), except salbutamol (maximum dose: 1.600 µg over 24 hours) and salmeterol. Oral administration of salbutamol can induce ergogenic effects in athletes. It has been documented that when given orally β2 agonists can improve performance in endurance disciplines, increase muscle strength and improve anaerobic power. However, according to scientific evidence, inhaled β2 agonists do not have a relevant performance-enhancing effect in nonasthmatic athletes.

Beta-2 agonistas de ultra longa duração para o tratamento de asma: há espaço? / Ultra long-term beta-2 agonists for treatment of asthma: is there a place?

Objetivos: Revisar a eficácia e a tolerabilidade dos agentes beta-2 agonistas de longa ação (ultra-BALA) em asmáticos. Métodos: Foi conduzida uma revisão sistemática de estudos clínicos que investigaram a eficácia e tolerabilidade de fármacos beta-2 agonistas administrados 1 vez ao dia, por via inalatória para o tratamento de pacientes com diagnóstico de asma brônquica. A pesquisa incluiu todos os manuscritos publicados na íntegra nos últimos 20 anos, na língua inglesa, utilizando as palavras-chaves ultra-long-acting-beta agonits, carmoterol, indacaterol, vilanterol, arfomoterol, bronchodilators, combination therapy, once-daily AND (asthma treatment [Mesh] OR asthma/drug therapy [Mesh] OR bronchial asthma/therapy [Mesh]) AND randomized controlled trial. Resultados: Foram selecionados 8 ensaios clínicos que avaliaram 975 pacientes asmáticos. O indacaterol foi o agente farmacológico que apresentou estudos publicados em fases mais avançadas em asmáticos. Em estudos pré-clínicos e clínicos o indacaterol mostrou boa eficácia, segurança e tolerabilidade. O início de ação broncodilatadora é rápida e duradoura por 24 horas. Os efeitos adversos mais comuns foram tosse, cefaleia e nasofaringite; geralmente mínimos e de leve intensidade. Conclusões: Os fármacos ultra-BALA podem constituir-se em opções promissoras para uso em dose única diária para um subgrupo de asmáticos que apresenta resposta terapêutica insuficiente e baixa aderência ao tratamento.

Objectives: To review the efficacy and tolerability of the ultra- longactingbeta 2 agonists agents (ultra-LABA) in asthmatics. Methods: We conducted a systematic review of clinical studies that investigated the efficacy and tolerability of inhaled beta-2 agonist drugs administered once daily for the treatment of patients with bronchial asthma. The search included all full-length manuscripts published in the last 20 years, in English, by using the keywords ultra-long-acting beta-agonits, carmoterol, indacaterol, vilanterol, arfomoterol, bronchodilators, combination therapy, once-daily AND (asthmatreatment [Mesh] OR asthma/drug therapy [Mesh] OR bronchial asthma/therapy [Mesh]) AND randomized controlled trial. Results: We selected 8 clinical trials that evaluated 975 patients with asthma. Indacaterol was the pharmacological agent that presented published studies at later stages in asthmatics. In preclinical and clinical studies indacaterol showed good efficacy, safety and tolerability. The bronchodilator effect is fast and lasts for 24 hours. The most common adverse events were cough, headache and nasopharyngitis, often minimal or mild. Conclusions: The ultra-LABA can become promising options for a single daily dose regime for a subgroup of patients presenting insuficiente therapeutic response and low adherence to treatment.

Differences in blood glucose increase between horses receiving xylazine and detomidine for surgical and non-surgical clinical procedures / Diferenças no aumento da glicemia entre equinos recebendo xilazina e detomidina para procedimentos clínicos cirúrgicos e não-cirúrgicos

The aim of this prospective randomized clinical study was to compare blood glucose and cortisol levels between horses receiving xylazine and detomidine for surgical and non-surgical procedures. Horses from non-surgical groups received 0.5 mg/kg of xylazine (GX group, n=5) or 0.01 mg/kg of detomidine (GD group, n=5) for gastroscopic examination. Horses from the surgical groups received similar doses of xylazine (AX group, n=7) or detomidine (AD group, n=7), followed by anesthetic induction with 2 mg/kg of ketamine and 0.05 mg/kg of diazepam for an arthroscopic procedure under isoflurane anesthesia. Blood samples were obtained prior to the alpha-2 agonist administration (baseline) and after 10, 30, 60 and 90 minutes. All groups had a significant increase in blood glucose from 30 to 90 minutes after alpha-2 agonist administration, compared to baseline. After receiving the alpha-2 agonist, the AD group had blood glucose levels (118-150 mg/dL) significantly higher than GD (99-119 mg/dL) and AX (97-116 mg/dL) groups. Cortisol had no significant changes within a group. However, the AX group had cortisol levels (3.6-3.7 mg/dL) significantly lower than GX group (5.4-5.7 mg/dL) from 30 to 90 minutes after xylazine administration. We concluded that blood glucose levels were when detomidine was administered for surgical procedure, compared to xylazine also for surgical procedure, and non-surgical procedure. Serum cortisol was minimally affected by administration of xylazine and detomidine regardless procedures were surgical or non-surgical.

O objetivo deste estudo clínico, radomizado e prospectivo, foi comparar as concentrações sanguíneas de glicose e cortisol entre equinos recebendo xilazina e detomidina para procedimentos cirúrgicos e não-cirúrgicos. Os equinos dos grupos nãocirúrgicos receberam 0,5 mg/kg de xilazina (grupo GX, n=5) ou 0,01 mg/kg de detomidina (grupo GD, n=5) para realização de exame gastroscópico. Os equinos dos grupos cirúrgicos receberam doses semelhantes de xilazina (grupo AX, n=7) ou detomidina (grupo AD, n=7), seguindo-se a indução anestésica com 2 mg/kg de cetamina e 0,05 mg/kg de diazepam para realização de procedimento artroscópico durante anestesia com isofluorano. As amostras de sangue foram coletadas antes da administração do alfa-2 agonista (basal) e após 10, 30, 60 e 90 minutos. Todos os grupos tiveram um aumento significativo da glicemia, a partir de 30 até 90 minutos da administração do alfa-2 agonista, em relação ao basal. Após receber o alfa-2 agonista, o grupo AD apresentou glicemia (118-150 mg/dL) significativamente maior que os grupos GD (99-119 mg/dL) e AX (97-116 mg/dL). Não houve diferenças significativas da concentração de cortisol dentro de cada grupo. Entretanto, o grupo AX apresentou níveis de cortisol (3,6-3,7 mg/dL) significativamente mais baixos que o grupo GX (5,4-5,7 mg/dL), a partir de 30 até 90 minutos da administração de xilazina. Concluímos que a glicemia apresentou valor mais elevadoapós a administração de detomidina para realização de procedimento cirúrgico, comparado à xilazina administrada também para procedimento cirúrgico, e para procedimento não-cirúrgico. A concentração sérica de cortisol foi minimamente influenciada pela administração de xilazina e detomidina independentemente dos procedimentos serem cirúrgicos ou não-cirúrgicos.

<b>On Prescription of Beta 2 Agonists for Pediatric Patients </b><b>with Acute Bronchitis in Japan </b> / 薬剤疫学

<b>Objective: </b>In Japan, beta 2 agonist (BA) has an indication for acute bronchitis with airway obstruction. To investigate BA prescribing practices for children whose diagnosis were acute bronchitis without asthma in Japan, a database study and interviews with pediatricians were conducted.<br><b>Design: </b>Database study<br><b>Methods: </b>We conducted a database study. Using the Japan Medical Data Center database, medical receipts of about 100,000 children younger than 18 years old were obtained between 2005 and 2008. First we identified all the new incidences (362,287 cases) of upper respiratory tract infection, influenza, or acute bronchitis. Outcome measure was prescription of BA within 21 days of the incidence. We calculated the prescription proportions of BA for the asthma group (41,064 cases) and the non-asthma group (321,223 cases). We then interviewed 10 pediatricians to elucidate the reason why they prescribe BA for patients.<br><b>Results: </b>The proportion of children prescribed BA at least once a year in 3-5 years old was 49.9 %. Among 3-5 year olds with acute bronchitis, the BA prescription proportions in the asthma group (58.6%) was nearly as high as that in the non-asthma group (56.6%). Although BA prescription proportions in the asthma group decreased annually with the exception of 0-2 years old, those in the non-asthma group remain unchanged. Based on the interview study, we found interpretations of airway obstruction for acute bronchitis without asthma were broadly-divided into 2 types: the effect of inducing bronchospasm and the effect of producing large amounts of secretions in the airways.<br><b>Conclusion: </b>In this study, it was revealed that pediatric patients with acute bronchitis were commonly prescribed BA in Japan. To promote an appropriate use of BA, prescriptions of BA to non-asthma pediatric patients should be carefully watched. (Jpn J Pharmacoepidemiol 2012; 17(1): 1-12)

Tratamiento farmacológico para el control de la crisis aguda de asma

En el manejo del episodio agudo de asma, dos aspectos son básicos: la valoración de la gravedad del cuadro y los diferentes escalones en el tratamiento del mismo. La clasificación de la gravedad se basa en parámetros clínicos y funcionales. Los síntomas del asma se asocian no sólo con la broncoconstricción, sino también con inflamación de la vía aérea. Los β2-Agonistas inhalados tienen un rápido inicio de acción broncodilatadora mediada principalmente por un efecto relajante sobre el músculo liso respiratorio. Los corticosteroides también tienen efectos clínicos rápidos que pueden suprimir la inflamación de las vías inferiores. La decisión de hospitalizar se debe basar en el criterio clínico del médico (severidad de la crisis y respuesta a la terapia inicial), así como en factores sociales y comportamentales de cada paciente.

Two aspects are basic in the management of an acute episode of asthma: the assessment of its severity and the different steps that should be taken in its treatment. Classification of severity is based on clinical and functional parameters. Asthma symptoms are associated not only with bronchoconstriction but also with inflammation of the respiratory airway. Inhaled β2-agonists have a rapid onset of bronchodilator action that is mainly mediated by a relaxing effect on the airway smooth muscle. Corticosteroids also have rapid clinical effects that can suppress lower airway inflammation. The decision to hospitalize should be based on the physician's clinical criteria (severity of the crisis and response to initial therapy), as well as social and behavioral factors of each patient.