ABSTRACT
PURPOSE: Globally breast cancer accounts for 24.5% in incidence and 15.5% in cancer deaths in women. The triple-negative subtype lacks any specific therapy and is treated with chemotherapy, resulting in significant side-effects. We aimed to investigate if the dose of chemotherapeutic drugs could be diminished by co-administering it with the ß2-agonist salbutamol. METHODS: Cell proliferation was measured by thymidine incorporation; gene expression, by real-time PCR and protein phosphorylation by WB. Apoptosis was assessed by acridine orange / ethidium bromide and TUNEL tests. Public patient databases were consulted. Cells were inoculated to nude mice and their growth assessed. RESULTS: The ß2-agonist salbutamol synergizes in MDA-MB-231 cells in vitro with paclitaxel and doxorubicin on cell proliferation through ADRB2 receptors, while the ß-blocker propranolol does not. The expression of this receptor was assessed in patient databases and other cell lines. Triple negative samples had the lowest expression. Salbutamol and paclitaxel decreased MDA-MB-231 cell proliferation while their combination further inhibited it. The pathways involved were analyzed. When these cells were inoculated to nude mice, paclitaxel and salbutamol inhibited tumor growth. The combined effect was significantly greater. Paclitaxel increased the expression of MDR1 while salbutamol partially reversed this increase. CONCLUSION: While the effect of salbutamol was mainly on cell proliferation, suboptimal concentrations of paclitaxel provoked a very important enhancement of apoptosis. The latter enhanced transporter proteins as MDR1, whose expression were diminished by salbutamol. The expression of ADRB2 should be assessed in the biopsy or tumor to eventually select patients that could benefit from salbutamol repurposing.
Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Animals , Mice , Humans , Female , Paclitaxel , Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Mice, Nude , Albuterol/pharmacology , Albuterol/therapeutic use , Cell Line, Tumor , Cell Proliferation , Propranolol , Adrenergic Agonists/pharmacology , Adrenergic Agonists/therapeutic use , ApoptosisABSTRACT
OBJECTIVES: To characterize and compare the type and frequency of a range of common and uncommon adverse effects (AEs) associated with α-2 adrenergic agonist (A2A) and stimulant treatment of attention-deficit/hyperactivity disorder at preschool-age as well as to evaluate the impact of age on common AEs. STUDY DESIGN: This was a retrospective electronic medical record review of children <72 months of age (n = 497) evaluated at outpatient developmental-behavioral pediatric practices at 7 US academic medical centers within the Developmental-Behavioral Pediatrics Research Network. Data on AEs were abstracted for children who had treatment initiated by a developmental-behavioral pediatrician with an A2A or stimulant medication between January 2013 and July 2017; follow-up was complete by February 2019. RESULTS: A2A and stimulants had distinctive AE profiles. A2A compared with stimulants had a greater proportion with daytime sleepiness and headaches; stimulants had significantly greater proportions for most other AE, including moodiness/irritability, difficulty with sleep, appetite suppression, stomachaches, skin picking/repetitive behaviors, withdrawn behavior, and weight loss. Younger age was associated with disruptive behavior and difficulty with sleep. CONCLUSIONS: Stimulants had a greater rate of most AEs compared with A2A. AE profiles, together with efficacy, should inform clinical decision-making. Prospective randomized clinical trials are needed to fully compare efficacy and AE profiles of A2A and stimulants.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Central Nervous System Stimulants , Drug-Related Side Effects and Adverse Reactions , Pediatrics , Child , Child, Preschool , Humans , Attention Deficit Disorder with Hyperactivity/drug therapy , Retrospective Studies , Prospective Studies , Central Nervous System Stimulants/adverse effects , Adrenergic Agonists/therapeutic useABSTRACT
Anaphylaxis is a severe allergic reaction with a rapid onset and it is potentially life-threatening. Its clinical manifestations are varied; they may affect the skin, the cardiovascular system, the respiratory system, and the digestive system, among others. The treatment of choice, which is an intra-muscular injection of epinephrine (adrenaline), must be applied promptly. Therefore, being prepared to recognize it properly is of crucial importance. The objective of this clinical practice guide is to improve the knowledge of health professionals about anaphylaxis and, consequently, to optimize the treatment and long-term management of this reaction. This guide is adapted to the peculiarities of Latin America; especially in matters regarding the treatment. The need to introduce epinephrine auto-injectors in countries that don't have them yet is highlighted.
La anafilaxia es una reacción alérgica grave de instauración rápida y potencialmente mortal. Sus manifestaciones clínicas son muy variadas, pudiendo afectar la piel, el sistema cardiovascular, el aparato respiratorio y el digestivo, entre otros. El tratamiento de elección, mediante la inyección intramuscular de adrenalina, debe ser precoz. Por lo anterior, es vital estar preparados para reconocerla adecuadamente. El objetivo de la presente guía de actuación clínica es mejorar el conocimiento de los profesionales sanitarios sobre anafilaxia y, consecuentemente, optimizar el tratamiento y manejo a largo plazo de esta entidad. La guía está adaptada a las peculiaridades de América Latina, especialmente en los aspectos relativos al tratamiento. Se destaca la necesidad de introducir los autoinyectores de adrenalina en los países que no dispongan de ellos.
Subject(s)
Anaphylaxis , Practice Guidelines as Topic , Adrenergic Agonists/administration & dosage , Adrenergic Agonists/therapeutic use , Adult , Algorithms , Anaphylaxis/diagnosis , Anaphylaxis/epidemiology , Anaphylaxis/etiology , Anaphylaxis/therapy , Cardiopulmonary Resuscitation , Child , Combined Modality Therapy , Disease Management , Drug Administration Routes , Epinephrine/administration & dosage , Epinephrine/therapeutic use , Glucagon/administration & dosage , Glucagon/therapeutic use , Humans , Immunologic Tests , Patient Education as Topic , Self Administration , Vasoconstrictor Agents/administration & dosage , Vasoconstrictor Agents/therapeutic useSubject(s)
Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Urinary Bladder, Overactive/diagnosis , Urinary Bladder, Overactive/physiopathology , Urinary Bladder, Overactive/drug therapy , Urinary Bladder, Overactive/therapy , Urinary Incontinence , Clinical Protocols , Physical Therapy Modalities , Adrenergic Agonists/therapeutic use , Botulinum Toxins, Type A/therapeutic use , Estrogens/therapeutic use , NocturiaABSTRACT
BACKGROUND AND PURPOSE: ß-Adrenoceptors are expressed in human and experimental animal breast cancer cells. However, the effect of the agonists and antagonists reported on cell proliferation and tumour growth was paradoxical, precluding their utilization as possible adjuvant therapy, mainly in the cases of refractory tumours. EXPERIMENTAL APPROACH: ß-Adrenoceptor expression was analysed by immunofluorescence and RT-PCR. Cell proliferation was assessed by [(3) H]-thymidine incorporation, tumour growth by measuring with a calliper and ERK 1/2 phosphorylation by Western blotting. KEY RESULTS: ß(2) -Adrenoceptor expression was confirmed in the mouse and human cells tested. Cell proliferation was increased by adrenaline (by α(2) -adrenoceptor action) and decreased in every tested cell line by the ß-adrenoceptor agonist isoprenaline and the ß(2) -adrenoceptor agonist salbutamol. Isoprenaline and salbutamol reduced tumour growth in every tumour tested (mouse C4-HD and CC4-3-HI and human IBH-4, IBH-6 and MDA-MB-231 cell lines growing as xenografts in nude mice). These effects were reversed by the ß-adrenoceptor antagonist propranolol. The α(2) -adrenoceptor antagonist rauwolscine and the ß(2) -adrenoceptor agonist salbutamol were equally effective in diminishing tumour growth. ERK 1/2 activation analysed in IBH-4 tumours correlated with tumour growth, with the ß-adrenoceptor agonists decreasing its activation. Inhibition of ERK 1/2 phosphorylation in vitro was mainly mediated by the PKA pathway. CONCLUSIONS AND IMPLICATIONS: In our experimental models, the ß-adrenoceptor agonists inhibited breast cancer cell proliferation and tumour growth, probably mediated by inhibition of ERK 1/2 phosphorylation. The ß-adrenoceptor agonists were as effective as the α(2) -adrenoceptor antagonist rauwolscine, providing possible novel adjuvant treatments for breast cancer.
Subject(s)
Adrenergic Agonists/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Receptors, Adrenergic, alpha-2/metabolism , Receptors, Adrenergic, beta-2/metabolism , Adrenergic Agonists/pharmacology , Adrenergic Antagonists/pharmacology , Adrenergic Antagonists/therapeutic use , Albuterol/pharmacology , Animals , Antineoplastic Agents/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Humans , Isoproterenol/pharmacology , Mice , Mice, Inbred BALB C , Mice, Nude , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Propranolol/pharmacology , Xenograft Model Antitumor Assays , Yohimbine/pharmacologyABSTRACT
Os fundamentos do tratamento clínico do glaucoma, em especial o conceito de pressão-alvo, são apresentados, bem como os principais grupos de drogas atualmente utilizadas e os conceitos de terapia clínica máxima e mínima.
The fundamentals of the clinical treatment of glaucoma, especially the concept of target pressure, are presented, as well as the main groups of drugs currently used and the concepts of minimum and maximum medical therapy.
Subject(s)
Humans , Glaucoma/drug therapy , Cholinergic Agents/therapeutic use , Adrenergic Agonists/therapeutic use , Carbonic Anhydrase Inhibitors/therapeutic use , Prostaglandins, Synthetic/therapeutic useABSTRACT
Estudaram-se as alterações produzidas por doses equipotentes de xilazina e romifidina e os efeitos da administração subseqüente de ioimbina em oito cabras mestiças. Respeitou-se um intervalo de sete dias entre os seguintes tratamentos: A- 250µg/kg/IM de xilazina e 0,1ml/kg/IV de solução fisiológica, B- 250µg/kg/IM de xilazina e 250µg/kg/IV de ioimbina, C- 25µg/kg/IM de romifidina e 0,1ml/kg/IV de solução fisiológica, D- 25µg/kg/IM de romifidina e 250µg/kg/IV de ioimbina. Foram mensurados a freqüência respiratória, o pH, as pressões parciais de oxigênio e dióxido de carbono, a concentração de íon bicarbonato, o excesso de bases e a saturação de oxigênio no sangue arterial. Utilizou-se um delineamento experimental crossover, e as médias foram comparadas pelo teste Duncan (Pmenor ou igual a 0,05). Xilazina e romifidina reduziram a pressão arterial de oxigênio e aumentaram a pressão arterial de dióxido de carbono. A ioimbina reverteu os efeitos da xilazina e da romifidina sobre as pressões parciais de oxigênio e dióxido de carbono no sangue arterial.
Subject(s)
Animals , Adrenergic Agonists/administration & dosage , Adrenergic Agonists/adverse effects , Adrenergic Agonists/therapeutic use , Goats , Yohimbine/administration & dosage , Yohimbine/antagonists & inhibitors , Yohimbine/adverse effects , Yohimbine/therapeutic use , Xylazine/administration & dosage , Xylazine/adverse effects , Xylazine/therapeutic useABSTRACT
Estudaram-se as alterações produzidas por doses equipotentes de xilazina e romifidina e os efeitos da administração subseqüente de ioimbina em oito cabras mestiças. Respeitou-se um intervalo de sete dias entre os seguintes tratamentos: A- 250µg/kg/IM de xilazina e 0,1ml/kg/IV de solução fisiológica, B- 250µg/kg/IM de xilazina e 250µg/kg/IV de ioimbina, C- 25µg/kg/IM de romifidina e 0,1ml/kg/IV de solução fisiológica, D- 25µg/kg/IM de romifidina e 250µg/kg/IV de ioimbina. Foram mensurados a freqüência respiratória, o pH, as pressões parciais de oxigênio e dióxido de carbono, a concentração de íon bicarbonato, o excesso de bases e a saturação de oxigênio no sangue arterial. Utilizou-se um delineamento experimental crossover, e as médias foram comparadas pelo teste Duncan (Pd<0,05). Xilazina e romifidina reduziram a pressão parcial de oxigênio e aumentaram a pressão parcial de dióxido de carbono. A ioimbina reverteu os efeitos da xilazina e da romifidina sobre as pressões parciais de oxigênio e dióxido de carbono no sangue arterial.(AU)
With the purpose to assess some of the clinical and laboratorial features induced by xylazine and romifidine, at equipotent sedative doses, followed by the use of yohimbine, eight crossbred female goats were assigned randomly to four treatments at the following dose rates: A- 250µg/kg/IM xylazine plus 0.1ml/kg/IV saline solution, B- 250µg/kg/IM xylazine plus 250µg/kg/IV de yohimbine, C- 25µg/kg/IM romifidine plus 0.1ml/kg/IV saline, D- 25µg/kg/IM romifidine plus 250µg/kg/IV yohimbine. Breath rate, pH, oxygen and carbon dioxide tensions, concentration of hydrogen carbonate, base excess and fraction of oxyhemoglobin of arterial blood were measured. A crossover experimental design was used and the comparisons of treatment means were performed by Duncan test (Pd<0.05). Xylazine and romifidine induced a decrease in partial pressure of oxygen and an increase in partial pressure of carbon dioxide in arterial blood. Yohimbine reversed the effects of xylazine and romifidine on arterial oxygen carbon partial pressures.(AU)
Subject(s)
Animals , Xylazine/administration & dosage , Xylazine/adverse effects , Adrenergic Agonists/administration & dosage , Adrenergic Agonists/adverse effects , Yohimbine/administration & dosage , Yohimbine/therapeutic use , Xylazine/therapeutic use , Adrenergic Agonists/therapeutic use , GoatsABSTRACT
Se realizó una revisión del tratamiento médico del glaucoma donde se enfatiza en los fármacos de nueva incorporación a nivel mundial, sus mecanismos de acción y efectos secundarios, así como su dosificación(AU)
Subject(s)
Humans , Adrenergic Agonists/therapeutic use , Carbonic Anhydrase Inhibitors/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Prostaglandins/therapeutic use , Intraocular PressureABSTRACT
Se realizó una revisión del tratamiento médico del glaucoma donde se enfatiza en los fármacos de nueva incorporación a nivel mundial, sus mecanismos de acción y efectos secundarios, así como su dosificación
Subject(s)
Humans , Adrenergic beta-Antagonists , Adrenergic Agonists/therapeutic use , Carbonic Anhydrase Inhibitors/therapeutic use , Intraocular Pressure , ProstaglandinsABSTRACT
Se realiza una revisión sobre el tratamiento inhalatorio de la crisis asmática. La inhaloterapia está ampliamente difundida en la práctica médica habitual, implicando importantes costos económicos. Sin embargo, se estima a nivel mundial que hay una administración inadecuada en un procentaje importante, lo que resulta en fracasos terapéuticos y gastos innecesarios. Esto adquiere relevancia cuando se conoce el aumento de la mortalidad por asma en las últimas décadas y se detecta que tanto los pacientes como los médicos y paramédicos carecen mayoritariamente de los conocimientos básicos y habilidades para su adecuado manejo. Se establece los objetivos de la inhaloterapia y se consideran los aspectos fundamentales (físicos, generadores de aerosoles, farmacología). Se estudian y comparan los distintos sistemas de generación de aerosoles y también se analizan los diferentes fármacos inhalados. Se exponen con detalle los beta agonistas, anticolinérgicos y corticoides en sus formas inhaladas. También se presentan otros tratamientos inhalatorios no tradicionales como el sulfato de magnesio y una mezcla gaseosa heliox. En los distintos tópicos se recurre en lo posible a revisiones sistemáticas o metaanálisis para establecer preferencias o elegir tratamientos. Los autores proponen algunas estrategias terapéuticas avaladas en su experiencia, documentada en la bibliografía aportada. (AU)
Subject(s)
Asthma/drug therapy , Asthma/therapy , Acute Disease , Status Asthmaticus/therapy , Aerosols/therapeutic use , Adrenergic Agonists/therapeutic use , Cholinergic Antagonists/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Oxygen Inhalation TherapyABSTRACT
Se realiza una revisión sobre el tratamiento inhalatorio de la crisis asmática. La inhaloterapia está ampliamente difundida en la práctica médica habitual, implicando importantes costos económicos. Sin embargo, se estima a nivel mundial que hay una administración inadecuada en un procentaje importante, lo que resulta en fracasos terapéuticos y gastos innecesarios. Esto adquiere relevancia cuando se conoce el aumento ded la mortalidad por asma en las últimas décadas y se detecta que tanto los pacientes como los médicos y para médicos carecen mayoritariamente de los conocimientos básicos y habilidades para su adecuado manejo. Se establece los objetivos de la inhaloterapia y se consideran los aspectos fundamentales (físicos, generadores de aerosoles, farmacología). Se estudian y comparan los distintos sistemas de generación de aerosoles y también se analizan los diferentes fármacos inhalados. Se exponen con detalle los beta agonistas, anticolinérgicos y corticoides en sus formas inhaladas. También se presentan otros tratamientos inhalatorios no tradicionales como el sulfato de magnesio y una mezcla gaseosa heliox. En los distintos tópicos se recurre en lo posible a revisione ssistemáticas o metaanálisis para establecer preferencias o elegir tratamientos. Los autores proponen algunas estrategias terapéuticas avaladas en su experiencia, documentada en la biliografía aportada.
Subject(s)
Asthma , Acute Disease , Adrenal Cortex Hormones , Aerosols , Adrenergic Agonists/therapeutic use , Cholinergic Antagonists/therapeutic use , Status Asthmaticus/therapy , Oxygen Inhalation TherapySubject(s)
Humans , Adrenergic Agents/metabolism , Adrenergic Agents/therapeutic use , Adrenergic Agonists/therapeutic use , Splanchnic Circulation , Hemodynamics , Gastric Mucosa , Multiple Organ Failure , Perfusion , Sepsis , Shock, Septic/therapy , Acetylcysteine/metabolism , Acetylcysteine/therapeutic use , Critical Care , Dobutamine , Dopamine , Drug Combinations , Epinephrine , Epoprostenol , Norepinephrine , Nitric Oxide/metabolism , Nitric Oxide/therapeutic use , Phenylephrine , Phosphodiesterase Inhibitors , Receptors, VasopressinSubject(s)
Humans , Comparative Study , Adrenergic Agonists/therapeutic use , Splanchnic Circulation/drug effects , Adrenergic Agents/therapeutic use , Adrenergic Agents/metabolism , Hemodynamics/drug effects , Perfusion , Gastric Mucosa/drug effects , Sepsis/therapy , Sepsis/metabolism , Multiple Organ Failure/therapy , Shock, Septic/therapy , Critical Care , Epinephrine/metabolism , Epinephrine/therapeutic use , Norepinephrine/metabolism , Norepinephrine/therapeutic use , Phenylephrine/metabolism , Phenylephrine/therapeutic use , Dobutamine/metabolism , Dobutamine/therapeutic use , Drug Combinations , Dopamine/metabolism , Dopamine/therapeutic use , Epoprostenol/metabolism , Epoprostenol/therapeutic use , Acetylcysteine/metabolism , Acetylcysteine/therapeutic use , Nitric Oxide/metabolism , Nitric Oxide/therapeutic use , Phosphodiesterase Inhibitors/metabolism , Phosphodiesterase Inhibitors/therapeutic use , Receptors, VasopressinABSTRACT
Se estudiaron 36 pacientes con diagnóstico de glaucoma primario de ángulo abierto (GPAA), sin tratamiento previo, a los que se les indicó durante 2 meses, timolol 0,5 (por ciento) (1 gota 2 veces al día), y seguidamente, previo lavado de hipotensor, brimonidina 0,2 (por ciento); se evaluó la presión intraocular (PIO) y las reacciones adversas en la consulta inicial, 1ra semana, 1er mes y 2do mes de iniciado el tratamiento. Los resultados mostraron un descenso de la PIO media con respecto a la inicial (sin tratamiento) con ambos medicamentos durante los 2 meses de tratamiento; obteniéndose con el timolol una PIO media de 17,1 mm Hg y con la brimonidina de 16,1 mm Hg, lo que corresponde a un descenso de 7,7 mm Hg y de 6,9 mm Hg, respectivamente. Las reacciones adversas sistémicas más frecuentes con el uso de la brimonidina fueron: sequedad bucal y cefalea, mientras que las locales fueron: prurito ocular e hiperemia ocular. La intensidad de estos síntomas fue de leve a moderada. El estudio mostró que la brimonidina tiene una efectividad similar a la del timolol en la reducción de la presión intraocular, con buena tolerabilidad(AU)
Subject(s)
Humans , Glaucoma, Open-Angle/drug therapy , Treatment Outcome , Timolol/therapeutic use , Timolol/adverse effects , Adrenergic Agonists/therapeutic use , Adrenergic Agonists/adverse effects , Ocular Hypertension/drug therapyABSTRACT
Se estudiaron 36 pacientes con diagnóstico de glaucoma primario de ángulo abierto (GPAA), sin tratamiento previo, a los que se les indicó durante 2 meses, timolol 0,5 (por ciento) (1 gota 2 veces al día), y seguidamente, previo lavado de hipotensor, brimonidina 0,2 (por ciento); se evaluó la presión intraocular (PIO) y las reacciones adversas en la consulta inicial, 1ra semana, 1er mes y 2do mes de iniciado el tratamiento. Los resultados mostraron un descenso de la PIO media con respecto a la inicial (sin tratamiento) con ambos medicamentos durante los 2 meses de tratamiento; obteniéndose con el timolol una PIO media de 17,1 mm Hg y con la brimonidina de 16,1 mm Hg, lo que corresponde a un descenso de 7,7 mm Hg y de 6,9 mm Hg, respectivamente. Las reacciones adversas sistémicas más frecuentes con el uso de la brimonidina fueron: sequedad bucal y cefalea, mientras que las locales fueron: prurito ocular e hiperemia ocular. La intensidad de estos síntomas fue de leve a moderada. El estudio mostró que la brimonidina tiene una efectividad similar a la del timolol en la reducción de la presión intraocular, con buena tolerabilidad
Subject(s)
Humans , Adrenergic Agonists/adverse effects , Adrenergic Agonists/therapeutic use , Glaucoma, Open-Angle/drug therapy , Ocular Hypertension/drug therapy , Timolol , Treatment OutcomeABSTRACT
OBJECTIVE: To test the efficacy of single-dose dexamethasone (DXM) in the management of severe arterial hypotension of newborn infants. Our hypothesis was that epinephrine infusions could be discontinued in 70% of patients within 12 hours after DXM administration compared with 10% in the placebo group. STUDY DESIGN: Twenty preterm infants (median birth weight 690 g, gestational age 28 weeks, age at intervention 2 days) who did not respond to a standardized treatment protocol (blood/colloid followed by dopamine infusion stepwise increased to 15 micrograms/kg and minute) were started on an epinephrine infusion and were randomly allocated to receive either DXM (0.25 mg/kg) or placebo intravenously. The primary outcome criterion was the need for an epinephrine infusion 12 hours after treatment. RESULTS: Three infants were excluded. Epinephrine infusion was discontinued in 5 of 8 infants with DXM but in only 1 of 9 infants in the control group. The duration of epinephrine infusion was significantly shorter in the DXM group (exact log-rank test, P =. 023). CONCLUSIONS: DXM was effective for the management of severe arterial hypotension in preterm infants not responding to standardized treatment.