Guide of Hypertensive Crisis Pharmacotherapy.

BACKGROUND: Cardiovascular diseases (CVD) are the number one cause of death globally compared to any other cause. CVD accounts for approximately 17.3 million deaths per year and are rising. Hypertension is the leading risk factor for cardiovascular diseases. Approximately, 80 million people suffer from hypertension in the U.S. While, majority of these individuals are on antihypertensive medications only 54% of individuals with hypertension are optimally controlled. Heart failure and stroke are some of the devastating complications of uncontrolled hypertension. Hypertensive crisis can be classified as either an urgency or emergency; difference between the two is the presence of end organ damage, which is noted in hypertensive emergency. Hypertensive crisis is usually treated by parenteral antihypertensive medications. The main drug classes of drugs for treatment are nitrates, calcium channel blockers, dopamine-1 agonists, adrenergic-blocking agents etc. CONCLUSION: In this review, we discuss approach to management of hypertensive crisis and each drug class with its physiology and complications.

A Round-Up on Cost-Effectiveness of Hypertension Therapy Based on the 2014 Guidelines.

Cardiovascular diseases are the leading cause of death in the USA. Moreover, hypertension affects approximately 78 million people in the USA and is a major modifiable risk factor. Therefore, elevated blood pressure is listed as the primary contributory cause of death in 15 % of the 2.4 million deaths in 2009. Nonetheless, 44 % of the hypertensive population in the USA did not have it under control in 2014. Hypertension cost was averaged to be 40-50 billion dollars yearly including medications and services and currently rising. New hypertension guidelines recommend treating individuals between ages 35 and 74 with different stages of hypertension. Furthermore, individuals with existing co-morbidities such as chronic kidney disease and diabetes should have increased medication adherence and different blood pressure goal compared to those without co-morbidities. Studies utilizing quality-adjusted life-years (QUALYs) were conducted to asses the cost-effectiveness of treating previously untreated adults with hypertension. On average, treating adults between ages 35 to 74 years could prevent about 50,000 and 13,000 cardiovascular events and deaths, respectively. Overall, treating stage 1 and 2 hypertension adults including emphasis on medication adherence could be effective and cost saving. The purpose of this article is to review different methods and assess cost-effectiveness for hypertension therapy based on the 2014 guidelines.

[Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer]. / Expresión de proteínas relacionadas con resistencia a múltiples fármacos y resistencia a la quimioterapia en el cáncer de pulmón.

OBJECTIVE: Membrane transporters are proteins that play a crucial role in resistance to chemotherapy. The aim of this study was to assess the influence of membrane transporter protein expression on chemotherapeutic response. MATERIAL AND METHODS: One hundred and forty seven samples of tumor tissue were collected from 143 patients; 35 samples were obtained by bronchoscopy and 112 were surgical specimens. A total of 101 samples from 99 patients were adequate for study. Cryopreserved samples were subjected to immunohistochemical analysis to detect 3 proteins associated with multidrug resistance: P-glycoprotein (Pgp), multidrug-resistance-associated protein 1 (MRP1), and lung resistance protein (LRP). RESULTS: In 16 cases none of the proteins were expressed. A single protein was expressed in 32 (3 Pgp, 11 MRP1, and 18 LRP); 2 in 34 cases (24 Pgp and LRP; 5 MRP1 and Pgp; 5 MRP1 and LRP); and all 3 in 17 cases. No significant relationship was found between age and the expression of Pgp (P=.74), MRP1 (P=.95), or LRP (P=.26). Nor were there significant differences in number (P=.72) or type of coexpressed proteins (P=.39) by sex, by tumor stage (number, P=.55; type, P=.21), or by tumor grade (number, P=.59; type, P=.51). There was a highly significant trend toward coexpression of Pgp and LRP (P< .01) but not of Pgp and MRP1 (P=.18) or MRP1 and LRP (P=.26). MRP1 was expressed less often in adenocarcinoma. LRP was expressed less often in squamous cell carcinoma than in adenocarcinoma and undifferentiated large cell carcinoma. Coexpression of Pgp, MRP1, and LRP was observed most often in squamous cell carcinoma. CONCLUSIONS: Proteins associated with multidrug resistance are commonly expressed in lung cancer. Of the 3 proteins studied, LRP was the one most often found. Coexpression of more than 1 of the proteins was found in a considerable percentage of patients. Pgp was mainly found to be coexpressed with LRP. Pgp expression and the number of coexpressed proteins seemed to have a negative impact on response to chemotherapy.

Expresión de proteínas relacionadas con resistencia a múltiples fármacos y resistencia a la quimioterapia en el cáncer de pulmón / Expression of proteins associated with multidrug resistance and resistance to chemotherapy in lung cancer

Objetivo: Las proteínas transportadoras de membrana desempeñan un papel esencial en la resistencia a la quimioterapia. El objetivo del estudio ha sido intentar valorar la influencia de su expresión en la respuesta a la quimioterapia. Material y métodos: Se recogieron 147 muestras tumorales procedentes de 143 pacientes. De ellas, 35 eran broncoscópicas y 112 quirúrgicas. Resultaron válidas para el estudio 101, correspondientes a 99 pacientes. Las muestras tumorales criocongeladas se sometieron a análisis inmunohistoquímico para la detección de las 3 proteínas relacionadas con resistencia a múltiples fármacos (MDR-proteínas): Pgp, Mrp1 y Lrp. Resultados: No expresaban ninguna proteína 16 casos. Se encontró expresión de una sola proteína en 32 casos (3 Pgp, 11 Mrp1 y 18 Lrp); de 2 proteínas en 34 casos (24 Pgp + Lrp; 5 Mrp1 + Pgp; 5 Mrp1 + Lrp), y de las 3 proteínas en 17. No encontramos relación significativa entre la edad y la expresión de Pgp (p = 0,74), Mrp1 (p = 0,95) o Lrp (p = 0,26). No observamos diferencias significativas entre sexos por el número (p = 0,72) ni por el tipo (p = 0,39) de proteínas expresadas de forma simultánea. Tampoco detectamos diferencias significativas entre estadios tumorales por el número (p = 0,55) ni por el tipo (p = 0,21) de MDR-proteínas. No encontramos diferencias significativas entre los diferentes grados histológicos ni por el número (p = 0,59) ni por el tipo (p = 0,51) de MDR-proteínas expresadas simultáneamente. La tendencia de Pgp y Lrp a expresarse asociadas resultó muy significativa (p < 0,01), pero no fue así en el caso de la asociación de Pgp y Mrp1 (p = 0,18) o Mrp1 y Lrp (p = 0,26). Los adenocarcinomas expresaron menos la Mrp1. Los carcinomas escamosos fueron los que con más frecuencia expresaron Pgp, Mrp1 y Lrp de forma simultánea. Los carcinomas escamosos expresaron menos Lrp que los adenocarcinomas y carcinomas indiferenciados de células grandes. Conclusiones: El cáncer de pulmón expresa con frecuencia MDR-proteínas. De las 3 estudiadas (Pgp, Mrp1 y Lrp), la más frecuentemente observada fue Lrp. En una proporción importante de pacientes se halló expresión simultánea de más de una MDR-proteína. Pgp se expresó fundamentalmente asociada a Lrp. La expresión de Pgp y el número de proteínas expresadas simultáneamente parecieron afectar de forma negativa a la respuesta a la quimioterapia

Objective: Membrane transporters are proteins that play a crucial role in resistance to chemotherapy. The aim of this study was to assess the influence of membrane transporter protein expression on chemotherapeutic response. Material and methods: One hundred and forty seven samples of tumor tissue were collected from 143 patients; 35 samples were obtained by bronchoscopy and 112 were surgical specimens. A total of 101 samples from 99 patients were adequate for study. Cryopreserved samples were subjected to immunohistochemical analysis to detect 3 proteins associated with multidrug resistance: P-glycoprotein (Pgp), multidrug-resistance­associated protein 1 (MRP1), and lung resistance protein (LRP). Results: In 16 cases none of the proteins were expressed. A single protein was expressed in 32 (3 Pgp, 11 MRP1, and 18 LRP); 2 in 34 cases (24 Pgp and LRP; 5 MRP1 and Pgp; 5 MRP1 and LRP); and all 3 in 17 cases. No significant relationship was found between age and the expression of Pgp (P=.74), MRP1 (P=.95), or LRP (P=.26). Nor were there significant differences in number (P=.72) or type of coexpressed proteins (P=.39) by sex, by tumor stage (number, P=.55; type, P=.21), or by tumor grade (number, P=.59; type, P=.51). There was a highly significant trend toward coexpression of Pgp and LRP (P<.01) but not of Pgp and MRP1 (P=.18) or MRP1 and LRP (P=.26). MRP1 was expressed less often in adenocarcinoma. LRP was expressed less often in squamous cell carcinoma than in adenocarcinoma and undifferentiated large cell carcinoma. Coexpression of Pgp, MRP1, and LRP was observed most often in squamous cell carcinoma. Conclusions: Proteins associated with multidrug resistance are commonly expressed in lung cancer. Of the 3 proteins studied, LRP was the one most often found. Coexpression of more than 1 of the proteins was found in a considerable percentage of patients. Pgp was mainly found to be coexpressed with LRP. Pgp expression and the number of coexpressed proteins seemed to have a negative impact on response to chemotherapy

[Expression of multiple-drug resistant proteins in lung cancer]. / Expresión de proteínas relacionadas con resistencia a múltiples fármacos en el cáncer de pulmón.

BACKGROUND: Reduction of intracellular drug accumulation plays an important role in resistance to chemotherapy in neoplasms. MDR-proteins regulate this cell activity. MATERIAL AND METHOD: A total of 147 tumor samples were collected from 143 patients. Thirty-five samples were obtained by bronchoscopy and 112 were surgical specimens. One hundred and one samples from 99 patients were valid for the study. The samples underwent cryopreservation and immunohistochemistry for detection of three multiple-drug resistant proteins (MDR-proteins): Pgp, Mrp1 and Lrp. RESULTS: No proteins were expressed in 16 patients. A single protein was expressed in 32 patients: 3 Pgp, 11 Mrp1 and 18 Lrp=0. Two proteins were expressed in 34 patients: 24 Pgp and Lrp, 5 Mrp1 and Pgp, 5 Mrp1 and Lrp=0. All three proteins were expressed in 17 patients. No differences were observed in expression according to age (Pgp [p=0.74], Mrp1 [p=0.95], Lrp [p=0.26]). No differences were found according to sex, when both the number (p=0.72) and type (p=0.39) of simultaneously expressed proteins were analyzed. No differences were observed according to tumoral stage [number (p=0.55), type (p=0.21)] or histological grade [number (p=0.59), type (p=0.51)]. The tendency toward simultaneous expression of Pgp and Lrp was highly significant (p<0.01). The same tendency was not observed in the association between Mrp1 and Lrp (p=0.26). CONCLUSIONS: MDR-proteins are frequently expressed in lung cancer. Of the three MDR-proteins studied, Lrp was the most frequent. Adenocarcinoma expressed less Mrp1 than other histological types. Squamous carcinoma expressed less Lrp than adenocarcinomas and large-cell undifferentiated carcinomas. In a considerable number of patients, more than two proteins were expressed simultaneously. Squamous-cell carcinomas tended to express Pgp, Mrp1 and Lrp simultaneously. Pgp was usually expressed in association with Lrp.

Expresión de proteínas relacionadas con resistencia a múltiples fármacos en el cáncer de pulmón / Expression of multiple-drug resistant proteins in lung cancer

Introducción. La reducción de la acumulación intracelular de los fármacos es uno de los mecanismos más frecuentes de resistencia a los antineoplásicos. Las proteínas transportadoras de membrana desempeñan un papel esencial en este fenómeno. Material y método. Se recogieron 147 muestras tumorales procedentes de 143 pacientes. De éstas, 35 eran broncoscópicas y 112 quirúrgicas. Resultaron válidas para el estudio 101 muestras correspondientes a 99 pacientes. Las muestras tumorales criocongeladas fueron sometidas a análisis inmunohistoquímico para la detección de las tres proteínas relacionadas con resistencia a múltiples fármacos (MDR-proteínas), Pgp, Mrp1 y Lrp. Resultados. No expresaban ninguna proteína, 16 casos. Expresaban una sola proteína, 32 casos: 3 Pgp, 11 Mrp1 y 18 Lrp = 0. Expresaban dos proteínas, 34 casos: 24 Pgp y Lrp, 5 Mrp1 y Pgp, 5 Mrp1 y Lrp = 0. Expresaban las tres proteínas, 17 casos. No hemos detectado relación significativa entre la edad y la expresión de Pgp (p = 0,74), Mrp1 (p = 0,95) o Lrp (p = 0,26). No detectamos diferencias significativas entre sexos, tanto al analizar por el número (p = 0,72), como por el tipo (p = 0,39) de proteínas expresadas de forma simultánea. Tampoco detectamos diferencias significativas entre los distintos estadios tumorales, tanto para el número (p = 0,55) como para el tipo (p = 0,21) de MDR-proteínas expresada. Tampoco detectamos diferencias significativas entre los diversos grados histológicos, tanto para el número (p = 0,59) como para el tipo (p = 0,51) de MDR-proteínas expresadas simultáneamente. La tendencia de Pgp y Lrp a expresarse asociadas ha resultado muy significativa (p < 0,01), pero no ocurrió lo mismo para la asociación Pgp y Mrp1 (p = 0,18) o Mrp1 y Lrp (p = 0,26). Conclusiones. El cáncer de pulmón expresa con frecuencia MDR-proteínas. De las tres MDR-proteínas estudiadas, Pgp Mrp1 y Lrp, esta última es la que se expresa con más frecuencia. Los adenocarcinomas expresan menos Mrp1 que el resto de los tipos histológicos. Los carcinomas escamosos expresan menos Lrp que los adenocarcinomas y los carcinomas indiferenciados de célula grande. Una proporción importante de pacientes expresa de forma simultánea más de una MDR-proteína. Los carcinomas escamosos son los que con más frecuencia expresan Pgp, Mrp1 y Lrp de forma simultánea. Pgp se expresa fundamentalmente asociada a Lrp (AU)

Background. Reduction of intracellular drug accumulation plays an important role in resistance to chemotherapy in neoplasms. MDR-proteins regulate this cell activity. Material and method. A total of 147 tumor samples were collected from 143 patients. Thirty-five samples were obtained by bronchoscopy and 112 were surgical specimens. One hundred and one samples from 99 patients were valid for the study. The samples underwent cryopreservation and immunohistochemistry for detection of three multiple-drug resistant proteins (MDR-proteins): Pgp, Mrp1 and Lrp. Results. No proteins were expressed in 16 patients. A single protein was expressed in 32 patients: 3 Pgp, 11 Mrp1 and 18 Lrp=0. Two proteins were expressed in 34 patients: 24 Pgp and Lrp, 5 Mrp1 and Pgp, 5 Mrp1 and Lrp=0. All three proteins were expressed in 17 patients. No differences were observed in expression according to age (Pgp [p=0.74], Mrp1 [p=0.95], Lrp [p=0.26]). No differences were found according to sex, when both the number (p=0.72) and type (p=0.39) of simultaneously expressed proteins were analyzed. No differences were observed according to tumoral stage [number (p=0.55), type (p=0.21)] or histological grade [number (p=0.59), type (p=0.51)]. The tendency toward simultaneous expression of Pgp and Lrp was highly significant (p<0.01). The same tendency was not observed in the association between Mrp1 and Lrp (p=0.26). Conclusions. MDR-proteins are frequently expressed in lung cancer. Of the three MDR-proteins studied, Lrp was the most frequent. Adenocarcinoma expressed less Mrp1 than other histological types. Squamous carcinoma expressed less Lrp than adenocarcinomas and large-cell undifferentiated carcinomas. In a considerable number of patients, more than two proteins were expressed simultaneously. Squamous-cell carcinomas tended to express Pgp, Mrp1 and Lrp simultaneously. Pgp was usually expressed in association with Lrp (AU)