Maternal and fetal parameters in pregnant woman undergoing tocolysis with nifedipine / Parâmetros maternos e fetais em gestante submetida a tocólise com nifedipina

Abstract Objectives: to evaluate the effects of nifedipine with tocolysis under maternal and fetal parameters. Methods: a cohort study with 40 pregnant women admitted at a high-risk pregnancy ward to inhibit premature labor between September/2010 to May/2012. Nifedipine was used as a 20mg sublingual attack dose and maintained 20mg every six and eight hours orally. The variables of the analysis were fetal heart rate (FHR), maternal heart rate (MHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), and amniotic fluid index (AFI). All the variables were evaluated prior to administrating nifedipine and approximately after 6 hours and every 24 hours, until hospital discharge. Results: there were no modification of the FHR (p=0.48) and the SBP (p=0.29). The MHR increased after 24 hours, but with no statistical difference (p=0.08), returning to similar levels as at admission within 48 hours. The DBP decreased at 6 (p=0.04) to 72 hours, being stable afterwards. The AFI decreased significantly at 24, 48 and 72 hours. Conclusions: the use of high doses of nifedipine with tocolysis causes a decrease of the maternal's diastolic blood pressure and consequently decreases the amniotic fluid index, but probably without any clinical repercussions.

Resumo Objetivos: avaliar os efeitos da nifedipina utilizada na tocólise sobre os parâmetros maternos e fetais. Métodos: estudo de coorte incluindo 40 gestantes admitidas na enfermaria de alto risco para inibição do trabalho de parto prematuro entre setembro/2010 a maio/2012. Utilizou-se a nifedipina sublingual na dose de ataque de 20mg e uma manutenção de 20mg por via oral a cada seis e oito horas. As variáveis avaliadas foram os batimentos cardio-fetais (BCF), frequência cardíaca materna (FCM), pressão arterial sistólica (PAS) e diastólica (PAD) e índice de líquido amniótico (ILA). Todas as variáveis foram avaliadas antes da administração da nifedipina e aproximadamente após 6h e cada 24h até alta hospitalar. Resultados: não houve modificação dos BCF (p=0,48) e da PAS (p=0,29). A FCM aumentou após 24h, mas sem significância estatística (p=0,08) retornando a níveis similares ao da admissão com 48h. A PAD diminuiua partir de 6h (p = 0,04)até 72h, mantendo-se constante. O ILA diminuiu significativamente em 24h, 48h e 72h. Conclusão: a utilização de altas doses de nifedipina para tocóliseocasio na diminuição dos níveis pressóricos diastólicos maternos e consequentemente diminuição do ILA, mas provavelmente sem repercussões clínicas.

Impact of topical nifedipine on wound healing in animal model (pig) / Impacto da nifedipina tópica na cicatrização de feridas em modelo animal (porco)

Abstract Background The human skin is an extremely sophisticated and evolved organ that covers the whole body. External agents or the patient's own diseases can cause skin injuries that can challenge healthcare professionals and impose high social, economic and emotional costs. Objectives To evaluate the impact of topical nifedipine on skin wound healing, specifically on polymorphonuclear cells, vascular proliferation, and collagen. Methods We used three pigs, and created eight injuries in the dorsal region of each animal. We applied 1%, 10%, and 20% concentration nifedipine creams to four of the wounds in animals 1, 2, and 3 respectively and treated the other twelve wounds with saline solution 0.9% only. We analyzed the presence of polymorphonuclear cells, vascular proliferation, and collagen at six different times (days 1, 3, 7, 14, 21, and 28). Results The evaluation of polymorphonuclear levels showed mild cell activity at all times in the control group, while in the nifedipine groups, marked levels were more frequent at all times during the experiment. There was a 4.84-fold increase in the chance of marked vascular proliferation (p = 0.019) and, at the same time, a decrease in collagen formation (OR 0.02 / p = 0.005) in animal 3. Conclusions Topical NFD may have an impact on skin wound healing mechanisms. Our study showed that polymorphonuclear cells and vascular proliferation increased. We also demonstrated that collagen formation decreased. Therefore, topical NFD may have a positive impact on skin wound healing. Additional studies are needed to confirm our results.

Resumo Contexto A pele humana é um órgão extremamente sofisticado e evoluído que cobre todo o corpo. As lesões cutâneas podem ser causadas por agentes externos ou pelas próprias doenças do paciente, e podem representar um desafio para os profissionais de saúde com altos custos sociais, econômicos e emocionais. Objetivos Avaliar o impacto da nifedipina tópica na cicatrização de feridas cutâneas, especialmente em relação a polimorfonucleares, proliferação vascular e colágeno. Métodos Utilizamos três porcos e realizamos oito ferimentos na região dorsal de cada animal. Aplicamos as concentrações de nifedipina creme a 1%, 10% e 20% para os animais 1, 2 e 3, respectivamente, sendo que, em quatro ferimentos, aplicamos o creme e, nos outros quatro ferimentos, apenas soro fisiológico a 0,9%. Analisamos a presença de polimorfonucleares, proliferação vascular e colágeno em seis momentos diferentes (dias 1, 3, 7, 14, 21 e 28). Resultados A avaliação dos níveis polimorfonucleares mostrou atividade celular discreta em todos os momentos no grupo controle, enquanto nos grupos nifedipina, os níveis marcados foram mais frequentes em todos os momentos do experimento. Houve aumento de 4,84 vezes na chance de uma produção marcada (p = 0,019) da proliferação vascular e, ao mesmo tempo, diminuição da formação do colágeno (odds ratio, OR 0,02; p = 0,005) no animal 3. Conclusões A nifedipina tópica pode ter impacto no mecanismo de cicatrização cutânea. Nosso estudo mostrou que há aumento dos polimorfonucleares e da proliferação vascular. Além disso, há diminuição da formação do colágeno. Assim, a nifedipina tópica pode ter impacto positivo na cicatrização das feridas cutâneas. Estudos adicionais são necessários para confirmar nossos resultados.

Regression of carotid intima-media thickness with nifedipine in hypertensive patients / Regresión del grosor de la interfase íntima-media carotídea con nifedipina en pacientes hipertensos (REINA)

Background: Calcium channel blockers (CCBs) have proved to reduce both blood pressure levels and cardiovascular outcomes, including the development of atherosclerosis. The INSIGHT study showed a less pronounced progression of carotid intima-media thickness (IMT) in patients treated with nifedipine (NIF) vs. those treated with diuretics, but because IMT was normal in both groups, it was difficult to assess the anti-atherosclerotic effect of NIF. We compared the effect of NIF or hydrochlorothiazide (HCTZ) on atherosclerosis regression in hypertensive patients with abnormally thick IMT. Patients and methods: 37 hypertensive patients were randomly assigned to be treated with slow release-NIF (30 mg) and 46 to HCTZ (25 mg), all of them with IMT > 0.6 mm. IMT, lipid profile, and serum uric acid, potassium, and glucose were analyzed at baseline and 12 months later. Results: Blood pressure was equally well controlled with both treatments. No biochemical abnormality was observed in neither groups. IMT was reduced 35% in the NIF group in comparison to 9.3% in HCTZ group. Discussion: BBCs restore endothelial function, exert antioxidant activity and limit smooth muscle cells growth and proliferation, thus inhibiting fundamental atherogenic phenomena. Our results show a clear regression of IMT, marker of subclinical atherosclerosis with NIF. Conclusion: Both treatments were equally effective reducing blood pressure. HCTZ did not cause metabolic disarrays, but only NIF induced IMT regression. Basal IMT is a main determinant of regression.

Antecedentes: Los bloqueadores de los canales de calcio (BCC) han demostrado reducir tanto los niveles de presión arterial como los eventos cardiovasculares, incluyendo el desarrollo de la aterosclerosis. El estudio INSIGHT mostró una progresión menos pronunciada del grosor de la capa íntima-media de la carotídea (GIMC) en pacientes tratados con nifedipina (NIF) vs. los tratados con diuréticos, pero debido a que el GIMC fue normal en ambos grupos, resultó difícil evaluar el efecto anti-aterosclerótico de la NIF. El presente estudio comparó el efecto de la NIF o hidroclorotiazida (HCTZ) en la regresión de aterosclerosis en pacientes hipertensos con GIMC anormalmente gruesa. Pacientes y métodos: 37 pacientes hipertensos fueron asignados al azar para ser tratados con NIF de liberación lenta (30 mg) y 46 a HCTZ (25 mg), todos ellos con GIMC > 0.6 mm. GIMC, perfil lipídico, y ácido úrico en suero, potasio y glucosa se analizaron al principio y 12 meses más tarde. Discusión: Los BCC restauran la función endotelial, ejercen actividad antioxidante y limitan el crecimiento y la proliferación de las células del músculo liso, inhibiendo así fenómenos aterogénicos fundamentales. Nuestros resultados muestran una clara regresión del GIMC, marcador de aterosclerosis subclínica, con NIF. Conclusión: Ambos tratamientos fueron igualmente efectivos para reducir la presión arterial. HCTZ no causó desorden metabólico, pero sólo la NIF induce la regresión del GIMC. El GIMC basal es un determinante principal de la regresión.

Efecto del bloqueo de canales ionotrópicos voltaje dependiente de calcio sobre las descargas neuronales mecanorreceptivas / Effect of voltage dependent calcium channels block on mechanoreceptive neuronal discharges

El presente trabajo evaluó las modificaciones en los patrones de descarga neuronal mecanoreceptiva inducidas por la nifedipina (inhibidor de canales voltaje-dependientes de calcio tipo L) en el modelo de la pata de la cucaracha P. americana. Se disecaron las patas metatoráxicas de adultos machos, sumergiéndolas en solución Ringer(RIN) o enRinger más nifedipina (100μg.mL-1) por 5 minutos, luego se realizó el registro electrofisiológico durante actividad espontánea (10min) y estimulación mecánica con flexióntibio-femoral (desplazamiento=5mm; aplicación 10s; retiro 10s, por 10min). Los registros multiunitarios se amplificaron y digitalizaron a 11,8KHz. Se analizaron los registros convencionalmente y por procesos puntuales durante laactividad espontánea y con estimulación.Se usó pruebas no paramétricas con significancia en P<0,05. En 44 experimentos con 1000 a 5000 espigas multiunitarias cada uno, se observó quetodas las distribuciones de intervalos interespiga (IIE) se ajustaron a funciones poissonianas, la desviación estándar fue mayor a la media de los IIE,característico de descargas en salvas. No se evidenciaron efectos de la nifedipina sobre los IIE en actividad espontánea (P=0,72) o estimulada (P=0,47), ni sobre los valores de descargas en salvas espontáneas (P=0,32) o estimuladas (P=0,37). Sin embargo, se evidenció una disminución significativa en la frecuencia de descarga del mecanoreceptor durante la fase de inicial de la aplicación del estímulo y un retraso en la fase de adaptación mecanoreceptiva (P<0,001), evidenciando el efecto de la nifedipinay su acción sobre los canales de calcio tipo L en los mecanoreceptores. Esto podría explicar los reportes de pacientes con efectos colaterales durante el uso de la nifedipina en relación a la propiocepción.

Changes of neuronal mechanoreceptive discharge pattern induced by nifedipine (voltage activated L-type calcium channel inhibitor) were evaluatedin the cockroach (P. americana) leg model. Methathoracic legs from male adult insects were dissected and submerged in Ringer solution (RIN) or Ringer with nifedipine (100μg.mL-1) for 5 minutes, thereafter, electrophysiological recordings were made in background activity (10min) and during mechanical tibio-femoral flexion (displacement=5mm; 10s:10s on:off for 10min). Multiunitary recordings were amplified and digitalized at 11.8KHz. Conventional and Point process techniques were used for analysis. Non parametrical test with significance at P<0.05 were used. From 44 experiments with 1000 to 5000 multiunitary spikes recorded on each one, all interspike intervals (ISI) distributions fit to a poissonian function. ISI Standard deviation > ISI arithmetic mean which point out to burst discharges. No evidence of nifedipine effect were found on ISI during background activity (P=0.72) nor mechanical stimulation (P=0.47) not even on burst discharge values (P=0.32 and P=0.37 respectively). However, nifedipine induced a significant reduction on the mechanoreceptor discharge frequency during the early phase of the stimulus and a lengthening of the adaptation phase (P<0.001) which evidences the effect of nifedipine and L-type calcium channel on mechanoreceptors. These could explain sensory and proprioceptive collateral effects reported by patient using nifedipine.

Doppler de las arterias uterinas, umbilical y cerebral media fetal en embarazada con amenaza de parto pretérmino tratada con nifedipina oral / Doppler of uterine, umbilical and middle cerebral fetal arteries in pregnant women with preterm labor treated with oral nifedipine

Determinar las modificaciones en Doppler de las arterias uterinas, umbilical y cerebral media fetal en embarazadas con amenaza de parto pretérmino tratada con nifedipina oral como tocolítico. Se seleccionaron 50 pacientes con diagnóstico de amenaza de parto pretérmino. Las pacientes recibieron nifedipina a una dosis inicial de 30 mg sublinguales seguida por una dosis oral de 20 mg dos a cuatro veces al día. La dosis máxima fue de 120 mg cada 24 horas. Se midieron los índices de pulsatilidad, índice de resistencia y relación de flujo sistólico / diastólica de las arterias uterinas, umbilical y cerebral media fetal antes y después del tratamiento. Servicio de Ginecología y Obstetricia. Hospital Central "Dr. Urquinaona". Maracaibo, Estado Zulia. La edad materna promedio al inicio del estudio fue de 26,9 ± 6,9 años y la edad gestacional promedio fue de 30,3 ± 2,6 semanas. La duración promedio del tratamiento fue de 4,8 ± 1,5 días. No se encontraron diferencias estadísticamente significativas en los valores promedio de la frecuencia cardíaca materna y fetal, presión arterial sistólica, presión arterial diastólica antes y después del tratamiento con nifedipina oral (P = ns). No se encontraron diferencias significativas en los índices de pulsatilidad, índice de resistencia y relación de flujo sistólico / diastólica en las arterias uterinas, umbilical y cerebral media fetal antes y después del tratamiento con nifedipina oral (P = ns). El uso de nifedipina oral como tocolítico no produce modificaciones significativas en las mediciones Doppler de las arterias uterinas, umbilical y cerebral media fetal en embarazadas con amenaza de parto pretérmino

To determine modifications of Doppler of uterine, umbilical and fetal middle cerebral arteries in pregnant women with threatened pre-term labor treated with oral nifedipine as tocolytic agent. Fifty patients with diagnosis of threatened pre-term labor were selected. Patients received an initial dose of 30 mg of sub lingual nifedipine followed by an oral dose of 20 mg twice to four times a day. A maximum dosage was of 120 mg each 24 hours. The pulsatility index, resistance index and systolic/diastolic blood flow ratio of uterine, umbilical and fetal middle cerebral arteries were measured before treatment and after treatment. Servicio de Ginecologia y Obstetricia. Hospital Central "Dr. Urquinaona". Maracaibo, Estado Zulia. Maternal mean age at beginning of study was 26.9 ± 6.9 years-old and gestational mean age was 30.3 ± 2.6 weeks. Mean duration of treatment was 4.8 ± 1.5 days. There were not found significant differences in mean values of maternal and fetal heart rate, systolic blood pressure and diastolic blood pressure before and after treatment with oral nifedipine (p = ns). There were not found significant differences in pulsatility index, resistance index and systolic/diastolic blood flow ratio of uterine, umbilical and fetal middle cerebral arteries before and after treatment (p = ns). The use of oral nifedipine as tocolytic agent did not produce significant modifications in Doppler measurements of uterine, umbilical and fetal middle cerebral arteries in pregnant women with threatened pre-term labor

Agrandamientos gingivales inducidos por fármacos / Drug-induced gingival enlargements

El término agrandamiento gingival por fármacos se refiere a un crecimiento anormal de la encía, secundario al uso de una medicación sistémica. Si bien se reporta una larga lista de medicamentos relacionados, se encontró una fuerte asociación sólo con la Fenitoína , la Nifedipina y la Ciclosporina A. La prevalencia del Agrandamiento Gingival varía ampliamente, sin embargo la prevalencia relacionada con el uso de la Fenitoína es aproximadamente del 50 por ciento. La Nifedipina y la ciclosporina producen cambios en el 25 por ciento de los pacientes tratados. Existe controversia entre la dosis y el riesgo o severidad del Agrandamiento.El grado de Agrandamiento gingival parece estar relacionado con la susceptibilidad del paciente y el grado dehigiene bucal de éste. Después de 1 a 3 meses de iniciada la medicación del fármaco los agrandamientos originadosen la papila interdental, se expande afectando otras áreas de la encía llegando a cubrir en casos extremosuna porción importante de los dientes principalmente en los segmentos anteriores por vestibular. El uso discontinuo de la medicación por el médico de cabecera y más aún la sustitución del fármaco por otroresulta en la regresión y el cese del Agrandamiento. (AU)

Agrandamientos gingivales inducidos por fármacos / Drug-induced gingival enlargements

El término agrandamiento gingival por fármacos se refiere a un crecimiento anormal de la encía, secundario al uso de una medicación sistémica. Si bien se reporta una larga lista de medicamentos relacionados, se encontró una fuerte asociación sólo con la Fenitoína , la Nifedipina y la Ciclosporina A. La prevalencia del Agrandamiento Gingival varía ampliamente, sin embargo la prevalencia relacionada con el uso de la Fenitoína es aproximadamente del 50 por ciento. La Nifedipina y la ciclosporina producen cambios en el 25 por ciento de los pacientes tratados. Existe controversia entre la dosis y el riesgo o severidad del Agrandamiento.El grado de Agrandamiento gingival parece estar relacionado con la susceptibilidad del paciente y el grado dehigiene bucal de éste. Después de 1 a 3 meses de iniciada la medicación del fármaco los agrandamientos originadosen la papila interdental, se expande afectando otras áreas de la encía llegando a cubrir en casos extremosuna porción importante de los dientes principalmente en los segmentos anteriores por vestibular. El uso discontinuo de la medicación por el médico de cabecera y más aún la sustitución del fármaco por otroresulta en la regresión y el cese del Agrandamiento.

Nifedipine-Induced gingival overgrowth / Aumento gengival induzido por nifedipina

Objective: The objective of the present study was to evaluate gingival overgrowth induced by nifedipine and to correlate it with plaque accumulation. Material and Methods: Sixty patients were divided into a treated group (n=30) consisting of hypertensive patients long-term treated with nifedipine and a control group (n=30) consisting of patients without arterial hypertension. The following exams were performed on the first visit: anamnesis, measurement of blood pressure, weight and height, extra- and intraoral examination, and determination of the vertical and horizontal gingival overgrowth indices, plaque index, and bleeding index. The measurements were repeated after 30 days. Results: Most patients using nifedipine (60.7%) presented grade I horizontal gingival overgrowth (1 to 2 mm), with 3.6% showing minimum vertical gingival overgrowth. On the return visit, the plaque index was reduced by 8.3% and bleeding on probing was reduced by 1.5%. The individuals of control group, presented neither vertical gingival overgrowth nor horizontal, the plaque index was reduced by 7.2% and bleeding on probing was reduced by 5.3%. A significant difference in the horizontal gingival overgrowth index was observed between the treated and control groups (chi-square test, p = 0.015, p < 0.05). Conclusions: In the present study, authors conclude that the presence of dental biofilm and inflammation influences the degree of gingival overgrowth in patients using nifedipine.

Objetivo: O objetivo deste estudo foi avaliar o aumento gengival induzido por nifedipina e correlacioná-lo com o acúmulo de placa. Material e Métodos: Sessenta pacientes foram divididos em um grupo de hipertensos crônicos, sob tratamento contínuo com nifedipina, (n=30) e um grupo controle, pacientes saudáveis, sem hipertensão (n=30). Os seguintes exames foram realizados na primeira consulta: anamnese, aferição da pressão arterial, peso, altura, exame intra e extra-bucal, índices de aumento gengival vertical e horizontal, índice de placa e índice de sangramento. Os exames foram realizados novamente após 30 dias. Resultados: A maioria dos pacientes sob uso de nifedipina (60,7%) apresentou aumento gengival horizontal grau I (1 a 2 mm), e 3,6% demonstraram mínimo aumento gengival vertical. Na visita de retorno, o índice de placa foi reduzido em 8,3% e sangramento à sondagem em 1,5%. Os indivíduos do grupo controle não apresentaram aumento gengival vertical e nem horizontal, o índice de placa foi reduzido em 7,2% e sangramento à sondagem em 5,3%. Diferença significativa no índice de aumento gengival horizontal foi observada entre os grupos teste e controle (p = 0,015, p < 0,05). Conclusão: Neste estudo os autores concluíram que a presença do biofilme dental e a inflamação influenciam no grau de aumento gengival em pacientes sob tratamento com nifedipina.

Legrado uterino o nifedipina durante el posparto en pacientes con preeclampsia severa / Curettage or nifedipine during the postpartum period in patients with severe preeclampsia

Comparar la eficacia del legrado uterino o la nifedipina durante el posparto en pacientes con preeclampsia severa. Maternidad “Dr. Nerio Belloso”, Hospital Central “Dr. Urquinaona”, Maracaibo. Estado Zulia. Se realizó una investigación en 60 pacientes con diagnóstico de preeclampsia severa que fueron divididas de la siguiente manera: grupo A (n = 30) que fueron sometidas a legrado uterino inmediatamente después del parto y grupo B (n = 30) que recibieron nifedipina (10 mg vía oral cada 8 horas x 24 horas). Se evaluaron los cambios en la presión arterial, contaje de plaquetas, parámetros de laboratorio y efectos adversos. La edad materna, edad de la gestación al momento del parto y tipo de parto fueron similar para las pacientes del grupo nifedipina y las pacientes del grupo de legrado uterino (p = ns). No se encontraron diferencias significativas en los valores promedio de presión arterial sistólica, presión arterial diastólica y contaje de plaquetas en ninguno de los períodos estudiados entre ambos grupos de estudio (p = ns). Tampoco encontraron diferencias estadísticamente significativas entre los grupos en los valores inicial y a las 24 horas de hemoglobina, hematocrito, bilirrubina y transaminasas (p =ns). El único efecto adverso que presentó una diferencia estadísticamente significativa y una alta incidencia fue la cefalea en el grupo de preeclámpticas severas tratadas con nifedipina (26 casos, P < 0,05). La nifedipina es tan eficaz como el legrado uterino durante el posparto en pacientes con preeclampsia severa

To compare the efficacy of uterine curettage or nifedipine during postpartum in patients with severe preeclampsia. Maternidad “Dr. Nerio Belloso”, Hospital Central “Dr. Urquinaona”, Maracaibo. Estado Zulia. A research was done in 60 patients with diagnosis of severe preeclampsia that were divided of following way: group A (n = 30) who were submitted to uterine curettage and group B (n = 30) who received nifedipine (10 mg orally every 8 hours x 24 hours). Blood pressure changes, platelet count, laboratory parameters and adverse effects were evaluated. Maternal age, gestational age at the moment of delivery and type of delivery were similar to patients of group nifedipine and patients of uterine curettage group (p = ns). There were not significant differences in mean values of systolic blood pressure, diastolic blood pressure and platelet count between groups (p = ns). There was also not significant differences between groups in initial and at 24-hours values of hemoglobin, hematocrit, bilirubin and transaminases (p = ns). The only adverse effect that presented a significant difference and a high incidence was headache in group of severe preeclamptic patients treated with nifedipine (26 cases; P < 0.05). Nifedipine is as effective as uterine curettage during postpartum in patients with severe preeclampsia

Tocólisis con clorhidrato de isoxuprina o nifedipina en la amenaza de parto pretérmino / Tocolysis with isoxuprine hydrochloride or nifedipine in preterm labor

Comparar la eficacia del clorhidrato de isoxuprina o la nifedipina en la tocólisis de la amenaza de parto pretérmino. Se seleccionaron 82 pacientes con edad gestacional entre 24 y 34 semanas y diagnóstico de amenaza de parto pretérmino. Las pacientes se dividieron al azar en 2 grupos para recibir clorhidrato de isoxuprina (grupo A) o nifedipina (grupo B). Se determinaron el tiempo de cese de las contracciones, tensión arterial materna, concentraciones de glucosa y efectos adversos maternos. Maternidad "Dr. Nerio Belloso", Hospital Central "Dr. Urquinaona", Maracaibo. Estado Zulia. Se logró una tocólisis efectiva en las primeras 24 horas en 61,0 por ciento y 70,7 por ciento de las pacientes del grupo A y B, respectivamente (P = ns). Después de 7 días de tratamiento, 36,6 por ciento de las pacientes en el grupo A y 31,7 por ciento de las pacientes en el grupo B aun permanecían sin contracciones (P = ns). Se logró un retraso del parto hasta las 34 semanas o más en 26,8 por ciento y 29,3 por ciento de las pacientes de los grupos A y B, respectivamente. En el grupo de pacientes tratadas con clorhidrato de isoxuprina se observó un aumento significativo de las concentraciones séricas de glucosa (P < 0,001). Los efectos adversos maternos fueron significativamente más frecuentes en el grupo de clorhidrato de isoxuprina después de 2 y 24 horas de tratamiento (P < 0,05). La nifedipina es igual de efectiva que el clorhidrato de isoxuprina en la tocólisis de la amenaza de parto pretérmino y produce menos efectos adversos

To compare the efficacy of isoxuprine clorhidrate or nifedipine in tocolysis of threatened preterm labor. 82 patients with a gestational age between 24 and 34 weeks and threatened preterm labor diagnosis were selected. Patients were randomly divided in 2 groups to receive isoxuprine clorhidrate (group A) or nifedipine (group B). Time of cease of contractions, maternal blood pressure, glucose concentrations and maternal adverse effects were determined. Maternidad "Dr. Nerio Belloso", Hospital Central "Dr. Urquinaona", Maracaibo. Estado Zulia. An effective tocolysis was obtained within 24 hours in 61.0 percent and 70.7 percent for patients in group A and B, respectively (P = ns). After 7 days of treatment, 36.6 percent of patients in group A and 31,7 percent of patients in group B were still without contractions (P = ns). A delay in labor till 34 weeks or more was made in 26.8. percent and 29.3 percent of patients in group A and B, respectively. In the group of patients treated with isoxuprine clorhidrate a significant raise of glucose concentrations was observed (P < 0.001). Maternal adverse effects were significant more frequent in isoxuprine clorhidrate group after 2 and 24 hours of treatment (P < 0,05). Nifedipine has a similar effectivity than isoxuprine clorhidrate for tocolysis in threatened preterm labor and produces less adverse effects

Epidemiological analysis of nifedipine and phenytoin-induced gingival overgrowth in users of the Primary Health Care System / Análise epidemiológica do aumento gengival induzido por nifedipina e fenitoína em usuários da Atenção Primária à Saúde

Purposes: The aim of this study was to evaluate the prevalence of drug-induced gingival overgrowth (DIGO) in Brazilian users of nifedipine and/or phenytoin and to determine the presence of predisposing/modifying factors. Methods: Demographic, pharmacological, and periodontal data were obtained from 100 users of the Brazilian Primary Health Care System in Diamantina, Jequitinhonha Valley, Minas Gerais state, Brazil, who were taking nifedipine and/or phenytoin. Clinical evaluations including gingival overgrowth analysis were carried out by a single calibrated examiner. Bivariate analysis (Chi-square test or Student's t-test) were used to identify demographic, periodontal and drug-related significant factors associated with gingival overgrowth severity. Multivariate analysis (Poisson regression) was used to assess confounding factors. Results: The prevalence of DIGO was high (86%), but its severity was predominately mild. The prevalence of DIGO was significantly higher in phenytoin users than in nifedipine users (p=0.01). There was no association between DIGO and demographic, pharmacological or periodontal variables. Conclusion: The high occurrence of DIGO among users of nifedipine and phenytoin emphasizes the importance of the dentist as part of the public health team to provide the prevention, early diagnostic, and control of this alteration.

Objetivo: Avaliar a prevalência dos aumentos gengivais medicamentosos em usuários brasileiros de nifedipina e fenitoína e determinar a presença de fatores preditores/modificadores. Metodologia: Dados demográficos, farmacológicos e periodontais foram obtidos de 100 pacientes usuários da Atenção Primária no Vale do Jequitinhonha que usavam nifedipinae/ou fenitoína. Avaliações clínicas, incluindo a análise do aumento gengival, foram feitas por um avaliador calibrado. Análises bivariadas (teste do qui-quadrado ou teste t de Student) foram usadas para identificar fatores demográficos, periodontais e medicamentosos que apresentassem associação com a severidade do aumento gengival. Foi utilizada análise multivariada (regressão de Poisson) para estimar a razão de prevalência e intervalo de 95% de confiança para identificar os fatores de risco associados ao desenvolvimento do AG. Resultados: A prevalência do aumento gengival foi elevada (86%), mas a gravidade mais comumente observada foi a leve. A prevalência foi maior em usuários de fenitoína do que de nifedipina (P=0.01). Não houve associação entre aumento gengival e as variáveis demográficas, farmacológicas e periodontais. Conclusão: A alta prevalência do aumento gengival medicamentoso entre os usuários de nifedipina e fenitoína enfatiza a importância do cirurgião dentista no diagnóstico, prevenção e controle dessa alteração.

Desenvolvimento de excipiente específico para cápsulas de nifedipina preparadas magistralmente: parte I / Development of specific excipient for compounded nifedipine capsules. Part I

O presente trabalho tem o objetivo de desenvolver um excipiente específico para cápsula de nifedipina preparada magistralmente, o qual permita o cumprimento dos requisitos farmacopéicos e legais, conforme preconiza a RDC nº 87 de 21 de novembro de 2008. Para isso, foram propostas 6 formulações contendo 10mg de nifedipina, sendo, quatro destas, denominadas A, B, C e D, baseadas na composição de um medicamento industrializado, enquanto as formulações, E e F baseadas em sugestões opcionais de excipientes em função do Sistema de Classificação Biofarmacêutico. Em seguida, estas foram submetidas aos testes de uniformidade de conteúdo e de dissolução utilizando absorção por espectrofotometria na região da ultravioleta (λ = 236nm) para obtenção dos resultados. As amostras (n = 3) se comportaram de forma adequada no teste de uniformidade de conteúdo, entretanto, no teste de dissolução, as formulações não apresentaram uma quantidade satisfatória de ativo dissolvido em 20 min. Pode-se observar uma evolução das formulações quanto à presença de Tween 80 na E, e na F. Entretanto, o aumento na concentração deste agente, não ampliou o perfil de dissolução da nifedipina, pois não houve diferença significativa deste parâmetro entre as duas (E e F). Dentre as fórmulas propostas neste trabalho, concluiu-se que não foi possível determinar uma, que fosse adequada para a aprovação do produto, com a liberação de apenas 20 a 40% do ativo, indicando que há necessidade de novos estudos.

The objective of this study was to develop a specific excipient for extemporaneously compounded nifedipine capsules, which would comply with the specifications of the pharmacopoeia and the legal requisites, set out in Brazilian Health Regulation RDC 87 of November 21, 2008. To this end, 6 formulations for capsules containing 10mg of nifedipine were proposed, the first four (A, B, C and D) being based on the composition of a manufactured medicine, while formulations E and F were based on an alternative excipient, suggested in accordance with the Biopharmaceutical Classification System. After preparation, the formulated capsules were subjected to content uniformity and dissolution tests, using UV absorption spectrophotometry (λ = 236nm) to assay the drug. The samples (n = 3) were found to have adequate content uniformity; however, in the dissolution test, the formulations did not show a satisfactory quantity of dissolved drug in 20 minutes. The formulations E and F were designed with differing amounts of Tween 80. However, increasing the concentration did not improve the dissolution profile of the nifedipine, as there was no significant difference in this parameter between E and F. It was concluded that none of the formulations proposed in this paper could be indicated as suitable for product approval, given that only 20 to 40% of the active component was released, indicating that there is a need for further studies.

O impacto da saúde bucal na qualidade de vida de usuários do sistema único de saúde que fazem uso contínuo de nifedipina e fenitoína em Diamantina, Minas Gerais / The impact of oral health in the quality of life in the Unique System of Health users with continuous nifedipine and phenytoin at Diamantina, Minas Gerais

O uso continuado de alguns medicamentos, como anifedipina e fenitoína, pode acarretar o desenvolvimento de um aumento de volume gengival descrito como aumento gengival medicamentoso. Este estudo teve por objetivo a avaliação do impacto da saúde bucal na qualidade de vida de usuários do Sistema Único de Saúde (SUS) que faziam uso continuado destes medicamentos em Diamantina (MG) levando em consideração a presença/ausência de dentes e a presença do aumento gengival medicamentoso. Foram aplicados 152 questionários em indivíduos edêntulos e não-edêntulos abrangendo aspectos gerais, condição médica e odontológica e informações relacionadas ao uso de medicamentos. Avaliações clínicas, incluindo a análise do aumento gengival, foram feitas por um avaliador calibrado pelo teste-reteste. O impacto da saúde bucal na qualidade de vida foi avaliado através do OHIP-14, apresentando um valor médio de impacto de 4,49 pontos. Os resultados desta análise demonstraram que 43% dos indivíduos avaliados tinham aumento gengival. Houve correlação significativa entre o OHIP, a idade e profissão dos indivíduos avaliados, bem como com a presença de dentes e com o aumento gengival (p< 0,05). O aumento gengival apresentou correlação com 8 dos 14 itens do OHIP, demonstrando afetar 5 das 7 dimensões avaliadas. A alta ocorrência do aumento gengival entre usuários de nifedipinae fenitoína e o impacto desta alteração na qualidade devida enfatizam a importância do desenvolvimento de estratégias para avaliação e controle da saúde bucal desses pacientes.

The continuous use of some drugs such as nefidipine and phenytoin could develop a gingival enlargement calleddrug-induced gingival overgrowth. This study aimed to evaluate the oral health impact in the quality of life of the Unique Health System users who were under treatment with these drugs considering the presence/absence of teeth and gingiva lovergrowth. 152 questionnaires were applied to dentate and non dentate subjects enclosing general aspects, medical and dental condition and information related to the medicine use. Clinical evaluations, including the analysis of the gingival overgrowth was made by an appraiser calibrated for theretest-test. The impact of the oral health in the quality of life was evaluated through the OHIP-14, presenting an averagevalue of impact of 4.49 points. The results of this analysis showed that 43% of examined subjects had gingival overgrowth. It was also demonstrated a significant association between OHIP and age, and OHIP and profession of the evaluated subjects, as well as with the tooth presence and the gingival overgrowth (p< 0.05). The gingival overgrowth showed correlation with 8 of the 14 item of the OHIP, demonstrating to affect 5 of the 7 evaluated dimensions. The higher occurrence of the gingival overgrowth among users of nifedipine and phenytoin and the impact of this alteration in the quality of life emphasize the importance of the development of strategies for evaluation and controlof the oral health of these patients.

Avaliação manométrica anal pré e pós tratamento da fissura anal crônica com nifedipina tópica 0,2 por cento / The role of nifedipine 0,2 percent in cronic anal fissure-manometric study pre and post treatment

No tratamento da fissura anal, novas drogas têm sido utilizadas, dentre elas os bloqueadores de canais de cálcio. O objetivo desta pesquisa foi à avaliação manométrica de pacientes com fissura anal crônica após tratamento com nifedipina tópica 0,2 por cento, correlacionando com a cicatrização e a dor. Trata-se de estudo prospectivo realizado em pacientes atendidos no ambulatório de Coloproctologia do Hospital Universitário de Taubaté. Os pacientes foram submetidos ao exame manométrico antes e após 30 dias da utilização de nifedipina tópica gel 0,2 por cento três vezes ao dia no ânus e margem anal. Para a análise estatística foi utilizado o teste de Mann-Whitney considerando significante, se p<0,05. Os dez pacientes não demonstraram nenhuma alteração manométrica provocada pelo tratamento com nifedipina, mas 50 por cento deles relataram melhora dos sintomas e 40 por cento dos pacientes apresentaram cicatrização da fissura, mostrando que a nifedipina foi efetiva no tratamento da fissura anal e segura do ponto de vista funcional, por não causar lesões esfincterianas. A avaliação manométrica demonstrou não haver alterações nas pressões anais demonstrando, entretanto, melhora da dor em 50 por cento e cicatrização em 40 por cento dos pacientes.

In the treatment of the anal fissure, calcium channel blockers are among the new drugs which have been used. The objective of this research was the manometric evaluation of patients with chronic anal fissure after topic treatment with 0.2 percent nifedipine and correlation with the healing and pain. This is a prospective study of patients from Coloproctology Clinic of the University of Taubaté Hospital. The patients had been submitted to a manometric examination before and after 30 days of the use of topic 0.2 percent nifedipine gel three times a day in the anus and anal edge. For the statistics analysis Mann-Whitney test was applied to a significance of p= 0,05. Ten patients did not exihibit manometric alteration associated with nifedipina treatment, however 50 percent of them reported improvement of the symptoms and 40 percent depicted healing of the fissure. The results demonstrated that nifedipine was effective and safe for anal fissure treatment and considering the functional point of view it did not cause injuries as well. The manometric evaluation did not demonstrate alterations in the anal pressure; however, it was observed that 50 percent of the patients had improvement in pain and 40 percent in healing.

Estudio comparativo entre nifedipina y captopril en crisis hipertensiva en niños / Nifedipine and captopril in hypertensive crisis in children

Introducción: La crisis hipertensiva es una urgencia pediátrica que se debe manejar con medicamentos de rápida acción, de fácil administración y sin mayores efectos secundarios. El medicamento usado tradicionalmente ha sido el nitroprusiato de sodio endovenoso en infusión continua lo que implica hospitalización en cuidados intensivos con mayores costos y riesgos. Objetivos: Comparar la eficacia y seguridad de la nifedipina y el captopril sublingual en crisis hipertensivas. Material y métodos: Se llevó a cabo un estudio prospectivo en niños entre 1 y 12 años de edad que ingresaron al servicio de pediatría urgencias del Hospital Universitario del Valle en Cali, Colombia, con diagnóstico de crisis hipertensiva. Se realizó monitoreo de la presión arterial sistólica, diastólica y media y de la frecuencia cardíaca antes de administrar los medicamentos y a los 5, 15, 30, 60, 120, 180, 240, 300 y 360 minutos después de administrados. Los dos medicamentos se dieron por vía sublingual a dosis de 0.2 mg/kg. Se vigilaron efectos secundarios después de su administración. Resultados: Durante 16 meses ingresaron 21 pacientes, 10 asignados a nifedipina y 11 a captopril, 13 niños y 8 niñas, con un promedio de edad de 7 años. La reducción de la presión arterial por debajo del percentil 95 inducida por la nifedipina sublingual fue más rápida, en promedio a los 20 minutos, que con captopril (50 minutos). Hasta los 30 minutos las cifras de presión arterial sistólica, diastólica y media fueron estadísticamente inferiores con nifedipina que con captopril, para luego tener una actividad muy similar. Se necesitó una segunda dosis en tres pacientes con nifedipina y uno con captopril. No hubo respuesta en dos pacientes con captopril. No se presentaron efectos secundarios mayores. Con la nifedipina se observó aumento promedio de 10% en la frecuencia cardíaca a los 5 minutos después de ser administrada.

Introduction: Hypertensive crisis is a pediatric emergency which implies medications with fast action and minimal side effects. Sodium nitroprusiate in continuous infusion has been the treatment of choice but implicates admission to intensive care unit. Objectives: To evaluate efficacy and safety of nifedipine and captopril in hypertensive crisis in children. Methodology: A prospective study was performed to evaluate efficacy and safety of sublingual nifedipine and captopril, in children 1-12 years old who were admitted with diagnosis of hypertensive crisis, to the Pediatric Emergency Service at the University Hospital in Cali, Colombia. Systolic, diastolic, mean blood pressure and heart rate were monitored in all patients before administration of the medicaments, time 0, and after the administration at time 5, 15, 30, 60, 120, 180, 240, 300, and 360 minutes. Side effects were observed carefully after the administration. Results: During a period of 16 months, 21 patients were enrolled in the study: 10 were assigned to nifedipine and 11 to captopril; 13 were boys and 8 were girls, with a mean age of 7 years old. Both medications were given sublingual at 0.2mg/kg/dose. Blood pressure reduction under 95 percentil induced by sublingual nifedipine was faster, mean time 20 minutes compared to captopril (50 minutes). Up to 30 minutes post medication systolic, diastolic and mean blood pressure were statistically lower with nifedipine than with captopril; but after 30 minutes both medications had similar activity. Three patients with Nifedipine and 1 with captopril required a second dose. Two patients with captopril had no response. No side effects were registered in either group. Nifedipine induced a 10% asymptomatic heart rate increase at 5 minutes after its administration, captopril did not increase heart rate.

Magnitud, velocidad y eficacia antihipertensiva de la Nifedipina de liberación programada en microgránulos en el tratamiento de pacientes con hipertensión arterial esencial

La magnitud, velocidad y eficacia antihipertensiva de la nifedipina de liberación programada en microgránulos (NLPM) fue evaluada en pacientes con hipertensión moderada a severa. Un total de ciento treinta y cinco pacientes fueron evaluados durante seis semanas en un estudio prospectivo, abierto, comparativo y cruzado. 25.9% (n = 35) fueron pacientes controles normales, del resto eran pacientes hipertensos, 40% (n = 54 pacientes) recibieron 30 mgrs (8am ó 8pm) de NLPM y 20.7% (n = 28 pacientes) recibieron 60 mgrs (8am ó 8pm) de NLPM, el 13.3% de los pacientes admitidos (n = 18) fueron considerados como fracasos de la medicación. Ambas dosis a los distintos horarios de la toma disminuyeron significativamente las presiones arteriales (p < 0.05). En los pacientes que lograron el punto deseado con 30 mgrs, éste se logró desde la 3ra. semana de administrado el medicamento manteniéndose en los niveles tensionales buscados hasta el final del estudio, siendo la magnitud más elevada de reducción de: 8am PAS 15.5 mmHg (12.2%), PAD 12 mmHg (12.6%), PAM 12.2 mmHg (10.9%) y 8pm de: PAS 14.1 mmHg (9.7%), PAD 9.5 mmHg (10.6%) y PAM 11.2 mmHg (10.05%), en cambio en aquellos que lograron el punto deseado con la administración de 60 mgrs, se observaron reducciones desde la 3ra. semana obteniéndose el efecto máximo a la 6ta.semana siendo la magnitud más elevada de reducción de: 8am PAS 26.3 mmHg (16.34%), PAD 18.5 mmHg (17.69%) y PAM 20.9 mmHg (17.0%) y 8pm PAS 22.5 mmHg (15.15%), PAD 18 mmHg (18.1%) y PAM 21.8 mmHg (18.5%). La magnitud de la respuesta antihipertensiva de la NLPM fue numéricamente mayor con 60 mgrs que con 30 mgrs, pero la velocidad de respuesta fue mayor con 30 mgrs probablemente debido a que las cifras tensionales al inicio del estudio eran mayores en el grupo que requirió 60 mgrs, (p < 0.05) llegándose al final del estudio (6ta. semana) a cifras tensionales normales y similares en ambos grupos (p > 0.05). La FC en el grupo de 30 mgrs (8am y 8pm) mostró una disminución significativa luego del tratamiento (p < 0.05), en cambio en el grupo de 60 mgrs éstas se mantuvieron inalteradas (p > 0.05). En conclusión NLPM demostró ser eficaz para el manejo de los pacientes con hipertensión leve a moderada, obteniéndose con la dosis de 60 mgrs mayor magnitud en el efecto hipotensor que con la dosis de 30 mgrs, exhibiendo esta última mayor velocidad de respuesta antihipertensiva.

The magnitude, velocity and antihypertensive effectiveness of the nifedipine liberation programmed in microgranules (NLPM) was evaluated in patients with moderate to severe hypertension. A total of one hundred and thirty five patients were evaluated during six weeks in a prospective, open, comparative and crossed study. Of that group, 25.9% (n = 35) were normal patients, the remainder of them were hypertensive patients, 40% (n = 54 patients) received 30 mgrs (8am or 8pm) of NLPM and 20.7% (n = 28 patients) received 60 mgrs (8am or 8pm) of NLPM, 13.3% of the admitted patients (n = 18) were considered as failures of the medication. Both doses at different schedules of the taking diminished the arterial pressures significantly (p <0.05). There were patients that reached the end point a 30 mgrs dose, this achievement was obtained from the 3rd week of medication keeping on these pressure levels until the end of the study, being the highest magnitude of reduction were: 8am PAS 15.5 mmHg (12.2%), PAD 12 mmHg (12.6%), PAM 12.2 mmHg (10.9%) and 8pm of: PAS 14.1 mmHg (9.7%), PAD 9.5 mmHg (10.6%) and PAM 11.2 mmHg (10.05%), on the other hand, in those who achieved the end point with the administration of 60 mgrs, reductions were observed from the 3rd week obtaining the maximum effect at the 6th week being the highest magnitude of reduction of: 8am PAS 26.3 mmHg (16.34%), PAD 18.5 mmHg (17.69%) and PAM 20.9 mmHg (17.0%) and 8pm PAS 22.5 mmHg (15.15%), PAD 18 mmHg (18.1%) and PAM 21.8 mmHg (18.5%). The magnitude of the antihypertensive response of the NLPM was numerically bigger with 60 mgrs than with 30 mgrs, but the response velocity was bigger with 30 mgrs maybe because the blood pressure at the beginning of the study were bigger in that group that required 60 mgrs, (p <0.05) arriving at the end of the study (6th week) to normal pressure figure, similar in both groups (p> 0.05). The heart rate in the group of 30 mgrs (8am and 8pm) showed a significant decrease after the treatment (p <0.05), on the other hand in the group of 60 mgrs these stayed unaffected (p> 0.05). In conclusion NLPM demonstrated to be effective for the managing of patients with light to moderate hypertension, obtaining a bigger magnitude in the blood pressure effect with a dose of 60 mgrs than with a dose 30 mgrs, however, with this last dose, the antihypertensive response was more fast.

Uso y abuso del nifedipino por vía sublingual en nuestros sistemas de urgencia

Se observa que el incremento de la prevalencia de pacientes hipertensos en nuestras comunidades, y la implantación del Programa Nacional para el control de la hipertensión arterial, no han podido disminuir la cantidad de pacientes que acuden con cifras altas de su presión arterial a nuestros servicios de urgencia con decisiones terapéuticas indiscriminadas y agresivas. Se ha generalizado el uso del nifedipino sublingual, incluso en pacientes de la tercera edad, lo que produce bajadas bruscas de la presión arterial por disminución en la sensibilidad de los barorreceptores y con ellas una alteración de los mecanismos de autorregulación del flujo hístico. Se señala que las complicaciones producidas no son alarmantes, pero con un uso racional y si se cumplen algunas normas, podrían disminuirse aún más.

It is observed that the prevalence increase of hypertensive patients in our communities and the implementation of the National Program for the Hypertension Control have not so far been able to reduce the number of hypertensive patients going to our emergency medical services by applying indiscriminate and aggressive therapeutical methods. The use of sublingual administered nifedipine is extensive even in elderly patients, which may cause a sharp blood pressure drop and also a change in the hystic flow self-regulating mechanisms. It is stressed that complications are not serious but if this drug is more rationally used and some directions are fulfilled, then these complications will be further reduced.

Dinitrato de isosorbide sublingual en la urgencia hipertensiva

Se investigó el uso del dinitrato de isosorbide sublingual en la urgencia hipertensiva. Se estableció además una correlación con la nifedipina, de eficacia probada para este fin. Se estudiaron 80 pacientes con este diagnóstico, distribuidos aleatoriamente en 2 grupos, que recibieron 10 mg de nifedipina o dinitrato de isosorbide, si a los 45 min de la primera dosis no se había alcanzado el control se administró una segunda dosis. Se obtuvo la primera dosis de dinitrato de isosorbide, un mayor número de pacientes controlados (n = 29) a diferencia de la nifedipina (n = 19). Ambos fármacos lograron el control de 36 pacientes con la segunda dosis. La nifedipina causó cefalea ligera. En conclusión, el dinitrato de isosorbide resultó ser un medicamento eficaz, de fácil administración y con escasos efectos secundarios en el tratamiento de la urgencia hipertensiva y puede constituir una alternativa más en los servicios de urgencia.

The use of sublingual isosorbide dinitrate in the hypertensive urgency was investigated. It was also established a correlation with nifedipine, whose efficacy has been proved to this end. 80 patients with this diagnosis were studied and divided at random into 2 groups, who received 10 mg of nifedipine or isosorbide dinitrate and a second dosage if their pressure was not controlled 45 minutes after the first dosage. With the first dosage of isosorbide dinitrate a higher number of patients were controlled (n = 29) compared with nifedipine (n = 19). 36 patients were controlled with the second dosage of both drugs. Nifedipine caused mild cephalalgia. To conclude, isosorbide dinitrate proved to be an efficient drug, easy to administer and with a few side effects in the treatment of hypertensive urgency. It may be another alternative for urgency services.

Estudo multicêntrico comparativo da felodipina-ER e nifedipina-OROS no tratamento da hipertensão arterial leve e moderada / Multicenter comparative study of felodipine-ER and nifedipine-OROS in the treatment of mild-to-moderate arterial hypertension

PURPOSE: To compare the efficacy and tolerance of felodipine-ER and nifedipine OROS, both once daily, in the treatment of mild-to-moderate uncomplicated arterial hypertension (AH). METHODS: This was a multicentric, opened, randomized, paralled trial, that selected 121 patients with uncomplicated, mild to moderate essential AH (diastolic blood pressure (DBP) > or = 95 and < or = 110 mmHg; not under anti-hypertensive medication. All patients received placebo for two weeks. After that period, they would take either 5mg/day of felodipine, or 30mg/day of nifedipine OROS, both once daily, in a randomized fashion. Patients underwent laboratory tests and electrocardiogram (ECG) at the begining and at the end of the study, and heart rate and blood pressure (BP) measurements, nearly 24 hours after the last active drug dose. RESULTS: Completed the study 111 patients, 60 in the felodipine group and 51 in the nifedipine group. Compared to baseline, the average of systolic BP and DBP decreased from 162.5 +/- 14.3mmHg and from 102.2 +/- 5.1mmHg to 143.3 +/- 14.6 and 87.9 +/- 7.2mmHg, respectively, at the end of the treatment in the felodipine group; and from 160.5 +/- 16.3mmHg and 102.5 +/- 6.2mmHg to 136.1 +/- 14.2 and 86.7 +/- 7.0mmHg, respectively in nifedipine group (p < 0.0001 for all diferences). Adequate BP response to the treatment (DBP normalization or reduction > 10mmHg from baseline) occured in 47/60 (78.3) patients in the felodipine group and in 38/51 (74.5) in the nifedipine group (NS). Side effects, occured in approximately 15 of the cases, and were similar in both groups. These were usually moderate and transient, but were responsible for the withdrawal from the study of two cases in the felodipine group and of three cases in the nifedipine group. CONCLUSION: Felodipine-ER and nifedipine OROS, are similarly effective and generally well tolerated in patients with mild-to-moderate essential hypertension.

Objetivo - Comparar a eficácia e a tolerabilidade da felodipina-ER com a nifedipina-OROS, ambas em dose diária única, no tratamento da hipertensão arterial (HA) leve e moderada, não complicada. Métodos - Estudo multicêntrico, aberto, randomizado e paralelo, incluindo 121 pacientes com HA essencial e nível de pressão arterial diastólica (PAD) >95 e <110mmHg, sem medicação anti-hipertensiva. Após período de 2 semanas de placebo, os pacientes foram randomizados para receber felodipina-ER, 5mg uma vez ao dia, ou nifedipina-OROS, 30mg uma vez ao dia, durante 4 semanas. As medidas da freqüência cardíaca e da pressão arterial (PA) foram sempre registradas cerca de 24h após a última dose. Exames laboratoriais e eletrocardiograma (ECG) foram realizados ao início e ao final do tratamento. Resultados - Completaram o estudo 111 pacientes, 60 no grupo felodipina e 51 no grupo nifedipina. Em comparação com os valores basais, as médias da PA sistólica e da PAD reduziram-se de 162,5±14,3mmHg e de 102,2±5,1mmHg para 143,3±14,6 e 87,9±7,2mmHg, respectivamente, ao final do tratamento, no grupo felodipina; e de 160,5±16,3mmHg e 902,5±6,2mmHg para 136,1±14,2 e 86,7±7,0mmHg, respectivamente, no grupo nifedipina (p< 0,001 para todas as diferenças). Resposta adequada da PA ao tratamento (normalização da PAD ou redução >10mmHg) ocorreu em 47/60 (78,3%) pacientes do grupo felodipina e em 38/51 (74,5%) do grupo nifedipina (NS). Efeitos colaterais, ocorreram em aproximadamente 15% dos casos, com padrão similar em ambos os grupos. Foram em geral moderados e transitórios, porém responsáveis pelo abandono do tratamento em 2 casos do grupo felodipina e em 3 do grupo nifedipina. Conclusão - Felodipina-ER e nifedipina-OROS, foram igualmente eficazes no tratamento da HA leve e moderada, com bom e similar perfil de tolerabilidade

Estudo multicêntrico nacional para avaliação da eficácia e tolerabilidade da nifedipina oros em hipertensão arterial leve a moderada / Multicenter National Study for the evaluation of the efficacy and tolerance of nifedipine oral release osmotic system in mild to moderate hypertension

PURPOSE--Evaluation of the efficacy and tolerability of nifedipine oros in patients with mild to moderate essential hypertension without major target organ damage and the anti-hypertensive effect along the 24 hours. METHODS--Two hundred and three patients were studied. After two weeks placebo running period single dose of nifedipine oros (30 mg/day) was administered for 8 weeks. At the end of the 4th week, the non-responders (diastolic blood pressure > 90 mmHg or reduction in diastolic pressure < 10 mmHg), had the dosage increased to 60 mg/day. Laboratory tests and 24h blood pressure monitoring (60 patients) were performed at the beginning and at the end of the study. RESULTS--One hundred and ninety one patients completed the study. Fifty nine percent were considered responders at the end of the 4th week with nifedipine oros 30 mg/day and 41 needed dosage increment to 60 mg/day. At the end of the 8th week, all patients were considered responders to nifedipine oros. The blood pressure control extended throughout the 24h of the day. The most common adverse events were edema (14.6) and headache (12.4). Good and very good tolerability were informed by 85 of the patients. CONCLUSION--Nifedipine oros was able to control blood pressure efficaciously along the 24h period without important side effects. The possibility of once day dosage, increases the patient adherence to anti-hypertensive therapy.