RESUMO
PURPOSE: Dopamine agonists (DA) are the gold-standard for prolactinoma and hyperprolactinemia treatment. Intolerance to DA leading to drug drop out occurs in 3 to 12% of cases. We provide here a review of published data about DA intolerance and present a case report concerning the use of intravaginal cabergoline. METHODS: We review the literature on the definition, the pathogenesis, frequency and management of DA intolerance. In addition, the review provides strategies to enhance tolerability and avoid precocious clinical treatment withdrawal. RESULTS: Cabergoline is often cited as the most tolerable DA and its side effects tend to ameliorate within days to weeks. Restarting the same drug at a lower dose or switching to another DA can be used in cases of intolerance. The vaginal route can be tried specifically if there are gastrointestinal side effects in the oral administration. Symptomatic treatment could be attempted, although mainly based on a strategy used in other diseases. CONCLUSIONS: Due to limited data, no guidelines have been developed for the management of intolerance in DA treatment. The most frequent management is to perform transsphenoidal surgery. Nevertheless, this manuscript provides data derived from published literature and expert opinion, suggesting new approaches to this clinical issue.
Assuntos
Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Feminino , Humanos , Prolactinoma/tratamento farmacológico , Prolactinoma/complicações , Agonistas de Dopamina/uso terapêutico , Agonistas de Dopamina/efeitos adversos , Cabergolina/uso terapêutico , Neoplasias Hipofisárias/patologia , Hiperprolactinemia/tratamento farmacológico , Bromocriptina/uso terapêutico , Ergolinas/efeitos adversosRESUMO
Rotigotina e outros medicamentos antiparkinsonianos, com ênfase em agonistas dopaminérgicos (bromocriptina e pramipexol). Indicação: Tratamento da doença de Parkinson. Pergunta: Há superioridade de eficácia e segurança da rotigotina, comparado aos agonistas dopaminérgicos disponíveis atualmente no SUS para o tratamento da doença de Parkinson? Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PubMed e utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Foram selecionadas três revisões sistemáticas que atendiam aos critérios de inclusão. A rotigotina não apresenta eficácia e segurança superiores ao pramipexol; não há quantidade de estudos suficientes para comparação com a bromocriptina
Rotigotine and other antiparkinsonians medicines, with emphasis on dopaminergic agonists (bromocriptine and pramipexole). Indication: Treatment of Parkinson disease. Question: Is rotigotine more effective and safer than other dopamine agonists available in the Brazilian Public Health System for the treatment of Parkinson's Disease? Rapid evidence review (overview) from systematic reviews, with a literature search in the PubMed database by employing a structured strategy. The methodological quality of systematic reviews was evaluated using AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Three systematic reviews that met the inclusion criteria were selected. Rotigotine has not shown superior efficacy and safety when compared to pramipexole; there are insufficient studies for comparison with bromocriptine
Assuntos
Doença de Parkinson/tratamento farmacológico , Bromocriptina/uso terapêutico , Agonistas de Dopamina , Pramipexol/uso terapêutico , Antiparkinsonianos/uso terapêuticoRESUMO
Neuroleptic malignant syndrome is a rare and potentially fatal clinical condition frequently associated with the use of antipsychotics. In the literature, there is only one case report associated with the intake of organophosphates. We present the case of a patient who presented with a clinical picture compatible with neuroleptic malignant syndrome, after the ingestion of an organophosphate (chlorpyrifos). A 57-year-old man who consulted for attempted suicide, acute deterioration of consciousness, torpid neurological evolution, and associated autonomic instability associated with rigidity, persistent hyperthermia, and elevated CPK. Bromocriptine treatment was offered, which resolved the clinical picture. The association with the ingestion of an organophosphate was established, and he was discharged without sequelae. The diagnosis of neuroleptic malignant syndrome is clinical and should be considered in any case of exposure to substances that may lead to dysregulation of dopaminergic neurotransmission in order to initiate timely therapy and impact outcomes.
El síndrome neuroléptico maligno es una condición clínica rara y potencialmente letal que frecuentemente se asocia con el uso de antipsicóticos. En la literatura especializada se encontró únicamente un reporte de caso relacionado con la ingestión de organofosforados. Se presenta un paciente con un cuadro clínico correspondiente al síndrome neuroléptico maligno posterior a la ingestión de clorpirifós. Como resultado de un intento de suicidio con el mencionado organofosforado, el hombre de 57 años presentó deterioro agudo del estado de consciencia, evolución neurológica tórpida e inestabilidad autonómica asociada a rigidez e hipertermia persistentes, así como incremento de la creatina-fosfocinasa (creatine phosphokinase, CPK). Se le administró tratamiento con bromocriptina, con lo cual el cuadro clínico remitió, y fue dado de alta sin secuelas. El diagnóstico del síndrome neuroléptico maligno es clínico y debe contemplarse en cualquier caso de exposición a sustancias que puedan resultar en una desregulación de la neurotransmisión dopaminérgica, con el fin de iniciar el tratamiento oportuno y contrarrestar efectivamente los efectos.
Assuntos
Antipsicóticos , Clorpirifos , Síndrome Maligna Neuroléptica , Intoxicação por Organofosfatos , Antipsicóticos/efeitos adversos , Bromocriptina/uso terapêutico , Clorpirifos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Maligna Neuroléptica/diagnóstico , Síndrome Maligna Neuroléptica/etiologia , Síndrome Maligna Neuroléptica/terapia , Intoxicação por Organofosfatos/complicaçõesRESUMO
El síndrome neuroléptico maligno es una condición clínica rara y potencialmente letal que frecuentemente se asocia con el uso de antipsicóticos. En la literatura especializada se encontró únicamente un reporte de caso relacionado con la ingestión de organofosforados. Se presenta un paciente con un cuadro clínico correspondiente al síndrome neuroléptico maligno posterior a la ingestión de clorpirifós. Como resultado de un intento de suicidio con el mencionado organofosforado, el hombre de 57 años presentó deterioro agudo del estado de consciencia, evolución neurológica tórpida e inestabilidad autonómica asociada a rigidez e hipertermia persistentes, así como incremento de la creatina-fosfocinasa (creatine phosphokinase, CPK). Se le administró tratamiento con bromocriptina, con lo cual el cuadro clínico remitió, y fue dado de alta sin secuelas. El diagnóstico del síndrome neuroléptico maligno es clínico y debe contemplarse en cualquier caso de exposición a sustancias que puedan resultar en una desregulación de la neurotransmisión dopaminérgica, con el fin de iniciar el tratamiento oportuno y contrarrestar efectivamente los efectos.
Neuroleptic malignant syndrome is a rare and potentially fatal clinical condition frequently associated with the use of antipsychotics. In the literature, there is only one case report associated with the intake of organophosphates. We present the case of a patient who presented with a clinical picture compatible with neuroleptic malignant syndrome, after the ingestion of an organophosphate (chlorpyrifos). A 57-year-old man who consulted for attempted suicide, acute deterioration of consciousness, torpid neurological evolution, and associated autonomic instability associated with rigidity, persistent hyperthermia, and elevated CPK. Bromocriptine treatment was offered, which resolved the clinical picture. The association with the ingestion of an organophosphate was established, and he was discharged without sequelae. The diagnosis of neuroleptic malignant syndrome is clinical and should be considered in any case of exposure to substances that may lead to dysregulation of dopaminergic neurotransmission in order to initiate timely therapy and impact outcomes.
Assuntos
Inseticidas Organofosforados , Síndrome Maligna Neuroléptica , Rabdomiólise , Bromocriptina , Colinesterases , FebreRESUMO
WHAT IS KNOWN AND OBJECTIVE: Hyperprolactinemia is a neuroendocrine disease that is responsible for a quarter of cases of secondary amenorrhea, which can lead to infertility in women. Dopaminergic agonists (bromocriptine, cabergoline, quinagolide) can be used in the treatment. However, there is a lack of secondary studies that compare their efficacy and safety, especially through a network meta-analysis. Thus, to contribute to the decision-making, a systematic review and network meta-analyses (NMA) were performed to evaluate the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. METHODS: Randomized clinical trials (RCT) were retrieved through PubMed, Web of Science and Scopus databases. The efficacy and safety of the drugs were compared, considering the following outcomes: prolactin (PRL) levels, number of patients with galactorrhoea, menstrual irregularities and adverse drug reactions. NMA was built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals. Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA) and Stochastic multicriteria acceptability analysis (SMAA). RESULTS AND DISCUSSION: Seventeen RCTs were included in the systematic review and fifteen in the meta-analyses. The drugs had similar efficacy, considering the PRL levels. The SUCRA analysis showed that quinagolide (0.075 and 0.05 mg/day) was superior for reducing irregular menstruation, whereas bromocriptine was the best (97%) for galactorrhoea. Cabergoline proved to be the safest drug, except for abdominal pain at a dose of 1 mg/week. The SMAA demonstrated similar results to SUCRA. WHAT IS NEW AND CONCLUSION: This is the first network meta-analysis that evaluated the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. The results of this review revealed that these drugs have similar efficacy, but cabergoline has a better safety profile.
Assuntos
Agonistas de Dopamina/uso terapêutico , Hiperprolactinemia/tratamento farmacológico , Hiperprolactinemia/epidemiologia , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Feminino , Galactorreia/epidemiologia , Humanos , Distúrbios Menstruais/epidemiologia , Metanálise em Rede , Prolactina/sangue , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Non-pharmacological early weaning (NPEW) induces liver damage in male progeny at adulthood; however, pharmacological early weaning (PEW) does not cause this dysfunction. To elucidate this difference in liver dysfunction between these two models and determine the phenotype of female offspring, de novo lipogenesis, ß-oxidation, very low-density lipoprotein (VLDL) export, and gluconeogenesis in both sexes were investigated in the adult Wistar rats that were weaned after a normal period of lactation (control group) or early weaned either by restriction of access to the dams' teats (NPEW group) or by reduction of dams' milk production with bromocriptine (PEW group). The offspring received standard diet from weaning to euthanasia (PN180). NPEW males had higher plasma triglycerides and TyG index, liver triglycerides, and cholesterol by de novo lipogenesis, which leads to intracellular lipids accumulation. As expected, hepatic morphology was preserved in PEW males, but they showed increased liver triglycerides. The only molecular difference between PEW and NPEW males was in acetyl-CoA carboxylase-1 (ACC-1) and stearoyl-CoA desaturase-1 (SCD-1), which were lower in PEW animals. Both early weaning (EW) females had no changes in liver cholesterol and triglyceride contents, and the hepatic cytoarchitecture was preserved. The expression of microsomal triglyceride transfer protein was increased in both the female EW groups, which could constitute a protective factor. The changes in hepatic lipid metabolism in EW offspring were less marked in females. EW impacted in the hepatic cytoarchitecture only in NPEW males, which showed higher ACC-1 and SCD-1 when compared to the PEW group. As these enzymes are lipogenic, it could explain a worsened liver function in NPEW males.
Assuntos
Lipogênese/fisiologia , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Acetiltransferases/análise , Acetiltransferases/metabolismo , Animais , Bromocriptina/administração & dosagem , Modelos Animais de Doenças , Feminino , Antagonistas de Hormônios/administração & dosagem , Humanos , Lactação/efeitos dos fármacos , Lactação/fisiologia , Lipoproteínas VLDL/metabolismo , Fígado/enzimologia , Fígado/crescimento & desenvolvimento , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Oxirredução , Prolactina/antagonistas & inibidores , Prolactina/metabolismo , Ratos , Ratos Wistar , Fatores Sexuais , Estearoil-CoA Dessaturase/análise , Estearoil-CoA Dessaturase/metabolismo , Fatores de Tempo , Triglicerídeos/análise , Triglicerídeos/metabolismo , DesmameRESUMO
Prolactinomas are the most common pituitary tumors and pathological hyperprolactinemia. Therefore, women harboring prolactinomas frequently present infertility due to the gonadal axis impairment. The gold-standard treatment is dopamine agonist (DA) which can reverse hyperprolactinemia and hypogonadism, and promote tumor shrinkage in the majority of cases. Therefore, reports of pregnancy in such cohort become more common. In this scenario, bromocriptine is still the DA of choice due to its shorter half-life and larger experience as compared to cabergoline. In DA resistant cases, transsphenoidal pituitary surgery is indicated. However, potential risks of DA-induced pregnancies include fetal exposition and symptomatic tumor growth. Dopamine agonist should be discontinued as soon as pregnancy is confirmed in microprolactinomas and intrasellar macroprolactinomas (MAC). Concerning expansive/invasive MAC, DA maintenance should be considered. Periodically clinical evaluation should be performed during pregnancy, being sellar imaging indicated if tumor symptomatic growth is suspected. In such cases, if DA treatment fails, neurosurgery is indicated.
Assuntos
Agonistas de Dopamina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/tratamento farmacológico , Bromocriptina/uso terapêutico , Feminino , Humanos , GravidezRESUMO
PURPOSE: Early weaning (EW) is a risk factor for obesity development. Brown adipose tissue (BAT) hypofunction is related to obesity onset. Here, we evaluated whether sympathetic nervous system (SNS) activity in BAT and the thermogenic function of BAT are decreased in adulthood in obese rats from two EW models. METHODS: At the time of birth, lactating Wistar rats and their pups (three males and three females) were separated into three groups: the control group, in which pups consumed milk throughout lactation; the non-pharmacological EW (NPEW) group, in which suckling was interrupted with a bandage during the last 3 days of lactation; and the pharmacological EW (PEW) group, in which dams were treated with bromocriptine (0.5 mg/twice a day) 3 days before weaning. The offspring were sacrificed on PN180. RESULTS: Adult male rats from both EW models exhibited lower BAT SNS activity. Female rats from the PEW group showed a decrease in BAT SNS activity. The protein levels of UCP1 were lower in the NPEW males, while PGC1α levels were lower in both PEW and NPEW males. Both groups of EW females showed reductions in the levels of ß3-AR, TRß1, and PGC1α. The UCP1 protein level was reduced only in the NPEW females. The EW groups of both sexes had lower AMPK protein levels in BAT. In the hypothalamus, only the PEW females showed an increase in AMPK protein levels. In both groups of EW males, adrenal catecholamine was increased and tyrosine hydroxylase was decreased, while in EW females, adrenal catecholamine was decreased. CONCLUSIONS: Early weaning alters the thermogenic capacity of BAT, which partially contributes to obesity in adulthood, and there are sex-related differences in these alterations.
Assuntos
Tecido Adiposo Marrom , Lactação , Animais , Feminino , Masculino , Ratos , Ratos Wistar , Termogênese , DesmameRESUMO
Introduction: Prolactinomas are preferentially treated with dopamine agonists. However, a few adenomas are resistant to this treatment. Objective: To evaluate the characteristics of patients with resistance to dopamine agonists in the long-term. Method: A retrospective study of six cases was made. Patients who did not achieve normalized prolactin blood concentrations and a reduction of more than 50% of the tumor volume with the minimum dose of 3.5 mg per week of cabergoline for 3 months or the maximum supported dose of bromocriptine for 6 months were considered resistant to dopamine agonists. Patients were followed up at the Clinic of Neurology and Endocrinology or the University Hospital of Brasilia. Results: Six patients were selected. Three patients were initially treated with bromocriptine prior to treatment with cabergoline. Four patients were men, and two were women. At the time of diagnosis, ages ranged from 9 to 62 years. Initial prolactin concentrations ranged from 430 to 14,992 ng/mL and in the last assessment ranged from 29.6 to 2,169 ng/mL. The tumor volume ranged from 0.77 to 24.0 mm3. Tumor regression occurred in all patients, ranging from 20 to 100%, but total disappearance of the adenoma with an empty sella occurred in one patient. The maximum weekly doses of cabergoline ranged from 3.0 to 4.5 mg. Follow-up time ranged from seven to 17 years. Normalization of prolactin concentrations occurred only in one woman after 17 years of treatment. Three patients also underwent surgery, but only one woman was cured of the disease. Conclusion: This study confirms that tumors resistant to dopamine agonists are more aggressive, since we did not have any microadenoma; treatment with high dose of cabergoline may reduce the size of the tumor without its disappearance, and that normalization of prolactin concentration rarely occurs. To our knowledge, this is the longest follow-up of a series of cases with resistance to dopamine agonists.
RESUMO
Despite the androgenic dependence, other hormones, growth factors, and cytokines are necessary to support prostatic growth and maintain the glandular structure; among them, prolactin is a non-steroidal hormone secreted mainly by the pituitary gland. However, extra-pituitary expression of prolactin, such as in the prostate, has also been demonstrated, highlighting the paracrine and autocrine actions of prolactin within the prostate. Here, we investigated whether prolactin modulation alters ventral prostate (VP) morphophysiology in adult castrated rats. Sprague Dawley rats were castrated and after 21 days, divided into ten experimental groups (n = 6/group): castrated control: castrated animals that did not receive treatment; castrated+testosterone: castrated animals that received T (4 mg/kg/day); castrated+PRL (PRL): castrated animals receiving prolactin (0.3 mg/kg/day); castrated+T+PRL: castrated animals that received a combination of testosterone and prolactin; and castrated+bromocriptine (BR): castrated animals that received bromocriptine (0.4 mg/kg/day). The control group included intact animals. The animals were treated for 3 or 10 consecutive days. At the end of experimental period, the animals were euthanized, and the blood and VP lobes were collected and analyzed by different methods. The main findings were that the administration of prolactin to castrated rats did not exert anabolic effects on the VP. Although we observed activation of downstream prolactin signaling after prolactin administration, this was not enough to overcome the prostatic androgen deficiency. Likewise, there was no additional glandular involution in the castrated group treated with bromocriptine. We concluded that despite stimulating the downstream signaling pathway, exogenous prolactin does not act on VP in the absence or presence of high levels of testosterone.
Assuntos
Envelhecimento/metabolismo , Castração , Terapia de Reposição Hormonal , Prolactina/metabolismo , Próstata/metabolismo , Testosterona/uso terapêutico , Animais , Western Blotting , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Ratos Sprague-Dawley , Receptores Androgênicos/metabolismoRESUMO
Non-pharmacological early weaning (NPEW) leads offspring to obesity, higher liver oxidative stress and microsteatosis in adulthood. Pharmacological EW (PEW) by maternal treatment with bromocriptine (BRO) causes obesity in the adult progeny but precludes hepatic injury. To test the hypothesis that BRO prevents the deleterious changes of NPEW, we injected BRO into the pups from the NPEW model in late lactation. Lactating rats were divided into two groups: dams with an adhesive bandage around the body to prevent breastfeeding on the last 3 days of lactation and dams whose pups had free suckling (C). Offspring from both groups were subdivided into two groups: pups treated with BRO (intraperitoneal (i.p.) 4 mg/kg per day) on the last 3 days of lactation (NPEW/BRO and C/BRO) or pups treated with the vehicle (NPEW and C). At PN120, offspring were challenged with a high fat diet (HFD), and food intake was recorded after 30 minutes and 12 hours. Rats were killed at PN120 and PN200. At PN120, adipocyte size was greater in the NPEW group but was normal in the NPEW/BRO group. At PN200, the NPEW group presented hyperphagia, higher adiposity, adipocyte hypertrophy, hyperleptinaemia, glucose intolerance and increased hepatic triglycerides. These parameters were normalized in the NPEW/BRO group. In the feeding test, BRO groups showed lower HFD intake at 30 minutes than did their controls; however, at 12 hours, the NPEW group ate more HFD. The treatment with BRO can preclude some deleterious effects of the NPEW model, which prevented the development of overweight and its comorbidities.
Assuntos
Bromocriptina/farmacologia , Hiperfagia/prevenção & controle , Gordura Intra-Abdominal/efeitos dos fármacos , Lactação/metabolismo , Fígado/efeitos dos fármacos , Triglicerídeos/metabolismo , Desmame , Animais , Feminino , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Hiperfagia/complicações , Gordura Intra-Abdominal/citologia , Lactação/sangue , Leptina/sangue , Fígado/metabolismo , Masculino , Obesidade/complicações , Ratos , Ratos WistarRESUMO
Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE), and new evidence has confirmed a significant correlation between serum PRL levels and disease activity. PRL participates in activation of SLE during pregnancy and in pathogenesis of lupus nephritis, neuropsychiatric, serosal, hematologic, articular, and cutaneous involvement. Hyperprolactinemia was associated with increase IgG concentrations, anti-DNA antibodies, immune complex, glomerulonephritis, and accelerated mortality in murine lupus. Bromocriptine, a dopamine analog that suppresses PRL secretion, was associated with decreased lupus activity, prolonged lifespan, and restoration of immune competence in experimental model. In clinical trials, bromocriptine and derivative drugs showed beneficial therapeutic effect in treating human lupus, including pregnancy. Taken together, clinical and experimental results leave little doubt that PRL indeed contributes to the pathogenesis and clinical expression of SLE.
Assuntos
Bromocriptina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Hiperprolactinemia/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Complicações na Gravidez/imunologia , Prolactina/metabolismo , Imunidade Adaptativa , Animais , Anticorpos Antinucleares/sangue , Modelos Animais de Doenças , Feminino , Humanos , Hiperprolactinemia/tratamento farmacológico , Hiperprolactinemia/epidemiologia , Imunidade Inata , Imunocompetência , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/tratamento farmacológico , Camundongos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Prolactina/imunologia , Receptores da Prolactina/metabolismoRESUMO
BACKGROUND: The aim of this paper was to characterize the blood pressure CR in patients with end stage chronic kidney disease (ESCKD) before and after treatment with bromocriptine compared to healthy volunteers. METHODS: Fifteen patients and nine healthy volunteers were included. Both groups underwent ambulatory 24 hours blood pressure (24 h ABPM). Patients received 2.5 mg every 8 hours of bromocriptine for eight weeks, at the end of the treatment 24 h ABPM was repeated; blood pressure CR was compared before and after treatment and with healthy volunteers. The CR was identified by the method of Cosinor. RESULTS: 64% of volunteers showed a 24 h CR, against 27% of patients (p < 0.05). After the treatment with bromocriptine 40% of patients showed RC 24 h. The mean arterial pressure decreased from 129 ± 1 mmHg to 106 ± 1 mmHg. A 12 h rhythm was identified in 45% of volunteers and 73% of patients before treatment (p < 0.05) against 60% at the end (p < 0.001), with no statistical difference with volunteers. CONCLUSIONS: The CR in blood pressure is altered in ESCKD and could be restored with bromocriptine. 12 hours rhythmicity was identified predominantly in patients with ESCKD; this rhythm was also present in the healthy volunteers.
INTRODUCCIÓN: el propósito de este estudio es caracterizar el ritmo circadiano (RC) de la presión arterial en pacientes con enfermedad renal crónica terminal (ERCT) en tratamiento con diálisis peritoneal continua ambulatoria (DPCA) antes y después del tratamiento con bromocriptina (BEC) comparándolos con voluntarios sanos. MÉTODOS: se incluyeron 15 pacientes del servicio de Nefrología y 9 voluntarios sanos. Se les realizó monitoreo ambulatorio de presión arterial de 24 horas (MAPA). Los pacientes recibieron 2.5 mg de BEC cada 8 hora durante ocho semanas, al final del tratamiento se repitió el MAPA; el RC de la presión arterial se comparó antes y después del tratamiento y con los voluntarios. Resultados: el 64% de los voluntarios exhibieron RC de 24 horas, frente al 27% de los pacientes (p < 0.05). Después del tratamiento con BEC, el 40% de pacientes mostraron RC de 24 h. El mesor de la presión arterial media disminuyó de 129 ± 1 mmHg a 106 ± 1 mmHg (p < 0.05). Se identificó un ritmo de 12 h en 45% de los voluntarios y en el 73% de los pacientes antes del tratamiento (p < 0.05) frente a 60% al final (p < 0.001), sin diferencia estadística con los voluntarios. CONCLUSIONES: el RC de la presión arterial esta alterado en la IRCT y se restableció con BEC. La ritmicidad de 12 h predominó en los pacientes con ERCT, también presente en los voluntarios sanos.
Assuntos
Anti-Hipertensivos/uso terapêutico , Bromocriptina/uso terapêutico , Hipertensão/tratamento farmacológico , Falência Renal Crônica/complicações , Determinação da Pressão Arterial , Estudos de Casos e Controles , Esquema de Medicação , Voluntários Saudáveis , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Falência Renal Crônica/fisiopatologia , Resultado do TratamentoRESUMO
Previously, we demonstrated that maternal prolactin inhibition at the end of lactation, using bromocriptine (BRO), leads to an increase in leptin transfer via milk and induces the adult progeny to present hypothyroidism, leptin resistance and metabolic syndrome (obesity, hyperglycemia, hypertriglyceridemia, lower HDL). To test if these alterations are due to direct BRO action on the pups, in the present study we evaluated the long-term effects of direct injection of BRO (0.1µg/once daily) in male Wistar rats from postnatal (PN) day 1 to 10 (early treatment) or from PN11 to 20 (late treatment) on: food intake, body mass, cardiovascular parameters, hormone profile, hypothalamic leptin signaling, glucose homeostasis and thyroid hormone-dependent proteins. The respective controls were injected with methanol-saline. Offspring were killed at adulthood (PN180). Adult PN1-10 BRO-treated animals had lower food intake, hypoprolactinemia, lower leptin action (lower OBR-b, STAT-3 and SOCS-3 mRNA levels in the arcuate nucleus), lower TRH-TSH-thyroid axis as well as lower thyroid hormone markers. On the other hand, adult animals that were BRO-treated during the PN11-20 period showed hyperphagia, higher blood pressure, higher prolactinemia and OBR-b, higher TRH and plasma T3, hypercorticosteronemia as well as higher Dio2 and UCP1 mRNA expression in the brown adipose tissue. Glucose homeostasis was not changed treatment in either period. Our data show that early and late dopamine overexposure during lactation induces diverse metabolic disturbances later in life, increasing the risk of thyroid dysfunction and, consequently, changes in prolactinemia.
Assuntos
Bromocriptina/farmacologia , Prolactina/sangue , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue , Animais , Animais Recém-Nascidos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Leptina/metabolismo , Masculino , Ratos , Ratos Wistar , Glândula Tireoide/metabolismoRESUMO
ABSTRACT Objetive The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL 5t5and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. Conclusions Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.
Assuntos
Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adenoma/patologia , Progressão da Doença , Menopausa/sangue , Neoplasias Hipofisárias/patologia , Prolactina/sangue , Prolactinoma/patologia , Adenoma/sangue , Adenoma/tratamento farmacológico , Bromocriptina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Ergolinas/uso terapêutico , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/sangue , Prolactinoma/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Suspensão de TratamentoRESUMO
The importance of dopamine in central nervous system function is well known, but its effects on glucose homeostasis and pancreatic ß cell function are beginning to be unraveled. Mutant mice lacking dopamine type 2 receptors (D2R) are glucose intolerant and have abnormal insulin secretion. In humans, administration of neuroleptic drugs, which block dopamine receptors, may cause hyperinsulinemia, increased weight gain and glucose intolerance. Conversely, treatment with the dopamine precursor l-DOPA in patients with Parkinson's disease reduces insulin secretion upon oral glucose tolerance test, and bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients as well as in non diabetic obese animals and humans. The actions of dopamine on glucose homeostasis and food intake impact both the autonomic nervous system and the endocrine system. Different central actions of the dopamine system may mediate its metabolic effects such as: (i) regulation of hypothalamic noradrenaline output, (ii) participation in appetite control, and (iii) maintenance of the biological clock in the suprachiasmatic nucleus. On the other hand, dopamine inhibits prolactin, which has metabolic functions; and, at the pancreatic beta cell dopamine D2 receptors inhibit insulin secretion. We review the evidence obtained in animal models and clinical studies that posited dopamine receptors as key elements in glucose homeostasis and ultimately led to the FDA approval of bromocriptine in adults with type 2 diabetes to improve glycemic control. Furthermore, we discuss the metabolic consequences of treatment with neuroleptics which target the D2R, that should be monitored in psychiatric patients to prevent the development in diabetes, weight gain, and hypertriglyceridemia.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Dopaminérgicos/uso terapêutico , Glucose/metabolismo , Acromegalia/tratamento farmacológico , Animais , Bromocriptina/uso terapêutico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Dopaminérgicos/efeitos adversos , Homeostase , Humanos , Doença de Parkinson/tratamento farmacológico , Polimorfismo Genético , Prolactinoma/tratamento farmacológico , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismoRESUMO
Male sexual satiety has been associated with a decrease in dopamine levels. Spontaneous recovery of copulatory behavior begins at least 72 h after sexual satiety is reached or in the condition in which a sexually-satiated male is exposed to a new receptive female distinct from the one with which sexual satiety was reached. The aim of the present study was to explore whether dopaminergic activation by bromocriptine (BrCr) can reactivate copulatory behavior with the same sexual mate immediately after sexual satiety is reached. Male rats were divided into three groups exposed to one of the following three conditions: 1) administration of 2 mg/kgs.c. of BrCr and exposure to the same female with whom sexual satiety was previously reached; 2) administration of 0.3 mLs.c. of the vehicle solution with exposure to the same female with whom sexual satiety was reached; and, 3) exposure to a new receptive female after sexual satiety was reached. Results showed that BrCr significantly reactivated copulatory capability in sexually-satiated males with the same receptive female. In contrast, no males in the vehicle group ejaculated with the same female after reaching sexual exhaustion. Copulation was reactivated by BrCr in a way similar to that observed in untreated males exposed to a new receptive female (i.e., the Coolidge effect). The reversal of sexual satiety in the males treated with BrCr could be explained by its action on D2 family receptors, which promotes a reactivation of sexual motivation at a level sufficient to allow renewed copulation with the same female mate.
Assuntos
Bromocriptina/farmacologia , Copulação/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Saciação/efeitos dos fármacos , Animais , Copulação/fisiologia , Ejaculação/efeitos dos fármacos , Ejaculação/fisiologia , Masculino , Distribuição Aleatória , Ratos Wistar , Receptores de Dopamina D2/metabolismo , Saciação/fisiologia , Fatores de TempoRESUMO
AIMS: Studies have demonstrated that early weaning can promote metabolic syndrome during adulthood and that obesity increases oxidative stress. Thus, we aimed to evaluate redox status in a pharmacological early weaning rodent model programmed for metabolic syndrome at adulthood. MAIN METHODS: Lactating dams were randomly assigned into 2 groups: the early weaning group (BRO), which was treated intraperitoneally with bromocriptine (1 mg/day) to inhibit prolactin secretion for the last 3 days of lactation, and the control group (C), which received the BRO diluent for the same time period. The offspring were killed at 90 (PN90) and 180 (PN180) days after birth. KEY FINDINGS: Early weaning induced greater visceral adiposity and dyslipidemia. At PN90, the BRO offspring showed glucose intolerance with normoinsulinemia and increased plasma and liver superoxide dismutase, and liver glutathione peroxidase activities, which reduced the liver malondialdehyde but not the increased plasma malondialdehyde levels. However, the BRO offspring showed insulin resistance at PN180 and increased plasma glutathione peroxidase, liver superoxide dismutase, and catalase activities. These changes reduced the plasma and liver malondialdehyde levels, which aided in hepatocyte architecture preservation. Additionally, we observed that sirtuin 1 was overexpressed in the BRO group at PN90, but the increased expression was not maintained through PN180, which suggests unfavorable metabolic conditions in the older offspring. SIGNIFICANCE: Despite the observed obesity and glucose homeostasis dysfunction, our data suggest that the early weaning programming induced by bromocriptine can improve the offspring's redox status and may prevent liver damage during adulthood.
Assuntos
Bromocriptina/farmacologia , Glucose/metabolismo , Obesidade/etiologia , Estresse Oxidativo/efeitos dos fármacos , Desmame , Adiposidade , Animais , Dislipidemias/etiologia , Feminino , Injeções Intraperitoneais , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/prevenção & controle , Masculino , Oxirredução , Prolactina/metabolismo , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Se presenta el caso clínico de una mujer de 20 años que presenta insuficiencia cardíaca de rápida instalación, asociada a síntomas de infección respiratoria viral, 9 semanas post parto. Previamente había presentado hipertensión en el puerperio precoz. Se demostró una severa disfunción sistólica (FE 12 por ciento). Se recuperó con medidas convencionales del tratamiento de Insuficiencia cardíaca y finalmente recibió bromocriptina basado en reportes favorables de la literatura respecto del uso de este fármaco. En el control al año de su alta, se mantenía asintomática pero persistía severa disminución de la FE (18 por ciento) y dilatación de cavidades izquierdas. Se revisa la información acerca de esta patología.
A 20 year old woman developed rapidly progressive heart failure 9 weeks after delivery. For a few weeks she was hypertensive. A severe systolic dysfunction with an EF of 12 percent was shown on echocardiography. She recovered on conventional treatment of congestive heart failure. Eventually she received bromocriptine con the basis of favorable literature reports. A follow up control at one year showed an asymptomatic patient, however severe systolic dysfunction with EF 18 percent was still present.
Assuntos
Humanos , Adulto , Feminino , Adulto Jovem , Bromocriptina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca , Complicações Cardiovasculares na Gravidez , Período Pós-PartoRESUMO
El Síndrome Neuroléptico Maligno (SNM) descrito por primera vez hace casi cinco décadas, es una peculiar y peligrosa complicación del tratamiento con fármacos antipsicóticos, que se caracteriza por fiebre, rigidez muscular severa y cambios en el estado autonómico y mental. Es una complicación imprevisible y rara, potencialmente mortal de medicamentos antipsicóticos, presuntamente relacionada con el bloqueo dopaminérgico. Prácticamente todos los neurolépticos son capaces de inducir el síndrome, incluyendo laclozapina, risperidona y olanzapina. Estimaciones retrospectivas de incidencia varían desde 0.02 hasta 3.23% de los pacientes psiquiátricos que reciben neurolépticos, tasas de mortalidad reportados están en el rango de 10-20%; es más común en pacientes con esquizofrenia o trastornos afectivos.Se presenta el caso clínico de una paciente que desarrollo Síndrome Neuroléptico Maligno: femenina de18 años de edad, con diagnóstico de esquizofrenia hebefrenica, tratada con antipsicóticos por 39 días, inicia con sialorrea, rigidez generalizada y sudoración profusa. Al examen físico se encontró: ritmo cardiaco de 140 latidos por minuto, presión arterial de 130/90 mmHg, frecuencia respiratoria de 26 por minuto, temperatura de 38.6°C. Los estudios de laboratorio relevantes fueron: recuento de leucocitos de 11,170 células ml y nivel de creatina quinasa de 2,563 UI. Se realizó el diagnóstico de SNM y se inició tratamiento con bromocriptina 5mg vía oral cada 6 horas durante 10 días; la paciente respondió de forma favorable. A continuación se revisa la incidencia, las características clínicas, los factores de riesgo, la mortalidad y el tratamiento del SNM...