RESUMEN
Monotherapy is the recommended initial treatment for early Parkinson's disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson's disease.
Asunto(s)
Antiparkinsonianos , Agonistas de Dopamina , Levodopa , Enfermedad de Parkinson , Humanos , Levodopa/administración & dosificación , Levodopa/uso terapéutico , Levodopa/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológico , Antiparkinsonianos/uso terapéutico , Antiparkinsonianos/farmacología , Antiparkinsonianos/administración & dosificación , Agonistas de Dopamina/uso terapéutico , Agonistas de Dopamina/administración & dosificación , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Cabergoline is the treatment of choice for prolactinomas. However, 10-20% of prolactinomas are resistant to cabergoline. Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor-cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro. The aim of this study is to test the effects of metformin addition to cabergoline treatment on prolactin levels in patients with resistant prolactinomas. SUBJECTS AND METHODS: This is a prospective study performed in an outpatient clinic in a reference center. Ten adult patients (26-61 years) with prolactinomas (7 M), persistent hyperprolactinemia (38-386 ng/mL) under cabergoline treatment (2-7 mg/week) for at least 6 months (6-108 months), features of metabolic syndrome, and not taking metformin were included. Metformin (1.0-2.5 g v.o./day) was given according to patients' tolerance. Cabergoline doses were kept unchanged. Serum prolactin levels were measured before and after short- (30-60 days) and long-term (120-180 days) metformin treatment. RESULTS: Mean prolactin levels did not show any significant changes (148 ± 39 vs. 138 ± 42 vs. 133 ± 39 ng/mL, before, at 30-60 days, and at 120-180 days, respectively, p = 0.196) after metformin (mean dose: 1.25 g/day; range: 1.0-2.0 g/day). No patient reached a normal prolactin level during metformin treatment. Two patients were considered partial responders for exhibiting prolactin decreases ≥50% at a single time point during metformin. CONCLUSION: Metformin addition to ongoing high-dose cabergoline treatment in patients with cabergoline-resistant prolactinomas failed to show a consistent inhibitory effect in serum prolactin levels.
Asunto(s)
Cabergolina/farmacología , Agonistas de Dopamina/farmacología , Hiperprolactinemia/tratamiento farmacológico , Hipoglucemiantes/farmacología , Síndrome Metabólico/tratamiento farmacológico , Metformina/farmacología , Prolactina/efectos de los fármacos , Prolactinoma/tratamiento farmacológico , Adulto , Cabergolina/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Resistencia a Medicamentos/fisiología , Quimioterapia Combinada , Femenino , Humanos , Hiperprolactinemia/sangre , Hipoglucemiantes/administración & dosificación , Síndrome Metabólico/sangre , Metformina/administración & dosificación , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Proyectos Piloto , Prolactina/sangre , Prolactinoma/sangre , Estudios ProspectivosRESUMEN
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.
Asunto(s)
Agonistas de Dopamina/uso terapéutico , Hiperprolactinemia/tratamiento farmacológico , Hiperprolactinemia/epidemiología , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/efectos adversos , Femenino , Galactorrea/epidemiología , Humanos , Trastornos de la Menstruación/epidemiología , Metaanálisis en Red , Prolactina/sangre , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The development of sensitization is one of the hallmarks of addictive drugs. Consistent with this relationship many studies have demonstrated that the highly addictive opioid agonist morphine induces sensitization effects. In this study, we administered morphine (10 mg/kg) (MOR) to induce sensitization. In that sensitization is considered to involve associative processes and that dopamine activity is an important contributor to learning and memory processes, we administered a dopamine inhibitory treatment using apomorphine (0.05 mg/kg) (APO) during memory consolidation following a morphine sensitization treatment protocol. Seemingly, a decrease in dopamine activity during consolidation would impair the salience of the association of the morphine response with the contextual cues during consolidation and interfere with the development of morphine sensitization. In two separate experiments, MOR or vehicle (VEH) were administered pre-trial and either VEH or APO were administered post-trial over 5 and 10 days of treatment, respectively. In both the 5 and 10 drug treatment sessions post-trial experiments, MOR groups given VEH immediately post-trial exhibited strong sensitization effects. These sensitization effects were substantially attenuated in the MOR groups given APO immediately post-trial but not in the MOR groups given APO after a 15 min. post-trial delay. In subsequent conditioning and sensitization challenge tests, the MOR groups that had been given APO immediately post-trial exhibited diminished sensitization and conditioned responses relative to MOR groups that had received VEH or APO delayed post-trial. This MOR-APO interaction effect was unique in that it occurred post-trial so that it was only expressed in a pre-trial test in which only MOR was administered. Seemingly, the inhibitory dopamine effect of APO was incorporated into memory during the post-trial consolidation process suggesting that drug/drug interactions can occur during consolidation.
Asunto(s)
Apomorfina/farmacología , Conducta Animal/efectos de los fármacos , Sensibilización del Sistema Nervioso Central/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Agonistas de Dopamina/farmacología , Consolidación de la Memoria/efectos de los fármacos , Morfina/farmacología , Narcóticos/farmacología , Animales , Apomorfina/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Masculino , Morfina/administración & dosificación , Narcóticos/administración & dosificación , Ratas , Ratas WistarRESUMEN
ABSTRACT Advances in combination medical treatment have offer new perspectives for acromegaly patients with persistent disease activity despite receiving the available medical monotherapies. The outcomes of combination medical treatment may reflect both additive and synergistic effects. This review focuses on combination medical treatment and its current position in acromegaly, based on clinical studies evaluating the efficacy and safety of combined medical treatment(s) and our own experiences with combination therapy. Arch Endocrinol Metab. 2019;63(6):646-52
Asunto(s)
Humanos , Somatostatina/análogos & derivados , Receptores de Somatostatina/administración & dosificación , Receptores de Somatostatina/antagonistas & inhibidores , Agonistas de Dopamina/administración & dosificación , Hormona de Crecimiento Humana/análogos & derivados , Calidad de Vida , Acromegalia/tratamiento farmacológico , Somatostatina/administración & dosificación , Hormona de Crecimiento Humana/administración & dosificación , Quimioterapia CombinadaRESUMEN
OBJECTIVE: To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. SUBJECTS AND METHODS: We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. RESULTS: Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). CONCLUSION: this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7.
Asunto(s)
Acromegalia/tratamiento farmacológico , Cabergolina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Hormona de Crecimiento Humana/análogos & derivados , Somatostatina/análogos & derivados , Adulto , Anciano , Argentina , Cabergolina/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Somatostatina/administración & dosificación , Somatostatina/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
ABSTRACT Objective To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. Subjects and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. Results Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). Conclusion this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Acromegalia/tratamiento farmacológico , Somatostatina/análogos & derivados , Agonistas de Dopamina/uso terapéutico , Hormona de Crecimiento Humana/análogos & derivados , Cabergolina/uso terapéutico , Argentina , Factor I del Crecimiento Similar a la Insulina/análisis , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Estudios de Seguimiento , Resultado del Tratamiento , Agonistas de Dopamina/administración & dosificación , Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/uso terapéutico , Quimioterapia Combinada , Cabergolina/administración & dosificaciónRESUMEN
BACKGROUND: Prolactinomas are tumors of the pituitary gland that usually respond very well to treatment with cabergoline. Resistance to cabergoline is very rare, but when it occurs, it is a difficult problem to resolve if the tumor is inoperable. CASE PRESENTATION: A 62-year-old white man was treated for a giant macroprolactinoma detected during investigation of a subacute subdural hematoma of the left frontal lobe. The patient was treated with cabergoline for 17 years with a dose ranging from 1.0 mg to 3.5 mg per week. We were not able to normalize his prolactin level, which initially was 14,992 ng/ml and ultimately 1754 ng/ml. The tumor significantly shrank during the follow-up period but persisted. The patient had cardiac valvulopathies that did not worsen. He had an ischemic stroke and developed a psychotic condition that was successfully treated by lowering the cabergoline and administering quetiapine and mirtazapine together. This regimen led to a small increase in the patient's prolactin that returned to previous levels and remained as such until the last medical evaluation. The tumor continued to shrink and had a cystic degeneration in the last evaluation. CONCLUSIONS: Combined use of cabergoline with quetiapine and mirtazapine to treat a psychotic crisis may have contributed to shrinking the tumor in our patient because these antipsychotics have action mediated by growth factors that interfere with growth of pituitary tumors.
Asunto(s)
Cabergolina , Mirtazapina/administración & dosificación , Neoplasias Hipofisarias , Prolactina/sangre , Prolactinoma , Trastornos Psicóticos , Fumarato de Quetiapina/administración & dosificación , Accidente Cerebrovascular/complicaciones , Cabergolina/administración & dosificación , Cabergolina/efectos adversos , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/efectos adversos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/tratamiento farmacológico , Neoplasias Hipofisarias/patología , Prolactinoma/sangre , Prolactinoma/complicaciones , Prolactinoma/tratamiento farmacológico , Prolactinoma/patología , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/etiología , Psicotrópicos/administración & dosificación , Accidente Cerebrovascular/diagnóstico , Resultado del Tratamiento , Carga TumoralRESUMEN
Administering clomipramine during the early days of life induced several behavioral and neurochemical alterations in adult male rats, which resemble major depression disorder. The alterations included poor sexual performance, which is considered a reward-seeking behavior regulated by dopaminergic system. Given that estrogen receptors are expressed in different areas of the brain involved in regulating reproductive behavior, motivation and mood. The objective of this study was to analyze the effect of a non-selective dopamine agonist (apomorphine) on sexual incentive motivation in rats exposed to clomipramine (CMI) in the neonatal period. In addition, we evaluated the expression of mRNA ERα and ERß in nucleus accumbens (NAcc) and septum of CMI rats. We found that only a few rats subjected to neonatal CMI treatment performed mounts, intromissions and ejaculations. Also, those rats spent less time exploring the sexual incentive zone and had lower preference scores; this effect was reverted by administering 0.1â¯mg/kg of apomorphine. Finally, the CMI rats presented higher levels of mRNA ERα and ERß, only in septum area. These data indicate that neonatal treatment with CMI altered the expression of mRNA ERα and ERß in the septum, which participates in regulating the motivational component of sexual behavior.
Asunto(s)
Apomorfina/farmacología , Clomipramina/farmacología , Copulación/efectos de los fármacos , Agonistas de Dopamina/farmacología , Receptor alfa de Estrógeno/genética , Receptor beta de Estrógeno/genética , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Tabique del Cerebro/efectos de los fármacos , Animales , Animales Recién Nacidos , Apomorfina/administración & dosificación , Clomipramina/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Femenino , Masculino , Motivación/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , ARN Mensajero/genética , Ratas , Ratas Wistar , Recompensa , Tabique del Cerebro/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Transducción de Señal/efectos de los fármacosRESUMEN
Advances in combination medical treatment have offer new perspectives for acromegaly patients with persistent disease activity despite receiving the available medical monotherapies. The outcomes of combination medical treatment may reflect both additive and synergistic effects. This review focuses on combination medical treatment and its current position in acromegaly, based on clinical studies evaluating the efficacy and safety of combined medical treatment(s) and our own experiences with combination therapy. Arch Endocrinol Metab. 2019;63(6):646-52.
Asunto(s)
Agonistas de Dopamina/administración & dosificación , Hormona de Crecimiento Humana/análogos & derivados , Receptores de Somatostatina/administración & dosificación , Receptores de Somatotropina/antagonistas & inhibidores , Somatostatina/análogos & derivados , Acromegalia/tratamiento farmacológico , Quimioterapia Combinada , Hormona de Crecimiento Humana/administración & dosificación , Humanos , Calidad de Vida , Somatostatina/administración & dosificaciónRESUMEN
ABSTRACT Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic tenet of this task entails tailored therapy, allowing for optimal motor function with the fewest adverse effects. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations, with potential positive effects on nonmotor symptoms, is the only antiparkinsonian agent whose capacity to control motor symptoms is comparable to that of levodopa. Subcutaneous administration, either as an intermittent injection or as continuous infusion, appears to be the most effective and tolerable route. This review summarizes the historical background, structure, mechanism of action, indications, contraindications and side effects, compares apomorphine infusion therapy with other treatments, such as oral therapy, deep brain stimulation and continuous enteral infusion of levodopa/carbidopa gel, and gives practical instructions on how to initiate treatment.
RESUMO A optimização do tratamento da doença de Parkinson idiopática se faz um desafio, pois tem impacto direto na qualidade de vida do paciente. O melhor esquema terapêutico é o que permite o melhor controle motor com os menores efeitos adversos, através de terapêutica individualizada. A apomorfina é o único medicamento antiparkinsoniano que pode ser comparável à potência da levodopa no controle dos sintomas motores. Trata-se de um agonista dopaminérgico empregado na terapia de resgate em pacientes com flutuações motoras e também contribui para a melhora de muitos sintomas não motores. A via subcutânea, com injeções intermitentes, ou com infusão contínua, parece ser a melhor opção pela eficácia e tolerabilidade. Essa revisão resume aspectos históricos, estrutura da molécula, mecanismo de ação, indicação, contra-indicação e efeitos colaterais, compara a terapia de infusão com apomorfina com outros tratamentos, como a terapia oral, estimulação cerebral profunda e infusão enteral contínua de levodopa/carbidopa gel, e fornece instruções práticas de como iniciar o tratamento.
Asunto(s)
Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Apomorfina/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Antiparkinsonianos/administración & dosificación , Carbidopa , Levodopa , Estimulación Encefálica Profunda , Combinación de MedicamentosRESUMEN
This investigation was undertaken to compare the sensitization/conditioned effects induced by apomorphine given pre-trial versus administered immediately post-trial or 15â¯min post-trial. We measured the effects on locomotor activity of 5 daily apomorphine treatments induced by an inhibitory low auto-receptor dose (0.05â¯mg/kg) and a stimulatory high postsynaptic dose (2.0â¯mg/kg). Three sets of four groups were used and each set of four groups was comprised of two vehicle and two apomorphine groups (0.05/2.0 apomorphine). The only difference among the three sets of four groups was when the treatments were administered relative to placement in the novel environment. One set received the treatment pre-test, another set was injected immediately after and the third set injected 15â¯min after 5â¯min test sessions in a novel environment. The repeated pre and immediate post-test apomorphine treatments induced locomotor sensitization over the 5â¯days of treatment. The low dose pre and immediate post-test treatments progressively decreased locomotion and the high dose pre and immediate post-test progressively increased locomotion. Critically, the tests for the immediate post-test groups were non-drug and for both the pre-test and immediate post-test groups, sensitization effects did not occur until the second test day. To control for non-associative apomorphine effects, the same apomorphine treatments were given post-test after a 15â¯minute delay and were found to be equivalent to vehicle. In a subsequent conditioning test, both the pre and immediate post-test low dose apomorphine groups showed conditioned behavioral inhibition and the pre and immediate post-test high dose apomorphine groups showed conditioned behavioral stimulation. We propose that the inhibitory low dose apomorphine decreased the salience/incentive of the novel environment association and thereby decreased the behavioral response and conversely that the high dose excitatory apomorphine treatment increased the salience/incentive value of the novel environment association and potentiated the behavioral response.
Asunto(s)
Apomorfina/farmacología , Condicionamiento Clásico/efectos de los fármacos , Agonistas de Dopamina/farmacología , Animales , Apomorfina/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas WistarRESUMEN
INTRODUCTION: Parkinson's disease (PD) is characterized by motor symptoms such as bradykinesia, rigidity, alteration of postural reflexes and tremor at rest and other non-motor symptoms such as changes in sleep patterns and sexual behavior. However, little is known about paraphilic sexual behaviors. AIM: To summarize the number of cases of zoophilic behaviors in patients with PD between January 2000 and December 2017. DEVELOPMENT: A review was carried out in PubMed, Scopus and Virtual Health Library. Eleven articles were identified by title; six were excluded because they did not present cases related to zoophilic behavior. We found five cases of men, usually with PD of several years of course, taking dopamine agonists and who presented the zoophilic behaviors followed increasing of the dose. The zoophilic behaviors decreased with reducing doses of dopamine agonists and taking atypical antipsychotic such as clozapine or quetiapine. CONCLUSIONS: It is limited the case reports of zoophilic behaviors in patients with PD. The patients reported are men in whom the dose of dopamine agonists was increased. It is important that the clinical follow-up of patients with PD disease includes a careful review of sexual behaviors including those of the paraphilic spectrum.
TITLE: Revision de casos de zoofilia en pacientes con enfermedad de Parkinson.Introduccion. La enfermedad de Parkinson (EP) se caracteriza por sintomas motores, como bradicinesia, rigidez, alteracion de reflejos posturales y temblor en reposo, y otros sintomas no motores, como cambios en el patron de sueño y el comportamiento sexual. Sin embargo, se conoce poco sobre los comportamientos sexuales parafilicos. Objetivo. Resumir el numero de casos de comportamientos zoofilicos en pacientes con EP entre enero de 2000 y diciembre de 2017. Desarrollo. Se realizo una revision en PubMed, Scopus y la Biblioteca Virtual en Salud. Se identificaron por el titulo 11 articulos; se excluyeron seis porque no presentaban casos relacionados con un comportamiento zoofilico. Se encontraron cinco casos de hombres, generalmente con EP de varios años de curso, polimedicados con agonistas dopaminergicos, quienes presentaron los comportamientos parafilicos despues del incremento de la dosis. Los comportamientos zoofilicos cedieron con la reduccion de la dosis de los agonistas dopaminergicos y antipsicoticos atipicos, como clozapina o quetiapina. Conclusiones. Es limitada la notificacion de casos de comportamientos zoofilicos en pacientes con EP. Los pacientes notificados son hombres en quienes se incremento la dosis de agonistas dopaminergicos. Es importante que el seguimiento clinico de los pacientes con EP incluya una revision de los comportamientos sexuales, incluidos los del espectro parafilico.
Asunto(s)
Trastornos Parafílicos/etiología , Enfermedad de Parkinson/psicología , Anciano , Animales , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/efectos adversos , Antiparkinsonianos/uso terapéutico , Antipsicóticos/uso terapéutico , Perros , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/efectos adversos , Agonistas de Dopamina/uso terapéutico , Relación Dosis-Respuesta a Droga , Equidae , Humanos , Masculino , Persona de Mediana Edad , Trastornos Parafílicos/tratamiento farmacológico , Trastornos Parafílicos/epidemiología , Enfermedad de Parkinson/tratamiento farmacológicoAsunto(s)
Cabergolina/administración & dosificación , Manejo de la Enfermedad , Imagen por Resonancia Magnética/métodos , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactinoma/tratamiento farmacológico , Adolescente , Biomarcadores de Tumor/sangre , Agonistas de Dopamina/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/diagnóstico , Prolactina/sangre , Prolactinoma/sangre , Prolactinoma/diagnósticoRESUMEN
CONTEXTO: A acromegalia é uma doença crônica, rara e debilitante, causada pela hipersecreção do hormônio do crescimento (GH), que leva a uma produção excessiva do fator de crescimento similar a insulina I (IGF-I), produzido pelo fígado. Resulta numa doença multissistêmica caracterizada por crescimento somático exagerado, comorbidades múltiplas, desfiguramento físico e redução de expectativa de vida. Os objetivos do tratamento são atenuar os sintomas da hipersecreção de GH, reduzir as comorbidades e o risco de mortalidade, preservando as funções normais da hipófise e melhorando a qualidade de vida destes pacientes, através da normalização dos níveis de GH e IGF-I. A adenoidectomia transesfenoidal permanece o tratamento primário da acromegalia e controla estes níveis em 50 a 75% dos pacientes, dependendo da morfologia do adenoma e da experiência do cirurgião. Para aqueles que permanecem com doença ativa após o tratamento cirúrgico, existe tratamento de segunda linha, com medicamentos e radioterapia. Os medicamentos disponíveis são os agonistas da dopamina, os análogos da somatostatina e o pegvisomanto. O pegvisomanto não é disponibilizado atualmente pelo SUS. TECNOLOGIA: Pegvisomanto (PEG-V). INDICAÇÃO: A acromegalia é uma doença crônica, rara e debilitante, causada pela hipersecreção do hormônio do crescimento (GH), que leva a uma produção excessiva do fator de crescimento similar a insulina I (IGF-I), produzido pelo fígado. Resulta numa doença multissistêmica caracterizada por crescimento somático exagerado, comorbidades múltiplas, desfiguramento físico e redução de expectativa de vida. PERGUNTA: O pegvisomanto é eficaz, seguro e custo-efetivo em pacientes com acromegalia refratária ao tratamento convencional? EVIDÊNCIAS CIENTÍFICAS: Os estudos disponíveis que avaliam o pegvisomanto são, em sua maioria, de baixa qualidade metodológica. Os principais desfechos localizados nos artigos foram os níveis de IGF-I e os desfechos clínicos apareceram nos estudos de forma secundária. O pegvisomanto foi eficaz nos estudos controlados quando se avaliaram como desfechos a redução dos níveis sanguíneos de IGF-I e o controle de alguns dos sinais e sintomas característicos da doença. Mesmo existindo estudos de longo prazo e com grande tamanho da amostra, as limitações metodológicas dos estudos trazem incertezas quanto aos benefícios do pegvisomanto na redução dos sinais e sintomas da doença. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: A estimativa de impacto orçamentário anual resultante da incorporação de pegvisomanto no SUS variou de aproximadamente 23 a 206 milhões, dependendo da dose de pegvisomanto utilizada. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros da CONITEC recomendaram por unanimidade a não incorporação no SUS do pegvisomanto para tratamento da acromegalia refratária ao tratamento convencional. CONSULTA PÚBLICA: O Relatório da CONITEC foi disponibilizado por meio da Consulta Pública nº 67/2017 entre os dias 29/11/2017 e 18/12/2017. Foram recebidas 14 contribuições, sendo 5 técnico-científicas e 9 de experiência ou opinião, das quais 7 foram excluídas por não tratar do tema em questão. Das 7 contribuições consideradas, 6 foram totalmente contra a recomendação da CONITEC e 1 foi totalmente a favor. Nas contribuições que foram contra a recomendação da CONITEC, os participantes argumentaram que o pegvisomanto é eficaz e seguro no tratamento de pacientes com acromegalia refratária ao tratamento convencional e fizeram críticas em relação ao impacto orçamentário, considerando-o superestimado. DELIBERAÇÃO FINAL: Os membros da CONITEC consideraram que não houve nenhuma informação nova sobre o tema que motivasse a mudança nas recomendações de não incorporação do pegvisomanto feitas em suas análises anteriores sobre o medicamento. Dessa forma, deliberaram por recomendar a não incorporação do pegvisomanto para acromegalia refratária ao tratamento estabelecido. DECISÃO: Não incorporar o pegvisomanto para acromegalia refratária ao tratamento estabelecido, no âmbito do Sistema Único de Saúde SUS, dada pela Portaria nº 14, publicada no DOU nº 61, do dia 29 de março de 2018, seção 1, pág. 240.(AU)
Asunto(s)
Humanos , Acromegalia/tratamiento farmacológico , Agonistas de Dopamina/administración & dosificación , Hormona de Crecimiento Humana/análogos & derivados , Somatostatina/administración & dosificación , Acromegalia/cirugía , Brasil , Análisis Costo-Beneficio , Evaluación de la Tecnología Biomédica , Sistema Único de SaludRESUMEN
Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic tenet of this task entails tailored therapy, allowing for optimal motor function with the fewest adverse effects. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations, with potential positive effects on nonmotor symptoms, is the only antiparkinsonian agent whose capacity to control motor symptoms is comparable to that of levodopa. Subcutaneous administration, either as an intermittent injection or as continuous infusion, appears to be the most effective and tolerable route. This review summarizes the historical background, structure, mechanism of action, indications, contraindications and side effects, compares apomorphine infusion therapy with other treatments, such as oral therapy, deep brain stimulation and continuous enteral infusion of levodopa/carbidopa gel, and gives practical instructions on how to initiate treatment.
Asunto(s)
Antiparkinsonianos/administración & dosificación , Apomorfina/administración & dosificación , Agonistas de Dopamina/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Carbidopa , Estimulación Encefálica Profunda , Combinación de Medicamentos , Humanos , LevodopaRESUMEN
INTRODUCTION: Prolactinomas are pituitary tumors with a very low prevalence in childhood and adolescence compared to adulthood. This condition is preferentially treated with dopamine agonists. Resistance to these drugs is rare. CASE REPORT: We describe the case of a boy diagnosed with macroadenoma at the age of 9 and followed up for 21 years. He did not fully respond to treatment with dopamine agonists. His initial prolactin level was 2,400 ng/mL (in males, normal values are <16.0 ng/mL) and never normalized. At the last assessment, his prolactin level was 21.5 ng/mL, recorded after 21 years of treatment with the dopamine agonist cabergoline at a dose as high as 4.5 mg per week. Although the prolactin level remained elevated throughout the follow-up period, the patient never presented a low testosterone level and had normal pubertal development. An MRI of the sella turcica showed that the tumor became progressively cystic and disappeared, but a normal pituitary gland was observed. The pituitary gland retained its normal functions despite a partially empty sella. DISCUSSION: Long-term treatment with high doses of cabergoline may cause cystic degeneration of a prolactinoma considered to be resistant to this treatment, but we cannot rule out the possibility that this outcome represents the natural development of the tumor.
Asunto(s)
Agonistas de Dopamina/administración & dosificación , Resistencia a Antineoplásicos , Ergolinas/administración & dosificación , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactinoma/tratamiento farmacológico , Cabergolina , Niño , Estudios de Seguimiento , Humanos , Masculino , Neoplasias Hipofisarias/sangre , Prolactina/sangre , Prolactinoma/sangreRESUMEN
Hyperprolactinemia is a frequent condition in clinical practice, responsible for 20-25% of secondary amenorrhea cases. We performed an electronic survey among members of the Brazilian Society of Metabolism and Endocrinology (SBEM) and the Brazilian Federation of Association of Gynecology and Obstetrics (FEBRASGO) to assess diagnostic and therapeutic preferences for management of hyperprolactinemia. Electronic addresses of SBEM and FEBRASGO members were obtained from the directories of these societies, and these members were invited, through electronic messages (e-mail), to answer an online questionnaire that included 10 questions about the treatment of micro and macropro-lactinomas, maximum dose of dopamine agonist, how to exclude primary hypothyroidism and macroprolactinemia, hyperprolactinemia and pregnancy. We received responses to the questionnaire by e-mail from 521 SBEM members and 233 FEBRASGO members. The results of this survey demonstrate that there are many area of agreement between SBEM and FEBRASGO members and most of their responses follow the latest Endocrine Society Guideline. Relative to a survey performed several years ago, our findings show that SBEM members have incorporated some of latest recommendations in this field. The principal issues of concern for both groups are duration of dopamine agonist treatment for patients with microprolactinoma and dopamine agonist withdrawal during pregnancy.
La hiperprolactinemia es una alteración frecuente, siendo responsable del 20 al 25% de los casos de amenorrea secundaria. Se realizó una investigación electrónica entre los miembros de la Sociedad Brasileña de Endocrinología y Metabología (SBEM) y de la Federación Brasileña de Ginecología y Obstetricia (FEBRASGO) para evaluar sus preferencias en el diagnóstico y el tratamiento de la hiperprolactinemia. Las direcciones electrónicas de miembros SBEM y de FEBRASGO se obtuvieron a partir de los directorios de esas sociedades. Se invitó a estos miembros a responder un cuestionario que incluía 10 cuestiones sobre el tratamiento de los micro y macroprolactinomas, dosis máxima del agonista dopaminérgico, hiperprolactinemia e hipotiroidismo primario, macroprolactinemia, prolactinoma y embarazo. Hemos recibido respuestas de 521 miembros de la SBEM y de 233 miembros FEBRASGO. Los resultados demuestran que hay bastantes áreas de concordancia entre los miembros de la SBEM y de la FEBRASGO y que la mayoría de las respuestas están de acuerdo con el último consenso de la Endocrine Society. En cuanto a una encuesta similar realizada hace años, nuestros resultados muestran que los socios de SBEM incorporaron algunas de las últimas recomendaciones propuestas en esa área. Los principales aspectos de interés en ambos grupos son la duración del tratamiento con el agonista dopaminérgico y la retirada del mismo durante el embarazo.
Asunto(s)
Humanos , Femenino , Hiperprolactinemia/diagnóstico , Hiperprolactinemia/terapia , Brasil , Prolactinoma/terapia , Agonistas de Dopamina/administración & dosificación , Informe de InvestigaciónRESUMEN
Sexual partner preferences can be strengthened, weakened or even drastically modified via Pavlovian conditioning. For example, conditioned same-sex partner preference develops in sexually-naïve male rats that undergo same-sex cohabitation under the effects of quinpirole (QNP, D2 agonist). Here, we assessed the effect of prior heterosexual experience on the probability to develop a conditioned same-sex preference. Naïve or Sexually-experienced males received either Saline or QNP and cohabited during 24h with a male partner that bore almond scent on the back as conditioned stimulus. This was repeated every 4days for a total of three trials and resulted in four groups (Saline-naïve, Saline-experienced, QNP-naïve, QNP-experienced). Social and sexual preference were assessed four days after the last conditioning trial in a drug-free test in which experimental males chose between the scented familiar male and a novel sexually receptive female. Results showed that Saline-naïve, Saline-experienced and QNP-experienced displayed a clear preference for the female (opposite-sex). By contrast, only QNP-naïve males displayed a same-sex preference. Accordingly, QNP-experienced males were not affected by the conditioning process and continued to prefer females. We discuss the effects of copulation and D2 agonists on the facilitation and/or disruption of conditioned partner preferences.
Asunto(s)
Condicionamiento Psicológico/fisiología , Copulación/fisiología , Agonistas de Dopamina/farmacología , Preferencia en el Apareamiento Animal/fisiología , Quinpirol/farmacología , Receptores de Dopamina D2/agonistas , Animales , Condicionamiento Psicológico/efectos de los fármacos , Copulación/efectos de los fármacos , Agonistas de Dopamina/administración & dosificación , Masculino , Preferencia en el Apareamiento Animal/efectos de los fármacos , Quinpirol/administración & dosificación , Ratas , Ratas WistarRESUMEN
Problema de investigación: Describir los costos y la efectividad del pramipexol comparado con levodopa y cabergolina para el tratamiento de pacientes con síndrome de piernas inquietas.Tipo de evaluación económica\r\nAnálisis de costo-utilidad. Población objetivo: Población adulta con diagnóstico de síndrome de piernas inquietas. Intervención y comparadores: Intervención: Pramipexol, Comparadores: Levodopa y cabergolina. Horizonte temporal: 16 semanas. Perspectiva Sistema: General de Seguridad Social en Salud (SGSSS). Tasa de descuento: No aplica. Estructura del modelo: Modelo de Markov. Fuentes de datos de efectividad y \r\nseguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayos clínicos aleatorizados. Desenlaces y valoración: Años de vida ajustados por calidad (AVAC). Costos incluidos: Costos de medicamentos, Costos de procedimientos. Fuentes de datos de costos:SISMED, Manual tarifario ISS 2001. Resultados del caso base: En el escenario del caso base, pramipexol es una estrategia costo-efectiva con respecto a levodopa. El costo por AVAC ganado con pramipexol es de $7.480 comparado con levodopa. Análisis de sensibilidad: El análisis de sensibilidad determinístico y el diagrama de tornado mostraron que la variable con mayor impacto sobre las estimaciones de costo-efectividad es el precio de levodopa. No se realizó análisis de sensibilidad probabilístico. Conclusiones y discusión: Pramipexol ofrece una mejor relación entre costos y efectividad respecto a levodopa y cabergolina. De acuerdo con el criterio de los expertos clínicos la cabergolina no hace parte de la práctica clínica habitual para este trastorno y la \r\nlevodopa tiene un uso que requiere de supervisión por el efecto que agudiza las manifestaciones clínicas. La principal limitación de este estudio está relacionada con la poca información proveniente de estudios de investigación clínica y evaluaciones económicas.(AU)