RESUMO
BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). METHODS: In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10-40 apneas/hour of sleep) and BP within the systolic range of 140-159 mmHg or diastolic range of 90-99 mmHg. RESULTS: The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24-h, and nighttime ABP, but the two groups had no significant difference. CONCLUSION: Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01896661.
Assuntos
Amilorida , Anlodipino , Anti-Hipertensivos , Monitorização Ambulatorial da Pressão Arterial , Clortalidona , Hipertensão , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Método Duplo-Cego , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Clortalidona/uso terapêutico , Anlodipino/uso terapêutico , Apneia Obstrutiva do Sono/tratamento farmacológico , Apneia Obstrutiva do Sono/complicações , Amilorida/uso terapêutico , Diuréticos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Polissonografia/efeitos dos fármacos , IdosoRESUMO
Advancing with our project about the development of new antiparasitic agents, we have enzymatically synthesized a series of amides derived from amlodipine, a calcium channel blocker used as an antihypertensive drug. Through lipase-catalyzed acylation with different carboxylic acids, nineteen amlodipine derivatives were obtained, eighteen of which were new compounds. To optimize the reaction conditions, the influence of several reaction parameters was analyzed, finding different requisites for aliphatic carboxylic acids and phenylacetic acids. All synthesized compounds were evaluated as antiproliferative agents against Trypanosoma cruzi, the etiological agent of American trypanosomiasis (Chagas' disease). Some of them showed significant activity against the amastigote form of T. cruzi, the clinically relevant form of the parasite. Among synthesized compounds, the derivatives of myristic and linolenic acids showed higher efficacy and lower cytotoxicity. These results added to the advantages shown by the enzymatic methodology, such as mild reaction conditions and low environmental impact, making this approach a valuable way to synthesize these amlodipine derivatives with an application as promising antiparasitic agents.
Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Humanos , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Antiparasitários/uso terapêutico , Acilação , Ácidos Carboxílicos , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Doença de Chagas/tratamento farmacológicoRESUMO
Background: Primary hyperlipidemia is a condition that affects some specific breeds. It has been previously describedin Miniature Shnauzer, Beagles, Shetland Shepdog and West Highland White Terrier. There are no reports of primaryhyperlipidemia in Maltese dogs. It is a hereditary disorder of lipoprotein metabolism. The etiology is unknown and maybe related to a genetic problem in lipoprotein lipase or to the absence of apaprotein CII. Clinical signs include spontaneousarterosclerosis, retinal lipemia, cutaneous xanthomas, abdominal pain, lethargy, vomiting and / or diarrhea. Neurologicalmanifestations such as seizures and behavioral changes may also occur. The aim of this report is to describe a case ofreactive seizures due to hyperlipidemia in a dog.Case: A 5-year-old male Maltese dog was admitted with a history of seizures. Hypertension and abdominal distensionwith large amounts of intestinal gases were found in general physical examination. Neurological examination revealedimpaired nasal septum sensory perception, which was slightly bilaterally reduced, and pain on cervical palpation and inthe brachial plexus region. Based on history and clinical examination, it was possible to locate the lesion in the thalamocortical region and to suspect idiopathic epilepsy, reactive seizures, and symptomatic epilepsy due to meningoencephalitisof unknown origin. The diagnosis of primary hyperlipidemia was made by exclusion with the aid of laboratory tests andultrasound. After the establishment of a fat restriction diet, bezafibrate, phenobarbital, and omega-3 supplementation, theanimal improved significantly with the reduction of epileptic seizures.Discussion: The initial clinical suspicion was hyperadrenocorticism as the primary cause of hyperlipidemia. This suspicion was based on the presence of polyphagia, polydipsia, polyuria and abdominal distension, together with laboratory...(AU)
Assuntos
Animais , Masculino , Cães , Epilepsia/veterinária , Hiperlipidemias/veterinária , Doenças do Cão , Fenobarbital/uso terapêutico , Bezafibrato/uso terapêutico , Restrição Calórica/veterinária , Enalapril/uso terapêutico , Anlodipino/uso terapêutico , Ultrassonografia/veterináriaRESUMO
Background: Primary hyperlipidemia is a condition that affects some specific breeds. It has been previously describedin Miniature Shnauzer, Beagles, Shetland Shepdog and West Highland White Terrier. There are no reports of primaryhyperlipidemia in Maltese dogs. It is a hereditary disorder of lipoprotein metabolism. The etiology is unknown and maybe related to a genetic problem in lipoprotein lipase or to the absence of apaprotein CII. Clinical signs include spontaneousarterosclerosis, retinal lipemia, cutaneous xanthomas, abdominal pain, lethargy, vomiting and / or diarrhea. Neurologicalmanifestations such as seizures and behavioral changes may also occur. The aim of this report is to describe a case ofreactive seizures due to hyperlipidemia in a dog.Case: A 5-year-old male Maltese dog was admitted with a history of seizures. Hypertension and abdominal distensionwith large amounts of intestinal gases were found in general physical examination. Neurological examination revealedimpaired nasal septum sensory perception, which was slightly bilaterally reduced, and pain on cervical palpation and inthe brachial plexus region. Based on history and clinical examination, it was possible to locate the lesion in the thalamocortical region and to suspect idiopathic epilepsy, reactive seizures, and symptomatic epilepsy due to meningoencephalitisof unknown origin. The diagnosis of primary hyperlipidemia was made by exclusion with the aid of laboratory tests andultrasound. After the establishment of a fat restriction diet, bezafibrate, phenobarbital, and omega-3 supplementation, theanimal improved significantly with the reduction of epileptic seizures.Discussion: The initial clinical suspicion was hyperadrenocorticism as the primary cause of hyperlipidemia. This suspicion was based on the presence of polyphagia, polydipsia, polyuria and abdominal distension, together with laboratory...
Assuntos
Masculino , Animais , Cães , Doenças do Cão , Epilepsia/veterinária , Hiperlipidemias/veterinária , Anlodipino/uso terapêutico , Bezafibrato/uso terapêutico , Enalapril/uso terapêutico , Fenobarbital/uso terapêutico , Restrição Calórica/veterinária , Ultrassonografia/veterináriaRESUMO
Mining existing agents that enhance the therapeutic potential of ergosterol biosynthesis inhibitors (EBI) is a promising approach to improve Chagas disease chemotherapy. In this study, we evaluated the effect of ravuconazole, an EBI, combined with amlodipine, a calcium channel blocker, upon Trypanosoma cruzi experimental infection. In vitro assays confirmed the trypanocidal activity of both compounds in monotherapy and demonstrated an additive effect (sum of the fractional inhibitory concentration [ΣFIC] > 0.5) of the combined treatment without additional toxicity to host cells. In vivo experiments, using a murine model of the T. cruzi Y strain in a short-term protocol, demonstrated that amlodipine, although lacking trypanocidal activity, dramatically increased the antiparasitic activity of underdosing ravuconazole regimens. Additional analysis using long-term treatment (20 days) showed that parasitemia relapse until 60 days after treatment was significatively lower in mice treated with the combination (4 out of 14 mice) than ravuconazole monotherapy (10 out of 14 mice), even in the presence of immunosuppressant pressure. Furthermore, the combined therapy was well tolerated and protected the mice from mortality. The treatments also impacted on the cellular and humoral immune response of infected animals, inducing a reduction of serum cytokine levels in all ravuconazole-treated mice. Our findings demonstrate that amlodipine is efficacious in enhancing the antiparasitic activity of ravuconazole in an experimental model of T. cruzi infection and indicates a potential strategy to be explored in Chagas disease treatment.
Assuntos
Doença de Chagas , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Animais , Doença de Chagas/tratamento farmacológico , Camundongos , Nitroimidazóis/uso terapêutico , Parasitemia/tratamento farmacológico , Tiazóis , Triazóis , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêuticoRESUMO
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 22 artigos e 10 protocolos.
Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Progressão da Doença , Betacoronavirus/efeitos dos fármacos , Imunoglobulinas/uso terapêutico , Metilprednisolona/uso terapêutico , Nifedipino/uso terapêutico , Cloroquina/uso terapêutico , Anlodipino/uso terapêutico , Corticosteroides/uso terapêutico , Azitromicina/uso terapêutico , Ritonavir/uso terapêutico , Fluoroquinolonas/uso terapêutico , Combinação de Medicamentos , Lopinavir/uso terapêutico , Interferon alfa-2/uso terapêutico , Amoxicilina/uso terapêutico , Hidroxicloroquina/uso terapêuticoRESUMO
Introducción: El agrandamiento gingival es el aumento exagerado y desfigurante del volumen de la encía. Su aparición se asocia a fármacos, entre los que se encuentran los inmunosupresores y los bloqueadores de los canales de calcio como la ciclosporina A y amlodipino. Objetivo: Describir un caso clínico de agrandamiento gingival asociado a ciclosporina A y amlodipino, con periodontitis crónica subyacente, su tratamiento y prevención de recidiva. Presentación del caso: Paciente masculino, de 50 años de edad, antecedentes de hipertensión arterial, asma bronquial y hepatitis C, además de presentar insuficiencia renal crónica para la cual se le realizó un trasplante renal. Recibe tratamiento con ciclosporina A y amlodipino. Al examen clínico se observaron aumento de volumen generalizado en la encía, que cubría completamente la corona de los dientes, bolsas periodontales de 5 a 8 mm, sangramiento gingival y movilidad dentaria. Principales comentarios: El proceso diagnóstico permitió comprobar que además del agrandamiento gingival generalizado existía una periodontitis crónica generalizada. Conclusiones: La ingestión de un inmunosupresor como la ciclosporina A con el uso de un bloqueador de los canales de calcio, el amlodipino, y la influencia de factores de connotación local, parecen ser los responsables de la aparición combinada del agrandamiento gingival generalizado y la periodontitis crónica concomitante. La fase higiénica contribuyó considerablemente a mejorar el estado periodontal, cuya solución definitiva se alcanzó con la cirugía periodontal convencional. Se corrobora la importancia del examen periodontal en pacientes candidatos a trasplantes de órganos(AU)
Introduction: Gingival enlargement is an exaggerated and disfiguring increase in gum volume, associating its appearance with drugs like immunosuppressants and calcium channel's blockers such as cyclosporine A and Amlodipine. Objective: To describe a clinical case of gingival enlargement associated to cyclosporine A and amlodipine, presenting chronic underlying periodontitis, its treatment and prevention in case of recurrence. Case Presentation: Male patient, 50 years old with a history of arterial hypertension, bronchial asthma and hepatitis C, and presenting chronic renal failure leading renal transplant. The patient was treated with cyclosporine A and amlodipine. In the clinical examination was observed an increased volume in the gum, which completely covered the crown of the teeth, also periodontal bags of 5 to 8 mm, gingival bleeding and dental mobility. Main Comments: The diagnostic process allowed to verify that in addition to the generalized gingival enlargement there was a generalized chronic periodontitis. Conclusions: The ingestion of an immunosuppressant such as Cyclosporin A with the use of a calcium channel's blocker, amlodipine, and the influence of local connotation factors seem to be responsible for the combined appearance of generalized gingival enlargement and concomitant chronic periodontitis. The hygienic phase contributed considerably to improve the periodontal state, whose definitive solution was achieved with conventional periodontal surgery. The importance of periodontal examination in patients who are candidates for organ transplants is corroborated(AU)
Assuntos
Humanos , Masculino , Periodontite/diagnóstico , Ciclosporina/uso terapêutico , Anlodipino/uso terapêuticoRESUMO
Arterial hypertension is a highly manageable disorder due to a variety of drugs available for its treatment. Since the late 1990s, angiotensin II receptor blockers have been widely prescribed, achieving appropriate control in patients' blood pressure. Few cases of serious adverse effects have been reported to date. Here, we present a case of acute hepatocellular injury secondary to candesartan administration. Further studies should be performed in patients who present with this adverse effect, in order to prevent more serious outcomes.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Benzimidazóis/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Hipertensão/tratamento farmacológico , Tetrazóis/efeitos adversos , Adulto , Anlodipino/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Benzimidazóis/administração & dosagem , Compostos de Bifenilo , Pressão Sanguínea/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Relação Dose-Resposta a Droga , Humanos , Hipertensão/sangue , Testes de Função Hepática , Masculino , Tetrazóis/administração & dosagemRESUMO
Abstract Introduction: Antibiotics are frequently used for the treatment of rhinosinusitis. Concerns have been raised regarding the adverse effects of antibiotics and growing resistance. The lack of development of new antibiotic compounds has increased the necessity for exploration of non-antibiotic compounds that have antibacterial activity. Amlodipine is a non-antibiotic compound with anti-inflammatory activity. Objective: In this study we aimed to investigate the potential role of amlodipine in the treatment of rhinosinusitis by evaluating its effects on tissue oxidative status, mucosal histology and inflammation. Methods: Fifteen adult albino guinea pigs were inoculated with Staphylococcus aureus and treated with saline, cefazolin sodium, or amlodipine for 7 days. The control group was composed by five healthy guinea pigs. Animals were sacrificed after the treatment. Histopathological changes were identified using Hematoxylin-Eosin staining. Inflammation was assessed by Polymorphonuclear Leukocyte infiltration density. Tissue levels of antioxidants (superoxide dismutase, glutathione) and an oxidative product (malondialdehyde) were determined. Results: In rhinosinusitis induced animals, amlodipine reduced loss of cilia, lamina propria edema and collagen deposition compared to placebo (saline) and although not superior to cefazolin, amlodipine decreased polymorphonuclear leukocyte infiltration. The superoxide dismutase activity and glutathione levels were reduced, whereas the malondialdehyde levels were increased significantly in all three-treatment groups compared to the control group. Amlodipine treated group showed significantly increased superoxide dismutase and glutathione levels and decreased malondialdehyde levels compared to all treatment groups. Conclusion: The non-antibiotic compound amlodipine may have a role in acute rhinosinusitis treatment through tissue protective, antioxidant and anti-inflammatory mechanisms.
Resumo Introdução: Antibióticos são frequentemente usados para o tratamento de rinossinusite. Questões têm sido levantadas sobre os efeitos adversos dos antibióticos e a resistência crescente. A falta de desenvolvimento de novos compostos antibióticos aumentou a necessidade da exploração de compostos não antibióticos que têm atividade antibacteriana. A amlodipina é um composto não antibiótico com atividade anti-inflamatória. Objetivo: O objetivo desse estudo foi investigar o papel potencial da amlodipina no tratamento da rinossinusite, avaliando seus efeitos sobre o estado oxidativo do tecido, histologia da mucosa e inflamação. Método: Quinze cobaias albinas adultas foram inoculadas com Staphylococcus aureus e tratadas com solução salina, cefazolina ou amlodipina durante sete dias. O grupo controle incluiu cinco cobaias saudáveis. Os animais foram sacrificados após o tratamento. Alterações histopatológicas foram identificadas com a coloração de hematoxilina-eosina. A inflamação foi avaliada pela densidade de infiltração de leucócitos polimorfonucleares. Foram determinados os níveis teciduais de antioxidantes (superóxido dismutase, glutationa) e um produto de oxidação (malondialdeído). Resultados: Em animais com rinossinusite induzida, a amlodipina reduziu a perda dos cílios, edema da lâmina própria e deposição de colágeno em comparação com o grupo placebo (solução salina) e embora não seja superior à cefazolina, a amlodipina diminuiu a infiltração de leucócitos polimorfonucleares. Os níveis de atividade da superóxido dismutase e glutationa foram reduzidos, enquanto os níveis de malondialdeído aumentaram significativamente nos três grupos de tratamento em comparação ao grupo controle. O grupo tratado com amlodipina apresentou aumento significante dos níveis de superóxido dismutase e glutationa e diminuição dos níveis de malondialdeído em comparação com todos os grupos de tratamento. Conclusão: O composto não antibiótico amlodipina pode ter um papel no tratamento da rinossinusite aguda através de mecanismos protetores de tecido, antioxidantes e anti-inflamatórios.
Assuntos
Animais , Sinusite/tratamento farmacológico , Rinite/tratamento farmacológico , Anlodipino/farmacologia , Anti-Inflamatórios/farmacologia , Valores de Referência , Staphylococcus aureus , Superóxido Dismutase/análise , Ensaio de Imunoadsorção Enzimática , Distribuição Aleatória , Cefazolina/uso terapêutico , Cefazolina/farmacologia , Reprodutibilidade dos Testes , Resultado do Tratamento , Anlodipino/uso terapêutico , Glutationa/análise , Glutationa/efeitos dos fármacos , Cobaias , Malondialdeído/análise , Anti-Inflamatórios/uso terapêutico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologiaRESUMO
BACKGROUND: Emerging evidence has shown a significant deficit in the control of hypertension (blood pressure <140/90 mmHg) among Hispanics or Latinos in about 65%. This study aims to determine the efficacy of the combination in fixed doses of olmesartan and amlodipine (20/5, 40/5, and 40/10 mg) in hypertensive patients treated in daily clinical practice by Colombian doctors. METHODS: This was an observational, retrospective, open-label, multi-center, non-comparative study. The primary outcome was a change in systolic and diastolic blood pressure from the baseline to week 12; the secondary outcome was the proportion of patients achieving a target blood pressure of <140/90 mmHg. Safety and tolerability were also evaluated. For analysis, a student t test was used for paired data, McNemar test, and ANCOVA. RESULTS: A total of 428 patients were enrolled from 16 centers in Colombia. At 12 weeks, patients' systolic blood pressure decreased in response to all three doses: by 27.75 ± 20.73 mmHg in 20/5 mg, 31.13 ± 22.23 mmHg in 40/5 mg, and 46.96 ± 20.15 mmHg in 40/10 mg (all p < 0.001). Furthermore, the diastolic blood pressure decreased by 14.19 ± 12.89 mmHg in 20/5 mg, 16.25 ± 10.87 mmHg in 40/5 mg, and 24.83 ± 10.41 mmHg in 40/10 mg (all p < 0.001). The percentage of patients achieving target blood pressure was 71.31% in 20/5 mg, 70.16% in 40/5 mg, and 63.33% in 40/10 mg. CONCLUSIONS: This study demonstrates the efficacy of the combination in fixed doses of olmesartan and amlodipine in the treatment of Colombian hypertensive patients.