Anesthetic Profile of a Non-lipid Propofol Nanoemulsion

SummaryBackground and objectivesThe clinical use of a lipid propofol formulation causes pain during injection, allergic reactions, and bacterial growth. Propofol has been reformulated in different non-lipid presentations to reduce the incidence of adverse effects, but those changes can modify its pharmacokinetics and pharmacodynamics. In the present study, we investigate the pharmacology and toxicology of lipid propofol (CLP) and the non-lipid nanoemulsion (NLP).MethodsConventional lipid formulation of propofol and NLP were infused in the jugular veins of rats and blood pressure (BP), heart rate (HR), and respiratory rate (RR) were measured. Both formulations (1%) were infused (40 μL.min-1) over 1 hour. Hypnotic and anesthetic doses as well as recoveries were determined. The pain induced by the CLP and NLP vehicles was compared by counting the number of abdominal contortions (“writhing test”) after the intraperitoneal (i.p.) injection in mice. Acetic acid (0.6%) was used as positive control.ResultsHypnotic and anesthetic doses of 1% CLP (6.0 ± 1.3 and 17.8 ± 2.6 mg.kg-1, respectively) and 1% NLP (5.4 ± 1.0 and 16.0 ± 1.4 mg.kg-1, respectively) were not significantly different. Recovery from hypnosis and anesthesia was faster with NLP than with CLP. Changes in HR, BP, and RR caused by NLP were not significantly different from those caused by CLP. Acetic acid and the vehicle of CLP caused 46.0 ± 2.0 and 12.5 ± 0.6 abdominal contortions 20 min after i.p. injection, respectively. The absence of abdominal contractions was observed with the vehicle of NLP. Abdominal inflammatory response was not observed after the i.p. injection of both propofol vehicles.ConclusionsNon-lipid formulation of propofol can be a better alternative to CPL for intravenous anesthesia with fewer adverse effects

Derivados 1-metil-3,6,7,8 - tetrahidropirazolo [3,4,-b] pirrolo [4,3-d] piridina-6,8-diona, processo de preparação, composições farmacêuticas contendo os mesmos e usos relacionados

Em 27/07/2015:Anuidade de pedido de patente de invenção no prazo extraordinárioDepositadaA presente invenção se relaciona a novos derivados do núcleo 1-metil-3, 6, 7, 8-tetrahidropirazolo[3,4-b]pirrolo[4,3-d]piridin-6,8-diona, preferencialmente heterocíclicos, que atuam como hipnóticos e analgésicos com ação no sistema nervoso central, sendo, portanto, úteis no tratamento da ansiedade e hiperalgesia central, incluindo: o alívio da ansiedade; alívio da hiperalgesia central em mamíferos, preferencialmente humanos. São também descritas composições farmacêuticas contendo os referidos compostos e processo para sua preparação

Relaxantes musculares seletivos e composições farmacêuticas

Em 28/10/2013: Anuidade de pedido de patente de invenção no prazo ordinário.DepositadaA presente invenção se refere a substâncias capazes de promover relaxamento muscular seletivo, a composições farmacêuticas contendo tais compostos e seu uso no tratamento de doenças associadas ao tecido muscular, sendo que tais compostos obedecem a uma fórmula geral

Composto sulfonilidrazônico, processo de obtenção do composto sulfonilidrazônico e composições farmacêuticas

DepositadaDescreve um composto de certa fórmula, seu processo de obtenção e uso na fabricação de uma composição farmacêutica para estimular a produção de insulina. Especificamente, a presente invenção compreende uma série de sulfonilidrazonas que podem ser utilizadas na fabricação de uma composição farmacêutica para tratar diabetes. A presente invenção se situa nos campos da farmácia e da química

Efeitos hemodinâmicos do atracúrio e do cisatracúrio e o uso de difenidramina e cimetidina

JUSTIFICATIVA E OBJETIVOS: Haja visto que atracúrio pode causar hipotensão arterial no homem, investigaram-se os efeitos hemodinâmicos promovidos pelo atracúrio e pelo cisatracúrio e a proteção hemodinâmica conferida pela difenidramina e cimetidina em ratos. MÉTODO: 1) Ratos Wistar anestesiados com pentobarbital sódico e preparados de acordo com Brown e col. para avaliar doses de atracúrio e cisatracúrio para redução de T4/T1 da sequência de quatro estímulos maior ou igual a 95%. 2) Avaliação das alterações hemodinâmicas de atracúrio e cisatracúrio por injeção venosa, medindo-se a pressão arterial sistêmica da artéria carótida e eletrocardiograma de ratos. 3) Observação de proteção hemodinâmica pelo tratamento prévio com difenidramina (2 mg.kg-1) e/ou cimetidina (4 mg.kg-1) por injeção venosa. Análise estatística: teste t de Student, ANOVA. RESULTADOS: O atracúrio e o cisatracúrio não modificaram a pressão arterial média (PAM) nas doses de 1 mg.kg-1 e 0,25 mg.kg-1, respectivamente. Doses de 4 mg.kg-1 promoveram diminuição da PAM de 62,8 ± 4,5% do controle para o atracúrio, e de 82,5 ± 2,3% do controle para o cisatracúrio. Com difenidramina e cimetidina, a pressão sistólica diminuiu 95,4 ± 2,5% do controle. Com cimetidina, pressão diastólica diminuiu 82,7 ± 8,4% do controle. O efeito conjunto sobre as pressões sistólica e diastólica refletiu-se nos valores observados da PAM. CONCLUSÕES: A difenidramina e a cimetidina, isoladamente, não impediram a diminuição da pressão arterial média induzida pelo atracúrio. No entanto, associação destes dois fármacos foi eficaz na prevenção dos efeitos hemodinâmicos induzidos pelo atracúrio. O cisatracúrio nas doses do experimento não promoveu diminuição da pressão arterial que justificasse as medidas preventivas aplicadas nos grupos onde se utilizou o atracúrio

Vasodilator Activity of the Essential Oil from Aerial Parts of Pectis brevipedunculata and Its Main Constituent Citral in Rat Aorta

The essential oil of Pectis brevipedunculata (EOPB), a Brazilian ornamental aromatic grass, is characterized by its high content of citral (81.9%: neral 32.7% and geranial 49.2%), limonene (4.7%) and α-pinene (3.4%). Vasodilation induced by EOPB and isolated citral was investigated in pre-contracted vascular smooth muscle, using thoracic aorta from Wistar Kyoto (WKY) rats which was prepared for isometric tension recording. EOPB promoted intense relaxation of endothelium-intact and denuded aortic rings with the concentration to induce 50% of the maximal relaxation (IC50) of 0.044% ± 0.006% and 0.093% ± 0.015% (p < 0.05), respectively. The IC50 values for citral in endothelium-intact and denuded rings were 0.024% ± 0.004% and 0.021% ± 0.004%, respectively (p > 0.05). In endothelium-intact aorta, EOPB-induced vasorelaxation was significantly reduced by L-NAME, a nitric oxide synthase inhibitor. The vasodilator activity of citral was increased in the KCl-contracted aorta and citral attenuated the contracture elicited by Ca2+ in depolarized aorta. EOPB and citral elicited vasorelaxation on thoracic aorta by affecting the NO/cyclic GMP pathway and the calcium influx through voltage-dependent L-type Ca2+ channels, respectively

Multigenerational Brazilian family with malignant hyperthermia and a novel mutation in the RYR1 gene

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered in susceptible individuals by the administration of volatile halogenated anesthetics and/or succinylcholine, leading to the development of a hypermetabolic crisis, which is caused by abnormal release of Ca2+ from the sarcoplasmic reticulum, through the Ca2+ release channel ryanodine receptor 1 (RyR1). Mutations in the RYR1 gene are associated with MH in the majority of susceptible families. Genetic screening of a 5-generation Brazilian family with a history of MH-related deaths and a previous MH diagnosis by the caffeine halothane contracture test (CHCT) in some individuals was performed using restriction and sequencing analysis. A novel missense mutation, Gly4935Ser, was found in an important functional and conserved locus of this gene, the transmembrane region of RyR1. In this family, 2 MH-susceptible individuals previously diagnosed with CHCT carry this novel mutation and another 24 not previously diagnosed members also carry it. However, this same mutation was not found in another MH-susceptible individual whose CHCT was positive to the test with caffeine but not to the test with halothane. None of the 5 MH normal individuals of the family, previously diagnosed by CHCT, carry this mutation, nor do 100 controls from control Brazilian and USA populations. The Gly4932Ser variant is a candidate mutation for MH, based on its co-segregation with disease phenotype, absence among controls and its location within the protein