ABSTRACT
La anafilaxia es una reacción de hipersensibilidad sistemica y grave, de inicio rápido y potencialmente mortal. En los recién nacidos prematuros, el sistema inmunitario aún no ha madurado y, por lo tanto, tienen menos probabilidades de presentar anafilaxia. La administración de amikacina, que contenía metabisulfito de sodio, a un prematuro de 3 días de vida le indujo anafilaxia casi mortal. Debido a que se sospechaba un caso de anafilaxia, se inició la administración de amikacina en el bebé. Una vez comenzado el tratamiento, se observó una mejoría clínica. Al tercer día de tratamiento con amikacina, el recién nacido tuvo, repentinamente, taquipnea, taquicardia, angioedema y cianosis. Se le diagnosticó anafilaxia y se inició el tratamiento. Una hora después de la mejoría clínica, se produjo una reacción tardía. Inmediatamente, se intubó al recién nacido. La anafilaxia es una emergencia médica; por lo tanto, los médicos deben realizar una evaluación rápida y atenta para detectar esta reacción potencialmente mortal. Incluso después del tratamiento satisfactorio de la anafilaxia, el paciente debe permanecer bajo observación durante 72 horas dada la posibilidad de una reacción bifásica.
Anaphylaxis is a serious systemic hypersensitivity reaction that is rapid in onset and can cause death. Premature newborns, whose immunological system is immature, are less likely to develop anaphylaxis. Administration of amikacin, containing sodium metabisulfite, to a 3-day-old premature newborn, induced a near fatal anaphylaxis. After suspicion of sepsis, the baby was started on amikacin. Clinical improvement was observed after initiation of treatment. On the third day of treatment with amikacin, the newborn suddenly developed tachypnea, tachycardia, angioedema and cyanosis. Anaphylaxis was diagnosed and treated. Latent reaction occurred after one hour of clinical improvement. The baby was intubated immediately. Anaphylaxis is a medical emergency; therefore the clinicians should have a rapid and careful assessment about this potentially fatal reaction. Even after successful treatment of anaphylaxis, the patient should be under observation for 72 hours because of the possibility of a biphasic reaction.
Subject(s)
Humans , Male , Infant, Newborn , Sulfites/adverse effects , Amikacin/adverse effects , Anaphylaxis/etiology , Anti-Bacterial Agents/adverse effects , Infant, PrematureABSTRACT
Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.
Atualmente, antioxidantes são usados como excipientes eficientes, que retardam ou inibem o processo de oxidação de moléculas. Excipientes são frequentemente associados a efeitos adversos. Estudos de estabilidade podem ajudar na busca por possíveis soluções para minimizar ou retardar os processos de degradação. A habilidade de prever as reações de oxidação em diferentes fármacos é importante. O estudo foi conduzido com o objetivo de avaliar o uso racional de hidroxianisol butilado (BHA), hidroxitolueno butilado (BHT), metabissulfito sódico (SMB), galato de propila (PG) e cisteína (CYS) em formulações de comprimidos de sinvastatina e cetoconazol. Eles foram avaliados por parâmetros de estabilidade e pela relação entre a eficiência dos antioxidantes e a estrutura química do fármaco. Os resultados foram comparados com testes de DPPH e simulações em computador. BHT foi mais eficiente com relação a estabilidade da sinvastatina e às concentrações mais eficientes para manutenção de estabilidade foram 0,5 e 0,1%. Com relação ao cetoconazol, SMB foi mais eficiente em manter o conteúdo e o perfil de dissolução. A avaliação por DPPH mostrou que o maior percentual de redução de absorção foi observado para PG, enquanto que SMB mostrou ser mais eficiente e consumir menos DPPH. A mesma tendência foi observada com menos eficiência em todos os outros antioxidantes lipofílicos como o BHT e BHA. Os resultados do estudo de modelagem molecular demonstraram que as propriedades eletrônicas obtidas podem ser correlacionadas com a atividade antioxidante em solução, sendo útil para o desenvolvimento racional de formulações farmacêuticas líquidas, mas não para formulações sólidas orais. Este estudo demonstrou a importância de considerar parâmetros de estabilidade e modelagem molecular para elucidar os fenômenos químicos envolvidos na atividade antioxidante, sendo úteis para o uso racional de antioxidantes no desenvolvimento de formulações farmacêuticas.
Subject(s)
Pharmaceutical Preparations , Administration, Oral , Drug Utilization/classification , Antioxidants/analysis , Propyl Gallate/pharmacokinetics , Butylated Hydroxyanisole/pharmacokinetics , Butylated Hydroxytoluene/pharmacokinetics , Simvastatin/analysis , Cysteine/pharmacokinetics , Excipients/classification , Ketoconazole/analysisABSTRACT
AIM: To study the effects of sodium metabisulfite (SMB), sulfur dioxide (SO_2) and its derivatives in vivo, sodium bisulfite and sulfite, on Na~+ currents. The effects of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) against SMB were also studied in freshly dissociated hippocampal CA1 neurons in rats. METHODS: The whole-cell patch-clamp techniques were used in the experiments. RESULTS: ① SMB increased the voltage-activated Na~+ currents in a concentration-and voltage-dependent manner. The amplitudes of Na~+ currents was increased (22.36?3.28) % and (65.05?5.75)% (n=10) by SMB at 2 ?mol/L and 20 ?mol/L, respectively. ② SMB (10 ?mol/L) did not affect the activation process, but changed the inactivation process significantly. Before and after application of 10 ?mol/L SMB, the half-inactivation voltage was (-82.38)?0.54) mV and (-69.39)?0.41) mV (n=10, P