Terapia de insulina y glucosa para el tratamiento de intoxicación grave con bloqueantes de canales de calcio en pediatría. Reporte de un caso / Insulin/glucose therapy for the treatment of severe calcium channel blocker poisoning in pediatrics. Case report

La intoxicación por bloqueantes de los canales de calcio es un cuadro poco frecuente en la población pediátrica. Los signos y síntomas pueden progresar de forma rápida y llevar al colapso cardiovascular y muerte. El sostén hemodinámico con inotrópicos y vasopresores no suele ser efectivo. La terapia con insulina y glucosa es un complemento eficaz del tratamiento inicial, que está ampliamente estudiado, y se utiliza en diferentes patologías con compromiso hemodinámico. Se presenta el caso de una paciente pediátrica con antecedente de ingestión de dosis altas de amlodipina con fines suicidas, con descompensación hemodinámica refractaria al tratamiento de soporte inotrópico habitual. A partir del tratamiento con insulina y glucosa, se logró la estabilidad hemodinámica, con evolución favorable de la paciente.

Calcium channel blocker poisoning is a rare condition in the pediatric population. Signs and symptoms can be rapidly progressive and lead to cardiovascular collapse and death. Hemodynamic support with inotropics and vasopressors is usually not effective. The insulin/glucose therapy is an effective complement to the initial treatment, which is widely studied and used in different pathologies with hemodynamic compromise. The case of a pediatric patient with a history of high-dose ingestion of amlodipine for suicidal purposes, with hemodynamic decompensation refractory to usual inotropic support treatment, is presented. From the insulin/glucose treatment, hemodynamic stability was achieved with a favorable evolution

Periodontal management of a patient with chronic kidney disease: a case report

The association between periodontal disease and chronic kidney disease (CKD) has been recognized over the years. Gingival overgrowth may be a side effect of some of the drugs prescribed for patients with CKD. Objective: The objective of this manuscript was to report the dental management of a patient with chronic renal disease who presented periodontitis and gingival overgrowth. Case report: A 55 years old male patient sought dental treatment, and was diagnosed with generalized periodontitis in advanced stage and gingival overgrowth. The overgrowth was associated to the use of amlodipine, a longacting calcium channel blocker. The treatment consisted of interruption of amlodipine, sessions of oral hygiene instruction and basic periodontal therapy. Thereafter, conventional periodontal therapy, with scaling and root planning of the four hemiarches, surgical periodontal therapy and gingivectomy of the overgrowth were performed. Considering periodontal sites with a probing depth (PD) > 4mm at baseline, mean PD was reduced (baseline: 5.94 ± 1.80; follow-up: 2.76 ± 1.38), as well as mean clinical attachment loss (baseline: 5.55 ± 1.51; followup: 4.52 ± 1.47). Periodontal disease was controlled and there was no recurrence of gingival overgrowth after 18 months of follow-up. Conclusion: The management of the reported patient with CKD and periodontal involvement included discontinuation of amlodipine, basic and advanced periodontal therapy and gingivectomy. Proper oral hygiene may help to prevent recurrence of the gingival overgrowth and to maintain periodontal health.

Introdução: A associação entre doença periodontal e doença renal crônica (DRC) tem sido reconhecida nos últimos anos. O crescimento gengival excessivo pode ser um efeito colateral de alguns medicamentos prescritos para pacientes com DRC. Objetivos: O objetivo deste estudo foi relatar o manejo odontológico de um paciente com DRC que apresentava periodontite e aumento gengival. Relato do caso: Um paciente do sexo masculino, 55 anos, procurou atendimento odontológico e foi diagnosticado com periodontite generalizada em estágio avançado e crescimento gengival associado ao uso de anlodipina, um bloqueador dos canais de cálcio de ação prolongada. O tratamento consistiu em interrupção da anlodipina, sessões de instruções de higiene bucal e terapia periodontal básica. Posteriormente, foi realizada terapia periodontal convencional, com raspagem e alisamento radicular dos quatro hemiarcos, seguida de cirurgia periodontal a retalho e gengivectomia. Considerando os sítios periodontais com profundidade de bolsa à sondagem (PBS) > 4mm no início do tratamento, a média de PBS foi reduzida (início: 5,94 ± 1,80; final: 2,76 ± 1,38), bem como a média do nível clínico de inserção (início: 5,55 ± 1,51; final: 4,52 ± 1,47). A doença periodontal foi controlada e não houve recorrência do crescimento gengival após 18 meses de acompanhamento. Conclusão: O tratamento odontológico deste paciente com DRC e envolvimento periodontal incluiu a interrupção da anlodipina, terapia periodontal básica e avançada e gengivectomia. A higiene bucal adequada pode ajudar a prevenir a recorrência do crescimento gengival excessivo e a manutenção de um estado periodontal saudável.

Serie de Casos: Intoxicación por Amlodipino / Case Series: Amlodipine Intoxication

Resumen INTRODUCCIÓN: La intoxicación por distintas drogas es una importante causa de morbimortalidad en la edad pediátrica. No obstante, la intoxicación por amlodipino, que es un fármaco dihidropiridinico del grupo de calcioantagonistas ampliamente usado, no se encuentra bien documentada en Ecuador. El tratamiento se basa en implementar medidas para el shock clásico, en conjunto con medidas específicas para este tipo de intoxicación. CASOS CLÍNICOS: Presentamos dos reportes de casos clínicos de pacientes adolescentes ingresadas en unidad de cuidados intensivos pediátricos (UCIP), por intento autolítico mediante ingesta de amlodipino en conjunto con otros fármacos. EVOLUCIÓN: Durante su estancia hospitalaria presentaron cuadros evolutivos distintos. En ambos casos se necesitó manejo con drogas vasoactivas, modificando su dosis de acuerdo a respuesta clínica. En los dos casos se administró gluconato de calcio por horario y otras medidas de soporte descritas en el presente manuscrito. Finalmente, las dos pacientes presentaron buena evolución y fueron dadas de alta, con previa valoración y seguimiento de psicología y psiquiatría. CONCLUSIÓN: La intoxicación por amlodipino ha sido descrita escasamente debido a su baja frecuencia, a esto se añade el poco conocimiento basado en evidencia; motivos que la constituyen como un reto diagnóstico y terapéutico. Destacamos, en base a nuestra experiencia, la importancia de un alto índice de sospecha y de priorizar el inicio de vasopresores sobre la reanimación hídrica. Adicionalmente, recomendamos documentar la dosis exacta de ingesta e indagar sobre el consumo de otros fármacos para clasificar adecuadamente la gravedad de la intoxicación y establecer un plan de tratamiento. Finalmente, la monitorización y evaluación clínica constante y el apoyo de exámenes de laboratorio guiarán la conducta.(au)

BACKGROUND: Drug poisoning is an important cause of morbidity and mortality in pediatric patients. However, amlodipine poisoning, a widely used dihydropyridine calcium chanel blocker, is not fully documented in Ecuador. Treatment consists of classic measures for shock management and specific measures for this type of intoxication. CASE REPORTS: We present two case reports, both of teenage patients admitted into the pediatric intensive care unit for suicide attempt by taking amlodipine and some other drugs. EVOLUTION: During hospital stay, they presented a different evolutionary course. In both cases vasoactive drugs were needed, dosage was modified according to clinical course. Also in both patients, calcium gluconate was administered along with other support measures described in this paper. Finally, both patients presented a good outcome and were discharged after psychological and psychiatric assessment and follow up. CONCLUSION: The low frequency of amlodipine poisoning and the lack of evidence-based knowledge, constitute it as a diagnostic and therapeutic challenge. Based on our experience, we highlight the importance of early suspicion and prioritizing the use of vasopressors over fluid resuscitation. Additionally, we recommend documenting the exact dose of intake and inquiring about consumption of other drugs to properly classify the severity of the poisoning and stablish the treatment plan. Finally, constant clinical monitoring and support of laboratory tests will guide the conduct.(au)

Informe diário de evidências COVID-19: busca realizada em 16 e 18 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 16 and 18, 2020

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.

Trombolisis endovenosa post reversión de acenocumarol con complejo de protrombina: caso clínico / Intravenous thrombolysis after reversion of acenocoumarol anticoagulation: report of one case

We report an 89-year-old male under oral anticoagulant therapy with a therapeutic international normalized ratio, presenting at the emergency room with right side hemiparesis and aphasia. Neuroimaging was compatible with an acute middle cerebral artery ischemic stroke. Anticoagulation was reverted with the use of four factor prothrombin complex, followed by thrombolysis with alteplase, with a favorable evolution, returning to his basal functional status.

Agrandamiento gingival generalizado en un paciente con trasplante renal / Generalized gingival enlargement in a patient with renal transplant

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)

Circulating microparticles and central blood pressure according to antihypertensive strategy

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.

Is irrational use of intralipid emulsion justified in amlodipine toxicity? / 대한마취과학회지

No abstract available.

Pharmacokinetic comparison between fixed-dose combination of fimasartan/amlodipine 60/10 mg and the corresponding loose combination through partial replicated crossover study in healthy subjects

Combination therapies of antihypertensive drugs are recommended in cases where hypertension is not controlled by monotherapy. This study aimed to compare the pharmacokinetics (PKs) between fixed-dose combination (FDC) of fimasartan/amlodipine 60/10 mg and the corresponding loose combination. Because of the high intra-subject variability for maximum plasma concentration (C(max)) of fimasartan, a randomized, open-label, 3×3 partial replicated crossover design was adopted. Subjects received a single dose of FDC of fimasartan/amlodipine 60/10 mg or the corresponding loose combination in each period. Blood samples for PK analysis were collected up to 48 hours for fimasartan and 144 hours for amlodipine, respectively. Geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) of the FDC to the loose combination for C(max) and area under the concentration-time curve from time 0 to the last quantifiable time point (AUC(last)) were calculated. Sixty healthy subjects were randomized, and 57 subjects completed the study. The concentration-time profiles of fimasartan and amlodipine were similar between the FDC and loose combination. The GMRs (90% CIs) of the FDC to the loose combination for C(max) and AUC(last) were 1.0440 (0.9202–1.1844) and 1.0412 (0.9775–1.1090) for fimasartan, and 1.0430 (1.0156–1.0711) and 1.0339 (1.0055–1.0631) for amlodipine, respectively. The GMRs and its 90% CIs for C(max) and AUC(last) of fimasartan and amlodipine were included not only in the scaled bioequivalence criteria but also in the conventional bioequivalence criteria. In conclusion, FDC of fimasartan/amlodipine 60/10 mg showed comparable PK profiles with the corresponding loose combination, which suggests their bioequivalence.

Desenvolvimento e validação de método analí­tico indicativo de estabilidade por CLAE-DAD-CAD para besilato de anlodipino e seus produtos de degradação / Development and validation of analytical method indicative of stability by HPLC-DAD-CAD for amlodipine besylate and its degradation products

O presente estudo foi realizado com o objetivo de se desenvolver e validar uma metodologia analítica indicativa de estabilidade para separação e quantificação de anlodipino e seus produtos de degradação no medicamento besilato de anlodipino 5 mg por comprimido. Para tanto, realizou-se um estudo de degradação forçada, como forma de identificar os principais produtos de degradação, que podem vir a formar num estudo de estabilidade, bem como estabelecer possíveis rotas de degradação. Foi utilizada a técnica instrumental de separação, cromatografia a líquido (CL), com dois tipos de detectores: arranjo de diodos (DAD) e corona CAD (Detector de aerossol carregado), coluna cromatográfica Zorbax SB-Phenyl 1,8µm 4,6 x 50 mm Agilent® e fase móvel constituída por tampão pH3,0, metanol e acetonitrila sob condições de gradiente (75% de tampão pH 3,0, 15% de metanol e 10% de acetonitrila; no tempo de 10 minutos tem-se 20% de tampão pH3,0, 60% de metanol e 20% de acetonitrila; no tempo de 13 minutos tem-se 75% de tampão pH3,0, 15% de metanol e 10% de acetonitrila; e no tempo de 15 minutos tem-se 75% de tampão pH3,0, 15% de metanol e 10% de acetonitrila); fluxo de 1,0mL/min até 10 minutos; de 10,1 a 13 minutos tem-se fluxo de 0,5 mL/min; e de 13,1 a 15 minutos volta ao fluxo de 1,0 mL/min; e detecção em 238 nm. O método apresentou-se linear, preciso, exato, robusto e seletivo, e proporcionou resultados confiáveis, sem interferência de degradantes e impurezas

This study was conducted in order to develop an analytical methodology indicative of stability for separation and quantification of the antihypertensive amlodipine and its degradation products in the drug amlodipine besylate 5 mg per tablet. For this development was performed a forced degradation study, in order to identify the main degradation products that may form in a stability study, as well as establish possible degradation routes. It was used the instrumental separation technique, liquid chromatography (LC) with two types of detectors: diode array (DAD) and corona CAD (Charged Aerosol Detector), chromatographic column Zorbax SB-Phenyl 4.6 x 50 mm 1,8µm Agilent® and mobile phase of buffer pH3,0, methanol and acetonitrile under gradient conditions (75% buffer pH3,0, 15% methanol and 10% acetonitrile; 10 minutes has 20% buffer pH3,0, 60% methanol and 20% acetonitrile; 13 minutes has become 75% of buffer pH3,0, 15% methanol and 10% acetonitrile; and 15 minutes has become 75% of buffer pH3,0, 15% methanol and 10% acetonitrile); flow 1.0 mL/ min up to 10 minutes; a flow 0,5 mL/min is obtained from 10,1 to 13 minutes; and from 13,1 minutes the flows returns to 1,0 mL/min; and detection in 238 nm. The method is linear, precise, accurate, robust and selective, and provided reliable results without interference from degradation products and impurities

Amlodipine toxicity complicated by concurrent medications / 대한마취과학회지

No abstract available.

Amlodipine toxicity and lipid emulsion / 대한마취과학회지

No abstract available.

The influence of benazepril and amlodipine on the expression of secretin and somatostatin in spontaneously hypertensive rats / 中国应用生理学杂志

OBJECTIVES@#Investigate the influence of benazepril and amlodipine on the expression of secretin (PZ) and somatostatin (SS) in spontaneously hypertensive rats (SHR).@*METHODS@#Forty-five SHRs (14 weeks old, male) were randomly assigned into 3 groups (=15):SHR group, Benazepril group (which was given benazepril 0.90 mg·kg·d) and Amlodipine group (SHRs were given amlodipine 0.45 mg· kg·d), taking WistarKyoto(WKY) as normal control (=15), meanwhile, rats in SHR group and WKY group were given the same volume of distilled water. After 8 weeks of intervention, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was detected by enzyme-linked immunoassay and RT-PCR.@*RESULTS@#After 8 weeks of intervention, compared with the WKY group, the expression of protein and mRNA of PZ in duodenum and SS in sinuses ventriculi was increased significantly in SHR group (<0. 05). Compared with SHR group, the expression of PZ in duodenum and SS in sinuses ventriculi was decreased significantly in Benazepril group and Amlodipine group (<0.05). Compared with Benazepril group, in Amlodipine group the expression of PZ mRNA in duodenum and SS mRNA in sinuses ventriculi was decreased more significantly (<0.05).@*CONCLUSIONS@#The regulation disorder of PZ in duodenum and SS in sinuses ventriculi exists in SHR. The antihypertensive effect of benazepril and amlodipine may be realized by regulating the expression of PZ and SS, while the regulation of amlodipine is more obvious than benazepril.

The potential role of amlodipine on experimentally induced bacterial rhinosinusitis / O papel potencial da amlodipina na rinossinusite bacteriana induzida experimentalmente

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.

Amlodipino y choque vasodilatado en una unidad de cuidados intensivos de un hospital general: Reporte de caso / Amlodipine and vasodilated shock in an intensive care unit of a general hospital: Case report

Los calcio antagonistas son fármacos usados para diferentes patologías médicas; sin embargo la intoxicación puede ser grave. Presentamos el caso de una mujer joven intoxicada por amlodipino quien cursó con choque vasodilatado y disfunción multiorgánica, en quien se usó vasopresores múltiples a dosis por encima de las habituales para estabilizarla. (AU)

Calcium antagonists are used in a number of medical conditions, but intoxication with these drugs may be lethal.We present the case of a young women intoxicated with amlodipine who presented with vasodilated shock and multi organ disfunction in whom multiple vasopressors at maximum allowed doses were used to estabilize the patient. (AU)

Therapeutic drug monitoring of amlodipine and the Z-FHL/HHL ratio: Adherence tools in patients referred for apparent treatment-resistant hypertension

Background. Non-adherence to antihypertensives is a cause of 'pseudo-treatment-resistant' hypertension.Objective. To determine whether monitoring plasma amlodipine concentrations and inhibition of angiotensin-converting enzyme (ACE) can be adjunct adherence tools.Methods. Patients with hypertension who were prescribed enalapril and amlodipine were enrolled. Blood pressures (BPs) were monitored and an adherence questionnaire was completed. Steady-state amlodipine was assayed using liquid chromatography-mass spectrometry and degree of ACE inhibition using the Z-FHL/HHL (z-phenylalanine-histidine-leucine/hippuryl-histidine-leucine) ratio.Results. One hundred patients (mean (standard deviation) age 50.5 (12) years, 46% male) were enrolled. Based on plasma assays, 26/97 patients (26.8%) were unsuppressed by enalapril and 20/100 (20%) were sub-therapeutic for amlodipine. There were significant BP differences based on plasma levels of the medication: 21/20 mmHg lower in the group with suppressed ACE and 26/20 mmHg in the group with steady-state amlodipine concentrations.Conclusions. Monitoring antihypertensive adherence by assaying plasma medication concentrations is a feasible option for evaluating true v. pseudo-resistant hypertension

Development and validation of analytical method for the determination of radotinib in human plasma using liquid chromatography-tandem mass spectrometry

This study describes the development of an analytical method to determine radotinib levels in human plasma using high performance liquid chromatography (HPLC) coupled with triple quadrupole tandem mass spectrometry (MS/MS) for pharmacokinetic application. Plasma samples were sequentially processed by liquid-liquid extraction using methyl tert-butyl ether, evaporation, and reconstitution. Analytes were separated and analyzed using HPLC-MS/MS in selected reaction monitoring mode, monitoring the specific transitions of m/z 531 to 290 for radotinib and m/z 409 to 238 for amlodipine (internal standard). The HPLC-MS/MS analytical method was validated with respect to selectivity, linearity, sensitivity, accuracy, precision, recovery, and stability. Calibration curves were linear over a concentration range 5–3,000 ng/mL with correlation coefficients (r) > 0.998. The lower limit of quantification for radotinib in plasma was 5 ng/mL. The accuracy and precision of the analytical method were acceptable within 15% at all quality control levels. This method was suitable to determine radotinib levels in human plasma because of its simplicity, selectivity, precision, and accuracy.

Antihypertensive effect of ethanol extracts of Aralia elata in spontaneously hypertensive rats

Antihypertensive effects of ethanol extracts of Aralia elata (Miq.) Seem. (AE) were investigated in spontaneously hypertensive rats (SHR). SHR aged 14 weeks were treated for 8 weeks with AE (10 or 50 mg/kg/day) or amlodipine besylate (Am; 10 mg/kg/day) orally. Hypertension results in injury to several organs and can produce a significant increase in malondialdehyde (MDA) content as a result of lipid peroxidation and endothelial dysfunction. In this study, oral administration of AE and Am significantly reduced systolic blood pressure, organ weight index, and MDA content in tissues but increased significantly the plasma nitrite and nitrate concentrations. The endothelium-dependent relaxant activities of acetylcholine (10⁻¹⁰–10⁻³ M) in norepinephrine (NE)-precontracted aorta were increased in AE- and Am-treated rats. Particularly strong endothelium-dependent relaxant activities were observed in AE-treated (50 mg/kg) rats. The endothelium-independent relaxant activities of sodium nitroprusside (10⁻¹⁰–10⁻³ M) in NE-precontracted aorta were not changed. The results of this study suggest that AE has both antihypertensive and end-organ protective effects in SHR.