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1.
Am J Med ; 134(9): 1170-1174, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33864761

RESUMEN

BACKGROUND: Pseudohyperchloremia results in a very low or negative anion gap. Historically, the most common cause of this artifact was bromide poisoning. Bromide salts have been removed from most medications and bromism has become very uncommon. More recently, the introduction of chloride ion selective sensing electrodes (Cl-ISE) has generated a new cause of pseudohyperchloremia-salicylate poisoning. We describe 5 such patients and quantitate the error generated by this measurement artifact. METHODS: The magnitude of artifactual hyperchloremia generated by high salicylate levels was quantified in 5 patients by measuring chloride concentration with several Cl-ISEs from different manufacturers and with Cl-ISEs of different "ages," and comparing these results to measurements with a chloridometer (coulometric titration), which is free of the salicylate artifact. RESULTS: Cl-ISEs from different manufacturers generated a wide range of artifactual chloride concentration elevation. Furthermore, the same Cl-ISE generated increasingly severe pseudohyperchloremia as it was repeatedly reused over time and "aged." CONCLUSIONS: Salicylate interferes with measurement of the blood chloride concentration when a Cl-ISE is used. The severity of this artifact is related to the salicylate level, the specific Cl-ISE, and the "age" of the electrode. Toxic blood salicylate levels can generate marked pseudohyperchloremia, and consequently, an artifactual very small or negative anion gap. The large anion gap metabolic acidosis typical of salicylate poisoning is masked by this artifact. Salicylate has become the most common cause of pseudohyperchloremia, and physicians should immediately consider salicylate poisoning whenever the combination of hyperchloremia and a very small or negative anion gap is reported by the laboratory.


Asunto(s)
Acidosis , Aspirina/envenenamiento , Cloruros , Electrodos de Iones Selectos/normas , Salicilatos , Equilibrio Ácido-Base , Desequilibrio Ácido-Base/inducido químicamente , Desequilibrio Ácido-Base/diagnóstico , Desequilibrio Ácido-Base/terapia , Acidosis/sangre , Acidosis/inducido químicamente , Acidosis/diagnóstico , Acidosis/terapia , Artefactos , Cloruros/análisis , Cloruros/sangre , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención al Paciente/métodos , Salicilatos/sangre , Salicilatos/envenenamiento , Intento de Suicidio
2.
Clin Toxicol (Phila) ; 59(7): 655-657, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33245023

RESUMEN

INTRODUCTION: Suspected pediatric ingestions of greater than or equal to one teaspoon topical salicylate analgesic are recommended by poison control centers to be managed at healthcare facilities. This cutoff is applied for both liquid and non-liquid (cream, ointment, gel) formulations. METHODS: California poison control cases involving topical salicylate exposures in children less than 6-years-old who were evaluated at a health care facility between 2003 and 2018 were analyzed. RESULTS: Of 599 patient cases, the majority described no or minor symptoms, with gastrointestinal distress being the most common. Signs of salicylate toxicity (metabolic acidosis, tachypnea) occurred in six cases. Seven patients were hospitalized, six of whom were exposed to liquid preparations. DISCUSSION: In line with previous research, liquid salicylate preparations were more frequently associated with the signs of salicylate toxicity and hospitalization. CONCLUSION: There was a low frequency of severe side effects and low hospitalization rates among those referred to a healthcare facility, especially for non-liquid topical salicylate ingestions.


Asunto(s)
Salicilatos/toxicidad , Niño , Preescolar , Femenino , Hospitalización , Humanos , Lactante , Masculino , Estudios Retrospectivos , Riesgo , Salicilatos/administración & dosificación , Salicilatos/sangre
3.
BMJ Case Rep ; 13(11)2020 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-33257373

RESUMEN

A 79-year-old man presented to the emergency department with a 1-week history of worsening confusion, falls and hearing impairment. An initial workup for infectious, metabolic and structural causes was unrevealing. However, further history discovered that he had been ingesting one to two bottles of Pepto-Bismol (bismuth subsalicylate) daily for gastro-oesophageal reflux symptoms. On his second day of admission, the plasma salicylate concentration was 2.08 mmol/L (reference range 1.10-2.20 mmol/L), despite no sources of salicylate in hospital. He was diagnosed with chronic salicylate toxicity and Pepto-Bismol use was discontinued. The patient was treated supportively with isotonic intravenous fluids only and plasma salicylate concentration fell to less than 0.36 mmol/L. Concurrently, all his symptoms resolved. This case highlights the potential adverse effects of over-the-counter medications. The diagnosis of chronic salicylate toxicity is challenging, specifically in the elderly and in undifferentiated presentations, as it can be missed if not suspected.


Asunto(s)
Accidentes por Caídas , Bismuto/efectos adversos , Confusión/inducido químicamente , Trastornos de la Audición/inducido químicamente , Compuestos Organometálicos/efectos adversos , Salicilatos/efectos adversos , Anciano , Bismuto/sangre , Diagnóstico Diferencial , Humanos , Masculino , Compuestos Organometálicos/sangre , Salicilatos/sangre
4.
JAMA ; 323(3): 256-267, 2020 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-31961417

RESUMEN

Importance: A prior pilot study demonstrated the systemic absorption of 4 sunscreen active ingredients; additional studies are needed to determine the systemic absorption of additional active ingredients and how quickly systemic exposure exceeds 0.5 ng/mL as recommended by the US Food and Drug Administration (FDA). Objective: To assess the systemic absorption and pharmacokinetics of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate) in 4 sunscreen products under single- and maximal-use conditions. Design, Setting, and Participants: Randomized clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) was conducted in 48 healthy participants. The study was conducted between January and February 2019. Interventions: Participants were randomized to 1 of 4 sunscreen products, formulated as lotion (n = 12), aerosol spray (n = 12), nonaerosol spray (n = 12), and pump spray (n = 12). Sunscreen product was applied at 2 mg/cm2 to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals, and 34 blood samples were collected over 21 days from each participant. Main Outcomes and Measures: The primary outcome was the maximum plasma concentration of avobenzone over days 1 through 21. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, homosalate, octisalate, and octinoxate over days 1 through 21. Results: Among 48 randomized participants (mean [SD] age, 38.7 [13.2] years; 24 women [50%]; 23 white [48%], 23 African American [48%], 1 Asian [2%], and 1 of unknown race/ethnicity [2%]), 44 (92%) completed the trial. Geometric mean maximum plasma concentrations of all 6 active ingredients were greater than 0.5 ng/mL, and this threshold was surpassed on day 1 after a single application for all active ingredients. For avobenzone, the overall maximum plasma concentrations were 7.1 ng/mL (coefficient of variation [CV], 73.9%) for lotion, 3.5 ng/mL (CV, 70.9%) for aerosol spray, 3.5 ng/mL (CV, 73.0%) for nonaerosol spray, and 3.3 ng/mL (CV, 47.8%) for pump spray. For oxybenzone, the concentrations were 258.1 ng/mL (CV, 53.0%) for lotion and 180.1 ng/mL (CV, 57.3%) for aerosol spray. For octocrylene, the concentrations were 7.8 ng/mL (CV, 87.1%) for lotion, 6.6 ng/mL (CV, 78.1%) for aerosol spray, and 6.6 ng/mL (CV, 103.9%) for nonaerosol spray. For homosalate, concentrations were 23.1 ng/mL (CV, 68.0%) for aerosol spray, 17.9 ng/mL (CV, 61.7%) for nonaerosol spray, and 13.9 ng/mL (CV, 70.2%) for pump spray. For octisalate, concentrations were 5.1 ng/mL (CV, 81.6%) for aerosol spray, 5.8 ng/mL (CV, 77.4%) for nonaerosol spray, and 4.6 ng/mL (CV, 97.6%) for pump spray. For octinoxate, concentrations were 7.9 ng/mL (CV, 86.5%) for nonaerosol spray and 5.2 ng/mL (CV, 68.2%) for pump spray. The most common adverse event was rash, which developed in 14 participants. Conclusions and Relevance: In this study conducted in a clinical pharmacology unit and examining sunscreen application among healthy participants, all 6 of the tested active ingredients administered in 4 different sunscreen formulations were systemically absorbed and had plasma concentrations that surpassed the FDA threshold for potentially waiving some of the additional safety studies for sunscreens. These findings do not indicate that individuals should refrain from the use of sunscreen. Trial Registration: ClinicalTrials.gov Identifier: NCT03582215.


Asunto(s)
Propiofenonas/sangre , Absorción Cutánea , Protectores Solares/farmacocinética , Acrilatos/sangre , Acrilatos/farmacocinética , Adulto , Benzofenonas/sangre , Benzofenonas/farmacocinética , Cinamatos/sangre , Cinamatos/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Propiofenonas/farmacocinética , Salicilatos/sangre , Salicilatos/farmacocinética , Protectores Solares/efectos adversos
5.
Clin Toxicol (Phila) ; 58(1): 16-19, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-30900477

RESUMEN

Introduction: Salicylate toxicity is a common cause of morbidity and hospitalization. Animal and human studies suggest that salicylates cause a dose-dependent inhibition of the activation of factors 2, 7, 9, and 10. However, limited reports of coagulopathy or major bleeding from salicylate toxicity exist.Methods: This is a retrospective study examining subjects from January 1, 2001 to December 31, 2011 in whom at least one serum salicylate concentration was measured above 30 mg/dL. Cases were patients with elevated salicylate concentration and coagulopathy (INR > 1.5). Major bleeding cases were those with elevated salicylate concentration who developed hemorrhagic death; or bleeding from an intracranial, intraspinal, intraocular, retroperitoneal, pericardial, intramuscular site; or hemoglobin decrease of >2 g/dL, or transfusion of at least 2 units of packed RBCs during hospitalization.Results: Twelve percent of all cases of elevated salicylate concentration developed coagulopathy, 6% developed major bleeding, and 3% died. In a multivariate model, duration of elevated salicylate concentration and renal impairment were associated with coagulopathy and no variable was associated with major bleeding. Patients were more likely to develop major bleeding if they had coagulopathy, but not all cases of major bleeding had coagulopathy.Discussion: Coagulopathy and major bleeding during salicylate toxicity has been underrecognized. Renal impairment and duration of salicylate elevation contribute to the risk of coagulopathy, but no factors predict major bleeding. Patients with coagulopathy have a high risk of bleeding but some bleeding occurs without coagulopathy, suggesting that other factors, such as platelet dysfunction, may play a role.Conclusion: Coagulopathy and major bleeding develop in a clinically relevant percentage of cases of salicylate toxicity.


Asunto(s)
Trastornos de la Coagulación Sanguínea/inducido químicamente , Hemorragia/inducido químicamente , Salicilatos/toxicidad , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Salicilatos/sangre , Adulto Joven
7.
Artículo en Inglés | MEDLINE | ID: mdl-31302475

RESUMEN

Monitoring human exposure to chemical UV filters is essential for an accurate assessment of the health risk caused by the resorbed compounds. We developed different procedures for the determination of the prominent UV filters octocrylene (OC), avobenzone (AVO) and 2-ethylhexyl salicylate (EHS) as well as for two OC and EHS metabolites in human urine and OC, AVO and 2-cyano-3,3-diphenylacrylic acid (CDAA) in plasma samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since the development of a multi-method for all analytes proved to be difficult, three different procedures were established for the determination of AVO, OC and its metabolite CDAA in urine and plasma as well as for EHS and its metabolite 5-hydroxy-EHS in urine. The methods have been validated with good sensitivity, precision and accuracy. The procedures were satisfactorily applied to the determination of the target compounds in human samples collected from volunteers after sunscreen application. These new analytical procedures can provide information on the internal exposure to the UV filters OC, AVO and EHS, which has been little studied.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Protectores Solares/análisis , Protectores Solares/metabolismo , Espectrometría de Masas en Tándem/métodos , Acrilatos/sangre , Acrilatos/orina , Humanos , Propiofenonas/sangre , Propiofenonas/orina , Salicilatos/sangre , Salicilatos/orina , Orina/química
8.
Clin Toxicol (Phila) ; 57(2): 137-140, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30306804

RESUMEN

BACKGROUND: Salicylates are usually rapidly absorbed and quickly measurable in serum. An undetectable serum salicylate concentration ([ASA]) may occur early after ingestion and may be interpreted as evidence of non-exposure and not repeated. Although cases of delayed salicylate detection are reported rarely, the risk factors associated with this phenomenon are not known. RESEARCH QUESTION: What factors are associated with an early undetectable [ASA] in salicylate poisoning? METHODS: Records from a single regional poison center were searched from 2002 to 2016 for cases of salicylate toxicity treated with bicarbonate and [ASA] > 30 mg/dL. Cases were excluded if initial [ASA] was obtained >4 h after presentation. Case information, serial [ASA], and outcomes were recorded and compared between groups. RESULTS: A total of 313 records met all criteria with 11 initially undetectable [ASA] (3.5%) and 302 detectable [ASA] (96.5%). Time of first [ASA] occurred sooner in the undetectable [ASA] group (89 vs. 137 min, p = 0.011) while time to peak [ASA] was longer (640 vs. 321 min, p < .001). The longest interval between ingestion and undetectable [ASA] was 225 min. Peak [ASA] and reported mean ingested dose were similar in both groups (45 vs. 50 mg/dL, p = NS; 19.7 g vs. 32.9 g, p = NS). Coingestion of agents that delay gastric emptying were similar in both groups (18% [2/11] vs. 25% [76/302], p = NS, chi-square). Hemodialysis was performed in 9% (1/11) of undetectable [ASA] patients and 5.6% (17/302) of detectable [ASA] patients (p = NS, chi-square). A single death occurred in the entire cohort in a patient with an initially detectable [ASA]. DISCUSSION: In this series, a small but significant proportion (3.5%) of patients who developed [ASA] > 30 mg/dL had an initially undetectable [ASA]. Those with an undetectable [ASA] were measured earlier after ingestion with a longer time to peak [ASA]. However, neither coingestion of agents prolonging gastric emptying nor reported dose ingested was different between groups. Formulation was infrequently recorded but one undetectable [ASA] did ingest a non-enteric coated product. Limitations include the small number of patients with undetectable [ASA], use of single poison center data and partial data on co-ingestants and aspirin formulation. CONCLUSIONS: [ASA] may be undetectable early after an overdose and need for serial [ASA] in the evaluation of salicylate ingestion should be further explored. Additional research is needed to determine any causative factors and the optimal timing of [ASA] measurements.


Asunto(s)
Salicilatos/envenenamiento , Adolescente , Adulto , Sobredosis de Droga/sangre , Sobredosis de Droga/etiología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Salicilatos/sangre , Salicilatos/farmacocinética , Adulto Joven
9.
Clin Nutr ; 38(5): 2016-2022, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30274900

RESUMEN

BACKGROUND AND OBJECTIVE: Indoxyl sulphate (IS) and p-cresyl sulphate (PCS), which are difficult to excrete adequately out of the body, are closely related to the progression of chronic kidney disease (CKD) and various deuteropathy. Better than peritoneal dialysis (PD) and haemodialysis (HD), dietary fibre has been considered to reduce IS and PCS levels. In view of the absence of formal recommendations on fibre intake in CKD nutritional guidelines, we conducted this meta-analysis to assess the effects of dietary fibre on IS and PCS for CKD patients. METHODS: The effects were pooled and expressed in terms of weighted mean difference (WMD) with 95% confidence interval (95% CI). Q test and I2 statistics were used to assess the heterogeneity. RESULTS: A total of 12 relevant estimates from 7 reports, including 203 CKD patients, showed that dietary fibre significantly reduced their PCS level (WMD = -16.160, 95% CI: -23.824, -8.495). CONCLUSIONS: The meta-analysis produced a strong corroboration that dietary fibre intake does have a good therapeutic effect on patients with CKD. The conclusions need to be validated by randomised controlled experiments (RCT) with better design, larger samples, longer course of treatment and higher quality.


Asunto(s)
Cresoles , Fibras de la Dieta , Indicán , Insuficiencia Renal Crónica , Salicilatos , Adulto , Anciano , Cresoles/sangre , Cresoles/metabolismo , Fibras de la Dieta/administración & dosificación , Fibras de la Dieta/uso terapéutico , Femenino , Humanos , Indicán/sangre , Indicán/metabolismo , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Salicilatos/sangre , Salicilatos/metabolismo
10.
Drug Des Devel Ther ; 12: 3377-3392, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30349192

RESUMEN

PURPOSE: To develop an immediate release-type tablet containing varenicline salicylate (VRC-S), a smoking cessation agent, formulation and stability studies were performed. The in vitro dissolution and in vivo pharmacokinetic (PK) behavior of the tablets were compared with those of the commercial product (Champix) as a reference. MATERIALS AND METHODS: The characteristics of the powder were investigated by particle morphology, size distribution, solubility, hygroscopicity, differential scanning calorimetry, and powder X-ray diffraction. Based on the drug-excipient compatibility test, different VRC-S tablets were prepared with the selected excipients through direct compression or wet granulation method and subjected to a dissolution test. The stability of the most promising VRC-S tablet (F4) was evaluated under accelerated conditions (40°C and 75% relative humidity). Further, the dissolution and human pharmacokinetic profiles of the F4 tablet and Champix were compared. RESULTS: VRC-S showed a positively skewed unimodal size distribution with a specific surface area of 2.02 m2/g, single endothermic peak of 225.2°C in differential scanning calorimetry, crystalline internal structure in powder X-ray diffraction, aqueous solubility of 244.7 mg/mL, and hygroscopicity of 0.256 mg/g. The wet granulation method was preferred for tablet preparation and employed the following excipients: microcrystalline cellulose and anhydrous dibasic calcium phosphate as diluents, croscarmellose sodium as a disintegrant, and colloidal silicon dioxide and magnesium stearate as lubricants. The F4 tablet was stable for 6 months under accelerated conditions. The dissolution of VRC was pH independent, revealing f 2 values of 76.49 and 68.38 at pH 1.2 and pH 6.8, respectively. After the oral administration of F4 tablet and Champix to healthy human volunteers, pharmacokinetic parameters, including time to reach the maximum plasma concentration (Tmax), maximum plasma concentration (Cmax), and area under the curve from 0 to infinity (AUCinf), were compared. The values of 90% CI were 0.972-1.035 for Cmax and 0.982-1.075 for AUCinf, which was indicative of the bioequivalence of both products. CONCLUSION: VRC-S-containing F4 tablet might be a good candidate for smoking cessation treatment.


Asunto(s)
Composición de Medicamentos , Salicilatos/química , Salicilatos/farmacocinética , Vareniclina/química , Vareniclina/farmacocinética , Adulto , Cromatografía Liquida , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Salicilatos/sangre , Solubilidad , Comprimidos , Espectrometría de Masas en Tándem , Equivalencia Terapéutica , Vareniclina/sangre , Adulto Joven
11.
J Med Toxicol ; 14(4): 323-326, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30051204

RESUMEN

INTRODUCTION: 2,4-Dinitrophenol (DNP) is a known uncoupler of oxidative phosphorylation that clinically leads to hyperthermia, tachycardia, tachypnea, and metabolic acidosis. Intentional overdoses of DNP are often fatal. We present an analytically confirmed fatal case of DNP overdose with a falsely positive elevated salicylate concentration. We further explored this cross reactivity of DNP with two salicylate assays. METHODS: Clinically relevant serial dilutions of DNP were prepared in drug-free serum and analyzed using two different colorimetric NADH/NAD-based analytical methodologies. RESULTS: The enzymatic salicylate assay demonstrated a reproducible false elevation of salicylate starting at a DNP level of 100 mg/L while the EMIT-based methodology was without any such interference at the maximum concentration tested (150 mg/L). CONCLUSIONS: DNP cross reacts with some salicylate assays. This knowledge is important for providers, as there are significant variations in the management of DNP versus salicylate toxicity.


Asunto(s)
2,4-Dinitrofenol/envenenamiento , Sobredosis de Droga , Salicilatos/sangre , Autopsia , Colorimetría , Reacciones Cruzadas , Reacciones Falso Positivas , Resultado Fatal , Humanos , Masculino , Suicidio , Adulto Joven
12.
Talanta ; 181: 197-203, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29426501

RESUMEN

A method to introduce target analytes to a chromatograph from a single drop of whole blood was investigated for minimally invasive monitoring of anionic pharmaceuticals. In this work, salicylate and loxoprofen were examined as organic anions. A micro ion extractor (MIE) has been developed for extraction of inorganic trace anions from whole blood, but this device is not suitable for extraction of pharmaceuticals. In the present study, we improved and optimized the MIE device for organic anion extraction. Various supported liquid membranes were evaluated for use as the ion transfer membrane, with each membrane placed between a droplet sample (donor) and an acceptor solution. A supported liquid membrane of porous polypropylene impregnated with 1-butanol was selected. In addition, the methods for electric field creation and electrode contact were examined to improve the characteristics of the MIE device. The current and extraction time were also optimized. With the optimized method, salicylate and loxoprofen were successfully extracted from a single drop of whole blood. Changes in the concentrations of these pharmaceuticals in blood over time were monitored after administration. As only 25µL of whole blood was required for analysis, repeat measurements could be conducted to monitor changes in the concentrations. This MIE will be useful for monitoring pharmaceutical concentrations in blood.


Asunto(s)
Análisis Químico de la Sangre/métodos , Recolección de Muestras de Sangre/métodos , Membranas Artificiales , Preparaciones Farmacéuticas/aislamiento & purificación , Animales , Aniones/química , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Caballos , Humanos , Preparaciones Farmacéuticas/sangre , Preparaciones Farmacéuticas/química , Fenilpropionatos/sangre , Fenilpropionatos/química , Fenilpropionatos/aislamiento & purificación , Diálisis Renal/instrumentación , Diálisis Renal/métodos , Reproducibilidad de los Resultados , Salicilatos/sangre , Salicilatos/química , Salicilatos/aislamiento & purificación , Factores de Tiempo
13.
Nephron ; 138(3): 186-191, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29131112

RESUMEN

BACKGROUND: Acute metabolic acidosis is rarely associated with a reduced or negative anion gap (AG), but several case reports have described such an abnormality occurring in the setting of acute salicylate intoxication. The underlying cause of this phenomenon is unclear. METHODS: In this retrospective cohort study, we reviewed our institutional database to identify all patients admitted for salicylate intoxication at Mayo Clinic (Rochester, MN, USA) from January 2010 through December 2012. Serum chloride was measured with the Cobas INTEGRA 400 plus electrode (expedited laboratory test) or Cobas 6000 (routine laboratory test). We compared blood chloride levels measured by the 2 devices in the presence of positive blood salicylate level. RESULTS: Twelve adult patients with salicylate levels >20 mg/dL had markedly elevated chloride concentrations. The median (interquartile range) chloride level at admission was 120 (107-145) mmol/L on their initial laboratory studies, resulting in reduced or even negative AGs. None of the patients had bromide toxicity, nor did they have any other identifiable cause of hyperchloremia or decreased AG. Further testing of the same blood samples with an alternative measurement system (Roche Cobas 6000) yielded normal chloride values, indicating that falsely elevated chloride values with the initial testing led to the diminished or negative AG values. CONCLUSION: Circulating levels of salicylate can interfere with chloride measured by using routine techniques, resulting in spurious hyperchloremia outcomes and erroneous AG values. In patients with acute metabolic acidosis and abnormally reduced or negative AG, salicylate interference with chloride measurement should be suspected.


Asunto(s)
Cloruros/sangre , Salicilatos/sangre , Acidosis/sangre , Adolescente , Adulto , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Bromuros/efectos adversos , Estudios de Cohortes , Bases de Datos Factuales , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Desequilibrio Hidroelectrolítico , Adulto Joven
14.
BMJ Case Rep ; 20172017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-29196311

RESUMEN

For patients who have had a recent neurosurgical procedure, a visit to the emergency department for encephalopathy may automatically prompt a neurosurgical consult. We present a case of a patient with a history of Chiari malformation decompressed 6 months prior who presented with a 2-week history of slowly progressive altered mental status, headache and imbalance-symptoms consistent with her initial Chiari symptoms, so neurosurgery was consulted. Imaging showed no acute abnormality, but laboratory results revealed metabolic acidosis with high salicylate levels. When reporting medication use, this patient initially left out that she had been taking Goody's powder (845 mg aspirin) for headaches, and long-term use led to metabolic encephalopathy. Despite a recent history of surgery, it is important to keep the differential diagnosis broad especially when there are signs of metabolic derangement.


Asunto(s)
Acidosis/inducido químicamente , Encefalopatías/inducido químicamente , Encéfalo/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Salicilatos/efectos adversos , Acidosis/sangre , Cuidados Posteriores , Malformación de Arnold-Chiari/complicaciones , Malformación de Arnold-Chiari/cirugía , Encéfalo/diagnóstico por imagen , Encefalopatías/sangre , Encefalopatías/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Cefalea/diagnóstico , Cefalea/etiología , Humanos , Infusiones Intravenosas , Trastornos Mentales/diagnóstico , Trastornos Mentales/etiología , Persona de Mediana Edad , Salicilatos/sangre , Salicilatos/uso terapéutico , Bicarbonato de Sodio/administración & dosificación , Bicarbonato de Sodio/uso terapéutico , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento
15.
Biomed Pharmacother ; 95: 513-519, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28866418

RESUMEN

Through a simple PEG-conjugation of the natural product Amorfrutin B, we enhanced its pharmacokinetic profile. The PEGylated molecule displayed significantly improved gastrointestinal absorption (p<0.05) and had a longer systemic circulation life (p<0.05). Oral glucose tolerance study showed PEGylated Amorfrutin B displayed longer protection against oral glucose load compared to Amorfrutin B (p<0.05). It also showed significant improvement in glucose uptake in-vitro by T3T-L1 adipocytes (p<0.05). The PEGylated molecule also showed reduced propensity of crossing the blood brain barrier and accumulating in the brain (p<0.05). It also showed reduced accumulation in the adipose tissue. Preliminary liver and kidney toxicity screening showed no significant alteration in liver or kidney function of Amorfrutin B or its PEGylated form. In conclusion, PEG modification can be an attractive strategy to reduce lipophilicity and enhance pharmacokinetic properties of natural products, derived from traditional medicine.


Asunto(s)
Adipocitos/metabolismo , Fabaceae/química , Absorción Gástrica/efectos de los fármacos , Glucosa/metabolismo , Polietilenglicoles/química , Salicilatos/sangre , Salicilatos/farmacología , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Animales , Prueba de Tolerancia a la Glucosa , Semivida , Insulina/sangre , Riñón/efectos de los fármacos , Riñón/metabolismo , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Salicilatos/administración & dosificación , Salicilatos/química , Distribución Tisular/efectos de los fármacos , Tritio
17.
Eur J Pharm Sci ; 100: 155-162, 2017 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-28063969

RESUMEN

The main objective of this study was to develop reversed hexagonal (HII) mesophase for transdermal delivery of methyl salicylate. The formulation was prepared, characterized and evaluated for its skin penetration in vitro and skin retention in vivo. Preliminary pharmacodynamics and skin irritation were also investigated. The formulation was identified as hexagonal structure. In vitro study exhibited that HII mesophase enhanced the skin permeation by delivering 2.61 times more methyl salicylate than the commercially available cream. Meanwhile, HII mesophase presented higher bioavailability as AUC(0-24) and AUC(0-∞) were 32.894µg·mL-1 and 32.935µg·mL-1 respectively, while the cream were 12.791µg·mL-1 and 12.970µg·mL-1. Preliminary pharmacodynamics studies demonstrated that HII mesophase possessed anti-inflammatory and analgesic effects for inhibiting paw edema, granuloma and pain. MeSa HII mesophase showed no skin irritation on the normal rat skin. Thus, HII mesophase was considered as an effective delivery system for MeSa.


Asunto(s)
Analgésicos/administración & dosificación , Antiinflamatorios/administración & dosificación , Sistemas de Liberación de Medicamentos , Cristales Líquidos/química , Salicilatos/administración & dosificación , Administración Cutánea , Analgésicos/sangre , Analgésicos/farmacocinética , Analgésicos/uso terapéutico , Animales , Antiinflamatorios/sangre , Antiinflamatorios/farmacocinética , Antiinflamatorios/uso terapéutico , Disponibilidad Biológica , Edema/tratamiento farmacológico , Alcoholes Grasos/química , Femenino , Masculino , Ratones , Dolor/tratamiento farmacológico , Ratas Wistar , Salicilatos/sangre , Salicilatos/farmacocinética , Salicilatos/uso terapéutico , Piel/efectos de los fármacos , Piel/metabolismo , Absorción Cutánea , Pruebas de Irritación de la Piel
18.
Pediatr Emerg Care ; 33(11): e126-e127, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27749632

RESUMEN

We report the case of a 17-year-old girl with a 126-mg/kg nonenteric coated aspirin ingestion with nontoxic salicylate concentrations at 1.5 and 3.9 hours postingestion, who developed tinnitus and vomiting an estimated 8 hours postingestion, and who was subsequently found to have a toxic salicylate concentration at 22.7 hours postingestion. This case, as well as previous cases of delayed aspirin therapy, may prompt providers to consider educating patients and their care providers regarding the need to return for further testing if symptoms, such as vomiting or tinnitus, develop after an aspirin ingestion.


Asunto(s)
Antiinflamatorios no Esteroideos/envenenamiento , Aspirina/envenenamiento , Sobredosis de Droga/diagnóstico , Salicilatos/envenenamiento , Adolescente , Femenino , Humanos , Salicilatos/sangre , Factores de Tiempo
19.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1041-1042: 85-93, 2017 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-28013179

RESUMEN

A highly sensitive method using ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS) has been developed and validated for the simultaneous identification and quantification of ginkgolic acids and semi-quantification of their metabolites in rat plasma. For the five selected ginkgolic acids, the method was found to be with good linearities (r>0.9991), good intra- and inter-day precisions (RSD<15%), and good accuracies (RE, from -10.33% to 4.92%) as well. Extraction recoveries, matrix effects and stabilities for rat plasm samples were within the required limits. The validated method was successfully applied to investigate the pharmacokinetics of the five ginkgolic acids in rat plasma after oral administration of 3 dosage groups (900mg/kg, 300mg/kg and 100mg/kg). Meanwhile, six metabolites of GA (15:1) and GA (17:1) were identified by comparison of MS data with reported values. The results of validation in terms of linear ranges, precisions and stabilities were established for semi-quantification of metabolites. The curves of relative changes of these metabolites during the metabolic process were constructed by plotting the peak area ratios of metabolites to salicylic acid (internal standard, IS), respectively. Double peaks were observed in all 3 dose groups. Different type of metabolites and different dosage of each metabolite both resulted in different Tmax.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodos , Salicilatos/sangre , Administración Oral , Animales , Estabilidad de Medicamentos , Límite de Detección , Modelos Lineales , Ratas , Reproducibilidad de los Resultados , Salicilatos/administración & dosificación , Salicilatos/química , Salicilatos/farmacocinética
20.
Clin Toxicol (Phila) ; 54(9): 857-861, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27383649

RESUMEN

BACKGROUND: Salicylate absorption following overdose of aspirin (ASA) tablet formulations can be prolonged for greater than 24 h. Accordingly, serial serum concentrations are typically recommended to guide treatment. However, there are little published data on absorption following ingestion of powder ASA formulations, and it is not known if delayed ASA absorption occurs following overdose of powder formulations. The objective of this study is to compare the absorption characteristics of powder and tablet formulations of ASA in patients reported to a single poison center. METHODS: Electronic records from an accredited poison center were searched for single substance acute or acute on chronic ingestions of ASA in powder form between 1 January 2002 and 31 January 2014. An identical search for ingestions of ASA tablet products between 1 January 2012 and 31 December 2013 was undertaken as the comparator group. Other inclusion criteria were age >12 years, documented time of ingestion, treatment in a health care facility within nine hours of ingestion and at least two detectable serum salicylate concentrations. RESULTS: 16 of 25 powder and 22 of 49 tablet cases met inclusion criteria for analysis. Repeat serum salicylate concentrations following ingestion of tablets increased or insignificantly changed in 11 of 22 (50%) cases, and median serum salicylate concentrations in followed cases remained elevated for up to 12 h in some cases. In comparison, serum salicylate concentrations following powder ingestions declined in 15 of 16 (94%) cases. One patient, who ingested a powder product, underwent hemodialysis pursuant to an initial serum salicylate concentration of 96 mg/dL. CONCLUSIONS: In contrast to persistent concentrations following overdose of tablets, the majority of serum salicylate concentrations declined following ingestion of powder formulations. In this small study population, these findings suggest that prolonged absorption is unlikely following ingestions of ASA powders.


Asunto(s)
Antiinflamatorios no Esteroideos/envenenamiento , Aspirina/envenenamiento , Centros de Control de Intoxicaciones , Salicilatos/sangre , Adolescente , Adulto , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacocinética , Aspirina/administración & dosificación , Aspirina/farmacocinética , Sobredosis de Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polvos , Diálisis Renal/métodos , Estudios Retrospectivos , Comprimidos , Factores de Tiempo , Adulto Joven
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