Propranolol in Children: Safety-Toxicity

PEDIATRICS ◽  
1982 ◽  
Vol 70 (1) ◽  
pp. 30-31
Author(s):  
Michael Artman ◽  
Mitch Grayson ◽  
Robert C. Boerth
Keyword(s):  
Heart Rate Response ◽  
Plasma Concentrations ◽  
Caloric Intake ◽  
High Plasma ◽  
Intravenous Glucose ◽  
First Case ◽  
Acute Ingestion ◽  
Pharmacologic Effect ◽  
Propranolol Therapy ◽  
Very High

Four hours after acute ingestion of 400 to 1,200 mg of propranolol by a healthy, 3-year-old boy, his plasma concentration of propranolol was 2,289 ng/ml. The only pharmacologic effect observed was a diminished heart rate response to crying and activity. In a second case, a 4-year-old boy on chronic propranolol therapy for renovascular hypertension had a hypoglycemic seizure when solid food was refused for three days because of an oral wound. The hypoglycemia was easily managed with intravenous glucose, and there were no sequelae. The first case alludes to the safety of propranolol in a healthy child even with very high plasma concentrations. The second case suggests the necessity of anticipating and avoiding hypoglycemia that can develop in children on chronic propranolol therapy when caloric intake is impaired.

Metabolic Aspects of Hypothermia in the Elderly

1980 ◽  
Vol 59 (1) ◽  
pp. 19-27 ◽  
Author(s):  
H. B. Stoner ◽  
K. N. Frayn ◽  
R. A. Little ◽  
C. J. Threlfall ◽  
D. W. Yates ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ketone Bodies ◽  
Plasma Concentrations ◽  
The Elderly ◽  
High Plasma ◽  
Active Involvement ◽  
Esterified Fatty Acids ◽  
Lipid Metabolites ◽  
High Concentrations ◽  
Very High

1. Plasma concentrations of glucose, lactate, amino acids, non-esterified fatty acids, glycerol, ketone bodies, insulin and cortisol were measured in 43 elderly patients with hypothermia. In 15 of these patients forearm arteriovenous differences were also measured. Core temperatures ranged from 25.9 to 35.5°C. 2. The metabolic state was of mobilization of glycogen and triacylglycerol stores, with high plasma concentrations of lactate and lipid metabolites. The plasma concentration of glucose was raised in those with hypothermia of a short duration (<6 h). In other patients it was low in those with core temperatures around 30°C, but below this temperature it was variable and often high. Concentrations of other metabolites or hormones were not related to core temperature. 3. Plasma concentrations of cortisol were high and positively correlated with those of lactate and glycerol, suggesting active involvement in stimulation of muscle glycogenolysis and of lipolysis. 4. Plasma concentrations of insulin ranged from very low to very high and appeared to depend on the concentrations of both glucose and alanine. 5. Arteriovenous differences were generally small. There was peripheral release of lactate and of amino acids but no overall peripheral uptake of glucose. In nine out of 15 patients there was a significant peripheral release of glucose. 6. No differences in metabolism were observed between patients where the hypothermia appeared accidental and those with an obvious precipitating illness, despite a significantly lower mortality in the former group. 7. It was concluded that therapy should primarily involve rewarming of patients by physical means, without metabolic intervention.

HIGH CORTICOSTEROID LEVELS IN PLASMA OF ADULT AND FOETAL WEDDELL SEALS (LEPTONYCHOTES WEDDELLI)

1979 ◽  
Vol 90 (4) ◽  
pp. 718-726 ◽  
Author(s):  
G. C. Liggins ◽  
J. T. France ◽  
B. S. Knox ◽  
W. M. Zapol
Keyword(s):  
Lean Body Mass ◽  
Body Mass ◽  
Turnover Rate ◽  
Binding Capacity ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Affinity Constant ◽  
Weddell Seals ◽  
Very High ◽  
Main Factor

ABSTRACT Pregnant and non-pregnant Weddell seals and foetuses were found to have very high plasma concentrations of corticosteroids (1–7 μmol/l) that were unaffected by stress. Cortisol comprised most of the corticosteroid in the adult but only 50 % of that in the foetus. The affinity constant (4.30–5.53 × 107 l/mol) and specificity of CBG and the MCR (4.5 l/d/kg lean body mass) in adult seals were similar to those of Man. The binding capacity of CBG (1.48–1.86 μmol/l) which is approximately three times that of Man contributed to the high plasma corticosteroid concentrations but the main factor was the cortisol turnover rate of 3670 μmol/d (1.3 g/d) which is the highest value reported in any species.

Toxicological Studies in a Distalgesic Addict

1986 ◽  
Vol 5 (3) ◽  
pp. 207-210 ◽  
Author(s):  
I. Roberts ◽  
R. J. Flanagan ◽  
J. Strang ◽  
L. F. Prescott
Keyword(s):  
Peak Plasma ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Withdrawal Period ◽  
Total Recovery ◽  
Hepatocellular Damage ◽  
Elimination Half ◽  
Toxicological Studies ◽  
Kinetics Of ◽  
Very High

1 The disposition and kinetics of paracetamol, dextropropoxyphene and their metabolites were investigated in an addict who claimed to be taking 80–100 Distalgesic tablets daily regularly. 2 Plasma concentrations of paracetamol, dextropropoxyphene and their principal metabolites were measured after an oral dose of 15 Distalgesic tablets. 3 The absorption of paracetamol and dextropropoxyphene was rapid with peak plasma concentrations at 15 and 30 min respectively. The elimination half-life for paracetamol was 2.3 h. Nordextropropoxyphene remained at steady state with very high plasma concentrations (5 mg/l). The urinary excretion of paracetamol and metabolites was not abnormal. The total recovery of paracetamol was only 31% of the dose. 4 Apart from raised plasma γ-glutamyltransferase activity there was no biochemical evidence for paracetamol-induced hepatocellular damage despite ingestion of 97.5 g of paracetamol over the 11 days of the withdrawal period.

scholarly journals Plasma concentration and safety of lopinavir/ritonavir in patients with Covid-19: a short communication

2020 ◽  
Author(s):  
Laurent Chouchana ◽  
Sana Boujaafar ◽  
Ines Gana ◽  
Laure-Hélène ◽  
Lucile Regard ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Hiv Treatment ◽  
Off Label ◽  
High Plasma Concentration ◽  
Very High

ABSTRACTBackgroundLopinavir/ritonavir has been proposed as off-label treatment for Covid-19, although efficacy have not been proven. It has previously been shown that lopinavir plasma concentration is dramatically increased in inflammatory settings. As Covid-19 may be associated with major inflammation, assessing lopinavir plasma concentration and its safety in Covid-19 patients is essential.MethodsReal-world Covid-19 experience based on a retrospective study.ResultsOf 31 patients treated by lopinavir/ritonavir for Covid-19, we observed very high lopinavir plasma concentrations, increased of 4.6-fold (IQR, 3.6-6.2) with regards to average plasma concentrations in HIV. All except one patient were above the upper limit of the concentration ranges of HIV treatment. About one over four to five patients prematurely stopped treatment mainly secondary an adverse drug reaction related to hepatic or gastrointestinal disorders.ConclusionLopinavir plasma concentrations in patients with moderate to severe Covid-19 were higher than expected, associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, owing that high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2 as suggested by previous studies, it appears that, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Cautious is necessary as off-label use can be associated with a new drug safety profile.

Small-Angle Electron Scattering (SAES) of Polymers

1985 ◽  
Vol 43 ◽  
pp. 78-79
Author(s):  
Ralph Oralor ◽  
Pamela Lloyd ◽  
Satish Kumar ◽  
W. W. Adams
Keyword(s):  
Electron Scattering ◽  
Small Angle ◽  
Angular Resolution ◽  
Structural Features ◽  
Objective Lens ◽  
High Angular Resolution ◽  
Push Button ◽  
First Case ◽  
Diffraction Mode ◽  
Very High

Small angle electron scattering (SAES) has been used to study structural features of up to several thousand angstroms in polymers, as well as in metals. SAES may be done either in (a) long camera mode by switching off the objective lens current or in (b) selected area diffraction mode. In the first case very high camera lengths (up to 7Ø meters on JEOL 1Ø ØCX) and high angular resolution can be obtained, while in the second case smaller camera lengths (approximately up to 3.6 meters on JEOL 1Ø ØCX) and lower angular resolution is obtainable. We conducted our SAES studies on JEOL 1ØØCX which can be switched to either mode with a push button as a standard feature.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Morgan R. Peltier ◽  
Michael J. Fassett ◽  
Yuko Arita ◽  
Vicki Y. Chiu ◽  
Jiaxiao M. Shi ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Los Angeles ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Plasma Concentrations ◽  
First Trimester ◽  
High Plasma ◽  
Thyroid Stimulating Hormone ◽  
Spontaneous Preterm Birth ◽  
Increased Risk

Abstract Objectives Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. Methods Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. Results We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. Conclusions These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

scholarly journals Validation of an HPLC–MS/MS Method for the Determination of Plasma Ticagrelor and Its Active Metabolite Useful for Research and Clinical Practice

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 278
Author(s):  
Jennifer Lagoutte-Renosi ◽  
Bernard Royer ◽  
Vahideh Rabani ◽  
Siamak Davani
Keyword(s):  
Active Metabolite ◽  
Plasma Concentrations ◽  
Antiplatelet Agent ◽  
High Plasma ◽  
Therapeutic Drug ◽  
Routine Practice ◽  
Daily Routine ◽  
Limit Of Quantification ◽  
Wide Range

Ticagrelor is an antiplatelet agent which is extensively metabolized in an active metabolite: AR-C124910XX. Ticagrelor antagonizes P2Y12 receptors, but recently, this effect on the central nervous system has been linked to the development of dyspnea. Ticagrelor-related dyspnea has been linked to persistently high plasma concentrations of ticagrelor. Therefore, there is a need to develop a simple, rapid, and sensitive method for simultaneous determination of ticagrelor and its active metabolite in human plasma to further investigate the link between concentrations of ticagrelor, its active metabolite, and side effects in routine practice. We present here a new method of quantifying both molecules, suitable for routine practice, validated according to the latest Food and Drug Administration (FDA) guidelines, with a good accuracy and precision (<15% respectively), except for the lower limit of quantification (<20%). We further describe its successful application to plasma samples for a population pharmacokinetics study. The simplicity and rapidity, the wide range of the calibration curve (2–5000 µg/L for ticagrelor and its metabolite), and high throughput make a broad spectrum of applications possible for our method, which can easily be implemented for research, or in daily routine practice such as therapeutic drug monitoring to prevent overdosage and occurrence of adverse events in patients.

Laser-Induced Acoustic Waves for Measurement and Imaging

2000 ◽  
Author(s):  
Wen Li ◽  
Ronald A. Roy ◽  
Robin O. Cleveland ◽  
Lawrence J. Berg ◽  
Charles A. DiMarzio
Keyword(s):  
Acoustic Waves ◽  
Peak Power ◽  
Laser Light ◽  
Short Pulse ◽  
Laser Wavelength ◽  
Acoustic Imaging ◽  
Acoustic Energy ◽  
High Peak Power ◽  
First Case ◽  
Very High

Abstract A short pulse of laser light can act as a source of acoustic energy for acoustic imaging. Although there are a number of mechanisms by which the light pulse may generate sound, all require a pulse of high peak power density and short duration. In this work, we address examples where the material is highly absorbing at the laser wavelength, and the sound is generated near the surface. In these cases, there exist two different mechanisms which can convert the light to sound. The first is heating followed by expansion, and the second is generation of a plasma in the air above the surface. In the first case, sound generation occurs in the medium of interest and the energy efficiency can be very high, in the sense that no reflection losses occur. We present two applications from our own research.

Isavuconazole: Case Report and Pharmacokinetic Considerations

Chemotherapy ◽  
2018 ◽  
Vol 63 (5) ◽  
pp. 253-256 ◽  
Author(s):  
Francesco Marchesi ◽  
Corrado Girmenia ◽  
Bianca Maria Goffredo ◽  
Emanuela Salvatorelli ◽  
Atelda Romano ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Real Life ◽  
Concomitant Administration ◽  
Invasive Fungal Disease ◽  
High Plasma ◽  
Adult Patients ◽  
Therapeutic Drug ◽  
Hepatic Toxicity ◽  
Maintenance Chemotherapy

Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom treatment with amphotericin B is inappropriate. In clinical trials, IVZ showed linear pharmacokinetics and little or no evidence for interactions with other drugs. There is only modest evidence on IVZ pharmacokinetics and TDM in real-life settings. Here, we report on IVZ pharmacokinetics in a young adult with Ph chromosome-negative acute lymphoblastic leukemia (ALL) who developed a “probable” IA during induction chemotherapy. The patient was initially treated with VCZ, but she developed a severe hepatic toxicity that was associated to the high plasma levels of VCZ. Therefore, VCZ was discontinued and the patient was switched to IVZ. After a loading dose of IVZ, the patient remained on IVZ for 5 months while also receiving standard maintenance chemotherapy for ALL. At day 65 after the start of IVZ, the patient experienced a significant hepatic toxicity; however, no change in IVZ plasma concentrations was observed in the face of a concomitant administration of many other drugs (cancer drugs, antiemetics, other anti-infectives). Hepatic toxicity resolved after discontinuing maintenance chemotherapy but not IVZ. These results show that (i) IVZ plasma concentrations remained stable throughout and were not affected by concomitant ALL therapy, and (ii) there was no relation between IVZ plasma concentration and hepatic toxicity. Thus, in clinical practice IVZ may not require TDM.

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