scholarly journals Impact of insulin adsorption in various container during hyperkalemia treatment

2021 ◽  
Author(s):  
Thomas Robert ◽  
Patrice Vanelle ◽  
Philippe Brunet ◽  
Nathalie Martin ◽  
Stéphane Burtey ◽  
...  
Keyword(s):  
High Performance ◽  
Therapeutic Index ◽  
Insulin Delivery ◽  
Insulin Concentration ◽  
Narrow Therapeutic Index ◽  
Intravenous Insulin ◽  
Time Average ◽  
Clinically Significant ◽  
Glucose Therapy ◽  
Treatment Procedures

Abstract Background The insulin-glucose therapy in hyperkalemia treatment had a narrow therapeutic index for a safe and efficient use. We assess the variability of the effective delivered insulin under conditions used in the setting of hyperkalemia treatment. Methods A range of simulated insulin infusions was studied using different containers (bag or syringes) according of the different hyperkalemia treatment procedures of our institution. Insulin concentration was assayed using a chromatographic method on an automatic high-performance liquid chromatography. We calculated the effective delivered insulin and compared the time-average of percentage delivered insulin (TAdi) between all the procedures. Results The TAdi is significantly decreased to 63.3% of the expected insulin delivery in the polyurethane (PE) bag compared to allover container. The procedure duration and the insulin concentration influenced the variability of the insulin delivery in the PE and glass (G) bag. The polyvinyl chloride (PVC) bag have the highest TAdi at 93.8% without significant variation during the time. TAdi reach around 90% of the expected insulin with all the syringe procedure without variation according the solute used to dilute insulin. Conclusions Clinically significant variations in intravenous insulin delivery occur in the setting of hyperkalemia treatment according to the container. The use of propylene syringe limits the insulin delivery variation. In the future, clinical studies on hyperkalemia treatment by insulin-glucose therapy should detailed the procedure precisely.

scholarly journals Pharmacokinetic Disposition of Amiodarone When Given with an Intralipid Rescue Strategy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 539
Author(s):  
Sean N. Avedissian ◽  
Michelle Pham ◽  
Medha D. Joshi ◽  
Marc H. Scheetz ◽  
Ashkan Salamatipour ◽  
...  
Keyword(s):  
High Performance ◽  
Therapeutic Index ◽  
Hplc Method ◽  
Control Group ◽  
Swine Model ◽  
Narrow Therapeutic Index ◽  
Time Curve ◽  
Target Organs ◽  
Acute Overdose ◽  
Intravenous Amiodarone

While the antiarrhythmic drug amiodarone is commonly used in clinical practice, it has a narrow therapeutic index that can lead to acute overdose. One proposed method to deal with this toxicity is lipid emulsion therapy, which may potentially quench the free amiodarone in blood and prevent its further distribution to target organs and tissues. In this study, we utilize an established swine model to examine the effects of Intralipid™ (IL) administration for acute amiodarone toxicity. A total of 14 pigs received an overdose of intravenous amiodarone. After twenty minutes, half of the pigs (n = 7) received IL while the control group (n = 7) received normal saline. Serum concentrations of amiodarone were then analyzed using a validated high-performance liquid chromatography (HPLC) method. Noncompartmental pharmacokinetic analyses were performed on the observed concentrations. There were no statistical differences in the area under the concentration time curve (6 h) or clearance, but there was a difference in the half-life between the two groups (3.12 vs. 0.85 h, p = 0.01). The administration of IL did not statistically change the overall exposure of amiodarone in the blood in the first 6 h; however, trends toward prolonged blood retention in the IL group were seen.

scholarly journals Assessing Bioequivalence of Antiepileptic Drugs: Are the Current Requirements too Permissive?

2014 ◽  
Vol 17 (2) ◽  
pp. 220 ◽  
Author(s):  
Camila F Rediguieri ◽  
Jorge L Zeredo
Keyword(s):  
Antiepileptic Drugs ◽  
Geometric Mean ◽  
Therapeutic Index ◽  
Maximum Deviation ◽  
Strongly Correlated ◽  
Average Difference ◽  
Narrow Therapeutic Index ◽  
Subject Variability ◽  
Clinically Significant ◽  
Narrow Therapeutic Index Drugs

Purpose: In order to evaluate the permissiveness of current bioequivalence requirements for antiepileptic drugs we investigated how accurate Cmax and AUC0-t of generic antiepileptic drugs approved in Brazil are in comparison to reference products. Methods: Data collected from assessment reports of approved bioequivalence studies archived in the Brazilian regulatory agency in 2007-2012 were: geometric mean ratios and 90% confidence intervals (CI) for Cmax and AUC0-t, intra-subject variability (CV) of Cmax and AUC0-t and number of subjects. Results: The average difference in Cmax and AUC0-t between generic and reference products was 5% and 3%, respectively. Maximum deviation from 1.00 of the CI of Cmax can achieve 15-20% (demonstrated in 27% of studies); for AUC0-t, 25% of studies showed the deviation can be >10%. All studies that used adequate number of subjects for a 90% CI of 0.90-1.11 complied with it for AUC0-t, except one of carbamazepine, but only 33% complied with it for both AUC0-t and Cmax. The CV was strongly correlated to the maximum CI deviation for AUC0-t (CV of approximately 15% corresponding to deviation of 10%). Studies that presented maximum CI deviation ≤ 10 % together with CV ≤ 15% for AUC0-t represented 65% of the total. Weaker correlation was observed for Cmax and no correlation was seen between maximum CI deviation and number of subjects. Conclusions: Modification in legislation for bioequivalence of antiepileptic drugs is suggested, not only with constraint of AUC0-t 90% CI to 0.90-1.11, but also with limitation of the CV to 15%, as to assure similar variance in pharmacokinetics and diminish the risk of critical plasma-level fluctuation when switching between generic and reference formulations. Although most generics presented differences ≤ 10% in AUC0-t compared to their references, some narrow therapeutic index drugs displayed differences that could be clinically significant after product substitution.  This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals NARROW THERAPEUTIC INDEX DRUGS;

2017 ◽  
Vol 24 (04) ◽  
pp. 596-606
Author(s):  
Huma Ali ◽  
Farya Zafar ◽  
Ahmed Shaukat ◽  
Shazia Alam ◽  
Umer Ali ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Study Design ◽  
Study Participant ◽  
Therapeutic Index ◽  
Narrow Therapeutic Index ◽  
High Incidence ◽  
Hospital Stays ◽  
Clinically Significant ◽  
Narrow Therapeutic Index Drugs ◽  
Selection Of

Introduction: There are several clinically significant outcomes of drug-druginteractions (DDIs) which have been classified as one of the serious forms of adverse drugreactions that may lead to prolongation of hospital stays along with severe cases of mortality andmorbidities. It may cause due to the selection of two or more interacting drugs to be prescribedto patient. Objectives: Therefore it is indispensable to attain a collective level of therapeuticdecision making so that any potential DDIs can be minimized that ultimately turn out to be safeand beneficial to patient. Study Design: The current study is based upon surveys to evaluateutilization of medications that have a narrow therapeutic range with high incidence to developDDIs and to access the knowledge, attitude as well as practice of using such drug productsin relation to these facts, though very few such studies have been identified, yet the relevantdata is insufficient locally. The study design was selected to be qualitative and cross sectional.Period: January 2016 till August 2016 in Karachi, Pakistan. Settings: The questionnaire waswell constructed for physicians, pharmacists as well as nurses who were selected as theparticipant of the study and a former consent from the respondents was obtained. Method:Coefficient of spearman correlation & Cronbach’s α values were calculated in order to validatethe questionnaire (α = 0.927 and p = 0.918). The information based on practice along withdemographics of study participant was included as first segment of questionnaire while theirknowledge regarding drug interactions was included as second part. Mean scores werecalculated and responses were analysed by ANOVA in relation to the knowledge of membersrelating to drug interactions of vancomycin, warfarin and valproic acid. Results: Mean scores ofperception were found in order of 1.590.16, 1.549.02 and 2.020.83 for physicians, pharmacistsand nurses. No significant differences were observed between physicians and pharmacistscohorts in identifying the drug interactions whereas noteworthy variations were observed inthe group of nurses (p < 0.05). Conclusion: Such investigations are vital in their prospect tohighlight the importance for the design, implementation and monitoring of an effectual toolfor the guidance of various healthcare members involved in identification and management ofDDIs. Furthermore, results also signify the need of sophisticated support systems for valuableclinical judgments.

scholarly journals The art and science of drug titration

2020 ◽  
Vol 11 ◽  
pp. 204209862095891
Author(s):  
Aisling R. Caffrey ◽  
Eric P. Borrelli
Keyword(s):  
Real World ◽  
Therapeutic Index ◽  
Clinical Expertise ◽  
Coordination Of Care ◽  
Patient Centered ◽  
Narrow Therapeutic Index ◽  
Drug Dosing ◽  
Scientific Principles ◽  
Suboptimal Adherence ◽  
Personalized Approach

A “one-size-fits-all” approach has been the standard for drug dosing, in particular for agents with a wide therapeutic index. The scientific principles of drug titration, most commonly used for medications with a narrow therapeutic index, are to give the patient adequate and effective treatment, at the lowest dose possible, with the aim of minimizing unnecessary medication use and side effects. The art of drug titration involves the interplay of scientific drug titration principles with the clinical expertise of the healthcare provider, and an individualized, patient-centered partnership between the provider and the patient to review the delicate balance of perceived benefits and risks from both perspectives. Drug titration may occur as up-, down-, or cross-titration depending on whether the goal is to reach or maintain a therapeutic outcome, decrease the risk of adverse effects, or prevent withdrawal/discontinuation syndromes or recurrence of disease. Drug titration introduces additional complexities surrounding the conduct of clinical trials and real-world studies, confounding our understanding of the true effect of medications. In clinical practice, wide variations in titration schedules may exist due to a lack of evidence and consensus on titration approaches that achieve an optimal benefit-harm profile. Further, drug titration may be challenging for patients to follow, resulting in suboptimal adherence and may require increased healthcare-related visits and coordination of care amongst providers. Despite the challenges associated with drug titration, it is a personalized approach to drug dosing that blends science with art, and with supportive real-world outcomes-based evidence, can be effective for optimizing pharmacotherapeutic outcomes and improving drug safety.

scholarly journals Systematic treatment and prevention of cardiac digoxin toxicity

2021 ◽  
Author(s):  
Omar Rezk Alshaer ◽  
Abdullah Obaid Binobaid ◽  
Abdelelah Hesham Mofti ◽  
Mohannad Mahmood Sadagah ◽  
Khalid Mustafa Olwi ◽  
...  
Keyword(s):  
Therapeutic Index ◽  
Digoxin Toxicity ◽  
Clinical Settings ◽  
Clinical Effects ◽  
Systematic Treatment ◽  
Narrow Therapeutic Index ◽  
Serious Adverse Events ◽  
Treatment And Prevention ◽  
Cost Efficacy ◽  
The Cost

Digoxin has a narrow therapeutic index, such as complicated pharmacokinetics and dynamics.  Many drug interactions may occur when the administration of one drug alters the clinical effects of another. As a result, digoxin toxicity can be a common condition within clinical settings that might lead to the development of many morbidities and even mortality. Many studies were published to investigate the efficacy and safety of different management modalities to enhance the outcomes that follow digoxin administration. The aim of the study was to discuss the approaches to systematically treat and prevent the development of cardiac digoxin toxicity. The findings are based on evidence from previous studies in the literature. To be specific, Fab fragments are the most effective modalities that can be used to treat severe cases within ideal periods. However, evidence regarding their administration for asymptomatic or mild cases is still poor regarding the cost-efficacy and the development of serious adverse events. Physicians should primarily care for a better intervention as it is usually associated with a significantly more enhanced prognosis and clinical outcomes. Nevertheless, adequate monitoring of the patients and evaluation of their personal and medical history are important steps in the process, and further approaches are still needed. Also, detailed information about our intended outcomes is furtherly discussed within the manuscript.

Nano optical and electrochemical sensors and biosensors for detection of narrow therapeutic index drugs

2021 ◽  
Vol 188 (12) ◽  
Author(s):  
Omid Heydari Shayesteh ◽  
Reza Mahjub ◽  
Akram Ranjbar ◽  
Katayoun Derakhshandeh ◽  
Mahdi Jamshidi
Keyword(s):  
Electrochemical Sensors ◽  
Therapeutic Index ◽  
Narrow Therapeutic Index ◽  
Narrow Therapeutic Index Drugs

scholarly journals A comparative evaluation of lithium estimation for samples collected in different tubes and its stability on storage

2018 ◽  
Vol 10 (01) ◽  
pp. 056-059
Author(s):  
Saidaiah Ikkurthi ◽  
Srinivas Balachander ◽  
Bela Goyal ◽  
Altaf Ahmad Mir ◽  
Subho Chakrabarti ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Therapeutic Index ◽  
Blood Collection ◽  
Narrow Therapeutic Index ◽  
Glass Vial ◽  
Reference Collection ◽  
Collection Tube ◽  
Allowable Error ◽  
Bipolar Affective Disorders ◽  
Clot Activator

Abstract PURPOSE: Lithium (Li) is a well-established drug for the treatment of bipolar affective disorders. Li as a drug is known to possess a narrow therapeutic index. Thus, regular monitoring of blood Li in patients receiving Li therapy is essential. Plain tubes with clot activator are known to interfere with Li estimation. The current study was planned to compare Li estimation in sera from vacutainers with clot activator, and plasma from sodium heparinized vacutainers with that of Li estimation in sera from glass vials. The time-dependant stability of Li estimation on storage at 2°C–8°C for 48 h in these three set of tubes was also evaluated. MATERIALS AND METHODS: Blood from the patients on Li therapy (n = 100) was collected in 3 different collection tubes: plain vacutainer with clot activator (S), Sodium heparinized vacutainer (P) and Glass vial (G) and was analyzed by ion selective electrode (ISE) analyzer for Li levels. Secondary aliquots were also taken from each type of collection tube and stored at 2°C–8°C. Time-dependant stability of Li estimation was checked at 12 h, 24 h, and 48 h. ANOVA followed by Tukey's posttest was performed to calculate statistical significance taking glass vial as reference collection tube. Bland–Altman plots were plotted to compare between three collection tubes at baseline. Stability on storage was defined when >95% of the samples were within allowable error limit for that time point taking baseline levels as reference. RESULTS: A mean bias of 0.18 mmol/L and mean percentage bias of 19.9% in Li levels was observed between serum from (S) than serum from (G). This difference was found to be statistically significant. However, statistically nonsignificant mean bias of 0.02 mmol/L and mean percentage bias of 3.34% in Li levels was observed between plasma from (P) and serum from (G). Time-dependant stability was observed more in glass vials as compared to vacutainers with clot activator or sodium heparin. CONCLUSION: Serum from glass vial should be the preferred method for blood collection to determine Li levels.

Toxicity Related to Chloroquine Treatment of Resistant Vivax Malaria

2003 ◽  
Vol 37 (4) ◽  
pp. 526-529 ◽  
Author(s):  
Timothy ME Davis ◽  
David A Syed ◽  
Kenneth F Ilett ◽  
P Hugh R Barrett
Keyword(s):  
Vivax Malaria ◽  
Information Sources ◽  
Therapeutic Index ◽  
Narrow Therapeutic Index ◽  
Maximum Serum ◽  
Case Summary ◽  
Adequate Information ◽  
Chloroquine Treatment ◽  
Dosing Regimens ◽  
Maximum Serum Concentration

OBJECTIVE: To report a case of severe chloroquine toxicity in the presence of high-grade chloroquine-resistant Plasmodium vivax. CASE SUMMARY: A febrile 36-year-old seaman from Mumbai (Bombay) was prescribed >5 times the usual dose of chloroquine for malaria diagnosed empirically onboard ship. His fever resolved, but he developed symptoms consistent with those of chloroquine toxicity. Fever recurred 30 days after his initial presentation, and blood smear–positive vivax malaria was diagnosed. A serum chloroquine concentration at this time (91 μg/L) was above that considered effective for chloroquine-sensitive P. vivax (>15 μg/L). The patient responded to atovaquone plus proguanil followed by primaquine. DISCUSSION: The patient was given chloroquine by his captain in a dosage regimen appropriate for quinine (2 tablets 3 times daily for 7 d). Pharmacokinetic modeling suggested that the patient's initial over-treatment was as reported and that the predicted maximum serum concentration of chloroquine (902 μg/L) was within the range seen in fatal chloroquine overdose. CONCLUSIONS: Chloroquine-resistant vivax malaria is increasingly widespread, and transmission can occur within large tropical population centers. For drugs with a narrow therapeutic index such as chloroquine, recommended dosing regimens should be respected, and adequate information sources must be available where such drugs are dispensed by untrained personnel.

scholarly journals Polypharmacy May Be the Cause of Acute Lithium Intoxication at the Second Day of Treatment

Folia Medica ◽  
2016 ◽  
Vol 57 (3-4) ◽  
pp. 261-263 ◽  
Author(s):  
Irfan Tursun ◽  
Gokhan Tazegul ◽  
Ogur Karhan ◽  
Neslihan Gunes ◽  
Ece Ulukal ◽  
...  
Keyword(s):  
Mood Stabilizer ◽  
Therapeutic Index ◽  
Altered Mental Status ◽  
Muscle Rigidity ◽  
Lithium Intoxication ◽  
Lithium Level ◽  
Narrow Therapeutic Index ◽  
History Of ◽  
Acute Lithium ◽  
History Of Parkinson’S Disease

Abstract Lithium is frequently used as a mood stabilizer in patients with mood disorders. Lithium has a narrow therapeutic index and high toxicity. Predisposing factors for intoxication are advanced age, diet disturbances, comorbid medical conditions affecting heart, kidneys or central nervous system and polypharmacy. CASE REPORT: Here we present a case of a 74-year-old woman with a history of Parkinson’s disease, hypertension and bipolar disorder. She was using quetiapine, valsartan with hydrochlorothiazide and levodopa with carbidopa. She presented with altered mental status and muscle rigidity. The patient was admitted with acute lithium intoxication after her second dose of treatment. Blood lithium level increased to 3.58 mEq/L. The woman was hospitalized in the Internal Medicine Intensive Care Unit. With hydration, her symptoms resolved and her lithium level returned to normal after 118 hours. CONCLUSIONS: Prescribing physicians and emergency room physicians should be aware of conditions which may cause a decreased threshold for intoxication.

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