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 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 Population Pharmacokinetics Modelling and Simulation of Mitotane in Patients with Adrenocortical Carcinoma: An Individualized Dose Regimen to Target All Patients at Three Months?

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 566 ◽  
Author(s):  
Yoann Cazaubon ◽  
Yohann Talineau ◽  
Catherine Feliu ◽  
Céline Konecki ◽  
Jennifer Russello ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Plasma Concentrations ◽  
Therapeutic Index ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Concentration Data ◽  
Starting Dose ◽  
Dosing Regimens ◽  
Data Files

Mitotane is the most effective agent in post-operative treatment of adrenocortical carcinoma. In adults, the starting dose is 2–3 g/day and should be slightly increased to reach the therapeutic index of 14–20 mg/L. This study developed a population PK model for mitotane and to simulate recommended/high dosing regimens. We retrospectively analyzed the data files of 38 patients with 503 plasma concentrations for the pharmacokinetic analysis. Monolix version 2019R1 was used for non-linear mixed-effects modelling. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA ≥ 14 mg/L) at one month and at three months. Mitotane concentration data were best described by a linear one-compartment model. The estimated PK parameters (between-subject variability) were: 8900 L (90.4%) for central volume of distribution (V) and 70 L·h−1 (29.3%) for clearance (Cl). HDL, Triglyceride (Tg) and a latent covariate were found to influence Cl. The PTA at three months for 3, 6, 9, and 12 g per day was 10%, 55%, 76%, and 85%, respectively. For a loading dose of 15 g/day for one month then 5 g/day, the PTA in the first and third months was 57 and 69%, respectively. This is the first PKpop model of mitotane highlighting the effect of HDL and Tg covariates on the clearance as well as a subpopulation of ultrafast metabolizer. The simulations suggest that recommended dose regimens are not enough to target the therapeutic threshold in the third month.

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.

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.

scholarly journals UN METODO SPETTROSCOPICO PER LA QUANTIFICAZIONE DI FARMACI IN FLUIDI BIOLOGICI

2020 ◽  
Author(s):  
Paolo Maria Ossi, et al. (#)
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Concentration ◽  
Biological Fluids ◽  
Therapeutic Index ◽  
Spectroscopic Technique ◽  
Metallic Surface ◽  
Narrow Therapeutic Index ◽  
Anti Epileptic Drug ◽  
Spectroscopic Signatures

An innovative spectroscopic technique to determine the drug concentration in biological fluids is discussed. We introduce the context of drugs with narrow therapeutic index in relation to epilepsy and Parkinson’s disease. We then recapitulate the essentials of Raman and enhanced Raman spectroscopy that makes use of a corrugated metallic surface. Optimizing the intensification of the spectroscopic signatures of a given analyte critically depends on the metal choice and on the fine details of the induced surface nanostructuring. We review the topic with emphasis on noble metal surfaces synthesized by pulsed laser ablation in inert gas at high pressure. The performance of optimized surfaces to determine the drug concentration in different fluids, including human blood, is discussed with reference to carbamazepine, an anti-epileptic drug widely adopted in Developing Countries and to apomorphine, a drug used to treat via subcutaneous injection patients with important manifestations of Parkinson’s disease.

Concentration of Glutethimide and Associated Compounds in Human Serum and Cerebrospinal Fluid After Drug Overdose

1974 ◽  
Vol 20 (2) ◽  
pp. 195-199 ◽  
Author(s):  
Martin Gold ◽  
Ernest Tassoni ◽  
Michael Etzl ◽  
George Mathew
Keyword(s):  
Gas Chromatography ◽  
Cerebrospinal Fluid ◽  
Liquid Chromatography ◽  
Serum Concentration ◽  
Human Serum ◽  
Drug Overdose ◽  
Gas Liquid Chromatography ◽  
Maximum Serum ◽  
Maximum Serum Concentration ◽  
Maximal Serum Concentration

Abstract Serum and cerebrospinal fluid of patients in coma owing to glutethimide overdose was assayed for glutethimide and associated compounds. The sample was extracted with chloroform and the extract assayed by gas-liquid chromatography on a column of "3% OV-17." Up to six constituents were found in serum in addition to glutethimide, only three of which were ever present in substantial quantity. The peaks seen on gas chromatography were numbered in order of elution. Glutethimide was peak No. 2. Peak No. 1 usually reached a maximum serum concentration in 10 or less hours, as did peak No. 4. Peak No. 3 reached a maximal serum concentration in 10 h or sooner also, but at 20 h the amount had changed little in most patients. Ambre and Fischer [Res. Commun. Pathol. Pharmacol. 4, 307 (1972)] speculate that peak No. 3 plays an important role in maintaining coma. Neither the pattern of change nor the relative concentrations in serum or cerebrospinal fluid on waking support their hypothesis.

Case of Severe Acute-on-Chronic Lithium Intoxication with 8.6 mmol/l and Prompt Hemodialysis

2020 ◽  
Vol 53 (05) ◽  
pp. 235-236
Author(s):  
Robert Haussmann ◽  
Markus Donix ◽  
Michael Bauer ◽  
Simone von Bonin ◽  
Ute Lewitzka
Keyword(s):  
Bipolar Disorder ◽  
Gold Standard ◽  
Therapeutic Index ◽  
Clinical Problem ◽  
Term Treatment ◽  
Optimal Treatment ◽  
Lithium Intoxication ◽  
Narrow Therapeutic Index ◽  
Long Term Treatment

Lithium has been the gold standard in the long-term treatment of bipolar disorder for more than 40 years 1. Due to a narrow therapeutic index lithium intoxication still is a common but potentially avoidable clinical problem 2. The possibility of SILENT-syndrome (syndrome of irreversible lithium-effectuated neurotoxicity) illustrates that prevention and optimal treatment of lithium intoxication is vitally important 3.

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