Erratum to: Drug-Induced Phospholipidosis: Prediction, Detection, and Mitigation Strategies

2014 ◽  
pp. 387-387
Author(s):  
Umesh M. Hanumegowda ◽  
Alicia Regueiro-Ren
Keyword(s):  
Mitigation Strategies ◽  
Drug Induced

Drug-Induced QTc Prolongation: What We Know and Where We Are Going

2021 ◽  
Vol 16 ◽  
Author(s):  
Erinn Mangona ◽  
Elisa Sandonato ◽  
Todd N. Brothers ◽  
Jayne Pawasauskas
Keyword(s):  
Torsades De Pointes ◽  
Clinical Decision ◽  
Mitigation Strategies ◽  
Qtc Prolongation ◽  
Drug Induced ◽  
Drug Classes ◽  
Malignant Arrhythmia ◽  
Alternative Agent ◽  
Risk Scoring ◽  
Scoring Tool

: Drug-induced QTc prolongation is a concerning electrocardiogram (ECG) abnormality. This cardiac disturbance carries a 10% risk of sudden cardiac death due to the malignant arrhythmia, Torsades de Pointes. The Arizona Center for Education and Research on Therapeutics (AzCERT) has classified QTc prolonging therapeutic classes such as antiarrhythmics, antipsychotics, anti-infectives, and others. AzCERT criteria categorizes medications into three risk categories: “known,” “possible,” and “conditional risk” of QTc prolongation and Torsades de Pointes. The list of QTc prolonging medications continues to expand as new drug classes are approved and studied. Risk factors for QTc prolongation can be delineated into modifiable or non-modifiable. A validated risk scoring tool may be utilized to predict the likelihood of prolongation in patients receiving AzCERT classified medication. The resultant risk score may be applied to a clinical decision support system which offers mitigation strategies. Mitigation strategies including discontinuation of possible offending agents with selection of an alternative agent, assessment of potential drug interactions or dose adjustments through pharmacokinetic and pharmacodynamic monitoring, and initiation of both ECG and electrolyte monitoring are essential to prevent a drug-induced arrhythmia. The challenges presented by the COVID-19 pandemic have led to the development of innovative continuous monitoring technology, increasing protection for both patients and healthcare workers. Early intervention strategies may reduce adverse events and improve clinical outcomes in patients identified to be at risk of QTc prolongation.

FREEDOM: A phase 3b efficacy and safety study of fedratinib in intermediate- or high-risk myelofibrosis patients previously treated with ruxolitinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS7072-TPS7072 ◽  
Author(s):  
Srdan Verstovsek ◽  
Claire N. Harrison ◽  
Giovanni Barosi ◽  
Jean-Jacques Kiladjian ◽  
Daniela Buglio ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Mitigation ◽  
Reduction Rate ◽  
Symptom Assessment ◽  
Mitigation Strategies ◽  
International Prognostic Scoring System ◽  
Spleen Volume ◽  
Open Label ◽  
Drug Induced ◽  
Patient Reported

TPS7072 Background: Myelofibrosis (MF) is a serious life-threatening condition characterized by splenomegaly, constitutional symptoms, and shortened survival. Ruxolitinib (RUX) is currently the only approved drug for treatment (Tx) of Intermediate- (Int) or High-risk MF. RUX discontinuation rates are high, mainly due to lack of response, loss of efficacy, intolerance, and drug-induced cytopenias, resulting in an important unmet medical need for a JAK2 inhibitor that is effective after RUX failure. Fedratinib (FEDR) is an oral, JAK2-selective inhibitor that produces substantial spleen volume reduction (SVR) and improves constitutional symptoms as initial therapy of MF (Pardanani, 2015) and in pts resistant to or intolerant of RUX (Harrison, 2017). Methods: This multicenter, open-label, single-arm study (NCT03755518) is enrolling adult pts with primary, post-polycythemia vera, or post-essential thrombocythemia MF; Dynamic International Prognostic Scoring System (DIPSS) Int- or High-risk disease; splenomegaly; ECOG PS ≤2; and platelet counts ≥50 × 109/L. Pts must have received prior RUX Tx for ≥3 mo or during ≥28 days of RUX therapy were RUX-intolerant (developed RBC transfusion dependence [≥2 units/mo for 2 mo] or grade ≥3 thrombocytopenia, anemia, hematoma/hemorrhage). Pts receive continuous FEDR 400 mg QD in 28-day cycles. Spleen volume is assessed by MRI/CT scan at screening, after cycles 3, 6, and 12, and at end of treatment. Primary endpoint is spleen response rate (RR; ≥35% SVR from BL by cycle 6 end). Secondary endpoints include duration of spleen RR, spleen size reduction, rate and duration of symptom response (≥50% reduction in total symptom score on the Myelofibrosis Symptom Assessment Form), and safety. Risk mitigation strategies for gastrointestinal adverse events and Wernicke encephalopathy are evaluated. Exploratory endpoints include survival, patient-reported outcomes, and biomarkers of FEDR efficacy and biochemical activity. The study will enroll ~110 pts. Assuming a spleen RR of 35%, the study will have ~90% power to detect the lower bound of the 95% CI that excludes 20%. Enrollment is ongoing. Clinical trial information: NCT03755518.

Early Development of Drug-Induced Hepatic Necrosis

1971 ◽  
Vol 29 ◽  
pp. 576-577
Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser
Keyword(s):  
Early Development ◽  
Hepatic Necrosis ◽  
Screening Tests ◽  
Dense Matrix ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Drug Induced ◽  
Hepatocellular Damage ◽  
Sprague Dawley Rats ◽  
Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

Effect of piperacillin on morphology and viability of gram-negative bacteria

1984 ◽  
Vol 42 ◽  
pp. 218-219
Author(s):  
R. H. Liss
Keyword(s):  
Inhibitory Concentration ◽  
Cytoplasmic Membrane ◽  
Drug Binding ◽  
Gram Negative Bacteria ◽  
Bacterial Cells ◽  
Drug Induced ◽  
Penicillin Binding Proteins ◽  
Lactam Antibiotic ◽  
Drug Free ◽  
Tube Dilution

Piperacillip (PIP) is b-[D(-)-α-(4-ethy1-2,3-dioxo-l-piperzinylcar-bonylamino)-α-phenylacetamido]-penicillanate. The broad spectrum semisynthetic β-lactam antibiotic is believed to effect bactericidal activity through its affinity for penicillin-binding proteins (PBPs), enzymes on the bacterial cytoplasmic membrane that control elongation and septation during cell growth and division. The purpose of this study was to correlate penetration and binding of 14C-PIP in bacterial cells with drug-induced lethal changes assessed by microscopic, microbiologic and biochemical methods.The bacteria used were clinical isolates of Escherichia coli and Pseudomonas aeruginosa (Figure 1). Sensitivity to the drug was determined by serial tube dilution in Trypticase Soy Broth (BBL) at an inoculum of 104 organisms/ml; the minimum inhibitory concentration of piperacillin for both bacteria was 1 μg/ml. To assess drug binding to PBPs, the bacteria were incubated with 14C-PIP (5 μg/0.09 μCi/ml); controls, in drug-free medium.

Drug Induced Changes in Cell Organelles

1968 ◽  
Vol 26 ◽  
pp. 110-111
Author(s):  
Sarah A. Luse
Keyword(s):  
Clinical Medicine ◽  
Cell Organelles ◽  
Riboflavin Deficiency ◽  
Drug Induced ◽  
New Era ◽  
Health And Disease ◽  
In The Beginning ◽  
Cellular Pathology ◽  
Induced Changes ◽  
The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

Acetaminophen: Macula densa hypersecretory activity by induced hepatotoxicity

1987 ◽  
Vol 45 ◽  
pp. 934-935
Author(s):  
S.S. Poolsawat ◽  
C.A. Huerta ◽  
S.TY. Lae ◽  
G.A. Miranda
Keyword(s):  
Cell Proliferation ◽  
Liver Function ◽  
Chronic Inflammation ◽  
Foam Cell ◽  
Term Effect ◽  
Short Term ◽  
Drug Induced ◽  
Experimental Induction ◽  
Tissue Alterations ◽  
Toxic Responses

Introduction. Experimental induction of altered histology by chemical toxins is of particular importance if its outcome resembles histopathological phenomena. Hepatotoxic drugs and chemicals are agents that can be converted by the liver into various metabolites which consequently evoke toxic responses. Very often, these drugs are intentionally administered to resolve an illness unrelated to liver function. Because of hepatic detoxification, the resulting metabolites are suggested to be integrated into the macromolecular processes of liver function and cause an array of cellular and tissue alterations, such as increased cytoplasmic lysis, centrilobular and localized necroses, chronic inflammation and “foam cell” proliferation of the hepatic sinusoids (1-4).Most experimentally drug-induced toxicity studies have concentrated primarily on the hepatic response, frequently overlooking other physiological phenomena which are directly related to liver function. Categorically, many studies have been short-term effect investigations which seldom have followed up the complications to other tissues and organs when the liver has failed to function normally.

Drug-Induced Movement Disorders

2015 ◽  
Vol 25 (2) ◽  
pp. 70-77
Author(s):  
Amy Lustig ◽  
Cesar Ruiz
Keyword(s):  
Movement Disorders ◽  
Medical Management ◽  
Disease Process ◽  
Underlying Disease ◽  
Extrapyramidal Symptoms ◽  
Drug Induced ◽  
General Overview ◽  
Management Approaches ◽  
Broad Understanding ◽  
Underlying Disease Process

The purpose of this article is to present a general overview of the features of drug-induced movement disorders (DIMDs) comprised by Parkinsonism and extrapyramidal symptoms. Speech-language pathologists (SLPs) who work with patients presenting with these issues must have a broad understanding of the underlying disease process. This article will provide a brief introduction to the neuropathophysiology of DIMDs, a discussion of the associated symptomatology, the pharmacology implicated in causing DIMDs, and the medical management approaches currently in use.

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