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Drug toxicity: Drug–Drug Interaction01:30

Drug toxicity: Drug–Drug Interaction

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Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
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Pharmacokinetics: Drug–Drug Interactions01:25

Pharmacokinetics: Drug–Drug Interactions

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Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
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Bioequivalence of Drugs: Drugs with Multiple Indications01:09

Bioequivalence of Drugs: Drugs with Multiple Indications

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The concept of therapeutic equivalence (TE) in drugs with multiple indications is complex. A generic drug may be therapeutically equivalent to a brand-name product for one specific indication, but this doesn't necessarily mean it's equivalent for all other indications. Evidence of TE in one patient group and bioequivalence shown in healthy volunteers can support—but not confirm—TE for other indications. However, definitive proof requires individual clinical studies for each...
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FDA Approved Drugs: Changes to Approved Drugs01:26

FDA Approved Drugs: Changes to Approved Drugs

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Post-approval, manufacturers may modify an approved new or generic drug product. Such modifications can encompass alterations in the Active Pharmaceutical Ingredient (API), manufacturing process, formulation, batch size, manufacturing site, and container closure system (FDA Guidance for Industry, April 2004). Often, a drug product may undergo multiple changes.These modifications require careful evaluation to determine their potential impact on the drug product's identity, strength, quality,...
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Induced-fit Model01:13

Induced-fit Model

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Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
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Tissue-Drug Binding: Localization of Drugs and its Significance01:24

Tissue-Drug Binding: Localization of Drugs and its Significance

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Body tissues, comprising approximately 40% of the body weight, are crucial in drug distribution and localization. These tissues can serve as drug storage sites, competing with plasma binding sites for drug molecules.
Drugs can bind to different tissue components, enhancing their distribution and localization. The factors influencing drug localization in tissues include the drug's lipophilicity, structural characteristics, tissue perfusion rate, and pH differences. These factors determine...
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Related Experiment Video

Updated: Feb 14, 2026

Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis
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Partial Bile Duct Ligation in the Mouse: A Controlled Model of Localized Obstructive Cholestasis

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Drug-induced cholestasis.

Vinay Sundaram1, Einar S Björnsson2,3

  • 1Department of Medicine and Comprehensive Transplant Center Cedars-Sinai Medical Center Los Angeles CA.

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|February 7, 2018
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Summary

Diagnosing cholestatic drug-induced liver injury (DILI) is challenging due to varied presentations and lack of biomarkers. Prompt recognition and removal of the causative agent are crucial given DILI

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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

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Area of Science:

  • Hepatology
  • Clinical Medicine
  • Pharmacology

Background:

  • Cholestatic drug-induced liver injury (DILI) presents diagnostic challenges due to its varied clinical manifestations and the absence of specific biomarkers.
  • The condition encompasses presentations like bland cholestasis, cholestatic hepatitis, secondary sclerosing cholangitis, and vanishing bile duct syndrome.
  • With a potential mortality rate of up to 10%, timely identification and cessation of the offending drug are critical.

Purpose of the Study:

  • To review the presentation, diagnostic approach, risk factors, implicated medications, and management strategies for cholestatic DILI.
  • To provide a comprehensive overview of drug-induced cholestatic liver injury for clinicians.

Main Methods:

  • This is a review article summarizing existing literature and clinical knowledge.
  • The review synthesizes information on the clinical spectrum, diagnostic workup, and therapeutic interventions for cholestatic DILI.

Main Results:

  • Antibiotics, especially amoxicillin/clavulanate, are the most frequent cause of cholestatic DILI.
  • Other medications are also implicated, highlighting the broad range of potential culprits.
  • Risk factors include advanced age, genetic predispositions, and specific drug properties.

Conclusions:

  • Cholestatic DILI requires prompt recognition and management due to its significant mortality risk.
  • Understanding the diverse presentations and risk factors is essential for effective diagnosis and treatment.
  • Further research into diagnostic biomarkers and therapeutic targets for DILI is warranted.