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Related Concept Videos

Toxic Reactions: Overview01:26

Toxic Reactions: Overview

When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
Drug Toxicity: Overview01:00

Drug Toxicity: Overview

Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...
Effects of Chemicals: Overview01:27

Effects of Chemicals: Overview

Drugs, encompassing various chemical compounds from natural sources, lab synthesis, or genetic engineering, elicit different biological responses in living organisms. Some of these responses are desirable or therapeutic, while others are undesirable. The primary goal of administering a drug is to achieve a therapeutic effect, that is, to address a specific disease or health condition. Any concurrent effects outside of this therapeutic outcome are considered undesirable. These undesirable...
Drug toxicity: Drug–Drug Interaction01:30

Drug toxicity: Drug–Drug Interaction

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...
Toxicokinetics: Overview01:21

Toxicokinetics: Overview

Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...

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Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
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Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation

Published on: February 10, 2023

On-target and off-target-based toxicologic effects.

Daniel G Rudmann1

  • 1Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA. rudmanndg@lilly.com

Toxicologic Pathology
|October 23, 2012
PubMed
Summary
This summary is machine-generated.

Understanding the mechanism of toxicity is crucial for risk assessment. This involves categorizing adverse effects as chemical-based, on-target, or off-target to guide xenobiotic development strategies.

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Area of Science:

  • Toxicologic pathology
  • Drug development
  • Risk assessment

Background:

  • Adverse toxicologic effects are classified into three main categories: chemical-based, on-target, and off-target.
  • Chemical-based toxicity stems from a compound's physicochemical properties affecting cellular components.
  • On-target toxicity results from exaggerated pharmacologic effects at the intended site, while off-target toxicity arises from unintended target modulation.

Purpose of the Study:

  • To discuss the categorization of toxicologic effects.
  • To explore scientific approaches for differentiating between chemical-based, on-target, and off-target toxicities.
  • To enhance human risk assessment strategies for xenobiotics.

Main Methods:

  • Review and discussion of existing toxicologic and biologic data.
  • Formulation of testable hypotheses by toxicologic pathologists.
  • Literature review on target-specific effects.

Main Results:

  • Adverse effects can be mechanistically categorized into chemical-based, on-target, or off-target.
  • Understanding these mechanisms is essential for accurate risk assessment.
  • Differentiating toxicity types informs xenobiotic development and safety evaluation.

Conclusions:

  • Accurate classification of toxicity mechanisms is imperative for effective risk assessment.
  • Toxicologic pathologists play a key role in hypothesizing and determining toxicity mechanisms.
  • This understanding aids in the development of safer xenobiotics.