[Rechallenge in hepatotoxicity: proof of concept or therapeutic accident?]

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...

Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the...

Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...

Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...

Pharmaceutical poisoning can occur through various channels, impacting an estimated 2 million hospitalized patients in the U.S. annually with serious adverse drug responses. These scenarios encompass both therapeutic uses, such as drug toxicity, where even standard dosages can lead to severe central nervous system depression, and non-therapeutic exposures, including accidental ingestion by children, and environmental and occupational exposures.Unintentional poisonings often involve exploratory...