Lecture

Drug-Induced Liver Injury: Mitigation Strategies

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In course

CH-332: Medicinal chemistry

Sitting at the crossroad of organic chemistry and medicine, this course outlines how an initial hit compound transitions into a lead candidate, and ultimately a drug, in the modern drug discovery world. Note: the course is held only during 2nd half of spr ...

Description

This lecture delves into the complexities of Drug-Induced Liver Injury (DILI), a major safety concern in drug development. It covers the mechanisms of DILI, the role of cytochrome P450 enzymes, and the importance of Phase I and Phase II detoxification pathways. The instructor discusses case studies, such as the hepatotoxicity of acetaminophen and the structural alerts for potential DILI. The lecture also explores strategies to mitigate DILI, including Structure-Metabolism Relationship (SMR) studies and the importance of understanding reactive metabolites. Students will gain insights into the challenges of drug development and the critical role of liver metabolism in drug safety.

Instructor

Yimon Aye

Official source

Related concepts (32)

Hepatotoxicity

Hepatotoxicity (from hepatic toxicity) implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval. The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. paracetamol) and sometimes even when introduced within therapeutic ranges (e.

Drug metabolism

Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin.

Acute liver failure

Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complications are hepatic encephalopathy and impaired protein synthesis (as measured by the levels of serum albumin and the prothrombin time in the blood). The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes.

Toxication

Toxication, toxification or toxicity exaltation is the conversion of a chemical compound into a more toxic form in living organisms or in substrates such as soil or water. The conversion can be caused by enzymatic metabolism in the organisms, as well as by abiotic chemical reactions. While the parent drug are usually less active, both the parent drug and its metabolite can be chemically active and cause toxicity, leading to mutagenesis, teratogenesis, and carcinogenesis.

Liver disease

Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. File:Ground glass hepatocytes high mag cropped 2.jpg|Ground glass hepatocytes File:Primary biliary cirrhosis intermed mag much cropping.jpg|Primary biliary cirrhosis File:Buddchiari2.PNG|Budd-chiari syndrome File:Non-alcoholic_fatty_liver_disease1.

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