The liver performs many essential functions, including processing nutrients, manufacturing bile, and breaking down toxic substances. Inflammation of the liver can interfere with these processes. Drugs are a common cause of liver injury, with over 900 drugs reported to cause hepatotoxicity. Risk factors for drug-induced liver injury include both drug-related factors like dose and concomitant medications, as well as host-related factors like age, sex, preexisting liver disease, and genetic differences affecting drug metabolism. Common drugs that can damage the liver include antibiotics, antipsychotics, statins, antifungals, antihypertensives, and herbal supplements.
Drug induced liver injury (DILI) and HepatotoxicityDr. Ankit Gaur
In this presentation I have tried to explain the defination, Mechanism of drug induced liver injury (DILI) and hepatotoxicity with the help of few examples.
Drug induced liver injury Dr Suresh GorkaSuresh Gorka
Drug-induced liver injury (DILI) can present in various forms from asymptomatic elevation of liver enzymes to jaundice and acute liver failure. DILI is most commonly caused by antimicrobials worldwide and antituberculosis drugs in India. The mechanisms of DILI include intrinsic toxicity, idiosyncratic reactions, mitochondrial toxicity, and defects in bile transport. Diagnosing DILI requires excluding other causes of hepatitis since it is a diagnosis of exclusion. A liver biopsy may be considered to help identify chronic DILI or autoimmune features.
Definition, Patterns/types and mechanisms of drug induced liver disorders, assessment of drug induced liver disorders and its treatment (pharmacotherapeutics-3)
This document provides an overview of drug-induced liver disease (DILD). It defines DILD and discusses its epidemiology and risk factors. Two main mechanisms of hepatotoxicity are described - intrinsic and idiosyncratic. Various types of DILD are outlined including hepatocellular necrosis, steatosis, cholestasis, granulomatous hepatitis, and fibrosis/cirrhosis. Clinical manifestations, investigations, and treatment approaches are summarized. Assessment involves a patient history, liver enzyme levels, biopsy, and nutritional status evaluation. Treatment focuses on diagnosis, drug withdrawal, supportive care, and use of antidotes/corticosteroids if needed.
This document summarizes drug-induced liver injury (DILI). It notes that DILI occurs in 1 in 10,000 to 100,000 people and can cause significant morbidity and mortality. The document outlines various risk factors for DILI, including female sex, age, nutritional status, preexisting liver disease, and concomitant drug usage. It also describes the clinical spectrum of DILI, from elevated liver enzymes to fulminant hepatic failure, and specific types of injury like acute hepatocellular, cholestatic, and mixed injury patterns.
Drug induced liver disease can have a variety of presentations, from acute hepatitis to chronic cholestatic conditions. Making an accurate diagnosis requires correlating the clinical presentation and liver injury pattern with the temporal relationship to suspected medications, exclusion of alternative causes, and considering factors like dechallenge/rechallenge responses and precedents of the drug causing hepatotoxicity. International criteria provide guidance on evaluating suspected cases and assigning levels of certainty regarding causality.
Isoniazid is a drug used to treat tuberculosis that can cause liver toxicity. There are several mechanisms by which isoniazid can induce hepatotoxicity, primarily through the formation of reactive metabolites that cause cell death via necrosis or apoptosis in the liver. Risk factors include older age, female sex, genetic factors affecting isoniazid metabolism, and concomitant use of other hepatotoxic drugs. Management involves monitoring for signs of liver injury and administering treatments like N-acetylcysteine to support liver function.
1) Alcoholic hepatitis is caused by chronic excessive alcohol ingestion and can lead to fatty liver, alcoholic hepatitis, or alcoholic cirrhosis. Risk increases with more than 60-80 g of alcohol per day for 10 years in men or 20-40 g per day for 10 years in women.
2) Alcoholic hepatitis presents with fever, jaundice, abdominal pain, and muscle wasting. Liver tests show elevated AST and ALT levels and AST:ALT ratio over 2. Treatment involves alcohol abstinence, nutrition support, corticosteroids or pentoxifylline, and liver transplantation may be considered.
3) Drug-induced hepatitis can occur through direct toxicity or idiosyncratic reactions.
Drug induced liver injury (DILI) and HepatotoxicityDr. Ankit Gaur
In this presentation I have tried to explain the defination, Mechanism of drug induced liver injury (DILI) and hepatotoxicity with the help of few examples.
Drug induced liver injury Dr Suresh GorkaSuresh Gorka
Drug-induced liver injury (DILI) can present in various forms from asymptomatic elevation of liver enzymes to jaundice and acute liver failure. DILI is most commonly caused by antimicrobials worldwide and antituberculosis drugs in India. The mechanisms of DILI include intrinsic toxicity, idiosyncratic reactions, mitochondrial toxicity, and defects in bile transport. Diagnosing DILI requires excluding other causes of hepatitis since it is a diagnosis of exclusion. A liver biopsy may be considered to help identify chronic DILI or autoimmune features.
Definition, Patterns/types and mechanisms of drug induced liver disorders, assessment of drug induced liver disorders and its treatment (pharmacotherapeutics-3)
This document provides an overview of drug-induced liver disease (DILD). It defines DILD and discusses its epidemiology and risk factors. Two main mechanisms of hepatotoxicity are described - intrinsic and idiosyncratic. Various types of DILD are outlined including hepatocellular necrosis, steatosis, cholestasis, granulomatous hepatitis, and fibrosis/cirrhosis. Clinical manifestations, investigations, and treatment approaches are summarized. Assessment involves a patient history, liver enzyme levels, biopsy, and nutritional status evaluation. Treatment focuses on diagnosis, drug withdrawal, supportive care, and use of antidotes/corticosteroids if needed.
This document summarizes drug-induced liver injury (DILI). It notes that DILI occurs in 1 in 10,000 to 100,000 people and can cause significant morbidity and mortality. The document outlines various risk factors for DILI, including female sex, age, nutritional status, preexisting liver disease, and concomitant drug usage. It also describes the clinical spectrum of DILI, from elevated liver enzymes to fulminant hepatic failure, and specific types of injury like acute hepatocellular, cholestatic, and mixed injury patterns.
Drug induced liver disease can have a variety of presentations, from acute hepatitis to chronic cholestatic conditions. Making an accurate diagnosis requires correlating the clinical presentation and liver injury pattern with the temporal relationship to suspected medications, exclusion of alternative causes, and considering factors like dechallenge/rechallenge responses and precedents of the drug causing hepatotoxicity. International criteria provide guidance on evaluating suspected cases and assigning levels of certainty regarding causality.
Isoniazid is a drug used to treat tuberculosis that can cause liver toxicity. There are several mechanisms by which isoniazid can induce hepatotoxicity, primarily through the formation of reactive metabolites that cause cell death via necrosis or apoptosis in the liver. Risk factors include older age, female sex, genetic factors affecting isoniazid metabolism, and concomitant use of other hepatotoxic drugs. Management involves monitoring for signs of liver injury and administering treatments like N-acetylcysteine to support liver function.
1) Alcoholic hepatitis is caused by chronic excessive alcohol ingestion and can lead to fatty liver, alcoholic hepatitis, or alcoholic cirrhosis. Risk increases with more than 60-80 g of alcohol per day for 10 years in men or 20-40 g per day for 10 years in women.
2) Alcoholic hepatitis presents with fever, jaundice, abdominal pain, and muscle wasting. Liver tests show elevated AST and ALT levels and AST:ALT ratio over 2. Treatment involves alcohol abstinence, nutrition support, corticosteroids or pentoxifylline, and liver transplantation may be considered.
3) Drug-induced hepatitis can occur through direct toxicity or idiosyncratic reactions.
Drugs are a major cause of liver injury, accounting for 20-40% of instances. Certain groups are at higher risk, such as those with preexisting liver disease, genetic factors affecting drug metabolism, or who consume alcohol. Drugs can cause liver injury through various mechanisms, including disrupting hepatocytes, bile ducts, or mitochondrial function. Clinical manifestations range from asymptomatic elevated enzymes to fulminant hepatic failure.
This document discusses alcoholic liver disease (ALD). It begins by defining ALD and its stages - fatty liver, alcoholic hepatitis, and cirrhosis. It then discusses risk factors like gender, genetics, and drinking patterns. Symptoms for each stage are provided. The pathophysiology of steatosis, hepatitis, and cirrhosis are explained. Diagnostic tests including blood tests, imaging, and biopsy are outlined. Management of ALD focuses on abstinence, nutrition, medications to prevent complications, and potentially transplantation for late-stage disease.
Drug induced hematological disorders @rxvichu!!!RxVichuZ
This is my 35th powerpoint..published here in Google Slideshare...
And I wish to thank everyone who have supported me in my 2 year long journey......
This ppt is regarding DRUG INDUCED HEMATOLOGICAL DISORDERS, covering the definitions, causative drugs, pathophysiological mechanisms, manifestations,and management of 5 blood disorders.
Do go through this ppt, and send me ur reviews!!
Regards,
Vishnu.R.Nair.
The document discusses various drug-induced hematological disorders including thrombocytopenia, thromboembolic diseases, aplastic anemia, hemolytic anemia, neutropenia, and agranulocytosis. It provides information on the mechanisms, risk factors, signs and symptoms, diagnosis, morbidity and mortality, prevention, and management of each condition. Common causative agents are identified for each disorder.
Alcoholic liver disease a brief insight- by Rxvichu! :)RxVichuZ
Hello my friends and peer readers.............................
With utmost humility and bliss, I present to you my 25th POWERPOINT PRESENTATION...published in GOOGLE SLIDESHARE..............................:) :)
Thanks to all readers and critics worldwide...for ur constant support................:)
Presenting infront of you all....my ppt on ALCOHOLIC LIVER DISEASE................
It contains precise information on the disease involved under ALD...Mainly CIRRHOSIS and STEATOSIS has been stressed upon.
Do go through the slides, and keep sharing your reviews and ideas....for better enhancement of my future works in the same......................
Keep reading well........
Always remember, that its more worthwhile to WORK SMART, than to WORK HARD!
Thank you!
Vishnu.R.Nair,
5th year pharm.D,
National College of Pharmacy,
Kerala University of Health Sciences(KUHS), Kerala, India.
:) :)
DILI is possible consequence of ingestion of OTC drugs like PCM.
so it require careful clinical knowledge before taking drugs without doctors prescriptions...
This document discusses the pharmacotherapy of inflammatory bowel disease (IBD). IBD includes two major subtypes, ulcerative colitis and Crohn's disease, which are characterized by chronic inflammation of the intestinal tract. Treatment aims to induce and maintain remission of symptoms. First-line therapies include 5-aminosalicylic acid drugs and glucocorticoids. For cases that are steroid-dependent or resistant, immunosuppressants like azathioprine and anti-TNFα antibodies such as infliximab are used. Supportive care involves nutritional supplementation, antidiarrheals, and in severe cases of Crohn's, total parenteral nutrition may be given.
The number of drugs associated with adverse reactions involving the liver is extensive, but in clinical practice is dominated by alcohol, antibiotics, antiepileptic medications and acetaminophen.
Complementary (herbal) medicines contribute to Liver Dysfuntion.
This document summarizes a presentation on drug-induced liver injury (DILI). It discusses the liver's normal physiologic functions including detoxification, nutrient metabolism, and bile production. It then describes how drugs can cause liver injury through various mechanisms like interfering with metabolism or immune responses. Specific risk factors for DILI are outlined including genetic and environmental factors. Several examples of drug classes known to cause hepatotoxicity are discussed in more detail like antituberculosis drugs, anticonvulsants, and acetaminophen. The mechanisms of injury for some of these drugs are also described. Guidelines for diagnosing and managing suspected DILI cases are provided including recommendations on evaluating liver enzymes and symptoms.
Molecular mechanism of drug induced hepatotoxicityMadhava Priya
This document discusses molecular mechanisms of drug-induced hepatotoxicity. It begins with an introduction to hepatotoxicity and classification into intrinsic and idiosyncratic types. Mechanisms of liver damage include direct cell stress, mitochondrial impairment, and immune reactions. Specific drugs that commonly cause liver injury are also identified, such as acetaminophen, nonsteroidal anti-inflammatory drugs, and isoniazid. Patterns of injury include hepatocellular, cholestatic and mixed. Genetic and non-genetic risk factors also contribute to drug-induced liver damage. Images are also provided showing examples of liver damage.
This document discusses hepatotoxic drugs and their mechanisms of causing liver damage. It begins by classifying hepatotoxic drugs into intrinsic, idiosyncratic, and chronic categories. It then describes various mechanisms by which drugs can damage the liver, including by forming reactive metabolites, depleting glutathione, and interfering with mitochondrial functions. Specific hepatotoxic drugs are listed for different drug classes. Methods for evaluating hepatotoxicity both in vivo and in vitro are also presented.
Ulcerative colitis and Crohn's disease are forms of inflammatory bowel disease that can affect different parts of the gastrointestinal tract. Ulcerative colitis causes inflammation of the inner lining of the colon, while Crohn's disease causes transmural inflammation that may occur anywhere along the GI tract. Treatment depends on the severity and location of disease, and may include aminosalicylates, corticosteroids, immunosuppressants, antibiotics, and biologic agents. Surgical intervention is sometimes required for complications like toxic megacolon or for severe, treatment-resistant disease. Lifelong maintenance therapy is often necessary to prevent disease flare-ups.
This document discusses inflammatory bowel disease (IBD), specifically Crohn's disease and ulcerative colitis. It defines IBD as a group of conditions that cause inflammation of the digestive tract, and notes the two major types are Crohn's disease and ulcerative colitis. Crohn's disease can impact any part of the digestive tract and often spreads deep into tissues, while ulcerative colitis exclusively impacts the innermost lining of the large intestine and rectum. Symptoms for both include abdominal pain, diarrhea, weight loss and more. While causes are unknown, it is believed to involve defects in the immune system. Diagnosis involves blood tests, stool samples, imaging and endoscopy. Treatment depends on the severity but may include
In this presentation i have tried to thoroughly discuss about the concept of Drug induced kidney disease or injury, the mechanism behind it, its classification and how to access it.
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract that disrupt the ability to digest food and absorb nutrients. The two main types of IBD are ulcerative colitis, which causes inflammation of the inner lining of the large intestine and rectum, and Crohn's disease, which causes transmural inflammation that may affect any part of the gastrointestinal tract from mouth to anus. Diagnosis involves a review of symptoms, physical examination, blood tests, stool tests, endoscopy, biopsies and imaging studies to determine if inflammation is present and if other causes can be ruled out.
This document discusses drug induced pulmonary diseases. It defines drug induced pulmonary disease as any lung disease caused by a drug or medication. It then lists and describes 10 types of drug induced pulmonary diseases: 1) bronchospasm, wheezing and cough, 2) pulmonary edema, 3) pulmonary hypertension, 4) interstitial lung disease including interstitial pneumonia/infiltrates and pulmonary fibrosis, 5) pulmonary eosinophilia, 6) pleural inflammation, 7) diffuse alveolar hemorrhage/vasculitis, 8) diffuse alveolar damage, 9) drug hypersensitivity syndrome, and 10) amiodarone induced pulmonary toxicity. For each type of disease, it provides details on symptoms,
Drug use in hepatic and renal impairmentAkshil Mehta
- Drugs are more likely to accumulate and cause toxicity in patients with impaired liver or kidney function due to reduced drug metabolism and excretion. The pharmacokinetics of many drugs are altered in patients with hepatic or renal impairment.
- In liver disease, drug absorption, metabolism, protein binding, and elimination can all be affected. Dosage reductions are often required for drugs that are metabolized by the liver. Hepatotoxic drugs should be avoided when possible.
- In kidney disease, drug absorption and excretion may be altered. Drugs that are weak acids or bases can be "trapped" in the urine through changes in urine pH. Dosage adjustments are often needed for drugs excreted by
This document discusses alcoholic liver disease (ALD). It notes that ALD ranges in severity from fatty liver to alcoholic hepatitis to cirrhosis. Risk factors include the amount of alcohol consumed daily and genetically. Diagnosis involves blood tests like GGT and liver biopsy. Severe alcoholic hepatitis has high short-term mortality and is treated with corticosteroids or pentoxifylline to reduce inflammation. Prognosis can be predicted using scores like Maddrey DF and management involves lifestyle changes like abstaining from alcohol and adequate nutrition.
hepatitis induced by the usage of drugs. this condition is well stated and presented in this presentation. management and treatment is also stated. i hope this will help you all somehow
Drugs are a major cause of liver injury, accounting for 20-40% of instances. Certain groups are at higher risk, such as those with preexisting liver disease, genetic factors affecting drug metabolism, or who consume alcohol. Drugs can cause liver injury through various mechanisms, including disrupting hepatocytes, bile ducts, or mitochondrial function. Clinical manifestations range from asymptomatic elevated enzymes to fulminant hepatic failure.
This document discusses alcoholic liver disease (ALD). It begins by defining ALD and its stages - fatty liver, alcoholic hepatitis, and cirrhosis. It then discusses risk factors like gender, genetics, and drinking patterns. Symptoms for each stage are provided. The pathophysiology of steatosis, hepatitis, and cirrhosis are explained. Diagnostic tests including blood tests, imaging, and biopsy are outlined. Management of ALD focuses on abstinence, nutrition, medications to prevent complications, and potentially transplantation for late-stage disease.
Drug induced hematological disorders @rxvichu!!!RxVichuZ
This is my 35th powerpoint..published here in Google Slideshare...
And I wish to thank everyone who have supported me in my 2 year long journey......
This ppt is regarding DRUG INDUCED HEMATOLOGICAL DISORDERS, covering the definitions, causative drugs, pathophysiological mechanisms, manifestations,and management of 5 blood disorders.
Do go through this ppt, and send me ur reviews!!
Regards,
Vishnu.R.Nair.
The document discusses various drug-induced hematological disorders including thrombocytopenia, thromboembolic diseases, aplastic anemia, hemolytic anemia, neutropenia, and agranulocytosis. It provides information on the mechanisms, risk factors, signs and symptoms, diagnosis, morbidity and mortality, prevention, and management of each condition. Common causative agents are identified for each disorder.
Alcoholic liver disease a brief insight- by Rxvichu! :)RxVichuZ
Hello my friends and peer readers.............................
With utmost humility and bliss, I present to you my 25th POWERPOINT PRESENTATION...published in GOOGLE SLIDESHARE..............................:) :)
Thanks to all readers and critics worldwide...for ur constant support................:)
Presenting infront of you all....my ppt on ALCOHOLIC LIVER DISEASE................
It contains precise information on the disease involved under ALD...Mainly CIRRHOSIS and STEATOSIS has been stressed upon.
Do go through the slides, and keep sharing your reviews and ideas....for better enhancement of my future works in the same......................
Keep reading well........
Always remember, that its more worthwhile to WORK SMART, than to WORK HARD!
Thank you!
Vishnu.R.Nair,
5th year pharm.D,
National College of Pharmacy,
Kerala University of Health Sciences(KUHS), Kerala, India.
:) :)
DILI is possible consequence of ingestion of OTC drugs like PCM.
so it require careful clinical knowledge before taking drugs without doctors prescriptions...
This document discusses the pharmacotherapy of inflammatory bowel disease (IBD). IBD includes two major subtypes, ulcerative colitis and Crohn's disease, which are characterized by chronic inflammation of the intestinal tract. Treatment aims to induce and maintain remission of symptoms. First-line therapies include 5-aminosalicylic acid drugs and glucocorticoids. For cases that are steroid-dependent or resistant, immunosuppressants like azathioprine and anti-TNFα antibodies such as infliximab are used. Supportive care involves nutritional supplementation, antidiarrheals, and in severe cases of Crohn's, total parenteral nutrition may be given.
The number of drugs associated with adverse reactions involving the liver is extensive, but in clinical practice is dominated by alcohol, antibiotics, antiepileptic medications and acetaminophen.
Complementary (herbal) medicines contribute to Liver Dysfuntion.
This document summarizes a presentation on drug-induced liver injury (DILI). It discusses the liver's normal physiologic functions including detoxification, nutrient metabolism, and bile production. It then describes how drugs can cause liver injury through various mechanisms like interfering with metabolism or immune responses. Specific risk factors for DILI are outlined including genetic and environmental factors. Several examples of drug classes known to cause hepatotoxicity are discussed in more detail like antituberculosis drugs, anticonvulsants, and acetaminophen. The mechanisms of injury for some of these drugs are also described. Guidelines for diagnosing and managing suspected DILI cases are provided including recommendations on evaluating liver enzymes and symptoms.
Molecular mechanism of drug induced hepatotoxicityMadhava Priya
This document discusses molecular mechanisms of drug-induced hepatotoxicity. It begins with an introduction to hepatotoxicity and classification into intrinsic and idiosyncratic types. Mechanisms of liver damage include direct cell stress, mitochondrial impairment, and immune reactions. Specific drugs that commonly cause liver injury are also identified, such as acetaminophen, nonsteroidal anti-inflammatory drugs, and isoniazid. Patterns of injury include hepatocellular, cholestatic and mixed. Genetic and non-genetic risk factors also contribute to drug-induced liver damage. Images are also provided showing examples of liver damage.
This document discusses hepatotoxic drugs and their mechanisms of causing liver damage. It begins by classifying hepatotoxic drugs into intrinsic, idiosyncratic, and chronic categories. It then describes various mechanisms by which drugs can damage the liver, including by forming reactive metabolites, depleting glutathione, and interfering with mitochondrial functions. Specific hepatotoxic drugs are listed for different drug classes. Methods for evaluating hepatotoxicity both in vivo and in vitro are also presented.
Ulcerative colitis and Crohn's disease are forms of inflammatory bowel disease that can affect different parts of the gastrointestinal tract. Ulcerative colitis causes inflammation of the inner lining of the colon, while Crohn's disease causes transmural inflammation that may occur anywhere along the GI tract. Treatment depends on the severity and location of disease, and may include aminosalicylates, corticosteroids, immunosuppressants, antibiotics, and biologic agents. Surgical intervention is sometimes required for complications like toxic megacolon or for severe, treatment-resistant disease. Lifelong maintenance therapy is often necessary to prevent disease flare-ups.
This document discusses inflammatory bowel disease (IBD), specifically Crohn's disease and ulcerative colitis. It defines IBD as a group of conditions that cause inflammation of the digestive tract, and notes the two major types are Crohn's disease and ulcerative colitis. Crohn's disease can impact any part of the digestive tract and often spreads deep into tissues, while ulcerative colitis exclusively impacts the innermost lining of the large intestine and rectum. Symptoms for both include abdominal pain, diarrhea, weight loss and more. While causes are unknown, it is believed to involve defects in the immune system. Diagnosis involves blood tests, stool samples, imaging and endoscopy. Treatment depends on the severity but may include
In this presentation i have tried to thoroughly discuss about the concept of Drug induced kidney disease or injury, the mechanism behind it, its classification and how to access it.
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract that disrupt the ability to digest food and absorb nutrients. The two main types of IBD are ulcerative colitis, which causes inflammation of the inner lining of the large intestine and rectum, and Crohn's disease, which causes transmural inflammation that may affect any part of the gastrointestinal tract from mouth to anus. Diagnosis involves a review of symptoms, physical examination, blood tests, stool tests, endoscopy, biopsies and imaging studies to determine if inflammation is present and if other causes can be ruled out.
This document discusses drug induced pulmonary diseases. It defines drug induced pulmonary disease as any lung disease caused by a drug or medication. It then lists and describes 10 types of drug induced pulmonary diseases: 1) bronchospasm, wheezing and cough, 2) pulmonary edema, 3) pulmonary hypertension, 4) interstitial lung disease including interstitial pneumonia/infiltrates and pulmonary fibrosis, 5) pulmonary eosinophilia, 6) pleural inflammation, 7) diffuse alveolar hemorrhage/vasculitis, 8) diffuse alveolar damage, 9) drug hypersensitivity syndrome, and 10) amiodarone induced pulmonary toxicity. For each type of disease, it provides details on symptoms,
Drug use in hepatic and renal impairmentAkshil Mehta
- Drugs are more likely to accumulate and cause toxicity in patients with impaired liver or kidney function due to reduced drug metabolism and excretion. The pharmacokinetics of many drugs are altered in patients with hepatic or renal impairment.
- In liver disease, drug absorption, metabolism, protein binding, and elimination can all be affected. Dosage reductions are often required for drugs that are metabolized by the liver. Hepatotoxic drugs should be avoided when possible.
- In kidney disease, drug absorption and excretion may be altered. Drugs that are weak acids or bases can be "trapped" in the urine through changes in urine pH. Dosage adjustments are often needed for drugs excreted by
This document discusses alcoholic liver disease (ALD). It notes that ALD ranges in severity from fatty liver to alcoholic hepatitis to cirrhosis. Risk factors include the amount of alcohol consumed daily and genetically. Diagnosis involves blood tests like GGT and liver biopsy. Severe alcoholic hepatitis has high short-term mortality and is treated with corticosteroids or pentoxifylline to reduce inflammation. Prognosis can be predicted using scores like Maddrey DF and management involves lifestyle changes like abstaining from alcohol and adequate nutrition.
hepatitis induced by the usage of drugs. this condition is well stated and presented in this presentation. management and treatment is also stated. i hope this will help you all somehow
This document discusses drug-induced liver injury (DILI). It begins by stating that multiple drugs can cause hepatotoxicity through various mechanisms. It then discusses the epidemiology of DILI, noting that its worldwide annual incidence is estimated between 1.3 to 19.1 per 100,000 exposed individuals. The document outlines the pathogenesis, clinical presentation, diagnosis, classification, histology, and management of DILI. Regarding histology, it describes various patterns of injury that can be seen such as hepatocellular necrosis, cholestasis, steatosis, and sinusoidal obstruction syndrome. The primary treatment for DILI is withdrawal of the causative drug, with specific therapies for certain cases like
Synthetic Drugs/Hormones - Boon or Bane- Concept of Dooshivisha and Gara VishaIJARIIT
21st century is the world full of synthetics and everyone are living in the influence of synthetic substances. Altered life
styles, food habits and irregular sleep pattern had resulted not only Non communicable disease but also resulting in reduced
immunity and is risking the person more for infections. Pharma Industry has grown as big as hierarchy in recent centauries
and introduces new chemical molecules quoting as capable for treating diabetes, hypertension etc. But bitter truth is prolonged
usage these medications itself has adverse effect on liver and kidneys causes hepatotoxicity and nephrotoxicity or organs
specific toxicity.
Drug induced liver injury- pathophysiology and causes.pptxjyoti verma
Liver injury is a possible consequence of
ingestion of any xenobiotic, including industrial toxins, pharmacologic agents, and
complementary and alternative medications (CAMs).
Among patients with acute liver failure, drug-induced liver injury (DILI) is the most common cause.
ADRs
Classifications of ADRs
Thompson and DoTS system classification
Factors: age, gender, Co-morbidities, ethnicity, Pharmacogenetics,G6PD deficiency, porphyrias
Immunological reactions
Classifications
Epidemiology and pharmacovigilance of ADRs
Yellow card scheme,
Thalidomide tragedy
Factors that may raise or suppress suspicion of a drug
Polypharmacy appropriate and inappropriate based on risk and benefit assessment case study, negative consequences of polypharmacy, deprescribing tools,
This document discusses drug-induced diseases and adverse drug reactions. It begins by defining a drug-induced disease as an unintended effect of a drug that results in symptoms requiring medical attention or hospitalization. It then discusses various terms used to describe adverse drug effects such as adverse drug reactions, adverse events, unexpected adverse reactions, and serious adverse events. The document notes that drug reactions can be categorized as either type A reactions, which are exaggerated pharmacological effects, or type B reactions, which are unpredictable and idiosyncratic. It also discusses factors that can influence individual responses to drugs such as genetics, organ dysfunction, and fluid and electrolyte imbalances.
Therapeutic Roles of Medicinal Herbs for the Treatment of Jaundice and Hepati...ijtsrd
In the developing countries like India, understating of traditional medicine or medicinal plants is very important for the welfare of rural and tribal communities in the treatment of conventional illness. In the last several years the use of medicinal plants has been on rise across the world, including India. The liver diseases like Jaundice, Hepatitis B have been classically treated by several medicinal plants. Clinical treatment of Jaundice patients by the alternative approach of herbal medication is increasing day by day. Healthcare professionals are also advising the use of herbal medicines. The objective of our present work is to give an elaborate idea about jaundice, its occurrence, and the medicines which causes heptotoxicity and what is the present trend in the research of medicinal plants accredited with hepato protective activities. It is very much beneficial in the identification and the development of relevant compounds or medicinal plant products which are valuable in the treatment of Jaundice and Hepatitis B. Pankaj Varshney | Dr. Kailash Bhargava "Therapeutic Roles of Medicinal Herbs for the Treatment of Jaundice and Hepatitis-B" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-6 | Issue-4 , June 2022, URL: https://www.ijtsrd.com/papers/ijtsrd50100.pdf Paper URL: https://www.ijtsrd.com/chemistry/other/50100/therapeutic-roles-of-medicinal-herbs-for-the-treatment-of-jaundice-and-hepatitisb/pankaj-varshney
1) Nutraceuticals provide health benefits and can help prevent diseases. They are derived from foods and have therapeutic effects for conditions like cancer, diabetes, obesity, and cardiovascular and neurodegenerative diseases.
2) Specific nutraceuticals like curcumin, green tea, and omega-3 fatty acids have been shown to help with diseases by reducing inflammation, acting as antioxidants, and positively affecting insulin sensitivity and cholesterol levels.
3) While nutraceuticals show promise, there are also challenges to their use in cancer treatment including difficulties achieving high systemic concentrations and insufficient pre-clinical data to advance combinational therapies in clinical settings.
Drugs can harm the liver in a variety of ways. Some medications harm the liver directly, while the liver converts others into compounds that directly or indirectly damage the liver. (This may seem odd given the liver’s critical role in converting hazardous substances to harmless compounds, yet it happens.) Dose-dependent toxicity, idiosyncratic toxicity, and medication allergy are the three forms of liver toxicity.
If enough of a medicine that causes dose-dependent toxicity is consumed, it can cause liver disease in most persons. Overdosing on acetaminophen (Tylenol) is the most common cause of dose-dependent toxicity (discussed later in this article.).
The document presented here deals with the basic description of the Liver and its associated functions. The main concern here is regarding the brief description of the hepatic disorders prevalent in the world.
Priciples of therapeutics, Dosage Indiviualization, Herbal SupplimentsFarazaJaved
This presentation briefly covers the general aspect of therapeutics and drug development then its dose adjustment according to the pt. need and checking either patient comply to that therapy or not. last portion based on herbal supplements and its use.
Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. Get For More Info Visit Us http://www.jcehapatology.com
This document discusses drug-induced liver injury (DILI) caused by anti-tuberculosis drugs. It notes that isoniazid, rifampicin, and pyrazinamide, which are essential first-line drugs for tuberculosis treatment, can all cause hepatotoxicity. It outlines the mechanisms of anti-TB drug toxicity including direct toxicity, idiosyncratic reactions, and enzyme induction. Risk factors for anti-TB DILI are described. Diagnosis involves criteria such as elevated liver enzymes and bilirubin levels as well as tools like the RUCAM scoring system. Management recommendations include monitoring liver function tests during treatment, criteria for stopping drugs, second-line drug regimens after stopping first
Nutrition management in systemic lupus erythematosus (SLE) was explored. A search found few randomized trials on nutrition for SLE. The best results were from trials on dehydroepiandrosterone (DHEA), which reduced SLE activity, and N-acetylcysteine (NAC), which reduced SLE disease activity. However, trials on omega-3 fatty acids found no clear benefits and some potential adverse effects. Overall, the evidence is limited and inconclusive on specific nutrition interventions for SLE due to small sample sizes and limitations of current studies. Further large randomized controlled trials are still needed.
Drug use in elderly and techniques to avoid polypharmacyDrSahilKumar
The document discusses drug use in the elderly and techniques to avoid polypharmacy. It notes that the elderly population is growing and takes a significant portion of medications while also being more sensitive to drug effects due to physiological changes. Polypharmacy, defined as taking more than 5 medications, is common in the elderly due to multiple comorbidities and providers. This can increase risks of adverse drug reactions, interactions, and non-adherence. The document recommends techniques for optimal prescribing in the elderly like reviewing all medications, simplifying regimens, and eliminating unnecessary drugs to help prevent polypharmacy and its risks.
This document discusses adverse drug reactions and drug interactions. It defines an adverse drug reaction as an unintended, harmful response to a drug. Types of adverse reactions include side effects, toxic effects, intolerance, idiosyncrasy, allergic reactions, and iatrogenic diseases. Drug interactions occur when one drug alters the effects of another drug through pharmacokinetic or pharmacodynamic mechanisms. Pharmacokinetic interactions involve absorption, distribution, metabolism and excretion, while pharmacodynamic interactions involve drugs acting on the same receptors. The document emphasizes the importance of understanding adverse reactions and interactions to ensure safe drug use.
Hepatotoxicity, or liver toxicity, can result from anti-tuberculosis (TB) drugs and is known as drug-induced hepatitis (DIH). Patients at high risk include those with pre-existing liver conditions, alcohol use, and advanced TB. Monitoring of liver enzymes is important for high risk patients during TB treatment. Symptoms of DIH include fatigue, nausea, and jaundice. Diagnosis involves abnormal liver enzymes and symptom resolution after stopping anti-TB drugs. Management consists of gradual dose escalation while monitoring for toxicity.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
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1. Introduction
The liver is the second largest organ in the body (after the skin), and is essential in keeping
the body functioning properly. The liver is located in the upper right-hand side of the
abdomen. It performs many functions in the body, including processing the body's nutrients,
manufacturing bile to help digest fats, synthesizing many important proteins, regulating blood
clotting, and breaking down potentially toxic substances into harmless ones that the body
can use or excrete. Inflammation of the liver may, in severe cases, interfere with these
processes and allow potentially toxic substances to accumulate. Inflammation can occur
while the liver is performing its functions, such as metabolizing drugs.
The liver is able to regenerate or repair up to two-thirds of injured tissue, including
hepatocytes, biliary epithelial cells, and endothelial cells. Healthy cells take over the function
of damaged cells, either indefinitely or until the damage is repaired.
Drugs are an important cause of liver injury. Drug-induced hepatotoxicity poses a significant
problem in drug development and public health. Drug induced liver injury (DILI) is a rare
event. More than 900 drugs, toxins, and herbs have been reported to cause liver injury, and
drugs account for 20-40% of all instances of fulminant hepatic failure.
In the United States, drug-induced liver injury (DILI) is the most common cause of acute liver
failure. It can occur due to ingestion of any therapeutic drug, herbal product, or xenobiotic.
Further complicating matters is the fact that it has an unpredictable and heterogeneous
course, ranging from an asymptomatic rise in liver enzymes to acute liver failure.
1 of 52
2. Introduction
Approximately 75% of the idiosyncratic drug reactions result in liver transplantation or death.
Drug-induced hepatic injury is the most common reason cited for withdrawal of an approved
drug.
The common drugs causing DILI appear geographical. Although antimicrobials are the
commonest cause of drugs worldwide, the class of antimicrobials varies geographically, with
amoxicillin and flucloxacillin common in the Europe in contrast to antituberculosis drugs in
India.
DILI is a leading cause of acute liver failure (ALF) in the Western world, with paracetamol
being the commonest drug followed by antimicrobials. In India antituberculosis drugs are the
commonest cause of drug-induced ALF in adults and children, contributing to 5.7–22% of all
cases of ALF. Paradoxically, many could be preventable, as empirical treatment for
tuberculosis in 43–60% drives most of the reasons for antituberculous ALF.
2 of 52
3. Morbidity / Mortality
In the United States, approximately 2000 cases of acute liver failure occur annually and
drugs account for over 50% of them (39% are due to acetaminophen, 13% are
idiosyncratic reactions due to other medications). Drugs account for 2-5% of cases of
patients hospitalized with jaundice and approximately 10% of all cases of acute hepatitis.
Drug-induced hepatitis is vastly unrecognized and underreported, such that the true
incidence is unknown. Reported estimates range from 1:10,000 cases to 1:100,000 cases.
In reality, this could be more common given that in large areas of the world, the number of
people taking drugs which includes complementary or over the counter medicines cannot
be estimated. Depending upon the setting, in which it is sought, the incidence of DILI
varies.
Healthcare providers must be vigilant in identifying drug-related liver injury because early
detection can decrease the severity of hepatotoxicity if the drug is discontinued. The
manifestations of drug-induced hepatotoxicity are highly variable, ranging from
asymptomatic elevation of liver enzymes to fulminant hepatic failure. Knowledge of the
commonly implicated agents and a high index of suspicion are essential in diagnosis.
3 of 52
4. Drugs Known to Damage The Liver
Drugs that can damage the Liver: There are certain drugs and drug classes that have a
higher likelihood of damaging the liver. These substances include
Antibiotics:
Erythromycin.
Amoxicillin-clavulanate.
Tetracyclines (doxycycline,
minocycline, tetracycline).
Antipsychotic drugs:
Risperidone.
Chlorpromazine.
Statins (treats high cholesterol).
Antifungal drugs:
Terbinafine.
Ketaconazole.
Antihypertensives:
Lisinopril.
Captopril.
Methyldopa.
Halothane (anesthetic).
Birth control pills.
Antidepressants:
Setraline.
Fluoxetine.
Bupropion.
Anticonvulsants:
Phenobarbital.
Carbamazepine.
Phenytoin.
4 of 52
5. Drugs Known to Damage The Liver
Other Drugs
Supplements and herbs
Comfrey tea.
Chaparral.
Skullcap.
Kava.
Excess vitamin A and iron.
Pyrrolizidine alkaloids.
Camellia sinensis (in black and green
tea).
Pennyroyal oil (used in production of
teas).
Over the counter pain-relievers:
Acetaminophen.
Nonsteroidal anti-inflammatory drugs:
Naproxen.
Ibuprofen.
Anabolic steroids.
Recreational and illicit drugs:
Heroin
Inhalants
Cocaine
MDMA or Ecstasy.
Methamphetamine
5 of 52
6. Risk Factors for DILI
Risk factors for DILI can be classified in two main categories:
• Drug related (e.g., dose, concomitant medications, polypharmacy)
• Host related (e.g., age, gender, alcohol intake, concomitant infections).
Drug-related factors:
Hundreds of agents can lead to liver injury. In fact, the US National Library of Medicine and
the National Institute of Diabetes and Digestive and Kidney Diseases have created
LiverTox (http://www.livertox.nih.gov/), an online database that provides detailed
information on more than 600 such agents. Antibiotics are the most common cause of DILI,
followed by neuropsychiatric drugs, immunomodulatory agents, antihypertensives,
analgesics, antineoplastic drugs, and lipid-lowering agents.
Among antibiotics, the specific medication most often responsible for DILI varies by
geographical region. Amoxicillin/clavulanic acid is the most common causative antibiotic in
the United States, whereas anti-tuberculosis agents such as isoniazid, rifampin, and
pyrazinamide are the most common causative drugs in developing countries such as India,
where the prevalence of tuberculosis is still high. Herbal and dietary supplements are
emerging as an important cause of DILI.
The use of multiple drugs further increases the risk of developing DILI. Drugs with a
recommended daily dose of <50 mg are rarely associated with DILI.
6 of 52
7. Risk Factors for DILI
Host Factors:
Race: Some drugs appear to have different toxicities based on race. For example, blacks
and Hispanics may be more susceptible to isoniazid (INH) toxicity. The rate of metabolism
is under the control of P-450 enzymes and can vary from individual to individual.
Age: Apart from accidental exposure, hepatic drug reactions are rare in children. Elderly
persons are at increased risk of hepatic injury because of decreased clearance, drug-to-
drug interactions, reduced hepatic blood flow, variation in drug binding, and lower hepatic
volume. In addition, poor diet, infections, and multiple hospitalizations are important
reasons for drug-induced hepatotoxicity.
Sex: Although the reasons are unknown, hepatic drug reactions are more common in
females.
Alcohol ingestion: Alcoholic persons are susceptible to drug toxicity because alcohol
induces liver injury and cirrhotic changes that alter drug metabolism. Alcohol causes
depletion of glutathione (hepatoprotective) stores that make the person more susceptible to
toxicity by drugs.
7 of 52
8. Risk Factors for DILI
Liver disease: Preexisting liver disease has not been thought to make patients more
susceptible to drug-induced liver injury, but it may be that a diminished liver reserve or the
ability to recover could make the consequences of injury worse. Although the total
cytochrome P-450 is reduced in chronic liver disease, some may be affected more than
others. The modification of doses in persons with liver disease should be based on the
knowledge of the specific enzyme involved in the metabolism. Patients with HIV infection
who are co-infected with hepatitis B or C virus are at increased risk for hepatotoxic effects
when treated with antiretroviral therapy. Similarly, patients with cirrhosis are at increased
risk of decompensation by toxic drugs.
Genetic factors: A unique gene encodes each P-450 protein. Genetic differences in the P-
450 enzymes can result in abnormal reactions to drugs, including idiosyncratic reactions.
Debrisoquine is an antiarrhythmic drug that undergoes poor metabolism because of
abnormal expression of P-450-II-D6. This can be identified by polymerase chain reaction
amplification of mutant genes. This has led to the possibility of future detection of persons
who can have abnormal reactions to a drug.
Other comorbidities: Persons with AIDS, persons who are malnourished, and persons
who are fasting may be susceptible to drug reactions because of low glutathione stores.
Drug formulation: Long-acting drugs may cause more injury than shorter-acting drugs.
8 of 52
9. Risk Factors for DILI
Host factors: Factors that may enhance susceptibility to drugs, possibly inducing liver
disease, are as follows:
• Female - Halothane, nitrofurantoin, sulindac
• Male - Amoxicillin-clavulanic acid (Augmentin)
• Old age - Acetaminophen, halothane, INH, amoxicillin-clavulanic acid
• Young age - Salicylates, valproic acid
• Fasting or malnutrition - Acetaminophen
• Large body mass index/obesity - Halothane
• Diabetes mellitus - Methotrexate, niacin
• Renal failure - Tetracycline, allopurinol
• AIDS - Dapsone, trimethoprim-sulfamethoxazole
• Hepatitis C - Ibuprofen, ritonavir, flutamide
• Preexisting liver disease - Niacin, tetracycline, methotrexate
9 of 52
10. Pathophysiology and Mechanisms of DILI
Hepatocellular and Extracellular Mechanisms:
Disruption of the hepatocyte: Covalent binding of the drug to intracellular proteins can
cause a decrease in ATP levels, leading to actin disruption. Disassembly of actin fibrils at the
surface of the hepatocyte causes blebs and rupture of the membrane.
Disruption of the transport proteins: Drugs that affect transport proteins at the canalicular
membrane can interrupt bile flow. Loss of villous processes and interruption of transport
pumps such as multidrug resistance–associated protein 3 prevent the excretion of bilirubin,
causing cholestasis.
Cytolytic T-cell activation: Covalent binding of a drug to the P-450 enzyme acts as an
immunogen, activating T cells and cytokines and stimulating a multifaceted immune
response.
Apoptosis of hepatocytes: Activation of the apoptotic pathways by the tumor necrosis
factor-alpha receptor of Fas may trigger the cascade of intercellular caspases, which results
in programmed cell death.
Mitochondrial disruption: Certain drugs inhibit mitochondrial function by a dual effect on
both beta-oxidation energy production by inhibiting the synthesis of nicotinamide adenine
dinucleotide and flavin adenine dinucleotide, resulting in decreased ATP production.
Bile duct injury: Toxic metabolites excreted in bile may cause injury to the bile duct
epithelium.
10 of 52
12. Drug Toxicity Mechanisms
The classic division of drug reactions is into at least two major groups
1. Drugs that directly affect the liver and
2. Drugs that mediate an immune response, as follows:
Intrinsic or predictable drug reactions: Drugs that fall into this category cause
reproducible injuries in animals, and the injury is dose related. The injury can be due to the
drug itself or to a metabolite. Acetaminophen is a classic example of a known intrinsic or
predictable hepatotoxin at supertherapeutic doses. Another classic example is carbon
tetrachloride.
Idiosyncratic drug reactions: Idiosyncratic drug reactions can be subdivided into those that
are classified as hypersensitivity or immuno-allergic and those that are metabolic-
idiosyncratic. Regarding hypersensitivity reactions, phenytoin is a classic, if not common,
cause of hypersensitivity reactions. The response is characterized by fever, rash, and
eosinophilia and is an immune-related response with a typical short latency period of 1-4
weeks. A metabolic-idiosyncratic reaction occurs through an indirect metabolite of the
offending drug. Unlike intrinsic hepatotoxins, the response rate is variable and can occur
within a week or up to one year later. It occurs in a minority of patients taking the drug, and
no clinical manifestations of hypersensitivity are noted. INH toxicity is considered to fall into
this class. Not all drugs fall neatly into one of these categories, and overlapping mechanisms
may occur with some drugs (e.g., halothane).
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14. Drug Toxicity Mechanisms
The liver metabolizes virtually every drug or toxin introduced in the body. Most drugs are
lipophilic (fat soluble), enabling easy absorption across cell membranes. In the body, they
are rendered hydrophilic (water soluble) by biochemical processes in the hepatocyte to
enable inactivation and easy excretion.
Metabolism of drugs occurs in 2 phases: Phase 1 reaction: The drug is made polar by
oxidation or hydroxylation. All drugs may not undergo this step, and some may directly
undergo the phase 2 reaction.
Phase 1 reaction (The cytochrome P-450 enzymes catalyze): Most of these intermediate
products are transient and highly reactive. These reactions may result in the formation of
metabolites that are far more toxic than the parent substrate and may result in liver injury. As
an example, the metabolite of acetaminophen is N -acetyl-p-benzoquinone-imine (NAPQI)
and is produced with ingestion of high doses. NAPQI is responsible for the liver injury in
cases of toxicity. Cytochrome P-450 enzymes are hemoproteins located in the smooth
endoplasmic reticulum of the liver. At least 50 enzymes have been identified, and based on
structure, they are categorized into 10 groups, with groups 1, 2, and 3 being the most
important in drug metabolism. Each P-450 enzyme can metabolize many drugs. Drugs that
share the same P-450 specificity for biotransformation may competitively inhibit each other,
resulting in drug interactions. Several drugs can induce and inhibit the P-450 enzyme (see
below).
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15. Drug Toxicity Mechanisms
Phase 2 reactions may occur within or outside the liver. They involve conjugation with a
moiety (i.e., acetate, amino acid, sulfate, glutathione, glucuronic acid) that further increases
solubility. Subsequently, drugs with high molecular weight may be excreted in bile, while the
kidneys excrete the smaller molecules.
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17. Drug Toxicity Mechanisms
Drugs that induce the P-450 enzymes are as follows:
• Phenobarbital
• Phenytoin
• Carbamazepine
• Primidone
• Ethanol
• Glucocorticoids
• Rifampin
• Griseofulvin
• Quinine
• Omeprazole - Induces P-450 1A2
Drugs that inhibit the P-450 enzymes are as follows:
• Amiodarone
• Cimetidine
• Erythromycin
• Grape fruit
• Isoniazid
• Ketoconazole
• Metronidazole
• Sulfonamides
• Quinidine
• Omeprazole - Inhibits P-450 2C8
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18. Factors influencing Drug Metabolism
Genetics: Genetic alterations may contribute to diminished metabolism, lack of metabolism,
or excessive metabolism of a drug.
• Polymorphisms of CYP2C9 - affects the metabolism of S-warfarin, omeprazole,
tolbutamide
• Polymorphism of CYP2C19 - affects the metabolism of S-mephenytoin
• Polymorphism of glutathione s-transferase can affect metabolism of acetaminophen
• HLA (human leukocyte antigen)- association between certain HLA haplotypes and the
development of DILI from fluclox-, augmentin
Nutrition: A person’s nutritional status influences the expression of certain CYPs, both in
health and with underlying liver disease. Expression of CYP2E1 is increased by obesity, high
fat intake, and fasting
• Fasting/malnutrition - may increase risk of DILI from acetaminophen; this is thought to be
due to its affect on detoxifying cofactors such as glutathione
• Obesity - methotrexate, halothane
• Grapefruit juice - inhibits CYP3A, primarily acting on intestinal form of the enzyme;
affecting levels of absorption of several drugs including immunosuppressive meds-
cyclosporine and tacrolimus
18 of 52
19. Factors influencing Drug Metabolism
Multi-drug effect: A drug may either inhibit or enhance (inducer) another drugs metabolism.
Competitive inhibition of CYP can lead to clinically important drug interactions when there
are no alternative pathway for the metabolism of a toxic drug or its metabolite.
• Competition for phase 2 reactions such as glucuronidation and sulfation, for example, by
phenytoin, may lower the dose threshold for acetaminophen-induced hepatotoxicity.
• Phase 3 transporters have also been reported to be inhibited (e.g., atorvastatin,
carvedilol, clarithromycin, and sertraline) and induced (e.g., amiodarone, diltiazem,
erythromycin, and St John’s Wart); significantly altering the secretion activity of this group.
Age and sex: During adult life, the expression of some CYPs declines by up to 10% with
advancing age. Expression of CYP 3A4 and 2E1 seem to be different among men and
women, which may explain the enhanced metabolism of certain drugs, however it’s still
unclear whether this increases the risk of hepatic drug reactions.
Dose: Severe DILI rarely occurs from drugs taken at doses less than 10mg; drugs
administered at >/= 50mg are more likely to cause DILI.
19 of 52
20. Factors influencing Drug Metabolism
Disease-related changes - expression of CYP
• DM
• Hypothyroidism
Underlying liver disease
• Decreased P450: Cirrhosis is associated with decreased levels of total cytochrome P450
and also reduced hepatic perfusion; results in decreased clearance of such as
propranolol, which is usually metabolized rapidly by the liver.
• Decreased hepatic clearance.
20 of 52
21. Stages of Liver Toxicity
Fatty liver and inflammation: Fatty liver, also known as steatorrhoeic hepatosis, is the
build-up of excess fat in the liver cells. It is normal for the liver to contain some fat. But, if fat
accounts for more than 10% of the liver's weight, the individual has fatty liver. In countries
where obesity is becoming a serious health issue, fatty liver is predicted to affect
approximately 25% of the general population. Fatty liver occurs before inflammation is
present.
Sometimes, inflammation from a fatty liver is linked to alcohol abuse, known as alcoholic
steatohepatitis. Otherwise the condition is called nonalcoholic steatohepatitis, or NASH.
NASH is very common in overweight persons over the age of 30. The liver is invaded by an
excessive amount of fat and a normal healthy liver tissue is partially replaced with areas of
unhealthy fats. In such a liver, the liver cells and the spaces in the liver are filled with fat so
that the liver becomes slightly enlarged and heavier.
Hepatitis is an inflammation of the liver that can be caused by viruses, chemicals, drugs,
alcohol, inherited diseases, or the individual's own immune system. This inflammation can be
acute (short-term), flaring up and then resolving within a few weeks to months, or chronic
(long-term), lasting many years. Chronic hepatitis may begin to damage the liver for 20 years
or more before causing significant symptoms related to progressive liver damage such as
cirrhosis (scarring and loss of function), liver cancer, or death.
In the early stage of any liver disease, the liver may become inflamed, tender, and enlarged.
However, an inflamed liver may cause no discomfort at all.
21 of 52
22. Stages of Liver Toxicity
Fibrosis: If left untreated, the inflamed liver will start to scar. As excess scar tissue (a type of
fibrous tissue) grows, it replaces healthy liver tissue. This process is called fibrosis. Scar
tissue cannot function as healthy liver tissue can. Scar tissue may keep blood from flowing
through the liver. The healthy part of the liver now has to work harder. The liver can
regenerate, however, and may heal itself from fibrosis.
Cirrhosis: If left untreated, the liver may become so seriously scarred that it can no longer
heal itself. This stage, when the damage cannot be reversed, is called cirrhosis. Cirrhosis
can lead to a number of complications, including liver cancer. In some individuals, the
symptoms of cirrhosis may be the first signs of liver disease. Symptoms of cirrhosis include:
easy bruising; fluid buildup in the legs and/or abdomen; the skin and eyes may take on a
yellow color, a condition called jaundice; the skin may itch intensely; blood may back up in
vessels leading to the liver because of blockage and may burst; increased sensitivity to
medications and their side effects; developing insulin resistance and type-2 diabetes; or
buildup of toxins in the brain, causing problems with concentration, memory, sleeping, or
other mental functions.
22 of 52
23. Stages of Liver Toxicity
Liver failure: Liver failure means that the liver is losing or has lost all of its function. It is a
life-threatening condition that demands urgent medical care. The first symptoms of liver
failure are often nausea, loss of appetite, fatigue, and diarrhea. Because these symptoms
can have any number of causes, it may be hard to tell that the liver is failing.
As liver failure progresses, the symptoms become more serious. The individual may become
confused and disoriented, and extremely sleepy. There is a risk of coma and death.
Immediate treatment is needed. The medical team will try to save whatever part of the liver
that still works. If this is not possible, the only option may be a liver transplant.
23 of 52
24. Clinical Presentation
Clinical Presentation: Type of injury is reflected by the pattern of liver test abnormalities.
LFTs abnormal for less than 3 months; Chronic DILI- abnormal for more than 3 months
Hepatocelluar (cytotoxic) injury:
1. Aminotransferases are elevated much more than alkaline phosphatase levels (ALP)
2. Serum bilirubin may be elevated
3. Test of synthetic function abnormal
Cholestatic injury:
1. ALP elevated more so than aminotransferases
2. Serum bilirubin may be elevated
3. Test of synthetic function abnormal
Mixed injury
Mechanism of hepatotoxicity
Predictable
Idiosyncratic
Histologic findings (liver biopsy usually not necessary)
Hepatitis
Cholestasis
Steatosis
24 of 52
25. Clinical Presentation
Predictable - intrinsic hepatotoxins
• Predictably cause dose-dependent hepatocellular necrosis
• Latent period- brief (hours to a few days)
• Fairly consistent from person to person and among animal models
• Serum aminotransferases 8 to 500 times normal; ALP less elevated
• Often removed from clinical use
• Some still in use due to known dose-related toxicity
Hepatotoxic in large doses (i.e. acetaminophen, iron sulfate)
Known dose-effect (i.e. ethanol, IV tetracycline, L-asparaginase)
Idiosyncratic
• Unpredictable
• Species-specific, often cannot be reproduced in animal models
• Latent period- variable, generally 1 to 3 months
• Doses >50mg/day more likely to cause DILI compared to dosing <10mg
25 of 52
26. Clinical Presentation
Hepatocellular
- ALT/ALP ratio > 5
- ~ 50% of DILI is hepatocellular
- AST >> ALT- think muscle injury or alcoholic hepatitis
- Neither above 400
Cholestatic
- ALP > 2x ULN
- ALT/ALP ratio < 2
Mixed
- 5 > ALT/ALP ratio > 2
Hy’s law- serum bilirubin >2x ULN, aminotransferases >3x ULN
- Associated with worse prognosis
- Mortality as high as 14 percent
26 of 52
27. Clinical Presentation
• Acute DILI
– Mild asymptomatic liver test abnormalities - Asymptomatic abnormal liver
chemistries- 1/100 to 1/100,000 ; most resolve with drug cessation
– Cholestasis with pruritis
– Acute illness with jaundice- resembles viral hepatitis - 10 to 14% mortality due to
liver failure
– Acute liver failure
• Chronic DILI- may resemble
– AIH (Autoimmune Hepatitis)
– PBC (Primary Biliary Cirrhosis)
– Sclerosing cholangitis
– Alcoholic liver disease
27 of 52
28. Clinical Presentation
• Symptoms of Acute DILI
– Malaise
– Low-grade fever
– Anorexia
– Nausea and Vomiting
– RUQ pain
– Jaundice
– Acholic stools
– Dark urine
• Symptoms of Chronic DILI
– May present with signs of cirrhosis
– Jaundice
– Spider Angioma
– Palmer erythema
– Gynecomastia
– Ascites
– Encephalopathy
– Asterixis
28 of 52
29. Diagnosis
Physical examination:
History: If an acetaminophen over dosage has occurred, it is important to determine the
time and amount of acetaminophen taken. It is important to know what medications the
individual has ingested and how much. Having access to all medication bottles that the
person may have taken will help to determine the maximum amount taken.
Physical: Look for signs and symptoms of liver toxicity. These signs may include jaundice
(yellow skin), abdominal pain, vomiting, and ascites (fluid in the abdomen). On physical
examination, look for liver tenderness and enlargement using palpation.
29 of 52
30. Diagnosis
Blood Tests:
Albumin: Serum albumin levels measures the main protein made by the liver and tells how
well the liver is making this protein. Low levels of albumin may indicate liver damage.
Ammonia: An ammonia test measures the amount of ammonia in the blood. Most ammonia
in the body forms when protein is broken down by bacteria in the intestines. The liver
normally converts ammonia into urea, which is then eliminated in urine. Ammonia levels in
the blood rise when the liver is not able to convert ammonia to urea. This may be caused by
cirrhosis or severe hepatitis.
Alpha-fetoprotein (AFP) test: Alpha-fetoprotein (AFP) is a type of protein produced in the
developing embryo and fetus. In humans, AFP levels decrease gradually after birth, reaching
adult levels by 8-12 months. If an individual has high levels of alpha-fetoprotein in the blood,
it may be a sign of liver cancer. Healthy adult males and non-pregnant females typically have
less than 40 micrograms of alpha-fetoprotein per liter of blood.
Bilirubin: Bilirubin is a waste product made from old blood cells; it is a yellow compound that
causes jaundice and dark urine when present in increased amounts. Tests for bilirubin levels
help determine if the liver is functioning appropriately.
30 of 52
31. Diagnosis
Blood Tests:
INR: International normalized ratio (INR) is a blood-clotting test. It is used to measure how
quickly blood forms a clot, compared with normal clotting time. The liver produces certain
proteins (clotting factors) that help in blood clotting. If there is liver disease and cirrhosis, the
liver may not produce the normal amount of proteins and then the blood is not able to clot
normally. When a doctor is evaluating the function of the liver, a high INR usually means that
the liver is not working as well as it could because it is not making the blood clot normally.
Liver biopsy: A liver biopsy may be performed to determine the extent of liver damage and
to determine the best treatment option for the patient. During the procedure, a needle is
inserted into the liver and a small tissue sample is removed. The tissue is then analyzed
under a microscope in a laboratory.
Liver enzymes: Another blood test may be performed to check for elevated levels of liver
enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
These enzymes leak into the bloodstream when liver cells are injured. Also, alkaline
phosphatase (ALP) levels may be checked. ALP is an enzyme related to the bile ducts. ALP
levels are often increased when they are blocked. Liver enzymes help catalyze or start
chemical reactions in the liver cells. These enzymes are released into the bloodstream when
the liver is damaged.
31 of 52
32. Diagnosis
Blood Tests:
Transferrin saturation test: The transferrin saturation test reveals how much iron is bound
to the protein that carries iron in the blood. Transferrin saturation tests are used in
determining if hemochromatosis exists. Transferrin saturation values higher than 45% are
considered too high. The total iron binding capacity test measures how well the blood can
transport iron, and the serum ferritin test shows the level of iron in the liver. If either of these
tests shows higher than normal levels of iron in the body, THEN doctors can order a special
blood test to detect the genetic mutation for hemochromatosis, which will confirm the
diagnosis. If the mutation is not present, hereditary hemochromatosis is not the reason for
the iron buildup and the doctor will look for other causes.
32 of 52
33. Diagnosis
Diagnostic Tests:
In diagnosing liver toxicity, the doctor may use images of the liver obtained by an ultrasound
test, a computerized tomography (CT) scan, or a magnetic resonance imaging (MRI) scan.
These diagnostic tests can determine if the presence of liver damage exists. Evidence of
fatty liver or liver damage can be viewed by the doctor as dark spots or abnormal images.
A liver scan is a diagnostic procedure to evaluate the liver for suspected disease. A harmless
amount of a radioactive substance that concentrates in the liver is injected intravenously (IV
or into the veins) and the image of its distribution in the liver is analyzed to diagnose
abnormalities. Women who are pregnant or breastfeeding should not have this test.
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34. Differential Diagnosis
Differential diagnoses are as follows:
• Acute viral hepatitis
• Autoimmune hepatitis
• Nonalcoholic steatohepatitis (NASH)
• Shock liver/cardiovascular causes, especially right-sided heart failure
• Cholecystitis
• Cholangitis
• Budd-Chiari syndrome
• Alcoholic liver disease
• Cholestatic liver disease
• Pregnancy-related conditions of liver
• Malignancy
• Wilson disease
• Hemochromatosis
• Coagulation disorders
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35. Diagnosis
Laboratory studies
In general, an increase of serum alanine transaminase (ALT) to greater than 3 times the
upper limits of normal should be followed by repeat testing (hepatic function panel) within 72
hours to confirm the abnormalities and to determine if they are increasing or decreasing.
There also should be inquiry made about symptoms. Serum ALT may rise and fall quite
rapidly, and waiting a week or two before obtaining confirmation of elevations may lead to a
false conclusion that the initially observed abnormality was spurious. Of greater concern,
delay in retesting may allow progression to severe worsening if the initial abnormality was
the herald of a severe reaction to follow. The need for prompt repeat testing is especially
great if the ALT is much greater than 3 times the upper limits of normal and/or total bilirubin
level is greater than 2 times the upper limit of normal.
Initial testing should include complete blood cell count, basic metabolic profile, hepatic
function panel and urinalysis. Patients with a hepatocellular process generally have a
disproportionate elevation in serum aminotransferase levels compared with alkaline
phosphatase levels, while those with cholestasis have the opposite findings. Hepatitis B
serology (hepatitis B surface antigen, anti–hepatitis B surface antibody, anti–hepatitis B core
antibody, hepatitis C serology) and hepatitis A serology (anti–hepatitis A virus antibody)
should be performed to exclude an infectious etiology.
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36. Diagnosis
Laboratory studies
ANA testing may help in cases of possible autoimmune hepatitis. Positive ANA and ASMA
findings may add to the diagnostic evaluation but are usually confusing and hence not used.
The presence of antibodies to specific forms of CYP has been associated with
hypersensitivity to some drugs. For example, some antibodies and the associated drugs
involved are as follows: CYP 1A2, dihydralazine; CYP 3A1, anticonvulsants; and CPY 2E1,
halothane. Their role in pathophysiology is uncertain but may help in diagnosis. Lymphocyte
transformation to test drugs may be observed for drugs acting through immunologic
reactions, but this is not commonly used.
Imaging studies
Ultrasonography is inexpensive compared with CT scanning and MRI and is performed in
only a few minutes. Ultrasonography is effective to evaluate the gall bladder, bile ducts, and
hepatic tumors.
CT scanning can help detect focal hepatic lesions 1 cm or larger and some diffuse
conditions. It can also be used to visualize adjacent structures in the abdomen.
MRI provides excellent contrast resolution. It can be used to detect cysts, hemangiomas,
and primary and secondary tumors. The portal vein, hepatic veins, and biliary tract can be
visualized without contrast injections.
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37. Treatment
General: Therapies for liver toxicity focus on reducing the complications of the disease.
Individuals who knowingly have been exposed to the hepatitis B virus (HBV) should consult
their healthcare providers as soon as possible. Patients who receive an injection of hepatitis
B immune globulin within 24 hours of exposure to the virus may not develop HBV infection.
Patients should also receive the first of three injections of the hepatitis B vaccine.
Diuretics: Diuretics, or fluid tablets, are used in the treatment of fluid retention in the legs
(edema) or abdomen (ascites).
Laxatives: Laxatives, such as lactulose (Chronulac®), are used to prevent constipation and
to reduce the chances of the poisonous substances, such as ammonia, from the bowel
bypassing the liver and reaching the brain, causing drowsiness, confusion, and coma
(hepatic encephalopathy).
Weight loss and exercise: If the individual's body mass index (BMI) is above 25, a diet and
exercise program may reduce the amount of accumulated fat in the liver. BMI measures the
amount of fat the body contains. The most effective diet is rich in fiber and low in calories
and saturated fat, with total fat accounting for no more than 30% of total calories.
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38. Treatment
Diabetes control: Strict management of diabetes with diet, medications, or insulin lowers
blood sugar, which may prevent further liver damage. Blood sugar control may also reduce
the amount of accumulated fat in the liver.
Cholesterol control: Controlling elevated levels of cholesterol and triglycerides with diet,
exercise, and cholesterol-lowering medications may help stabilize or reverse nonalcoholic
fatty liver disease.
Avoidance of toxic substances: If an individual has nonalcoholic fatty liver disease,
especially nonalcoholic steatohepatitis (NASH), alcohol should not be consumed.
Medications and other substances that can cause liver damage should also be avoided,
such as acetaminophen (Tylenol®).
Ursodiol (Actigall®): Ursodiol (Actigall®) is a prescription medication most commonly used
to treat gallstones. Ursodiol decreases production of bile acids, which may in theory help
lower elevated levels of liver enzymes in individuals with liver disease.
Beta-blockers: For portal hypertension, the doctor may prescribe a beta blocker, such as
propranolol (Inderal®). These drugs are normally used in hypertension or high blood
pressure. Side effects include fatigue and loss of sexual desire.
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39. Treatment
N-acetyl cysteine (NAC): The antidote to acetaminophen overdose is N-acetylcysteine
(NAC). NAC is most effective when given within eight hours of ingesting acetaminophen.
Indeed, NAC can prevent liver failure if given early enough. For this reason, it is absolutely
necessary that acetaminophen poisoning be recognized, diagnosed, and treated as early as
possible. NAC can be purchase over-the-counter (OTC) as a dietary supplement, but when
used for acetaminophen toxicity, NAC is a concentrated solution that is prescribed by a
doctor and mixed appropriately by a pharmacist.
Other medications: Researchers are studying the effects of several medications on insulin
resistance and nonalcoholic fatty liver disease in individuals with and without diabetes.
These include metformin (Glucophage®, Glucophage XR®), pioglitazone (Actos®),
rosiglitazone (Avandia®), and betaine (Cystadane®). Another drug being investigated is
orlistat (Xenical®), a medication that blocks the absorption of some of the fat from food.
Early results indicate that orlistat may reduce the amount of fat in the liver.
Interferon: Interferons are natural proteins produced by the cells of the immune system in
response to challenges by foreign agents such as viruses, bacteria, parasites, and tumor
cells. Administering additional synthetic interferon may stimulate the body's immune
response to hepatitis B virus (HBV) and help prevent the virus from spreading. Two
interferon medications are available: interferon alfa-2b (Intron A®) and peginterferon alfa-2a
(Pegasys®). Intron A® is administered by injection several times a week. Pegasys® is given
by injection once a week.
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40. Treatment
Not everyone is a candidate for interferon treatment. In a few cases, interferon has
successfully eliminated the virus completely. However, the infection can return in the future.
Several side effects are associated with interferon, including depression, fatigue, muscle
pain, body aches, fever, and nausea. Interferon may also cause a decreased production of
red blood cells. Symptoms are usually worse during the first two weeks of treatment and in
the first four to six hours after receiving an injection of interferon.
Lamivudine (Epivir-HBV®): Lamivudine (Epivir-HBV®) is an antiviral medication that helps
prevent HBV from replicating in the body's cells. The medication is usually taken in tablet
form once daily. Side effects during treatment are generally mild, but some patients may
experience a severe worsening of symptoms when they stop taking the medication. Patients
should tell their healthcare providers if they have had any kidney problems or history of
pancreatitis before starting this medication. Patients should call their healthcare providers
immediately if they experience a worsening of jaundice (yellowing of the skin and eyes) or if
they experience any unusual bruising, bleeding, or fatigue while taking the medication.
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41. Treatment
Adefovir dipivoxil (Hepsera®): Adefovir dipivoxil (Hepsera®) is a tablet taken orally once a
day to help prevent HBV from replicating inside the body's cells. This drug is effective in
patients who are resistant to lamivudine. Like lamivudine, side effects are generally mild, but
symptoms may worsen when treatment is stopped. Hepsera® may cause kidney toxicity in
patients with underlying kidney disease. A change in the amount of urine produced or blood
in the urine may indicate kidney toxicity. Other side effects may include weakness,
headache, fever, increased cough, nausea, vomiting, diarrhea, or gas.
Entecavir (Baraclude®): Entecavir (Baraclude®) is an antiviral medication that was
approved by the U.S. Food and Drug Administration (FDA) in March 2005 for HPV (human
papilloma virus). HPV infection is a sexually transmitted disease that may lead to cervical
cancer in women. This medication is taken orally once a day. Studies comparing entecavir to
lamivudine in hepatitis treatment found that entecavir was more effective. Baraclude® may
cause symptoms of hepatitis to worsen once medication is discontinued.
Liver transplant: When the liver has been severely damaged, a liver transplant may be the
only treatment option. Liver transplants are increasingly successful. However, there are not
enough donor organs available for every patient who needs a transplant, and not all patients
are suitable transplant candidates. It is estimated that more than 10,000 living donor
transplants have been performed worldwide, and that the donor recipient death rate ranges
from 0.1-0.3%.
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42. Prevention / Patient Education
Reducing alcohol and drug consumption: Drink alcohol in moderation, if at all. Over many
years, more than one drink a day for women and more than two drinks a day for men may be
enough to lead to cirrhosis. Use of certain drugs, including some illegal drugs (such as
cocaine, heroin, and methamphetamine), may also cause liver disease. If fatty liver or
hepatitis exists, no alcohol should be consumed.
Only use prescription and nonprescription drugs when needed and take only the
recommended doses. Acetaminophen (Tylenol®) dosages should be followed specifically as
stated by the manufacturer or by a healthcare provider. The manufacturer has set a
maximum dose of 4 grams of acetaminophen (the equivalent of eight extra-strength tablets
or capsules, 500 milligrams each) per day. However, healthcare professionals recommend
that individuals who take prescription medications or drink alcohol daily should only take a
maximum of 2-3 grams per 24 hours. Many over-the-counter (OTC) products may also
contain acetaminophen (Tylenol®). It is important not to exceed the total daily dosage of four
grams acetaminophen. Acetaminophen should only be used for the short-term (no more than
two weeks) treatment of conditions such as minor aches and pains. Particular caution is
need in dosing infants with acetaminophen to ensure that the correct dose is given.
Do not mix other drugs with alcohol. Acetaminophen (Tylenol®) can be toxic to the liver even
if individuals drink in moderation.
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43. Prevention / Patient Education
Hepatitis vaccination: If an individual is at increased risk of contracting hepatitis or if they
already been infected with any form of the hepatitis virus, a doctor will recommend the
hepatitis B vaccine. A vaccine is also available for hepatitis A.
Dietary supplements: Herbal supplements that can be toxic to the liver may include kava
(Piper methysticum), chaparral (Larrea taridentata), comfrey (Symphytum officinale),
germander (Teucrium chamaedrys), kombucha tea, mistletoe (Viscum album), pennyroyal
(Mentha pulegium), and skullcap (Scutellaria laterifolia). Also, avoid high doses of fat soluble
vitamins, including vitamins A, D, E, and K, as they can also be potentially toxic to the liver.
Avoiding contact with blood and body fluids from others: Hepatitis viruses can be
spread by accidental needle sticks, improper cleanup of blood or body fluids, and sharing
intravenous needles. It is also possible to become infected by sharing razor blades or
toothbrushes or by having unsafe sex.
Avoiding chemical toxins: When using toxic chemicals such as cleaners, ventilating the
room or wearing a mask is important. Take similar protective measures when spraying
insecticides, fungicides, paint, and other toxic chemicals. When using insecticides and other
toxic chemicals, covering the skin with gloves, long sleeves, a hat, and a mask is
recommended by healthcare professionals. Chemical toxins may damage liver cells and
cause liver dysfunction.
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44. Prevention / Patient Education
Given the idiosyncratic nature of most drugs, it is difficult to predict who and when during the
course of treatment will develop hepatotoxicity. Rational drug prescribing is central to
minimizing DILI particularly in patients with risk factors such as old age, comorbid diseases,
HIV status, daily dose of drug >50 mg, or poly pharmacy.
Caution should be exercised in the empirical treatment for tuberculosis given the high
incidence of severe DILI including acute liver failure. Knowledge of drug–drug interaction and
drug–disease interaction is also important. Except for few drugs such as methotrexate,
clinically significant DILI is usually accompanied by symptoms, such that vigilance for
symptoms is the key in the detection of early onset DILI.
Patients and caregivers should be educated about the development of new symptoms such
as nausea, vomiting, anorexia, dark urine or jaundice. The suspected drug or drugs should
be stopped at the slightest suspicion of DILI, in order to prevent progressive liver damage.
Debate continues about the need and the timing of liver function tests particularly in those
who need to be on medications for a long duration. There is no clear evidence that such a
practice influences much in the detection or prevention of clinically significant liver injury.
Additional constraints include the costs and inconvenience of the tests, physician ambiguity
and varying guidelines with regard to timing of the tests.
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45. Prevention / Patient Education
Patients and caregivers should be educated about the development of new symptoms such
as nausea, vomiting, anorexia, dark urine or jaundice. The suspected drug or drugs should
be stopped at the slightest suspicion of DILI, in order to prevent progressive liver damage.
Debate continues about the need and the timing of liver function tests particularly in those
who need to be on medications for a long duration. There is no clear evidence that such a
practice influences much in the detection or prevention of clinically significant liver injury.
Additional constraints include the costs and inconvenience of the tests, physician ambiguity
and varying guidelines with regard to timing of the tests.
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46. Summary
The number of cases of DILI is expected to rise because of the increased availability of
prescription medications resulting from changes in insurance coverage and the burgeoning
HDS market. Pharmacists can play an integral role in helping prevent DILI and in identifying
DILI when it does occur so that the offending agent can be discontinued, if possible. In order
to best protect their patients, pharmacists must be knowledgeable about the drugs
associated with DILI, as well as their clinical features and the disease course. It is essential
to perform a thorough medication history in a patient suspected of experiencing DILI. Once
DILI is confirmed, patients should be followed for a minimum of 6 months to assess for the
development of chronic injury. Medication therapy management is one tool pharmacists can
use to help identify patients who have DILI or are at risk for it.
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47. Active Learning
Drug-induced liver injury (DILI) is an important clinical problem, which has received more
attention in recent decades. It can be induced by small chemical molecules, biological
agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP),
and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI
clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-
cholestatic mixed injury, and vascular injury based on the types of injured target cells. The
CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical
manifestation and gives 16 evidence-based recommendations on diagnosis, differential
diagnosis, treatment, and prevention of DILI.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419998/
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48. References
U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics
Evaluation and Research (CBER). Guidance for Industry, Drug-Induced Liver Injury: Premarketing Clinical Evaluation. Available at
http://www.fda.gov/downloads/Drugs/.../Guidances/UCM174090.pdf . Accessed: October 9, 2014.
Ahmad J, Odin JA. Epidemiology and Genetic Risk Factors of Drug Hepatotoxicity. Clin Liver Dis. 2017 Feb. 21 (1):55-72.
Björnsson ES. Hepatotoxicity of statins and other lipid-lowering agents. Liver Int. 2016 Nov 8.
Chen J, Raymond K. Roles of rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor. Ann
Clin Microbiol Antimicrob. 2006;5: 3.
Shi Q, Hong H, Senior J, Tong W. Biomarkers for drug-induced liver injury. Expert Rev Gastroenterol Hepatol. 2010;4: 225–34.
Riedmaier I, Pfaffl MW. Transcriptional biomarkers–High throughput screening, quantitative verification, and bioinformatical validation methods.
Methods. Elsevier Inc.; 2013;59: 3–9.
Vuppalanchi R., Liangpunsakul S., Chalasani N. Etiology of new-onset jaundice: how often is it caused by idiosyncratic drug-induced liver injury in the
United States? Am J Gastroenterol. 2007;102:558–562.
Reuben A., Koch D.G., Lee W.M. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52:2065–2076.
Kumar R., Shalimar, Bhatia V. Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome.
Hepatology. 2010;51:1665–1674
Devarbhavi H., Dierkhising R., Kremers W.K. Antituberculosis therapy drug-induced liver injury and acute liver failure. Hepatology. 2010;52:798–799.
Chalasani N., Fontana R.J., Bonkovsky H.L. Drug induced liver injury network (DILIN). Causes, clinical features, and outcomes from a prospective study
of drug-induced liver injury in the United States. Gastroenterology. 2008;135:1924–1934.
Verma S., Kaplowitz N. Diagnosis, management and prevention of drug-induced liver injury. Gut. 2009;58:1555–1564.
Davern T.J., Chalasani N., Fontana R.J. Acute hepatitis E infection accounts for some cases of suspected drug-induced liver injury. Gastroenterology.
2011;141:1665–1672.
Holt M.P., Ju C. Mechanisms of drug-induced liver injury. AAPS J. 2006;8:E48–E54.
Kaplowitz N. Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov. 2005;4:489–499.
Björnsson E., Talwalkar J., Treeprasertsuk S. Drug-induced autoimmune hepatitis: clinical characteristics and prognosis. Hepatology. 2010;51:2040–
2048.
Lheureux P.E., Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol (Phila) 2009;47:101–111.
Suk KT, Kim DJ. Drug-induced liver injury: present and future. Clin Mol Hepatol. 2012;18:249-257.
Andrade RJ, Robles M, Fernández-Castañer A, et al. Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists.
World J Gastroenterol. 2007;13:329-340.
Bell LN, Chalasani N. Epidemiology of idiosyncratic drug-induced liver injury. Semin Liver Dis. 2009;29:337-347.
48 of 52
49. References
Pandit A, Sachdeva T, Bafna P. Drug-induced hepatotoxicity: a review. J Appl Pharm Sci. 2012;2:233-243.
O’Donnell JT, Marks DH, Danese P, O’Donnell JJ III. Drug-induced liver disease: primer for the primary care physician. Dis Mon. 2014;60:55-104.
Yuan L, Kaplowitz N. Mechanisms of drug-induced injury. Clin Liver Dis. 2013;17:507-518.
Agarwal VK, McHutchison JG, Hoofnagle JH, et al. Important elements for the diagnosis of drug-induced liver injury. Clin Gastroenterol Hepatol.
2010;8:463-470.
Senior JR. Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: current status and challenges. Drug
Saf. 2014;37(suppl 1):S9-S17.
Seeff LB, Bonkovsky HL, Navarro VJ, Wang G. Herbal products and the liver: a review of adverse effects and mechanisms. Gastroenterology.
2015;148:517-532.
Chen M, Suzuki A, Borlak J, et al. Drug-induced liver injury: interactions between drug properties and host factors. J Hepatol. 2015;63:503-514.
Ortega-Alonso A, Stephens C, Lucena MI, Andrade RJ. Case characterization, clinical features and risk factors in drug-induced liver injury. Int J
Mol Sci. 2016;17:e714.
Corsini A, Bortolini M. Drug-induced liver injury: the role of drug metabolism and transport. J Clin Pharmacol. 2013;53:463-474.
Fontana RJ. Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives. Gastroenterology. 2014;146:914-928.
Chen M, Borlak J, Tong W. High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver
injury. Hepatology. 2013;58:388-396.
Au JS, Navarro VJ, Rossi S. Review article: drug-induced liver injury—its pathophysiology and evolving diagnostic tools. Aliment Pharmacol Ther.
2011;34:11-20.
Mitchell SJ, Hilmer SN. Drug-induced liver injury in older adults. Ther Adv Drug Saf. 2010;1:65-77.
Chughlay MF, Kramer N, Werfalli M, et al. N-acetylcysteine for non-paracetamol drug-induced liver injury: a systematic review protocol. Syst Rev.
2015;4:84.
Singh D, Cho WC, Upadhyay G. Drug-induced liver toxicity and prevention by herbal antioxidants: an overview. Front Physiol. 2016;6:363.
Andrade RJ, Lucena MI, Kaplowitz N, et al. Outcome of acute idiosyncratic drug-induced liver injury: long-term follow-up in a hepatotoxicity
registry. Hepatology. 2006;44:1581-1588.
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