Hepatotoxicity is chemically-driven liver damage caused by drugs or other exposures. The liver plays an important role in metabolizing chemicals and is susceptible to toxicity from overdoses of certain agents or even therapeutic levels sometimes. Hepatotoxicity can be classified as intrinsic or idiosyncratic, with the latter divided into allergic and non-allergic types. The liver is vulnerable to injury from substances due to its unique metabolism and blood flow from the GI tract. Damage to liver cells can release oxidative compounds and disrupt mitochondria, further harming the liver. Common symptoms include jaundice, fatigue, nausea and dark urine. Acetaminophen overdose is a major cause of acute liver failure and often

1. HEPATOTOXICITY
By: Dr. Sarita Sharma
Assistant Professor
Department of Pharmacology
Mumbai

2. Definition
 Hepatotoxicity chemically-driven liver damage caused by a
drug, or other exposure.
 Liver play an important role in transforming and clearing chemicals
and is susceptible to toxicity. Certain chemical agents when taken
in overdoses and sometimes even when introduced within
therapeutic ranges may injure the organ.
 Other chemical agents, such as those used in laboratories and
industries can also induce hepatotoxicity.
 Hepatotoxicants are the chemical agents that cause liver injury.

3. Classification
1) Intrinsic hepatoxicity
2) Idiosyncratic hepatotoxicity
• a) allergic
• b) non allergic

4. Mechanism of action

5. Mechanism of hepatotoxicity
 Due to its unique metabolism and close relationship with the GI tract, the liver is
susceptible to injury from drugs and other substances.
 75 % of blood coming to the liver, arise directly from gastrointestinal organs and then
spleen via portal vein which bring drugs and xenobiotics in concentrated form.
 Injury to hepatocytes and bile duct cells leads to accumulation of bile acid inside liver.
This promotes further liver damage.
 Many chemicals (hepatotoxicants) damage mitochondria, an intracellular organelle that
produce energy
 Its dysfunction release excessive amount of oxidants which in turn injures hepatic
cells.

6. Signs and symptoms
Yellowing of skin and whites of eyes (jaundice)
Fatigue
Loss of appetite
Nausea and vomiting
Weight loss
Dark or tea-coloured urine

7. Drugs causing liver damage
 Acetaminophen
 Atorvastatin
 Azathioprine/ 6-mercaptopurine
 Amoxicillin-clavulanate
 Carbamazepine
 Heparin
 Imatinib
 Ofloxacin

8. Case study
 Paracetamol: Overdose of acetaminophen (APAP), causing hepatotoxicity
remains a global issue, it accounts for more than 50% of overdose-related
acute liver failure and approximately 20% of the liver transplant cases.
 It causes adverse patient outcomes with increased morbidity and mortality
rates.
 N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but
liver transplantation might represent a life-saving procedure for selected
patients.
 Other therapies are: physically blocking APAP from the GI tract ,i.e ,
gastrointestinal decontamination, activated charcoal can be effective in limiting
drug absorption, etc.

9. THANK YOU!!