CORRELATION SEMINAR ON

GASTROINTESTINAL AND
HEPATOBILIARY SYSTEM

Viral Hepatitis

2076/03/20

Name: Nischal Neupane

Roll number: 1836
MBBS 38th Batch
1
 OBJECTIVES
1. To list the hepatotoxic drugs.
2. To describe different types of drug induced
hepatotoxicity.

2
1. Toxic word origin- ‘toxicum’(Latin) meaning
poison
2. Toxic means injurious
3. Toxin- having toxic effect
4. Hepatotoxic- toxic to liver
5. Effects seen due to overdose or prolonged use
of drug on liver are hepatotoxic effects-drugs
6. Poisons are accountable to dosage

3
INTRODUCTION TO HEPATOTOXIC
DRUGS
+ More than 900 drugs and substances have
been found to be hepatotoxic
+ More than 20 regularly used drugs are
hepatotoxic
+ Toxicity varies from elevation of liver enzymes
to acute liver failure
+ 30-40% of acute liver failure

4
 CLASSIFICATION OF
HEPATOTOXICITY
Predictable Unpredictable

intrinsic idiosyncratic

example- acetaminophen example- 1.chlorpromazine

causing acute liver failure causing cholestasis
2.halothane causing
immune mediated hepatitis
5
 FACTORS AFFECTING
HEPATOTOXICITY
Age and
gender
Drug – drug
interaction Genetics

Disease like
Alcohol and Drug induced HIV, HCV
cigarette liver injury
smoking

Dosage and
Kidney
duration of drug
damage
Obesity and
lifestyle 6
 DIFFERENT TYPES OF DRUG
INDUCED HEPATOTOXICITY
Clinical manifestation Drugs

elevated aminotransferase acetaminophen, NSAIDS, ACE

levels(ALT and AST) with inhibitors, sulphonamide,
acute hepatocellular injury erythromycin

elevated aminotransferase halothane, ketokonazole,

and bilirubin levels suggesting acetaminophen, phenytoin,
fulminant necrosis sertraline, naproxen, diclofenac

elevated alkaline phosphatase chlorpromazine, ciprofloxacin,

showing acute cholestatic erythromycin
injury
7
 CONTINUED…
Pathological manifestation Drugs

1.Acute cholestasis with Hormonal contraceptives, anabolic

decreased bile flow and steroids, chlorpromazine,
hepatic injury clopidogrel, erythromycin, statin

2.Hepatocellular necrosis methyldopa, acetaminophen,

phenytoin, halothane, isoniazid
3.Fatty liver disease corticosteroids, methotrexate,
valproate, tetracycline, aspirin,
amiodaron
4.fibrosis and cirrhosis methotrexate, enalapril

8
 CONTINUED…
Pathological manifestation Drugs

Chronic cholestasis with chronic amoxicillin-clavulanate,

portal inflammation and trimethoprim-sulphamethoxazole
degeneration of bile duct

Granulamatous hepatitis with non sulphonamide, quinidine,

ceseating epitheloid granulomas phenytoin

autoimmune hepatitis with methyldopa, lisinopril,

necroinflammatory lesion and nitrofurantoin
plasma cells plus ANA antibodies

9
 ACETAMINOPHEN INDUCED
HEPATOTOXICITY
1. Most commonly used over the counter drug
2. Present in 300+ drugs either in combination or solitary
3. Major metabolism and detoxification in liver
4. 95% detoxification in liver by phase 2 reaction and
excreted in urine as sulphate or glucuronate conjugate
5. 5% is metabolized by CYP2E enzyme to NAPQI(N-acetyl-
p-benzoquinineimine)
6. NAPQI causes liver injury by
I. Depleting glutathione and causing oxidative injury
II. Mitochondrial and cell membrane damage causing necrosis of
hepatocytes
10
 CONTINUED…
1. Acetaminophen tablets come in formulation of
0.3 to 0.5 gm per tablet
2. Case of toxicity is seen after 10 gm nearly about
150 mg/kg body weight
3. That’s why chance of toxicity rise due to its over
the counter availability and no restrictions in
usage and lack of awareness in general population

11
+ A 16 years old boy staying in a hostel in Kathmandu
for higher studies was found dead in his hostel bed.
Postmortem studies showed fulminant hepatic
failure due to acetaminophen overdose. It was found
that the boy complained of fever and headache the
day before and was given the drug by hostel warden
for quick relief.

<The relief was too quick for his breath to become air
12
 BIBLIOGRAPHY
+ Essentials of medical pharmacology,7th edition
+ Robbins and Cotran pathological basis of disease,
south Asia edition
+ https://emedicine.medscape.com/article/169814

13
Thank you

14