This is for education purpose of Pharmacy(Pharm.D) students.

1. DRUG INDUCED LIVER
DISORDERS
DR. AYUSHI ALAGIYA
PHARM.D

3. Epidemiology
 the incidence of idiosyncratic reactions for most drugs remains low,
occurring at therapeutic doses from 1 in every 1000 patients to 1 in every
100,000 patients.
 Not life-threatening

4. ALF
Symptomatic
disease
Mild liver injury

5.  patients who develop drug-induced acute liver failure (ALF)
the prognosis is poor, with a 60–80% mortality rate, unless
they receive a liver transplant.
 Many drugs cause elevated liver enzymes with apparently
no clinically significant adverse effect, although in a few
patients there may be significant hepatotoxicity.

6. Risk factors
 Pre-existing liver disease-increase the risk of developing
drug-induced hepatic injury with agents such as
methotrexate, cytotoxic agents, aspirin and sodium valproate.

7. Age
• Elderly
• Isoniazid
• Chlorpromazine
• Fatal
• Sodium
valproate
• Children
• Aspirin

8. Gender
 The frequency of drug-induced hepatotoxicity is thought to
be more common in females than males, particularly with
halothane, isoniazid, flucloxacillin, chlorpromazine,
erythromycin and nitrofurantoin.

9. Genetics
 Genetic differences that affect an individual's ability to metabolize
certain drugs may predispose to DILD.
 For example:-
 Isoniazid
 Halothane-induced injury

10. Enzyme induction
 Alcohol, rifampicin and other drugs that induce cytochrome
P450 isoenzyme, increase the risk of hepatotoxicity with
other drugs such as paracetamol, isoniazid and halothane.
 Anticonvulsants(phenytoin and phenobarbital)- risk for
sodium valproate.

11. Poly pharmacy
 NSAIDs + hepatotoxic drugs.

12. Concurrent diseases and pregnancy
 Pre-existing renal disease, diabetes, pregnancy and poor
nutrition may all affect the ability of the liver to metabolize
drugs effectively and may put the patient at risk of
developing liver damage.

13. Etiology
INTRINSIC (TYPE A)
predictable, dose-
dependent.
a short latency period.
ranging from hours to
weeks .
Eg.- paracetamol,
salicylates, methotrexate
and tetracycline.
IDIOSYNCRATIC (TYPE B)
less predictable and not
dose-related.
ranging from 5 to 90 days
from the initial ingestion.
Eg.- chlorpromazine,
halothane and isoniazid.

14. Hepatocellular necrosis
 Necrosis is characterized by cytotoxic cellular breakdown
(hepatocellular destruction) and is generally associated with a poor
prognosis.
 Lab- LFT abnormalities , Prolongation of the prothrombin time,
Microscopy reveals necrosis
 CP- anorexia, V, M, Ap, jaundice, dark urine, bruising, bleeding, oliguria,
anuria, renal failure

16. STEATOSIS
 Steatosis (fatty liver) is the accumulation of fat droplets within liver cells
and is associated with abnormal LFTs, although the elevation of alanine
aminotransferase is not as high as that seen in acute hepatocellular
necrosis. Hyperammonia, hypoglycaemia, acidosis and clotting factor
deficiency may also be present. Histologically, the liver damage
resembles the acute fatty liver of pregnancy
 Steatohepatitis
 fatigue, nausea, vomiting, hypoglycaemia and confusion. Jaundice

17. Cholestasis
 the slowing or stalling of bile flow through
your biliary system
 Inc. bilirubin and alanine aminotransferase,
alkaline phosphate
 CP- pruritus, dark urine, pale stools and
jaundice.
gastrointestinal symptoms

18. Acute hepatitis
 Lft raised
 The best indicator of severity is the prothrombin time.
 Cp- anorexia, nausea and vomiting, dark urine, pale stools and jaundice.

19. Chronic active hepatitis
 present as an acute injury or progress to cirrhosis.
 Serum transaminases
 CP- tiredness, lethargy and malaise, Gastro-intestinal symptoms, one or
more complications of severe liver disease, including ascites, bleeding
esophageal varices or hepatic encephalopathy.

20. Fibrosis
 the serum transaminase raised, microscopy shows deposition
of fibrous tissues,

21. Vascular disorders
 A variety of drugs can cause veno-occlusive disease, which is
characterised by non-thrombotic narrowing of small centrilobular veins,
and is typically caused by cytotoxic agents and some herbal remedies.
 CP- painful hepatomegaly, ascites and jaundice

22. Tumours
 CP- Weight loss, fatigue, anorexia, nausea and, occasionally, vomiting
and Ap.

24. Treatment
 Identifying the causative agent and stopping it is important
in reducing the morbidity and mortality associated with DILD.
 A detailed and thorough drug history,
 Idiosyncratic reactions- the literature consulted for previous
reports.

25. Withdrawal
 LFTs may take many months or even years to return to normal.

26. Rechallenge
 Rechallenge is not normally justified as this is potentially dangerous for the
patient, although a positive rechallenge is the most definitive confirmation of
drug-induced disease.

27. Management
If patients present a few hours post-ingestion, any unabsorbed drug may
best be removed by gastric lavage, rather than by use of emetics.
 Antidotes
 Corticosteroids- not for ALF
 Supportive treatment- fluid and electrolytes balance.

28.  Pruritus-
light clothing (avoid wool) and cooling the skin with tepid baths or calamine
lotion, and a general moisturising agent such as aqueous cream.
 Coagulation disorders
vitamin K deficiency with intravenous phytomenadione injection.
 Patient counselling