Drug Induced Liver Injury Flashcards
What does the hepatic triad consist of?
Portal vein, Hepatic artery, Bile duct
What does the liver do?
Cleans the blood
Makes transport proteins (albumin)
Metabolizes stuff
Makes coagulation factors
What are the Transaminases and what do they tell you?
AST and ALT
May become elevated in the event of hepatocyte death
Tell me about Alkaline Phosphatase.
It is found in a lot of tissues including the liver
Serum alkaline phosphatase levels maybe elevated in cholestatic diseases (bilirubin tract slows down)
Hyperbilirubinemia
high bilirubin in blood
signs and sx: Jaundice develops at >2mg/dL
Scleral icterus (yellow eyes)
Pruritus
Clay colored stool
increased heart rate
What can cause liver injury?
Non-alcoholic fatty liver disease
Alcohol associated hepatitis
Viral Hepatits
Ischemic hepatitis
Autoimmune hepatitis
Hepatotoxic medications/DILI
What are the types of DILI
Direct hepatotoxins
Idiosyncratic Rxns
other stuff
Describe Direct hepatotoxins
Direct hepatotoxic effect induces a dose-dependent liver injury
May be induced by metabolism of parent drug to toxic metabolites (occurs rapidly after med administration)
Drugs include: Acetaminophen, methotrexate
Idiosyncratic
Not dose or duration dependent
Variable presentation such as aberrant immune rxns
May occur months after med inxn
Eg: Antibiotics (Augmentin, cephalosporins, nitrofurantoin)
What are some other stuff that can cause DILI
Indirect Hepatotoxicity
Aberrations in calcium homeostasis
Carcinogens
Mitochondrial injury
Alteration in liver transport proteins
How does DILI present itself?
Asymptomatic
S/s of hepatitis: ab pain, Nausea, alcoholic stool, Jaundice
S/S of cholestasis: Pruritis, jaundice, feeling foggy
S/s Acute liver failure: Coagulopathy, Encephalopathy
How do you diagnose DILI
1) Other Causes must be excluded
2) One of the following lab profiles:
-AST or ALT >/= 5 x ULN
-Alk Phos >/= 2 x ULN
-Tbili >/= 2.5 mg/dL AND either ALT, AST or Alk phos elevated
-INR >/= AND either ALT, AST, or alk phos elevated
What are the labs for DILI?
Hep A/B/C negative
Anti-mitochondrial antibody </= 1:5
Ceruloplasmin within normal range
Antinuclear antibody </= 1:40
Anti smooth muscle antibody </= 1:40
(the last two are exceptions when it comes to drug induced autoimmune hepatitis)
DILI Assessment when a patient comes in
“Have u taken any new herbals/supplements in the last 6 months? Any new meds? When did u start, whats the dose, when did u start and stop?”
What is the R factor formula?
What are some DILI signatures I should remember? And where do I go if I am unsure?
What is the pathway towards DILI management?
How do I mange Pruritus caused by DILI?
Thought to be due to increases in serum bile salts.
Treated with cholestyramine 4 g daily or BID
ADRs: Constipation, fat-soluble vitamin deficiency, Increase Triglycerides
Separate from other meds by ~4 hours.
Drug induced Auto Immune Hepatitis
Prednisone ~40 mg QD can be considered
Watch for glucocorticoid ADRs
Describe APAP metabolism
What happens during APAP overdose?
During APAP overdose -> glutathione depletion -> NAPQI buildup -> hepatotoxicity
How do I treat APAP overdose?
Activated Charcoal: Adsorbs APAP, Indicated if presenting within 4 hours of overdose, 1g/kg (max 50g)
ADRs: Non protected airway, GI Perforation
N-acetyl cysteine (NAC): Refills hepatic cysteine stores increasing glutathione which rescues the liver from NAPQI
ADRs: Hypersensitivity, pruritus, urticaria, hypotension, N/V (PO only)
Hypersensitivity ADR less frequent with 2 bag method
When do I give NAC and what is the dosing?
Indicated:
-Time/Concentration matrix above Rumack-Matthew nomogram line
-Any evidence of liver injury present
-Detectable acetaminophen in serum >24 hrs after ingestion
Acute APAP ingestion of 150mg/kg or 7.5g (whichever is less) & serum levels cannot be obtained within 8 hrs of ingestion
Tell me about Isoniazid and how it can be a hepatotoxin
It is used to treat TB.
Baseline and monthly monitoring recommended: Symptom check (Anorexia, Nausea, fatigue, Jaundice, Abdominal Pain)
Physical exam
Liver function tests (LFTs)
