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Surgery- Liver, Spleen and Pancreas > Hepatotoxic Drugs > Flashcards

Hepatotoxic Drugs Flashcards

1
Q

Many drugs cause the asymptomatic elevation of hepatic enzymes, give an example of one of these drugs and hepatic enzymes:

A

Statins

  • ALT
  • AST
  • GGT
  • Alkaline phosphosphotase
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2
Q

Clinically significant liver injury is rare.

how does it present thouh?

A 
Jaundice 
Abdominal pain 
Pruritis 
Impaired liver function resulting in deficient protein synthesis. 
Prolonged PT with hypoalbuminemia
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3
Q

What happens in phase 1 metabolic reactions

A

Drug is taken in and absorbed, broken down into metabolites which will either:

  • Metabolite with modified activity
  • Metabolite is inactivated
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4
Q

What happens in phase 2 of metabolic reactions?

A

Conjugation of drug metabolites

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5
Q

What are some consequences of drug metabolism?

A
  • Product May become inactivated
    • Product may become active
    • Products May develop a new action
    • Metabolites might become toxic
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6
Q

Name 5 mechanisms of injury in, drug induced liver injury:

A
  1. Covelant binding of drug to cellular proteins -> immune injury
  2. Inhibition of metabolic pathways
  3. Induction of apoptosis
  4. Blockage of cellular transport pumps
  5. Interference with mitochondrion function
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7
Q

What factors increase the risk of drug induced liver disease?

A
  • Obesity
    • Over the age of 18
    • Pregnancy
    • Concomitant with alcohol consumption
    • Genetic polymorphism CYP2D6, CYP2C9
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8
Q

Name 3 drugs that pose as risk factors for DILI in old patients

A

Anti-TB drugs
Eruthromycine
Halothane
Flucloxacillin

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9
Q

Name 2 drugs that pose as risk factors for DILI in child patients:

A

Salicylate

Valproate

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10
Q

Name 2 drugs that pose as risk factors for DILI in obese patients:

A

Methotrexate

Halothane

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11
Q

Name a drug that pose as a risk factor for DILI in fasting/malnourished patients:

A

Acetaminophen

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12
Q

Name 3 drugs that pose as risk factors for DILI in female patients:

A 
Doclofenac
Erythromycin 
Isoniazid 
Flucloxacillin 
Halothane
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13
Q

Name 3 drugs that pose as risk factors for DILI in alcoholic patients:

A

Halothane
Methotrexate
Isoniazid
Acetominophen

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14
Q

Name 2 drugs that pose as risk factors for DILI in HIV patients:

A

Cotrimoxazole

Abacavir

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15
Q

Name 2 types of drugs that pose as risk factors for DILI in patients with HBV/HCV Co-infection :

A

Highly active ARV THERAPY

TB treatment

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16
Q

DILI can be classified into 2 types of reactions, what ar they?

A

Predictable reactions

Idiosyncratic reactions

17
Q

Explain the 2 classifications of DILI reactions:

A

Predictable reactions

  • Main example is paracetamol toxicity
  • Reaction is dose dependent
  • High incidence
  • Results from direct toxicity of the drug or its metabolites

Idiosyncratic reactions:

  • Variable latency: 1 week or 1 year ,after.
  • Not dose related.
  • Caused by major hepatotoxic drugs
  • ALT levels are more than 3 times the normal levels
  • ALP- Sign of liver toxicity
18
Q

What are the 3 types of liver injury?

A 
Hepatocellular
  - Elevated ALT
Cholestatic 
  - Elevated alkaline phosphatase (ALP) and total bilirubin 
Mixed 
  - Elevated alkaline phosphatase ALP
19
Q

How does hepatocellular damage maniafest.

A

Hepatocellular toxicity manifests as

  • Malaise
  • Right upper quadrant abdominal pain
  • Marked relegation in ALT AST
  • Hyperbilirubinaemia
20
Q

In hepatocellular damage, what us hepatocellular jaundice known as?

A

Hyperbilirubinaemia

  • Increases mortality rates by 50% if Bilirubin is 3X more than usual
  • Without biliary obstruction or Gilbert’s syndrome
21
Q

Drugs like paracetamol and isoniazid usually cause hepatocellular injury with a low chance of spontaneous recovery
(Liver transplant should be considered)
How does this kind of hepatocellular injury present?

A

Jaundice

Impaired hepatic synthesis

22
Q

Name a few common drugs causing hepatocellular injury:

A 
Rifampicin 
Purazinamide 
Statins 
Tetracycline 
Methotrexate 
NSAIDS
Allupurinol
Acarbose
23
Q

How does cholestatic hepatotoxicty present?

A

Elevated ALP
Pruritis
Jaundice

24
Q

Which 3 drugs are notorious for causing cholestatic hepatotoxicity?

A

Amoxicillin
Chlorpromazine
Clavulanate acid

25
Q

Which of the 3 hepatotoxicity injuries leads to:

  • Vanishing bile duct syndrome ( Progressive destruction of intrahepatic bile ducts)
  • Cronic liver disease.
A

Cholestatic hepatotoxicity

26
Q

Name a few drugs that cause cholestatic injury:

A 
Amoxicillin 
Clavulanate acid 
Chloropromazine 
Estrogens 
Oral contraceptives 
Erythromycin 
Tricyclic anti-depressants
27
Q

How does mixed type liver injury clinically present?

A

Neither ALP nor ALT elevations are clearly predominant in these syndromes.

28
Q

Give a drug type that usually Caucasus mixed hepatic injury:

A

Phenytoin.

29
Q

Give a few examples of drugs causing mixed hepatic injury:

A 
Phenytoin 
Captopril 
Analopril 
Sulfonamide 
Veparamil
30
Q

How is liver injury diagnosed?

A

Causality is assessed :

  • Relationship between drug initiation and development of abn liver enzymes
  • Individual susceptibility to DILI
  • Exclude all other causes of liver disease I.e.
    > Cirrhosis
    > HBV/ HCV
    > Auto-immune
    > Metabolic causes
31
Q

Name 2 things that improve the prognosis of liver injury:

A
  • Early recognition.

- Identification of hepatotoxin and pattern of liver test abnormality.

32
Q

What is the treatment for liver injury due to a hepatotoxic drug?

A
  • Early withdrawal
    • Antidotes if available I.e.
      > N-acetylcysteine for paracetamol toxicity
      > Silymarin or penicillin for Phalloides
33
Q

What drug is the antidote for hepatotoxic liver injury caused by Paracetemol?

A

N-acetylcysteine

34
Q

What drug is the antidote for hepatotoxic liver injury caused by amanita phalloides?

A

Silymarin

Penicillin

35
Q

What kind of drugs are considered hepatotoxic?

A

Herbs containing pyrrolizidine alkaloids.

  • Chinese herbal formulations
  • Kava Kava
  • Germander
  • Impala root
  • Comfrey
36
Q

What should be taken into consideration when prescribing medication for treating liver disease?

A
  • The drug should be devoid of hepatotoxic effects
    • Eliminated by the kidney
    • Large therapeutic index
    • No pharmacokinetic interactions

Surgery- Liver, Spleen and Pancreas (10 decks)

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