DRUGS AND THE LIVER

Question 1

What percentage of jaundice cases are drug induced?

Answer 1

Up to 10%

Question 2

What are the three types of liver pathology caused by drugs?

Answer 2

Acute hepatitis - 2/3 weeks after starting drug, normally resolves after cessation

Cholestasis - 4-6 weeks after starting drug. Inflammatory infiltration of bile ducts.

Necrosis - dose dependent. Toxic metabolites accumulate and liver necrosis follows. P450 inducers will often (but not always) make these individuals more susceptible to toxicity. Eg paracetamol

Question 3

What are the drugs that can cause an acute hepatitis pattern of liver damage?

Answer 3

Antituberculous: Rifampicin, Isoniazid
Antifungal: ketoconazole
Antihypertensive: atenolol, verapamil
Anaesthetics: halothane

Question 4

What are the drugs that can cause a cholestastic pattern of liver damage?

Answer 4

Antiarrhythmics: amiodarone
Antimetabolics: methotrexate
Allopurinol
Antipsychotics: chlorpromazine
Antibiotics: Erythromycin, clavulanic acid, flucloxacillin
Ciclosporin A
Oral contraceptive
Anabolic steroids

Question 5

What are the drugs that can cause a necrotic pattern of liver damage?

Answer 5

Paracetamol

Carbon tetrachloride

Question 6

What are the clinical features of drug induced cholestatic liver damage?

Answer 6

Dark urine
Jaundice
Pruritus
Steatorrhoea

Question 7

What would the LFTs show in a drug induced acute hepatitis?

Answer 7

Raised ALT

Raised AST

Question 8

What would the LFTs show in drug induced cholestatic liver damage?

Answer 8

Raised ALP

Raised GGT

Question 9

What are the clinical features of paracetamol overdose?

Answer 9

Often asymptomatic for the first 24 hours
Right upper quadrant pain
Nausea
Vomiting
Bleeding
Jaundice

Question 10

What are the risk factors for liver damage as a result of paracetamol overdose?

Answer 10

Co-ingestion of P450 inducing drugs
Chronic alcoholism
Low BMI
HIV

Question 11

What investigations would you do in someone with suspected paracetamol overdose?

Answer 11

Paracetamol levels
Clotting screen (most sensitive marker)
LFTs
Electrolytes
ABG
Blood glucose

Question 12

How do you treat someone with paracetamol overdose?

Answer 12

Give activated charcoal if less than one hour post ingestion
Start IV N-acetylcysteine (NAC)
Oral methionine can be given but absorption is reduced if vomiting

Question 13

What is the most sensitive marker in terms of liver damage during paracetamol overdose?

Answer 13

Prothrombin time

Question 14

What is the toxic metabolite in paracetamol overdose?

Answer 14

N-acetyl-p-benzoquinoneimine

Question 15

How is N-acetyl-p-benzoquinoneimine inactivated in a normal liver without a paracetamol overdose?

Answer 15

Conjugated with glutathione

Question 16

What do you do if N-acetylcysteine causes a mild anaphylactic reaction whilst you are treating a paracetamol overdose?

Answer 16

Pause infusion and then restart at slower pace with administration of anti-histamines

Question 17

What are the most important prognostic markers in someone who has taken a paracetamol overdose?

Answer 17

Prothrombin time - most sensitive. PT over 180s has 90% mortality
Creatinine more than 300 mmol/L has 70% mortality
pH below 7.3 - 85% mortality
Encephalopathy