Acute Liver Failure

Question 1

What is ALF?

Answer 1

Rapid deterioration in the liver function in a previously healthy individual

Question 2

What is the most common cause of ALF?

Answer 2

The most common cause is paracetamol overdose (NAPQI isn’t conjugated by Glutathione causing toxicity)

Question 3

What is affected by ALF?

Answer 3

Complicated.

The CNS, CV and renal systems are affected. Infection and bleeding can be life threatening.

Question 4

Give details about the Paracetamol overdose’s effect on the liver

Answer 4

Paracetamol at normal doses is conjucated to form glucuronate and sulphate metabolites, which are excreted renally. If this pathway is fully occupied, then another metabolism mechanism will start to produce a highly toxic metabolite called NAPQI. NAPQI is quickly inactivated by Glutathione (GSH) to prevent harm. If the reserves of GSH is 30% or less, then NAPQI will interact with the nucleophilic parts of the cell, causing necrosis-liver and kidney damage.

Question 5

How much paracetamol tablets would need to be taken to cause damage

Answer 5

20-30 tablets consumed within 24 hours can resilt in severe hepatocellular necrosis

Question 6

What are the symptoms of paracetamol overdose?

Answer 6

0-24 hrs: asymptomatic or non-specific signs
24-48 hrs: right upper quadrant pain (around liver area), jaundice and deranged bloods (Transaminase levels in the 1000s).
>72 hours - jaundice, drowsiness, liver failure

Question 7

What are the results of paracetamol overdose?

Answer 7

Cerebral oedema, shock, sepsis, renal failure

Question 8

Treatment of Overdose in the 1st hour:

Answer 8

Activated Charcoal

Question 9

Treatment of Overdose up to 36 hrs:

Answer 9

N-acetylcysteine which boosts GSH levels.
Almost 100% if effective given within 8hrs
Treatment is difficult if staggered ingestion

Question 10

How can pharmacists help prevent or spot paracetamol overdose?

Answer 10

Good knowledge of OTC preparations: overdose is not always intentional
Look at patient: Malnourished, alcohol misuse issues or other conditions that may affect the liver

Question 11

What are the Prescribing considerations?

Answer 11

Liver disease may alter the response of the liver to drugs in several ways. Prescribing should be kept to a minimum. The main problems occur in patients with Jaundice, Ascites, or evidence of Encephalopathy

Question 12

Considerations with impaired drug metabolism?

Answer 12

The liver is the main route of elimination for many drugs. The hepatic reserve is large, and the liver disease must be severe for clinically relevant changes.
Care should be taken with Rifampicin and Fusidic acid

Question 13

Hypoproteinaemia Considerations

Answer 13

Albumin is produced in the liver, so liver disease will effect highly protein bound drugs.

Question 14

Clotting considerations

Answer 14

Clotting factors are synthesised in the liver, and there is increased sensitivity to oral anticoagulations

Question 15

Hepatic encephalopathy considerations

Answer 15

Many drugs can impair cerebral function, care should be taken with sedative drugs, opioids and diuretics that decrease K levels.

Question 16

Ascites and Oedema considerations

Answer 16

Drugs that cause fluid retention should be avoided like NSAIDs and Corticosteroids.

Question 17

Hepatotoxic drugs considerations

Answer 17

These can be dose related or idiosyncratic. They should be avoided or used with extreme care.