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Flashcards in Acute Liver Failure Deck (17):

What is ALF?

Rapid deterioration in the liver function in a previously healthy individual


What is the most common cause of ALF?

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


What is affected by ALF?

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


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

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.


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

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


What are the symptoms of paracetamol overdose?

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


What are the results of paracetamol overdose?

Cerebral oedema, shock, sepsis, renal failure


Treatment of Overdose in the 1st hour:

Activated Charcoal


Treatment of Overdose up to 36 hrs:

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


How can pharmacists help prevent or spot paracetamol overdose?

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


What are the Prescribing considerations?

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


Considerations with impaired drug metabolism?

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


Hypoproteinaemia Considerations

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


Clotting considerations

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


Hepatic encephalopathy considerations

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


Ascites and Oedema considerations

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


Hepatotoxic drugs considerations

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