Introduction
Paracetamol, also known as acetaminophen, is a widely used over-the-counter pain medication and to reduce fever. It is commonly used to help with headaches, other minor aches and pains, and is a major ingredient in many cold medications.
Though paracetamol is used to treat inflammatory pain, it is not classified as an Non-steroidal anti-inflammatory drug (NSAID) because it exhibits only weak anti-inflammatory activity.
To date, the mechanism of action of paracetamol is not completely understood, though it is known that it acts on hypothalamus to produce antipyresis.
It may work peripherally to block pain impulse generation; and may also inhibit prostaglandin synthesis in CNS (hence acting as an analgesic).
Uses within SJA
- The relief of mild to moderate pain and fever. Can be given as an adjunct to opioid analgesia
Pharmacokinetics
Onset
- Onset of action is approximately 30 minutes after ingestion
Absorption
- After oral administration it is rapidly absorbed by the GI tract
Distribution
- The concentration in serum after a typical dose of paracetamol usually peaks below 30 µg/ml, which equals 200 µmol/L.[105] After 4 hours the concentration is usually less than 10µg/mL, which equals 66 µmol/L
Metabolism
- Paracetamol is metabolised primarily in the liver, into toxic and non-toxic products. At normal doses the toxic byproducts NAPQI (N-acetyl-p-benzoquinone imine) are quickly detoxified by conjugation with glutathione. And the final products are inactive, non-toxic, and eventually excreted by the kidneys.
- In high doses NAPQI is primarily responsible for the toxic effects of paracetamol.
- Acute overdoses of paracetamol can cause potentially fatal liver damage. According to the US Food and Drug Administration, "Acetaminophen can cause serious liver damage if more than directed is used." The risk may be heightened by frequent consumption of alcohol. Paracetamol toxicity is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia and New Zealand.
- Paracetamol is metabolised by the liver and is hepatotoxic; side effects are multiplied when combined with alcoholic drinks, and are very likely in chronic alcoholics or patients with liver damage.
- Untreated paracetamol overdose results in a lengthy, painful illness. Signs and symptoms of paracetamol toxicity may initially be absent or non-specific symptoms. The first symptoms of overdose usually begin several hours after ingestion, with nausea, vomiting, sweating, and pain as acute liver failure starts. People who take overdoses of paracetamol do not fall asleep or lose consciousness, although most people who attempt suicide with paracetamol wrongly believe that they will be rendered unconscious by the drug.[68] The process of dying from an overdose takes between 3-5 days to 4-6 weeks.
- The toxic dose of paracetamol is highly variable. In general the recommended maximum daily dose for healthy adults is 3 grams. Higher doses lead to increasing risk of toxicity. In adults, single doses above
- 10 grams or 200 mg/kg of bodyweight, whichever is lower, have a reasonable likelihood of causing toxicity
Excretion
- Urine (principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate)
Pharmacodynamics
Desired Effects
- Analgesia
- Fever reduction
Side Effects
- Gatrointestinal tract: Stomach pain, heart burn, nausea, vomiting, epigastric discomfort, ulceration
- Effects on hearing: Tinnitus (very common), vertigo, mild hearing loss
- Hypersensitivity: Angioedema, skin eruptions, paroxysmal bronchospasm
- Haematological: Iron deficiency anaemia, prolongation of bleeding time, may cause haemolytic anaemia in G6PD deficiency patients
- Liver: Hepatotoxicity (sometimes reversible)
- Kidney: Analgesic nephropathy, especially if combinations of NSAIDS are used
- Reye’s syndrome: Acute encephalopathy and hepatic injury in children, when used for antipyretic effects in viral infections such as flu or chicken pox
Duration of Action
- Duration of effects is 2-5 hours
Half-life
- Elimination in adults is 2-3hrs
Other Drug Interactions
- No fatal interactions have been reported
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