Acute overdoses of paracetamol can cause potentially fatal ; and, in rare individuals, a normal dose can do the same; the risk is heightened by alcohol consumption. 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.
It is the active metabolite of phenacetin, once popular as an analgesic and antipyretic (As APC tablets; A: Aspirin; P: Phenacetin; C: Caffeine) in its own right, but unlike phenacetin and its combinations, paracetamol is not considered carcinogenic at therapeutic doses.
The words acetaminophen (used in the United States, Canada, Japan, South Korea, Hong Kong, and Iran and paracetamol (used elsewhere) both come from chemical names for the compound: para-acetylaminophenol and para-acetylaminophenol.
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Researchers from King's College London and Lund University in Sweden have discovered that paracetamol works via a protein on nerve cells called TRPA1.
Transient receptor potential cation channel, subfamily A, member 1, also known asTRPA1, is a protein which in humans is encoded by the TRPA1 (and in other species by theTrpa1) gene.
TRPA1 is an ion channel located on the plasma membrane of many human and animal cells. This ion channel is best known as a sensor for environmental irritants, pain, cold and stretch.
A missense mutation of TRPA1 was found to be the cause of a hereditary episodic pain syndrome. A family from Colombia suffers from "debilitating upper body pain starting in infancy" which is "usually triggered by fasting or fatigue (illness, cold temperature, and physical exertion being contributory factors)".
The key role of TRPA1 is chemical sensing of pain pathway and is located on cell membrane of nociceptors in the sensory nerve endings.
Activation of the nociceptor then transmits afferent messages to the spinal cord dorsal horn, and in turn to the brain.
Metabolites of acetaminophen (paracetamol) have been demonstrated to activate TRPA1 receptors in the spinal cord of mice, causing an antinociceptive effects. This is suggested as the antinociceptive mechanism for acetaminophen.
Paracetamol or acetaminophen is a widely used over-the-counter analgesic (pain killer) and antipyretic (fever reducer). It is commonly used for the relief of headaches; minor aches and pains; and is a major ingredient in anti-cold drug combinations.
In combination with opioid analgesics, paracetamol is also prescribed for management of more severe pain; from post surgical pain, Osteoarthrosis pain to advanced stage cancer pain as a palliative care.
Patients usually take an additional pill apparently to get quick relief shortly after taking the first one; and that leads to overdose unknowingly.
It is available in strengths ranging from 250 milligrams, 500 milligrams, 650 milligrams to 10000 milligrams. The onset of analgesia is approximately 11 minutes after oral administration and its half-life is 1–4 hours.
Acetaminophen usually does not cause the stomach and intestinal ulcers in comparison to the extent can be caused by NSAIDs (Non-Steroidal Anti-Inflammatory and Analgesic Drugs) such as aspirin, ibuprofen and naproxen.
NAPQI (N-acetyl-p-benzoquinone imine) is a toxic byproduct of xenobiotic metabolism of paracetamol. It is normally produced only in small amounts, and then almost immediately detoxified in the liver.
However, under some conditions, usually in case of paracetamol overdose NAPQI is not effectively detoxified that causes severe damage to the liver. This becomes apparent after 3–4 days after ingestion.
Symptoms of overdose may include: nausea, vomiting, increased sweating, yellowing eyes/skin, dark urine, severe stomach/abdominal pain, extreme tiredness.
Researchers at Edinburgh University saw cases of "staggered overdose" at its hospital over a 16-year period. The 161 patients, who had taken a staggered overdose were more likely to develop liver, brain problems and need kidney dialysis or help with their breathing. They were also more likely to die of their complications.
Some take home messages:
- Take paracetamol as directed on the packet or patient information leaflet that comes with the medicine; and as directed by te physician.
- Each tablet usually contains 500mg
- Adults can take 1-2 tablets of paracetamol 4-6 hourly, up to four times a day
- This means you should not take more than 8 tablets (4g) in a 24-hour period
- If you accidentally take an extra dose of paracetamol, you should miss out the next dose so that you do not take more than the recommended maximum dose for a 24-hour period.
- If you are concerned or you feel unwell, contact your doctor.
Article Source: http://www.articlesbase.com/medicine-articles/the-way-paracetamol-acts-and-its-complications-from-slight-overdose-5432094.html