CHAPTER 15 – ANALGESICS Flashcards
Joan, a 57-year-old woman, has suffered from osteoarthritis for the last 2 years. Since Joan has a history of aspirin sensitivity (which manifests as bronchospasm), NSAIDs are contraindicated. She initially used paracetamol for analgesia, but due to worsening pain Joan’s general practitioner prescribed panadeine forte, two tablets 8 hourly. A tablet of panadeine forte contains paracetamol, 500 mg plus codeine, 30 mg. Joan obtains no additional benefit from panadeine forte, and in frustration she takes a couple of handfuls’(later estimated as about 30 tablets) of panadeine forte tablets. After 2 hours Joan felt nauseous and told her husband what she had done. Joan’s husband took her to emergency department of their local hospital.
Joan, a 57-year-old woman, has suffered from osteoarthritis for the last 2 years. Since Joan has a history of aspirin sensitivity (which manifests as bronchospasm), NSAIDs are contraindicated. She initially used paracetamol for analgesia, but due to worsening pain Joan’s general practitioner prescribed panadeine forte, two tablets 8 hourly. A tablet of panadeine forte contains paracetamol, 500 mg plus codeine, 30 mg. Joan obtains no additional benefit from panadeine forte, and in frustration she takes a couple of handfuls’(later estimated as about 30 tablets) of panadeine forte tablets. After 2 hours Joan felt nauseous and told her husband what she had done. Joan’s husband took her to emergency department of their local hospital.
Is the dose of paracetamol ingested by Joan potentially hepatotoxic?
Yes, as the dose of this product can lead to toxicity. Maximum daily intake is 4g and even lower in small elderly patients. Ingestion of 20 tablets or more can cause potentially fatally damage to the liver and kidneys and hypoglycaemia, due to toxic metabolite.
Joan was immediately administered activated charcoal, 50mg
Joan was immediately administered activated charcoal, 50mg
- Why was Joan administered activated charcoal? Is the use of activated charcoal justified?
Yes.Charcoal is used to treat poisoning as it has internal pores that help trap chemicals.
- What is the likelihood of hepatotoxicity, as assessed from the plasma paracetamol concentration?
Even normal doses (4g/day) can cause hepatotoxicity, especially in patients who have regular excessive alcohol use.
- What is the mechanism of paracetamol hepatoxcity?
When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) accumulates within the body. It is normally conjugated by glutathione, but when taken in excess, the body’s glutathione reserves are not sufficient to inactivate the toxic NAPQI.
Clinical symptoms as development of nausea and vomiting within 2–3 h of ingestion followed by abdominal pain in the right upper quadrant. Liver dysfunction occurred within 24 h and reached a maximum approximately 3–4 days after ingestion. In conjunction with these clinical symptoms, the elimination half-life of acetaminophen may be delayed and some patients may develop nephrotoxicity in addition to hepatotoxicity
Joan was treated with intravenous N-acetylcysteine, according to the standard protocol
Joan was treated with intravenous N-acetylcysteine, according to the standard protocol
- What is the mechanism of action of N-acetylcysteine?
Acetylcysteine acts to maintain or replenish depleted glutathione reserves in the liver and enhance non-toxic metabolism of acetaminophen.These actions serve to protect liver cells from NAPQI toxicity. It is most effective in preventing or lessening hepatic injury when administered within 8–10 hours after overdose
- Why is glutathione not used as an antidote?
Glutathione is not used as an antidote because although we need the body to replenish the depleted glutathione. We need the activated charcoal more as we want the paracetamol to be removed from the body as one of its metabolites NAPQI is what causes damage to the liver cells which leads to liver failure
Joan’s husband later admitted to the treating doctor that she had been drinking alcohol excessively for months.
Joan’s husband later admitted to the treating doctor that she had been drinking alcohol excessively for months.
- Can excessive ethanol intake affect the severity of paracetamol hepatotoxicity?
Yes, it can increase the likelihood of hepatoxicity occurring due to the damage that is already happening from the intake of alcohol to the liver.
- Is the amount of codeine taken by Joan likely to cause opioid toxicity?
Yes, as it enhances CNS depression, respiratory depression and hypotension
