Structure/Class |
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Pharmacodynamics |
- Functions as a COX-1 and COX-2 inhibitor. No anti-inflammatory properties.
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Absorption/administration |
- Well absorbed from the GIT.
- Peak plasma levels 30-60 minutes.
- It is slightly protein bound.
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Distribution |
- T ½ of 2-3 hours. This is increased in liver disease to >6 hours
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Metabolism |
- Hepatic
- >95% undergoes glucuronidation and sulfation.
- 5% will undergo metabolism via CYP 450 mechanisms (Phase 1 reaction – hydroxylation) to form NAPQI. NAPQI is toxic, but usually detoxified by glutathione.
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Excretion |
- Renal
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Indications |
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Contraindications |
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Special precautions |
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Interactions |
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Adverse events |
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Dosing/administration |
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Toxicology |
- A dose of >200mg/kg or >7g in adults is considered to be potentially toxic. The mechanism is as follows:
- Paracetamol normally undergoes glucuronidation and sulfation.
- In ODs à these pathways are saturated and then paracetamol is broken down by a Phase 1 reaction.
- More NAPQI is formed à this consumes glutathione (GSH). Once GSH is depleted, NAPQI then becomes hepatotoxic.
- Signs and symptoms
- Initially, nausea/vomiting and abdominal pain.
- Then signs of hepatic failure – raised transaminases and raised INR.
- Hepatic encephalopathy and death.
- Risk of toxicity is based on paracetamol nomogram.
- Treatment – NAC. It functions either as a sulfhydryl donor in order to inactivate NAPQI, or as a glutathione substitute.
- Liver transplant in severe cases.
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Withdrawal syndrome |
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Special notes |
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