Scenario 1 - Choice of analgesic

Janet Tweed, Faye Croxen, Kylies Foot 

This chapter concentrates on some drug choices in acute rather than chronic pain, but the same principles can be used to determine the appropriateness of other types of analgesic. The drugs considered in this section are paracetamol, non-steroidal anti-inflammatories (NSAIDs specifically diclofenac, ibuprofen, indometacin, naproxen, sulindac and tenoxicam) and opioids (codeine, dihydrocodeine, morphine, pethidine and tramadol). Unless otherwise stated, all pharmacokinetic data originate from standard reference sources [1-5] and apply to adults only. 

Most studies investigating paracetamol pharmacokinetics in patients with liver disease used single doses only. A 50% reduction in clearance and a corresponding increase in half-life have been seen in severe acute hepatitis, the longest half-life being seen in patients with a raised prothrombin time (PT). It may therefore be prudent to extend the dose interval in these patients. Cirrhotic patients with a low albumin and a raised PT were also noted to have a prolonged paracetamol half-life, although no accumulation or hepatotoxicity was observed when normal therapeutic doses were administered to these patients for up to five days. In contrast, cirrhotic patients with normal albumin and PT demonstrated 

There is a theoretical concern that chronic alcoholics are at an increased risk of paracetamol hepatotoxicity. However, from the shortterm data available in controlled situations, there seems to be no increased risk of hepatotoxicity when these patients are administered therapeutic doses of paracetamol. Some evidence suggests that the potential increased risk of hepatotoxicity may be related more to poor diet and fasting than to the effects of the alcohol. Longer-term controlled studies are still needed to assess the risks of chronic therapeutic dosing in alcoholics. 

The evidence suggests that paracetamol is safe to use in the majority of patients with liver disease, with no increased risk of hepatotoxicity when normal doses are used. 

---