Monday, March 16, 2015

Pain management in chronic liver disease

  1. Acetaminophen
·         Considering the factors leading to hepatic toxicity due to altered metabolism via CYP activity and depleted glutathione stores.
·         Has longer half life in Chronic stable liver disease (CSLD) patient.
·         Recommended maximum dose is 2-3g per day.

  1. NSAIDS
  • Metabolism is governed largely by hepatic CYP450 enzymes.
  • Should be avoided due to the risk of portal hypertension, esophageal varices, renal insufficiency, and hepatorenal syndrome and other complications.
  • The safety of using selective COX-2 inhibitors is not well studied.
  • It is not recommended to use in CLD patient.
  1. Opioids
  • Most opioids are metabolized by CYP450 and a few opioids are minimally metabolized by CYP450..
  • Morphine is largely metabolized by glucuronidation and poorly excreted in renal insufficiency. Hence, it should be avoided or require dose reduction in cirrhosis patient. 
  • Codeine is transformed into morphine via CYP2D6; therefore the serum concentration will be variable.
  • Fentanyl and hydromorphone have less toxicity in CSLD patient due to shorter half life (1-3hours) and do not required renal dose adjustment
  • Tramadol is occasionally used in low doses in patient with cirrhosis. Dose adjustment needed in renal failure patient.
  • Methadone maintenance for opioid addiction is likely to be safe in CLD patient. It is contraindicated in patients with concomitant alcoholism.
  1. Neuropathic agents
  • Gabapentin and pregabalin are not hepatically metabolized. They may be start at a low dose and gradually titrated up. Lower dosing adjustment is required in patient with concomitant renal insufficiency.
  • Carbamazepine is hepatically metabolized and known to cause hepatic toxicity. Therefore it should be avoided in CSLD.
  • Tricyclic antidepressants (nortriptyline, amitriptyline and imipramine) rely heavily on hepatic first-pass metabolism. They should be started on a low dose nightly and gradually titrated as tolerated. Lower maintenance dose compared to the healthy population.
  • Monitor the side effects for each agent.


References:
  1. Practical pain management. Safe Usage of Analgesics in Patients with Chronic Liver Disease: A Review of the Literature.

  1. Pain Management in the Cirrhotic Patient: The Clinical Challenge http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861975/

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