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.

2. 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.

3. 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.

4. 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.

http://www.practicalpainmanagement.com/treatments/pharmacological/non-opioids/safe-usage-analgesics-patients-chronic-liver-disease-review?page=0,1

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