ABSTRACT: Cirrhosis is a heterogeneous diagnosis that impacts liver function, including the metabolism and clearance of medications, but the exact effect. Opioids are the most common drug class for analgesia, particularly moderate and severe pain or pain not relieved by acetaminophen and NSAIDs.
It has been recommended to increase the dosing interval by as much as double to avoid drug accumulation, in both IV and oral administration.5 Morphine should be avoided in renal impairment, including hepatorenal syndrome, due to significant accumulation of its metabolites and risk for neurotoxicity.4. Morphine: Morphine is considered to have a high hepatic extraction on first-pass metabolism, making it only 30% to 40% bioavailable following oral dosing in healthy patients.4,5 Morphine is metabolized by the liver to morphine-6-glucuronide (active metabolite) and morphine-3-glucuronide (inactive metabolite with potential neurotoxic effects), which are then cleared renally.
Major categories of pain medications, including over-the-counter analgesics (OTCAs) such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as cyclooxygenase 2 (COX-2) inhibitors, anticonvulsants, antidepressants, and opioids, are largely metabolized by the liver.
36 Although methadone and fentanyl are also heavily protein bound and as such require reduced dosing in patients with cirrhosis, the metabolism of these agents does not yield toxic metabolites, and hence they, along with hydromorphone, may be better tolerated 37, 38 ( Table 2 ). Glucuronidation is thought to be less affected by cirrhosis, 2 but studies have consistently shown that the half-life of morphine, for instance, is prolonged in patients with cirrhosis. Ineffective drug metabolism in this patient population can also lead to decreased analgesic action of these medications.
Pain management in patients with liver disease poses unique challenges for clinicians. Many of the commonly used analgesics like acetaminophen, NSAIDs and opioids are metabolized through the liver. Adverse events from these pain relievers are frequent, potentially fatal, but often avoidable in patients.
Pain management in patients with liver disease poses unique challenges for clinicians. Because there are no evidence-based guidelines for the use of analgesics in this patient population, the pain management in these patients is challenging. Adverse events from these pain relievers are frequent, potentially fatal, but often avoidable in patients with chronic liver disease, especially in those with cirrhosis. Prescribing analgesics in these patients often raises the fear of precipitating or worsening renal failure, provoking hepatic encephalopathy, inducing portal hypertension and gastrointestinal bleeding, aggravating hepatic decompensation or causing addiction, especially in patients with a history of alcoholism or other addictive conditions.
Those with liver disease must be aware that the three most common pain relievers could be hazardous to a compromised liver – even at a reasonable dosage. Editor's Note: The information below is for educational purposes only and is not intended to replace, supersede or substitute medical advice.
It is very good for inflammation! I purchased ten kilos five years ago and the shelf life is very good if kept in a sealed container. I cannot recommend dosages and do not claim to be a physcian or claim this to be a cure. Naproxen can raise blood pressure. I only know it has helped me to reduce inflammation. I tried it for a short time and instead use Advil. I do not know of anything for pain which is not good for the liver I do know for a fact MSM does not have any known affects.
It neutralizes toxins and poisons found in food, water, air and medications and helps to improve the functional efficiency of the liver.
Many of the commonly used over-the-counter and prescription pain relievers like acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and opiates are metabolized through the liver. Articles reviews most commonly used analgesics and usage in patients with CLD.
When compared to normal patients, Forrest et al demonstrated similar levels of cysteine and mercapturic acid conjugates, suggesting intact detoxification of NAPQI.19. However, a study by Benson showed that repeated maximal dosing did not lead to accumulation in patients with chronic stable liver disease (CSLD).18 In that study, 20 patients with CSLD were given 4 grams per day of acetaminophen for 13 days without signs of toxicity. The half-life of acetaminophen is prolonged in patients with chronic liver disease.
In considering acetaminophen treatment in patients with chronic liver disease, the main variables to be concerned about are: what affect liver disease has on CYP2E1 levels, the patient’s probable glutathione stores, and the half life of acetaminophen itself.
It was discovered in several studies that patients with chronic liver disease had reduced plasma and hepatic glut-athione levels.11-13 Two other studies demonstrated that patients with liver disease either had mildly decreased or slightly increased levels of glutathione,14,15 Even at mildly decreased levels, risk of hepatic damage is minimal, as damage isn’t seen until glutathione stores decrease below 30%.