naloxone and Liver-Neoplasms

Pain management in cirrhosis is a clinical challenge. Most analgesics are metabolized in the liver and cirrhosis may deeply alter their concentration, favouring the appearance of side effects. We aimed to assess the efficacy and safety of oral prolonged-release association of oxycodone/naloxone tablets (OXN) in the treatment of moderate/severe cancer pain in cirrhotic patients with metastatic hepatocellular carcinoma (HCC).. We enrolled n = 32 HCC patients with moderate/severe cancer pain unresponsive to paracetamol alone or associated with codeine or tramadol. All patients received an initial OXN dose of 5 mg bid to be gradually increased in case of insufficient analgesia. At baseline and follow-up visits, we evaluated: pain intensity (using the Numerical Rating Scale, NRS), patients' autonomy in daily activities (Barthel Functioning Index); bowel dysfunction (Bowel Function Index, BFI), signs of hepatic encephalopathy (HE) and other opioid-induced side effects.. No clinically significant adverse effects were reported (median follow-up 122 days). No significant worsening of the BFI score was noted and no cases of HE were detected. Two patients (6.3%) discontinued treatment before T14 because of mild nausea and dizziness. The remaining n = 30 patients were assessed for efficacy. Treatment led to a significant reduction in the mean of pain scores both at T14 (-37.1 ± 16.3%, P < .001) and at T28 (-55.6 ± 21.5%, P < .001); Barthel scores showed gradual and significant increase from T0 (81.6 ± 13.0) to T14 (86.5 ± 11.4, P = .001) and to T28 (88.3 ± 13.6, P = .009).. OXN may be considered a safe and effective option in the fragile population of cirrhotic patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Analgesics, Opioid; Cancer Pain; Carcinoma, Hepatocellular; Chronic Pain; Delayed-Action Preparations; Drug Combinations; Female; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Naloxone; Narcotic Antagonists; Oxycodone; Preliminary Data; Quality of Life; Treatment Outcome

Topics: Aged; Analgesics, Opioid; Breast Neoplasms; Female; Humans; Liver Neoplasms; Naloxone; Narcotic Antagonists; Oxycodone; Pain

Buprenorphine, pentazocine, and naloxone are opioid drugs used for the treatment of pain and opioid dependence or overdose. Sulfation as catalyzed by the cytosolic sulfotransferases (SULTs) is involved in the metabolism of a variety of xenobiotics including drug compounds. Sulfation of opioid drugs has not been well investigated. The current study was designed to examine the sulfation of three opioid drugs, buprenorphine, pentazocine, and naloxone, in HepG2 human hepatoma cells and to identify the human SULT(s) responsible for their sulfation. Analysis of the spent media of HepG2 cells, metabolically labeled with [(35)S]sulfate in the presence of each of the three opioid drugs, showed the generation and release of their [(35)S]sulfated derivatives. A systematic analysis using eleven known human SULTs revealed SULT1A3 and SULT2A1 as the major responsible SULTs for the sulfation of, respectively, pentazocine and buprenorphine; whereas three other SULTs, SULT1A1, SULT1A2, and SULT1C4, were capable of sulfating naloxone. Enzymatic assays using combinations of these opioid drugs as substrates showed significant inhibitory effects in the sulfation of buprenorphine and pentazocine by naloxone. Differential sulfating activities toward the three opioid drugs were detected in cytosol or S9 fractions of human lung, liver, kidney, and small intestine. Collectively, these results imply that sulfation may play a role in the metabolism of buprenorphine, pentazocine, and naloxone in vivo.

Topics: Analgesics, Opioid; Buprenorphine; Carcinoma, Hepatocellular; Cytosol; Hep G2 Cells; Humans; Liver Neoplasms; Naloxone; Narcotic Antagonists; Pentazocine; Sulfates; Sulfotransferases

Topics: Aged; Analgesia, Epidural; Analgesics, Opioid; Anesthetics, Local; Antihypertensive Agents; Bupivacaine; Carcinoma; Cardiotonic Agents; Dobutamine; Enalapril; Female; Humans; Hypertension; Hypotension; Liver Neoplasms; Metoprolol; Morphine; Naloxone; Narcotic Antagonists; Norepinephrine; Thoracic Vertebrae; Time Factors; Vasoconstrictor Agents

Severe pruritus is a frequent complication of cholestasis. Both serotonin and opioids play an important role in the development of this symptom. Guidelines to provide rational management of pruritus of cholestasis do not exist. We describe a patient with complex and malignant course of pruritus. She responded to several measures proposed (among other naltrexone), but rapidly became tolerant to them. Buprenorphine with an ultra low dose of naloxone was able to control her symptoms without development of tolerance until her death.

Topics: Aged; Buprenorphine; Cholestasis; Colonic Neoplasms; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Liver Neoplasms; Naloxone; Narcotic Antagonists; Pruritus

Opioids modify hepatic function in vivo, however, a direct effect of this class of drugs on liver cells has not been demonstrated. The potential effect of opioids on liver parenchymal-type cells, therefore, was studied using cultured albumin-secreting rat hepatoma cells. Liver cells were incubated with methadone or naloxone individually or in combination. Dose-response analysis indicated that concentrations of either or both drugs in excess of 2.5 X 10(-5) M were clearly cytotoxic to cultured hepatoma cells. At a concentration (2.5 X 10(-7) M) at which no adverse effect on hepatoma cell viability or growth rate was observed, naloxone, methadone, or naloxone plus methadone produced a 26, 41, and 63% decrease in trichloroacetic acid-precipitable protein (per 10(6) cells), respectively, when compared to control. The inhibitory effect of naloxone, methadone, or naloxone plus methadone on albumin accumulation in the culture medium was greater than the drug-induced reduction of protein synthesis. These studies demonstrate that opioids have several direct effects on cultured hepatoma cells and, therefore, raise the question of whether clinically significant hepatic dysfunction may be produced by the direct action of opioids on the liver.

Topics: Albumins; Animals; Cell Division; Cell Line; Cells, Cultured; Liver; Liver Neoplasms; Liver Neoplasms, Experimental; Methadone; Naloxone; Rats; Selenomethionine