naloxone and Lung-Neoplasms

Topics: Aged; Cancer Pain; Delayed-Action Preparations; Drug Combinations; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Naloxone; Oxycodone; Pain Management; Retrospective Studies

Opioids can induce respiratory depression by invoking a centrally mediated decrease in involuntary respiratory rate, which in severe cases can cause a decrease in oxygen saturation. If respiratory depression is opioid induced, both low respiratory rate and low oxygen saturation will be present. If this is the case, oxygenation, rousing by verbal and physical stimulation and decreasing the opioid dose should be tried first. Naloxone, an opioid antagonist, should be avoided if at all possible but, if essential, titrate slowly to respiratory function administering 20-100 µg intravenously every two minutes. If used as a bolus for a patient on long-term opioids for chronic cancer pain, then refractory pain and symptomatic opioid withdrawal can result.

Topics: Analgesics, Opioid; Bone Neoplasms; Female; Humans; Lung Neoplasms; Male; Naloxone; Narcotic Antagonists; Oxygen Inhalation Therapy; Pain; Prostatic Neoplasms; Respiratory Insufficiency; Substance Withdrawal Syndrome

Several studies have shown that an oxycodone/naloxone combination (ratio 2:1) provides analgesia and less constipation in non-cancer patients receiving relatively low doses of this formulation. A case report of a cancer patient who was receiving increasing doses of oxycodone with an unexpected declining analgesia is presented. The substitution with the same doses (240 mg/day) of regular controlled-release oxycodone was effective in regaining adequate analgesia.

Topics: Aged; Analgesics, Opioid; Constipation; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Combinations; Humans; Lung Neoplasms; Male; Naloxone; Narcotic Antagonists; Oxycodone; Pain; Treatment Outcome

Topics: Aged; Bone Neoplasms; Carcinoma, Bronchogenic; Cholestasis; Humans; Lung Neoplasms; Male; Naloxone; Narcotic Antagonists; Nociceptors; Pruritus

In the present study, we measured the kinetics and distribution in vivo of the selective delta-opioid antagonist 11C-methylnaltrindole (11C-MeNTI) and the mu-opioid agonist 11C-carfentanil (11C-CFN) in patients with lung carcinoma using PET.. Paired measurements of 11C-MeNTI and 11C-CFN binding were performed in biopsy-proven small-cell (n = 2), squamous (n = 2), and adenocarcinoma (n = 3) lung cancer patients. Dynamic PET scans of increasing duration (0.5-8 min) were acquired over 90 min after an intravenous bolus injection of 370 MBq of tracer. Time-activity curves for tumor and normal lung parenchyma binding were generated using the region-of-interest (ROI) method. The mean activity at equilibrium was measured, and the specific-to-nonspecific binding ratio (tumor - lung)/lung was calculated. Four of 7 patients underwent an additional static 18F-FDG PET scan for clinical indications. Three of 7 patients underwent surgery, and stained sections of tumor were inspected for inflammation, necrosis, and scar tissue.. Increased binding of 11C-MeNTI and 11C-CFN was detected in all tumor types studied. 11C-MeNTI binding in tumor and healthy lung tissue was significantly more intense than that of 11C-CFN. The average specific-to-nonspecific binding ratio across cell types for 11C-MeNTI (4.32 +/- 1.31; mean +/- SEM) was greater than that of 11C-CFN (2.42 +/- 1.17) but lower than that of 18F-FDG (7.74 +/- 0.53). Intravenous naloxone produced 50% and 44% decreases in the specific-to-nonspecific binding ratios of 11C-MeNTI and 11C-CFN, respectively.. These data provide in vivo evidence for the presence of delta- and mu-opioid receptor types in the 3 major human lung carcinomas and suggest the suitability of 11C-MeNTI and 11C-CFN as investigational probes of lung carcinoma biology.

Topics: Adenocarcinoma; Aged; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Coloring Agents; Female; Humans; Inflammation; Lung Neoplasms; Male; Middle Aged; Naloxone; Narcotic Antagonists; Necrosis; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Opioid, delta; Receptors, Opioid, mu; Tissue Distribution

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Bucladesine; Calcium Channels; Carcinoma, Small Cell; Cell Division; Cyclic AMP; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Humans; Kinetics; Lung Neoplasms; Naloxone; Neurons; Receptors, Opioid, delta; Serotonin; Thapsigargin; Time Factors; Tumor Cells, Cultured

Previous reports have demonstrated that beta-endorphin stimulates the clonal growth of human small cell lung carcinoma (SCLC) cell lines. In this study, the human SCLC lines, NCI-H69, NCI-H345, and NCI-N417, were observed to be highly-enriched in saturable, high-affinity binding sites which are labeled by [125I]beta-endorphin. In contrast to conventional opioid receptors, [125I]beta-endorphin SCLC binding was insensitive to naloxone and other mu, delta, or kappa opioid ligands. Further analysis of the NCI-H69 cells demonstrated that specific (naloxone-insensitive) binding was dependent on receptor concentration, reversible, sensitive to sodium ion, but insensitive to the GTP analogue, Gpp(NH)p. These results suggest a role for naloxone-insensitive beta-endorphin in modulating SCLC metabolism.

Topics: Animals; beta-Endorphin; Binding Sites; Binding, Competitive; Carcinoma, Small Cell; Cell Membrane; Humans; Iodine Radioisotopes; Lung Neoplasms; Naloxone; Prosencephalon; Rats; Receptors, Opioid; Sensitivity and Specificity; Tumor Cells, Cultured

The present study was undertaken to determine the effect of the opioid receptor antagonist, naloxone, on the growth of B16 melanoma, a murine tumor known to possess opioid receptors. Naloxone inhibited the growth of B16 melanoma in vitro when monolayer cultures were continuously exposed to concentrations of greater than or equal to 0.25 mg/ml. Tumor cell proliferation as measured by [3H]thymidine ([3H]Tdr) incorporation is reduced by a continuous 48-h treatment with greater than or equal to 0.025 mg/ml but slightly enhanced by a 6-h treatment. The administration of naloxone to mice caused a transient inhibition of subcutaneous local tumor growth at doses of 0.1, 1 and 10 mg/kg daily. At a dose of 10 mg/kg daily, naloxone caused a slight reduction in the number of pulmonary metastases following the intravenous inoculation of tumor cells. The mechanism by which naloxone inhibits tumor growth in vivo is not clear, but factors other than direct cytotoxicity may also be involved. The results further support the role of the endogenous opioid system in the modulation of tumor growth.

Topics: Animals; Cell Division; Cell Line; Lung Neoplasms; Male; Melanoma; Mice; Mice, Inbred C57BL; Naloxone; Neoplasm Transplantation

Walker 256 carcinosarcoma cells produce subpleural pulmonary metastases when given intravenously to the Sprague-Dawley rat. The number of metastases increases when the rat is given morphine subsequent to the tumor load. The increase in the number of metastases can be blocked be pretreatment with the opiate antagonist naloxone. Naloxone itself does not influence the number of metastases. Pentazocine is an opiate that is agonistic to the endorphin kappa-type opiate receptor and partially antagonistic to the mu-type receptor, where morphine acts primarily. While pentazocine alone has no influence on metastases and may decrease the number when given early, pentazocine partially blocks the metastatic inducing effect of morphine.

Topics: Animals; Carcinosarcoma; Cell Division; Cell Line; Lung Neoplasms; Morphine; Naloxone; Neoplasm Transplantation; Pentazocine; Rats; Rats, Inbred Strains

Pulmonary metastases were counted 10 days after female rats received tail-vein injections of Walker-256 carcinosarcoma cells. Previous observations that halothane anesthesia plus hind-limb amputation increases the number of metastases were confirmed. Amputation under the analgesia of electrical stimulation of the midbrain was found to increase metastatic activity. However, the stimulus-produced analgesia alone also increased the number of metastases. Systemically administered naloxone blocked the analgesic effect of midbrain stimulation but did not block the increase in the number of pulmonary metastases.

Topics: Anesthesia; Animals; Carcinoma 256, Walker; Cerebral Aqueduct; Electric Stimulation; Immune Tolerance; Lung Neoplasms; Mesencephalon; Naloxone; Neoplasm Metastasis; Rats; Receptors, Opioid; Stress, Physiological