naloxone and Prostatic-Neoplasms

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

The effect of opiate receptor agonists upon cell growth of the prostatic carcinoma cell line DU145 were studied. Dynorphin-A increased growth significantly with a peak response at 10(-13) M, of 21 +/- 4% (mean +/- SEM). The dose response curve had a typical inverted-U shape. Dynorphin fragments 1-13 and 1-7 also increased growth at 10(-13) M, while the 2-13 fragment failed to increase growth. Naloxone increased growth at high concentration (10(-7) M) suggesting a stimulatory effect, while at the same time blocking the effect of dynorphin-A. This data demonstrates that agents which stimulate opiate receptors, especially the kappa receptor agonist dynorphin, increase the growth of prostatic carcinoma, and that this effect is controlled by changes at the N-terminal end of the peptide. This effect is blocked by Naloxone.

Topics: beta-Endorphin; Cell Division; Dose-Response Relationship, Drug; Dynorphins; Enkephalin, Leucine; Male; Morphine; Naloxone; Narcotics; Prostatic Neoplasms; Receptors, Opioid; Tumor Cells, Cultured

In order to clarify the effects of androgen blockade on the hypothalamic-pituitary-testicular axis in man, four patients with advanced prostate cancer, not previously treated, were given oral flutamide, 250 mg three times daily for 9 days. Before, and 7, 8 and 9 days after starting flutamide treatment, on separate days, the following tests were performed: a gonadotrophin pulsatility study, with 20 min interval blood sampling for 12 h, a naloxone test and a GnRH test. Flutamide induced a significant increase in both LH and FSH pulse frequency, while pulse amplitudes and plasma integrated concentrations (IC) of LH and FSH were unaffected. Plasma integrated concentrations of testosterone and oestradiol rose significantly, while that of prolactin was unaffected. The increase in plasma LH concentration induced by naloxone injection was abolished by flutamide treatment. On the other hand, the small FSH response to naloxone was unaffected by flutamide treatment. Response to GnRH was unaffected by flutamide. These results suggest that flutamide exerts effective androgen blockade at the hypothalamic level, since, despite increased plasma testosterone concentrations, gonadotrophin pulse frequency increased and the LH response to naloxone was abolished.

Topics: Anilides; Flutamide; Follicle Stimulating Hormone; Humans; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Male; Naloxone; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms; Testis