naloxone and Kidney-Failure--Chronic

A 57-year-old woman with metastasizing ovarian cancer and chronic renal failure was admitted for morphine treatment of an acute lumbospinal pain syndrome, ambulant treatment with analgesics having failed provide adequate pain relief. On admission due to pain the conscious patient presented with reduced general condition and lumbal pain sensitive to tapping. Lasègue's sign was positive on both sides, no other disturbed neurological functions were found.. On the 7th day of morphine administration she became somnolent and breathing became markedly depressed, indicating overdosage, metabolic and intracranial causes having been excluded. Naloxone, an opioid antagonist, was given i.v. and the breathing pattern improved. But drowsiness continued for another 48 hours and only regressed after repeated doses of naloxone.. Morphine-6-glucuronide (M6G), formed from morphine in the liver, accumulates in blood and penetrates the blood-brain barrier, binding with strong affinity to opiate receptors and exerts a strong analgesic effect. As M6G is excreted by the kidney, its concentration rises in renal failure and can lead to severe intoxication. Morphine dosage must therefore be carefully controlled in patients with renal failure.

Topics: Analgesics, Opioid; Diagnosis, Differential; Female; Humans; Kidney Failure, Chronic; Middle Aged; Morphine; Morphine Derivatives; Naloxone; Narcotic Antagonists; Ovarian Neoplasms; Pain, Intractable; Poisoning

The pharmacokinetics of oxycodone in patients with end-stage renal disease (ESRD) requiring haemodialysis are largely unknown. Therefore, we investigated the pharmacokinetics of oxycodone/naloxone prolonged release and their metabolites in patients with ESRD during and between haemodialysis sessions.. Single doses of oxycodone/naloxone (5/2.5 or 10/5 mg) were administered in nine patients with ESRD using a cross-over design on the day of dialysis and on a day between dialysis sessions. Plasma, dialysate and urine concentrations of oxycodone, naloxone and their metabolites were determined up to 48 h post-dosing using a liquid chromatography-tandem mass spectrometry system.. Haemodialysis performed 6-10 h after dosing removed ∼10% of the administered dose of oxycodone predominantly as unconjugated oxycodone and noroxycodone or conjugated oxymorphone and noroxymorphone. The haemodialysis clearance of oxycodone based on its recovery in dialysate was (mean ± SD) 8.4 ± 2.1 L/h. The geometric mean (coefficient of variation) plasma elimination half-life of oxycodone during the 4-h haemodialysis period was 3.9 h (39%) which was significantly shorter than the 5.7 h (22%) without haemodialysis. Plasma levels of the active metabolite oxymorphone in its unconjugated form were very low.. Oxycodone is removed during haemodialysis. The pharmacokinetics including the relatively short half-life of oxycodone in patients with ESRD with or without haemodialysis and the absence of unconjugated active metabolites indicate that oxycodone can be used at usual doses in patients requiring dialysis.

Topics: Adult; Aged; Analgesics, Opioid; Cross-Over Studies; Female; Humans; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Morphinans; Naloxone; Narcotic Antagonists; Oxycodone; Oxymorphone; Prognosis; Renal Dialysis; Tissue Distribution

The aim of the study was to answer the questions: 1) does the prolactin secretion in the TRH test (0.4 mg i.v.) differ in haemodialyzed patients with diabetes nephropathy in the end stage renal failure in comparison to haemodialyzed chronic renal failure patients with non-diabetic nephropathy and healthy subjects; 2) does the opiate receptors blockade with naloxone (2 mg i.v.) modify the prolactin secretion during the TRH test in those patients. 39 subjects were studied. The patients were divided into three groups: group I: 12 haemodialyzed patients with IDDM and diabetic nephropathy in the end stage renal failure, group II: 15 haemodialyzed chronic renal patients with non-diabetic nephropathy and the control group: 12 healthy persons. The basic prolactin secretion and area over basic value (AOBV) of the prolactin were estimated. Prolactin concentration was measured by LIA. 1) The basic prolactin secretion was significantly higher in the patients with chronic renal failure. 2) The basic prolactin secretion in IDDM patients with diabetic nephropathy in the end stage renal failure treated with haemodialysis was significantly lower than in haemodialyzed patients with chronic renal failure of non-diabetic etiology. 3) TRH and TRH with naloxone caused significant increase of prolactin secretion in all investigated groups, but the increase is significantly lower in chronic renal failure patients than in healthy subjects. 4) Naloxone decreases significantly the prolactin secretion during TRH test only in haemodialyzed patients with chronic renal failure of non-diabetic etiology.

Topics: Adult; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Middle Aged; Naloxone; Narcotic Antagonists; Prolactin; Renal Dialysis

We present this case to review the metabolism of oxycodone and the effects of end-stage renal disease on the elimination of oxycodone and its metabolites. A 42-year-old female with end-stage renal disease who was dependent on hemodialysis presented for left hamstring posterior capsule release. She had been receiving methadone for 2 years for chronic leg pain. On postoperative day 1, the patient's medication was changed from IV hydromorphone to oral oxycodone to treat breakthrough pain. By the next day, the patient was unarousable with notable respiratory depression. She did not fully recover after urgent hemodialysis but did have full recovery after receiving an IV naloxone infusion for 22 hours. Further study of the safety of oxycodone in hemodialysis patients is warranted.

Topics: Administration, Oral; Adult; Analgesics; Biotransformation; Chronic Pain; Female; Humans; Infusions, Intravenous; Joint Capsule Release; Kidney Failure, Chronic; Leg; Naloxone; Narcotic Antagonists; Oxycodone; Pain, Postoperative; Renal Dialysis; Respiratory Insufficiency; Treatment Outcome

Respiratory depression secondary to morphine intoxication occurred in an elderly patient with chronic renal failure (CRF). It was reversed with a continuous infusion of naloxone. Approximately 11 hours after the infusion was discontinued, the patient relapsed into respiratory depression consistent with opioid intoxication. He was rechallenged with a naloxone infusion with resolution of the opioid effects. This case suggests prolonged antagonism of opioid effects inconsistent with naloxone's reported pharmacologic effects. Serum naloxone concentrations measured after the end of the infusion suggest that the drug's pharmacokinetics were significantly altered. Further research is necessary to characterize pharmacokinetic changes that occur in CRF. In the absence of this information, similar patients should be closely monitored for relapse of respiratory depression after naloxone is discontinued.

Topics: Aged; Analgesics, Opioid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Morphine; Naloxone; Narcotic Antagonists; Respiratory Insufficiency; Time Factors

We report the case of a 61-year-old diabetic woman with end-stage renal disease who was on hemodialysis and who developed an encephalopathy and episodes of hypotension and hypoventilation, all of which showed rapid and dramatic responses on multiple occasions to the administration of the opiate antagonist naloxone. Improvement in encephalopathy was confirmed by electroencephalography. The patient had received no exogenous opiates and had a normal beta-endorphin level. She subsequently developed myoclonus and was treated for possible aluminum overload that was of borderline magnitude. We conclude that this patient had an encephalopathy that responded to opiate receptor blockade. Because of cerebrovascular disease, episodes of diminished blood pressure due to a state of increased opiate receptor stimulation may have unmasked this underlying encephalopathy. These effects may have been secondary to increased opiate-binding sites or to elevated central nervous system levels of endogenous opiates.

Topics: Brain Diseases; Diabetes Mellitus, Type 2; Electroencephalography; Female; Humans; Kidney Failure, Chronic; Middle Aged; Naloxone; Renal Dialysis

The present study aimed to assess the influence of opioid receptors on vasopressin (AVP) secretion in 12 kidney transplant patients (KTP) with stable graft function, and in 15 healthy subjects (control). Significantly lower basal plasma AVP levels were found in KTP than in controls. After blockade of opioid receptors by naloxone a significant increase of plasma AVP levels were observed in both examined groups. This increase was significantly higher in KTP than in healthy subjects. From data presented in this study participation of opioid receptors in the regulation of AVP secretion is highly likely both in KTP and controls. This participation seems to be significantly greater in KTP than in healthy subjects.

Topics: Adult; Arginine Vasopressin; Blood Pressure; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Naloxone; Receptors, Opioid; Stimulation, Chemical

In 72 patients with end-stage renal failure and 70 healthy subjects, the influence of blockade of opioid receptors by naloxone on secretion of prolactin, lutropin (LH), follitropin (FSH), adrenocorticotropin (ACTH), somatotropin (HGH), insulin (IRI), glucagon (IR-G), parathyroid hormone (PTH) and calcitonin (CT) was studied. Administration of naloxone stimulated luliberin-induced LH and FSH secretion quantitatively equally in patients and controls. Blockade of opioid receptors was followed by a less marked suppression of chlorpromazine-induced prolactin secretion but by a higher response of hypoglycemia-induced ACTH secretion in uremic patients than in controls. In addition, a less marked suppressive effect of naloxone was noted on hypoglycemia-induced HGH secretion in chronic renal failure as compared with controls. Blockade of opioid receptors improved significantly glucose tolerance and glucose-induced insulin secretion in uremic patients and suppressed nearly completely glucagon secretion response during the second phase of a glucose tolerance test. Finally, administration of naloxone was followed by a blunted response of Ca-induced CT secretion and suppression of PTH. Data presented in this paper suggest the existence of hyperendorphinism in end-stage renal failure.

Topics: Calcitonin; Endocrine System Diseases; Glucagon; Humans; Insulin; Insulin Secretion; Kidney Failure, Chronic; Male; Naloxone; Parathyroid Hormone; Pituitary Hormones, Anterior; Receptors, Opioid

Topics: Adult; Calcifediol; Calcitonin; Female; Humans; Kidney Failure, Chronic; Male; Naloxone; Parathyroid Hormone; Receptors, Opioid

Topics: Adult; Female; Glucagon; Humans; Insulin; Insulin Secretion; Kidney Failure, Chronic; Male; Naloxone; Pancreatic Function Tests

Topics: Acute Kidney Injury; Adult; Depression, Chemical; Endorphins; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Naloxone; Receptors, Opioid; Vasopressins

Topics: Adrenocorticotropic Hormone; Adult; Depression, Chemical; Endorphins; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Naloxone; Receptors, Opioid

In 5 uremic patients the role of opioid peptides in dialysis-induced hypotension was investigated through the administration of naloxone. An intravenous bolus injection of 1 mg of naloxone was administered immediately before starting a routine hemodialysis session and was repeated when the patients' systolic arterial pressure sank below 90 mm Hg. In our patients, naloxone had no effect on the resting arterial pressure or on dialysis-induced hypotension.

Topics: Blood Pressure; Female; Humans; Hypotension; Kidney Failure, Chronic; Male; Naloxone; Renal Dialysis; Uremia

Topics: Adult; Follicle Stimulating Hormone; Hormones; Humans; Kidney Failure, Chronic; Male; Middle Aged; Naloxone; Prolactin; Testosterone

Serum prolactin, luteinising hormone and follicle-stimulating hormone, determined by radioimmunoassay were measured during the infusion of 10mg naloxone or saline in eight male patients with chronic renal failure on regular dialysis and in seven normal controls. Neither saline nor naloxone caused any significant change in luteinising hormone, follicle-stimulating hormone or prolactin in patients with chronic renal failure. On the contrary, luteinising hormone secretion was significantly stimulated by naloxone in normal controls. Since naloxone is a specific antagonist of opiate receptors, the results would suggest a reduced hypothalamic opiate tone in patients with chronic renal failure. The data does not support the concept that the high circulating met-encephalin reported in chronic renal failure represents the pathogenetic cause of hyperprolactinaemia in chronic renal failure.

Topics: Adult; Endorphins; Gonadotropins, Pituitary; Humans; Kidney Failure, Chronic; Male; Middle Aged; Naloxone; Prolactin

Plasma methionine-enkephalin (Met-Enk) immunoreactivity has been determined in 24 patients with varying degrees of renal impairment and 14 patients with hepatic failure. Plasma Met-Enk immunoreactivity correlated inversely with creatinine clearance (r = -0.71, P less than 0.001) but was not affected by even severe hepatic failure in the absence of renal impairment. In two patients, with renal failure and elevated plasma prolactin, administration of naloxone (16 mg) had no effect on circulating prolactin concentrations. These studies indicate that the kidney has a major role in Met-Enk metabolism while the liver does not, and further suggest that elevated circulating endogenous opiates are not responsible for the increased production of prolactin found in renal failure.

Topics: Enkephalin, Methionine; Female; Humans; Hyperprolactinemia; Kidney; Kidney Diseases; Kidney Failure, Chronic; Liver; Liver Diseases; Male; Naloxone

The influence of the opiate antagonist naloxone on chlorpromazine induced prolactin secretion was examined in 12 patients with acute renal failure (ARF), 12 patients with chronic renal failure (CRF) and in 12 healthy subjects. In all examined groups naloxone showed a suppressive effect on chlorpromazine induced prolactin secretion, which was more accentuated in normals and patients with ARF then with CRF. The results of these investigations suggest that endogenous opiates may be of importance in the regulation of prolactin secretion both in normals and uremic patients.

Topics: Acute Kidney Injury; Adult; Chlorpromazine; Female; Humans; Kidney Failure, Chronic; Male; Naloxone; Prolactin