naloxone and Cerebrovascular-Disorders

Naloxone has enjoyed long-standing success as a safe and effective opioid antagonist and has been invaluable in defining the role of endogenous opioid pathways in the response to pathological states such as sepsis and hypovolemia. We look forward to exciting research to further elucidate these pathways and to improve outcome by modulating the patient's physiological response to these stresses.

Topics: Acute Disease; Adult; Animals; Asphyxia Neonatorum; Cerebrovascular Disorders; Child; Emergency Medicine; Humans; Infant, Newborn; Naloxone; Poisoning; Shock; Spinal Cord Injuries; Treatment Outcome

Multi-infarct dementia (MID) characteristically presents with an acute event followed by a stepwise and fluctuating downhill course. Progression is generally considered the consequence of recurrent stroke (Hachinski, 1983): the mainstay of treatment, therefore, is the prevention of further ischemic events.

Topics: Cerebrovascular Disorders; Dementia, Multi-Infarct; Dihydroergotoxine; Humans; Hypertension; Naloxone; Piracetam; Pyrrolidines

Topics: Acidosis; Adrenal Cortex Hormones; Anticoagulants; Barbiturates; Blood Viscosity; Brain Edema; Calcium Channel Blockers; Carbon Dioxide; Cerebrovascular Disorders; Dextrans; Hemodilution; Humans; Hypothermia, Induced; Lactates; Naloxone; Vasodilator Agents

Topics: Anesthetics; Animals; Arousal; Cerebrovascular Circulation; Cerebrovascular Disorders; Child, Preschool; Female; Gerbillinae; Humans; Male; Middle Aged; Naloxone; Poisoning; Rats; Respiration; Respiratory Insufficiency; Shock, Septic; Spinal Cord Injuries

Topics: Animals; Binding Sites; Cardiovascular System; Cerebrovascular Disorders; Endorphins; Humans; Hypertension; Naloxone; Narcotic Antagonists; Pressoreceptors; Shock; Shock, Septic; Spinal Cord Injuries; Thyrotropin-Releasing Hormone; Wounds and Injuries

Intravenous naloxone has been claimed to produce pain relief in opioid-resistant central post-stroke pain (CPSP, 'thalamic syndrome'). In a double-blind trial, carried out in 20 patients with established CPSP, naloxone (up to 8 mg in 20 ml vehicle) was tested against normal saline; each patient was randomly given naloxone or saline and the other substance 2 or 3 weeks later. VAS and verbal pain scores were obtained immediately before and after naloxone or saline injection, and subjective ratings followed for 2 weeks. Three patients obtained transient pain relief with naloxone, 4 with saline, and another 4 with both. Statistical tests failed to show any influence of giving naloxone first or second. In all cases except one, pain relief had disappeared by the evening of the day on which the test was performed; one case, following naloxone, continued to experience pain relief until the following morning. We therefore conclude that intravenous naloxone is of no value in alleviating the pain of CPSP.

Topics: Adult; Aged; Cerebrovascular Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone; Pain; Pain Measurement

Attention has focused on naloxone, an opiate receptor antagonist, because of its potential benefit in reversing neurological damage after acute cerebral ischemia. To evaluate the safety and possible efficacy of high-dose naloxone in ischemic stroke patients we planned a double blind pilot study. Between January 1989 and May 1990 24 patients were randomly assigned to the naloxone or placebo group according to age and neurological deficit. Naloxone was given in a loading dose of 5 mg/kg over 10 minutes followed by a 24-hour infusion at the rate of 3.5 mg/kg/h. 10 patients experienced minor side effects but none of them had to discontinue the treatment. 9 patients improved: 6 in the naloxone group and 3 in the placebo group, but no significant difference was found using the non parametric Mann-Whitney test. Our study suggests that naloxone is safe at the dose used, but the results do not support the planning of similar trials on a larger scale.

Topics: Acute Disease; Aged; Brain Ischemia; Cerebrovascular Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone

Naloxone was administered intravenously in a dose of 1.2 mg to 24 patients in the first 24 hours after they had suffered a stroke. Twenty patients were treated with placebo. In the naloxone-treated group a dose as low as 0.8 mg produced a slight but statistically significant improvement in neurologic status, and this improvement continued until the end of the observation period (two weeks). In the placebo group neurologic improvement was slower and less pronounced. The present results support a previous observation that naloxone may be a valuable drug in the early stage of acute cerebrovascular disease.

Topics: Acute Disease; Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Naloxone; Random Allocation

Topics: Adolescent; Adult; Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Hungary; Male; Middle Aged; Nalorphine; Naloxone

Topics: Acute Disease; Cerebrovascular Disorders; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Movement Disorders; Naloxone; Random Allocation

In Germany, an extended-release (ER) combination of the high-potency opioid (HPO) oxycodone and the antagonist naloxone was approved in 2006. In recent years, the cardio- and cerebrovascular safety of opioid antagonists and of opioids themselves has been discussed.. The objective of this study was to estimate the risk of major ischemic cardio- and cerebrovascular events in patients receiving ER oxycodone-naloxone compared with those receiving other ER HPOs.. We used the German Pharmacoepidemiological Research Database (GePaRD) to conduct a nested case-control study (2006-2011) within a cohort of ER HPO users. Cases were defined as patients hospitalized for acute myocardial infarction (MI) or ischemic stroke (IS). For each case, up to ten controls were selected by risk-set sampling. Using conditional logistic regression, confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were obtained for the risk of MI/IS associated with (1) current HPO treatment, (2) recent discontinuation, or (3) recent switch of HPO therapy compared with past treatment.. In 309,936 ER HPO users, 12,384 MI/IS events were detected, resulting in a crude incidence rate of 19.48 (95% CI 19.14-19.82) per 1000 person years. A small but significantly elevated aOR was found for morphine (1.12; 95% CI 1.04-1.22) but not for oxycodone-naloxone. Recent discontinuation and recent switch of any ER HPO also had a significant impact on the outcome (aOR 1.12; 95% CI 1.04-1.21 and 1.25; 95% CI 1.03-1.52, respectively).. Our study does not indicate an association between oxycodone-naloxone and ischemic cardio- or cerebrovascular events. However, our findings do suggest that every change in ER HPO therapy should be conducted with caution.

Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Case-Control Studies; Cerebrovascular Disorders; Delayed-Action Preparations; Female; Germany; Humans; Male; Middle Aged; Myocardial Ischemia; Naloxone; Oxycodone; Retrospective Studies; Risk

To evaluate the safety and possible efficacy of high-dose naloxone for the treatment of acute cerebral ischemia, 38 patients received a loading dose of 160 mg/m2 over 15 minutes followed by a 24-hour infusion at the rate of 80 mg/m2/hr. Nausea and/or vomiting were common side effects. Naloxone was discontinued in seven patients (because of hypotension in one, bradycardia and hypotension in two, myoclonus in one, focal seizures in two, and hypertension in one); all seven patients responded to treatment and no permanent sequelae to naloxone were noted. Twelve of the 38 patients showed early neurologic improvement (by completion of the naloxone loading dose). However, there was no correlation between such a loading dose response and clinical outcome at 3 months. Our experience suggests that naloxone is safe at the dose used, but data for efficacy are inconclusive.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Blood Pressure; Brain Ischemia; Cerebrovascular Disorders; Drug Evaluation; Female; Gastrointestinal Diseases; Humans; Infusions, Intravenous; Male; Middle Aged; Naloxone; Seizures

Endorphins and narcotics have been implicated in the exacerbation of neurologic deficits after stroke. To test the theory that narcotic antagonists might offer an improvement in neurologic sequelae following stroke, we administered various doses of naloxone intraperitoneally to 50 adult gerbils 45 minutes after carotid artery transsection. Low-dose naloxone therapy (1.0 to 2.5 mg/kg) was more effective in preventing death than either control (sterile saline) or high-dose naloxone (10 mg/kg). A naloxone dose of 1.0 or 2.5 mg/kg offered a significant improvement in mortality over both the control and the high-dose therapy (P = .026). It appears that an appropriate dose of naloxone (1.0 to 2.5 mg/kg), given early enough to alter outcome, offers an improved survival in the gerbil stroke model. This finding obviously has significant implications for the use of narcotic antagonists in human beings with stroke.

Topics: Animals; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Gerbillinae; Injections, Intraperitoneal; Naloxone; Nervous System Diseases; Time Factors

Topics: Animals; Cerebrovascular Disorders; Humans; Naloxone

Topics: Aged; Cerebrovascular Disorders; Female; Humans; Naloxone

Topics: Cerebrovascular Disorders; Female; Hemiplegia; Humans; Hypesthesia; Infusions, Intravenous; Male; Middle Aged; Naloxone; Palliative Care; Syndrome; Thalamic Diseases

Topics: Aged; Cerebrovascular Disorders; Endorphins; Hemiplegia; Humans; Male; Middle Aged; Naloxone

The effect of the opiate antagonist naloxone on both the neurological deficit and regional cortical blood flow after middle cerebral artery occlusion in the cat was investigated. In animals with mild symptoms, naloxone did not consistently produce a significant behavioral effect. In all cats with neurological deficits, including hemiplegia or severe hemiparesis, 2 mg/kg naloxone administered intravenously 4 h after the ischemic lesion produced a reversal of neurological symptoms. This effect began within 2 min following naloxone injection and lasted for approximately 20 min. Animals were then anesthetized and cortical blood flow was measured by the hydrogen clearance method. Average cortical blood flow on the side of the occlusion was 50% that of the control side. Naloxone produced a significant additional decrease of 19.5% in cortical blood flow in the ischemic hemisphere, whereas no effect on blood flow on the control side was noted. Thus, although naloxone appears to temporarily reverse the severe neurological deficits resulting from middle cerebral artery occlusion in the cat, this effect appears to be accompanied by a decrease in local blood flow to the ischemic cortex.

Topics: Animals; Cats; Cerebral Arteries; Cerebral Cortex; Cerebrovascular Circulation; Cerebrovascular Disorders; Female; Ischemic Attack, Transient; Male; Naloxone

The effects are reported of acute and long-term continuous administration of three opiate antagonists--naloxone, naltrexone, and diprenorphine--on neurological function, survival, and infarct size in a feline model of acute focal cerebral ischemia. All three drugs produced statistically significant improvement in motor function following acute administration without concomitant changes in level of consciousness; saline had no effect. Naloxone and naltrexone significantly prolonged survival (p less than 0.01); diprenorphine did not. Infarct size was not altered by any treatment administered. These findings confirm previous work suggesting that, with the appropriate methodology, treatment with opiate antagonists partially reverses neurological deficits. They also show that opiate antagonists prolong survival in certain conditions of acute and subacute focal cerebral ischemia without altering the area of infarcted tissue.

Topics: Animals; Brain Ischemia; Cats; Cerebrovascular Disorders; Consciousness; Diprenorphine; Disease Models, Animal; Male; Morphinans; Movement; Naloxone; Naltrexone; Pupil; Sensation

Coenzyme Q10 (CoQ10) and the opiate antagonist naloxone were compared as to their effect on the survival of mongolian gerbils with unilateral carotid ligation-induced stroke. Without medication all of the stroke gerbils died within 28 hours, but with a subcutaneous implantation of a 10 mg pellet of naloxone, 20% of the gerbils lived for 4 weeks. When a 250 mg pellet of CoQ10 was implanted subcutaneously, a definite effect on survival was observed, with 45% of the stroke gerbils living for 4 weeks. Considering that the action mechanisms of CoQ10 and naloxone are different, the combined use of these drugs in the treatment of stroke needs to be investigated.

Topics: Animals; Cerebrovascular Disorders; Coenzymes; Electron Transport; Gerbillinae; Levallorphan; Naloxone; Time Factors; Ubiquinone

Topics: Anticoagulants; Bloodletting; Cerebral Infarction; Cerebrovascular Disorders; Fibrinolytic Agents; Heparin; Humans; Intracranial Embolism and Thrombosis; Ischemic Attack, Transient; Naloxone; Recurrence; Vasodilator Agents; Warfarin

Cerebral blood flow (CBF) in the rat was monitored by a venous outflow technique with an extracorporeal circulation, which allows for the continuous recording of CBF over several hours. Morphine and the opiate antagonist, naloxone, were tested for their effects on the reactive hyperemia that follows a brief anoxic challenge. Morphine (5.0 mg/kg) significantly reduced the peak increase in flow during the hyperemia and, at both of the doses used (1.0 and 5.0 mg/kg), caused a small, nonsignificant increase in the duration of the reactive hyperemia. Naloxone (0.1 and 1.0 mg/kg) enhanced basal CBF rates and significantly prolonged the duration of the reactive hyperemia. These effects of naloxone may account for its beneficial effects in the treatment of cerebral ischemia.

Topics: Animals; Cerebrovascular Circulation; Cerebrovascular Disorders; Hyperemia; Hypoxia, Brain; Male; Morphine; Naloxone; Rats; Rats, Inbred Strains

Topics: Animals; Cerebrovascular Disorders; Humans; Migraine Disorders; Naloxone; Spinal Cord Injuries

Topics: Animals; Brain Injuries; Cats; Cerebrovascular Disorders; Humans; Naloxone; Rats; Spinal Cord Injuries; Thyrotropin-Releasing Hormone

Topics: Cerebrovascular Disorders; Humans; Naloxone

Naloxone has recently been reported to be of benefit in the treatment of central nervous system ischemia. To study the effect of naloxone in an experimental stroke model, we subjected 40 awake monkeys to middle cerebral artery (MCA) occlusion 2 weeks after the placement of a MCA ligature by a transorbital technique. Cerebral blood flow (CBF) was monitored with stereotactically placed H2 electrodes, and the neurological course was serially recorded. Infarct size was determined 2 weeks after MCA occlusion. Twenty animals served as control and received no naloxone; 10 of these underwent permanent occlusion, and 10 underwent 4-hour MCA occlusion. In 25 treatment animals, naloxone was administered in three different intravenous dosages: (a) naloxone, 2-mg/kg bolus 20 minutes postocclusion and 2 mg/kg/hour X 4 hours, in 10 animals with permanent MCA occlusion; (b) naloxone, 10-mg/kg bolus 20 minutes postocclusion and 10 mg/kg/hour X 4 hours, in 10 animals with 4-hour MCA occlusion; and (c) naloxone, 20-mg/kg bolus, in 5 animals with various neurological deficits. MCA occlusion typically produced a moderate deficit: hemiparesis, hemianopsia, and facial paresis. In most instances, naloxone in the 2- and 10-mg/kg dose regimens produced little or no change in the neurological function. CBF decreased after MCA occlusion and was unaffected by naloxone in most cases. Infarct size was not significantly different between the control and treated groups. However, the 20-mg/kg dose consistently produced a nonfunctional, transient increase in total body motor tone in normal and hemiparetic animals. Naloxone did not significantly improve useful neurological function, CBF, or infarct size in an experimental primate stroke model.

Topics: Animals; Brain Ischemia; Cerebral Infarction; Cerebrovascular Circulation; Cerebrovascular Disorders; Macaca fascicularis; Male; Models, Biological; Naloxone

Topics: Cerebrovascular Disorders; Hemiplegia; Humans; Male; Middle Aged; Naloxone

A highly predictive spinal "stroke" model in the unanesthetized rabbit was utilized to compare the effects of naloxone and the delta-selective opiate antagonist M154,129 on neurological recovery following ischemic injury to the central nervous system. Naloxone treatment protected against both moderate (20 min aortic occlusion) and severe (25 min aortic occlusion) degrees of ischemic spinal injury, whereas treatment with M154,129 failed to improve recovery in either model. These findings confirm that naloxone therapy can alter the pathophysiological sequelae caused by a critical reduction in blood flow to the central nervous system and suggests that its beneficial effects do not relate to actions at the delta-opiate receptor.

Topics: Animals; Cerebrovascular Disorders; Disease Models, Animal; Enkephalin, Leucine; Male; Motor Activity; Naloxone; Rabbits; Spinal Cord

Naloxone failed to improve motor strength in any of 19 patients with acute stroke, even though 4 patients eventually demonstrated complete recovery. Two patients worsened, and sensory abnormalities increased in two others. Motor tone increased in eight patients. Naloxone amelioration of stroke deficits is therefore not common, and this treatment may not be entirely benign.

Topics: Adult; Aged; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Naloxone; Nervous System Diseases

Topics: Animals; Brain Ischemia; Cerebrovascular Disorders; Gerbillinae; Hemiplegia; Levorphanol; Male; Morphine; Naloxone; Receptors, Opioid

The effects of naloxone and thyrotropin releasing hormone (TRH) were compared in an incremental air embolization model of experimental stroke in dogs. Naloxone treatment significantly improved the cortical somatosensory evoked response and had a beneficial effect on local cerebral blood flow, whereas TRH treatment had no effect on these variables. These findings may implicate endorphins in the pathophysiology of stroke and indicate that naloxone may have a therapeutic role in this condition. Moreover, the lack of effect of TRH in this model, in contrast to its therapeutic effect in experimental spinal injury, indicates that the pathophysiologic responses to ischemic cerebral injury and traumatic spinal injury may differ.

Topics: Animals; Brain Ischemia; Cerebrovascular Circulation; Cerebrovascular Disorders; Disease Models, Animal; Dogs; Evoked Potentials, Somatosensory; Male; Naloxone; Spinal Cord Injuries; Thyrotropin-Releasing Hormone

Topics: Adult; Aged; Animals; Cerebrovascular Disorders; Female; Gerbillinae; Humans; Naloxone