Single Dose Of Naloxone Research Articles

Naloxone Diminishes the Virulence and Modifies the Cellular Immune Responses of BALB/c Mice Infected with Leishmania major.

Leishmania major-infected BALB/c mice display strong susceptibility to the infection due to the induction of Th2 response. The aim of this study was to assess the effects of naloxone on virulence of L. major in BALB/c mice and the ensued cellular immuneresponse. The effects of injection of a single dose of naloxone in the footpad of L. major-infected BALB/c mice were investigated by evaluating the lesion sizes, the parasite burden, cell proliferation, secreted cytokines (IFN-γ, IL-4, IL-10 and IL-12) and their genes expressions due to naloxone treatment while the untreated mice were used as a control. Significantly lower lesion sizes and less parasite burden were measured in the treated mice. Significantly decreased productions of IFN-γ, IL-12, IL-4, and IL-10 were also observed in the treated mice at week 4 post-infection while the production IL-10 remained significantly hindered till 8weeks post-infection. Our data indicated that although the treatment of L. major-infected BALB/c mice with a single dose of naloxone was unable to improve the cellular immune response, it led to lower virulence, confirmed by significantly reduced lesions and parasite load.

The Role of Hydrogen Sulfide in the Development of Tolerance and Dependence to Morphine in Mice

Objective: Hydrogen sulfide is an endogenous gaseous mediator that has been indicated to have a role in pain mechanisms. In this study, we aimed to detect brain and spinal cord hydrogen sulfide levels during different phases of tolerance and dependence to morphine and to determine the effects of inhibition of endogenous hydrogen sulfide production on the development of tolerance and dependence. Methods: Morphine tolerance and dependence was developed by subcutaneous injection of morphine (10 mg/kg) twice daily for 12 days. Physical dependence was determined by counting the jumps for 20 min, which is a withdrawal symptom occurring after a single dose of naloxone (5 mg/kg) administered intraperitoneally (i.p.). Propargylglycine (30 mg/kg, i.p.), a cystathionine-γ-lyase inhibitor, and hydroxylamine (12.5 mg/kg, i.p.), a cystathionine-β-synthase inhibitor, were used as hydrogen sulfide synthase inhibitors. The tail-flick and hot-plate tests were used to determine the loss of antinociceptive effects of morphine and development of tolerance. Results: It was found that chronic and acute uses of both propargylglycine and hydroxylamine prevented the development of tolerance to morphine, whereas they had no effect on morphine dependence. Chronic and acute administrations of hydrogen sulfide synthase inhibitors did not exert any difference in hydrogen sulfide levels in brain and spinal cords of both morphine-tolerant and -dependent animals. Conclusion: It has been concluded that hydrogen sulfide synthase inhibitors may have utility in preventing morphine tolerance.

Delay-Dependent Impairments in Memory and Motor Functions After Acute Methadone Overdose in Rats.

Methadone is used as a substitution drug for the treatment of opioid dependence and chronic pain. Despite its widespread use and availability, there is a serious concern with respect to the relative safety of methadone. The purpose of this study was to characterize how acute methadone overdose affects the cognitive and motor performance of naïve healthy rats. The methadone overdose was induced by administering an acute toxic dose of methadone (15 mg/kg; ip; the equivalent dose of 80% of LD50) to adolescent rats. Resuscitation using a ventilator pump along with a single dose of naloxone (2 mg/kg; ip) was administered following the occurrence of apnea. The animals which were successfully resuscitated divided randomly into three apnea groups that evaluated either on day 1, 5, or 10 post-resuscitation (M/N-Day 1, M/N-Day 5, and M/N-Day 10 groups) in the Y-maze and novel object memory recognition tasks as well as pole and rotarod tests. The data revealed that a single toxic dose of methadone had an adverse effect on spontaneous behavior. In addition, Recognition memory impairment was observed in the M/N-Day 1, 5, and 10 groups after methadone-induced apnea. Further, descending time in the M/N-Day 5 group increased significantly in comparison with its respective Saline control group. The overall results indicate that acute methadone-overdose-induced apnea produced delay-dependent cognitive and motor impairment. We suggest that methadone poisoning should be considered as a possible cause of delayed neurological disorders, which might be transient, in some types of memory or motor performance in naïve healthy rats.

Combating opioid drug abuse with naloxone

Drug overdose deaths are now the number one cause of accidental death in the United States. The rise in the number of hospitalizations and deaths resulting from prescription drug misuse and abuse, particularly opioids, gave increased access to naloxone a role in the White House Office of National Drug Control Policy's 2014 National Drug Control Strategy, issued July 9. That same week, Kaleo announced the release of naloxone hydrochloride injection (Evzio), a newly FDA-approved prescription treatment for reversal of emergency opioid overdose that consists of a handheld auto-injector containing a single dose of naloxone.

Maternal and Neonatal Effects of Remifentanil at Induction of General Anesthesia for Cesarean Delivery

Use of remifentanil during general anesthesia for cesarean delivery has been described, but its maternal and neonatal effects have not been investigated by a controlled study. In a randomized, double-blind, controlled study, patients undergoing elective cesarean delivery received an intravenous bolus of 1 microg/kg remifentanil (n = 20) or saline (n = 20) immediately before induction of general anesthesia. The authors compared maternal hemodynamic changes and neonatal condition and measured plasma concentrations of remifentanil. The maximum increase in systolic arterial pressure from baseline after induction was smaller in the remifentanil group (median, 9 [range, -17 to 31] mmHg) compared with the control group (42 [6-73] mmHg, median difference, 33 mmHg; 95% confidence interval of difference, 23-45 mmHg; P < 0.0001). Maximum recorded values were smaller in the remifentanil group compared with the control group for systolic and mean arterial pressure and maternal heart rate. Apgar scores and time to sustained respiration were similar between groups. Two neonates in the remifentanil group were considered clinically depressed at birth and were given a single dose of naloxone. Remifentanil crossed the placenta with an umbilical venous/maternal arterial concentration ratio of 0.73 (SD, 0.17) and an umbilical arterial/umbilical venous concentration ratio of 0.60 (0.23). A single bolus of 1 microg/kg remifentanil effectively attenuated hemodynamic changes after induction and tracheal intubation. However, remifentanil crosses the placenta and may cause mild neonatal depression and thus should be used for clear maternal indications when adequate facilities for neonatal resuscitation are available.

Studies on the involvement of opioid mechanism in the locomotor effects of benzodiazepines in rats

The influence of the opioid receptor antagonist naloxone upon the reduced locomotor activity after administration of nitrazepam (NTZ) and upon the increased locomotion after chronic nitrazepam administration was tested. It was found that a single dose of naloxone counteracted both the reduced locomotion after acute administration of nitrazepam as well as the augmented locomotor activity after chronic application of nitrazepam. It is assumed that opioid mechanisms are involved in the locomotor effects of benzodiazepines.

Alfentanil for urgent Caesarean section in a patient with severe mitral stenosis and pul-monary hypertension

We present the case of a parturient with severe mitral stenosis and pulmonary hypertension who received general anaesthesia using alfentanil for urgent Caesarean section. Alfentanil promoted haemodynamic stability and allowed immediate postoperative extubation. Epidural morphine provided postoperative analgesia. This combination permitted early ambulation and prevention of thromboembolism. A disadvantage of this technique, neonatal respiratory depression, was promptly reversed with a single dose of naloxone. The anaesthetic management of mitral stenosis in pregnancy is discussed and the neonatal pharmacokinetics of maternally administered alfentanil are presented.

Alfentanil as an Anesthetic Induction Agent-A Comparison with Thiopental-Lidocaine

Alfentanil (0.175 mg/kg) and a combination of thiopental (3-4 mg/kg) and lidocaine (1.5 mg/kg) during anesthetic induction were compared. Each was administered rapidly to eight patients with cardiovascular disease (average age, 64 yr), followed by succinylcholine (1.5 mg/kg) for laryngoscopy and intubation. Chest wall rigidity or flexor spasm of arm and jaw were seen transiently in 7 of 8 patients receiving alfentanil. Both drugs led to decreases in mean arterial pressure averaging 31 mm Hg (P less than 0.01). In patients given thiopental-lidocaine, intubation led to a 28 mm Hg (P less than 0.01) increase over control in arterial pressure and a 10 beats . min-1 increase in heart rate (P less than 0.01). In patients given alfentanil, after intubation arterial pressure returned to levels no different from control and the heart rate remained stable. Five of the patients given alfentanil required a single dose of naloxone (0.08-0.15 mg) to achieve a PCO2 less than 50 torr at the end of surgery. Rapidly administered alfentanil blunted the cardiovascular response to intubation but decreased arterial pressure as much as thiopental-lidocaine.

Naloxone and alcohol intoxication in the dog.

1 The effects of naloxone upon ethanol-induced coma have been investigated in dogs. In a double blind study, 15 mongrel dogs received ethanol i.v. (4 g/kg) followed by a single dose of naloxone (12 micrograms/kg). 2 Naloxone failed to affect either the duration of respiratory arrest or the time to recovery of motor coordination. In similar animals treated with the narcotic analgesic, fentanyl, naloxone induced a dramatic and complete reversal of the narcotic effects within 30 seconds. 3 It is concluded that, if naloxone has any effect in alcoholic coma, it is not comparable with its dramatic action in narcotic coma.

Addictive agents and intracranial stimulation (ICS): Naloxone blocks morphine’s acceleration of pressing for ICS

Ten rats were fixed with chronically indwelling electrodes for intracranial stimulation (ICS) of the lateral hypothalamus. The rats were then trained to press a lever for the self administration of ICS at two current intensities; one intensity produced a low rate of pressing and the other a high rate of pressing for ICS. Subsequent to obtaining stable press rates for each intensity of ICS, five rats received daily injections of morphine (10 mg/kg) 4 h prior to testing and five rats were injected with saline. After a significant acceleration of pressing for ICS was demonstrated by the morphine group, both groups were injected with naloxone (1 mg/kg) 15 min prior to testing. No effect was shown for the placebo group, while naloxone blocked morphine’s potentiation of pressing for ICS. The blocking effect persisted for 3 days after the single dose of naloxone despite the continued administration of morphine (10 mg/kg/day), which had previously accelerated pressing for ICS.

DEGREE AND DURATION OF REVERSAL BY NALOXONE OF EFFECTS OF MORPHINE IN CONSCIOUS SUBJECTS

The effects of intravenous naloxone on several of the actions of intravenous morphine (mean dose 30 mg/70 kg) were studied in six volunteer subjects. Naloxone produced a well defined reversal of the respiratory depression, analgesia, and miotic and subjective effects of the morphine. The agonist action of morphine outlasted the antagonist action of a single dose of naloxone. The effect of repeated doses of naloxone was also short-lived, but continuous infusions were effective in maintaining reversal.