Effects Of Nalbuphine Research Articles

The Effects of Nalbuphine and Butorphanol Treatment on Cocaine and Food Self-Administration by Rhesus Monkeys

This study was designed to determine whether opioid mixed agonist-antagonist analgesics other than buprenorphine also selectively reduce cocaine self-administration by rhesus monkeys. The effects of daily treatment with nalbuphine (0.1 to 3 mg/kg/day) or (0.254 to 7.62 mumol/kg/day), butorphanol (0.01 to 0.3 mg/kg/day) or (0.0209 to 0.628 mumol/kg/day), and saline on cocaine and food self-administration were each studied for 40 sessions over 10 consecutive days. Cocaine (0.05 or 0.10 mg/kg/inj) and food (1-gm banana pellets) self-administration were maintained on a fixed ratio 4 (variable ratio 16:S) schedule of reinforcement. Both nalbuphine and butorphanol reduced cocaine self-administration (p < 0.0001) but this effect was not selective since food self-administration also decreased in a dose-dependent manner (p < 0.0001). Nalbuphine administration (1 to 3 mg/kg/day) decreased cocaine injections to 40% to 60% below baseline (p < 0.01) and food pellets 30% to 68% below baseline (p < 0.01). Lower doses of nalbuphine (0.10 and 0.30 mg/kg) did not change cocaine- or food-maintained responding significantly. All doses of butorphanol (0.01 to 0.3 mg/kg/day) reduced cocaine injections to 16% to 58% below baseline (p < 0.01). Food self-administration decreased to 21% to 70% below baseline (p < 0.01) at butorphanol doses of 0.03 to 0.3 mg/kg/day). These data suggest that these opioid mixed agonist-antagonist analgesics may not be useful as pharmacotherapies for the treatment of cocaine abuse.

Pressor effect of nalbuphine in hemorrhagic shock is dependent on the sympathoadrenal system

Nalbuphine, an analgesic with opiate agonist and antagonist properties, increases heart rate, mean arterial pressure (MAP), and cardiac function following a moderate hemorrhage in the rat. The interaction between opiate receptors and the sympathoadrenal system was examined in control, beta receptor-blocked, and adrenal-demedullated animals. MAP and heart rate were measured continuously in chronically instrumented conscious animals. Hemorrhage decreased MAP in the control group by 50%, and nalbuphine (1 mg/kg) returned this to prehemorrhage values within 5 min. MAP remained significantly greater in the nalbuphine-treated animals for 120 min. Heart rate fell with hemorrhage and increased above prehemorrhage values in the nalbuphine-treated animals. The pressor response to nalbuphine was abolished in both beta-blocked and adrenal-demedullated animals. Plasma catecholamines were not significantly elevated in the nalbuphine-treated as compared to control animals, which suggests that nalbuphine effects do not result from an enhancement of central mediated sympathoadrenal discharge. The opiate receptor antagonist naloxone, in a concentration that was not by itself effective in alleviating the hypotensive effects of hemorrhage, prevented the pressor response with nalbuphine. These results suggest that nalbuphine's beneficial effects in hemorrhagic shock depend on an intact sympathoadrenal system and on an interaction with opiate receptor sites, possibly in the heart.

The Effect of Nalbuphine on the Common Bile Duct Pressure

The Effect of Nalbuphine on the Common Bile Duct Pressure

Reversal of epidural morphine-induced respiratory depression and pruritus with nalbuphine

The effect of nalbuphine on the respiratory depression, pruritus and analgesia induced by epidural morphine was determined in a randomized, prospective, double-blind, placebo-controlled fashion. Twenty ASA physical status I women received 0.1 mg.kg-1 epidural morphine at induction of general anaesthesia for elective total abdominal hysterectomy. Group 1 (n = 14) received 0.3 mg.kg-1 nalbuphine intravenously six hours after the epidural morphine administration. Group 2 (n = 6) received saline. Prior to agent administration, six patients from the nalbuphine group and four patients from the saline group had respiratory depression indicated by a PaCO2 greater than 45 mmHg. After nalbuphine administration the PaCO2 (mean +/- SE) decreased from 49.5 +/- 1.2 mmHg to 42.5 +/- 0.7 mmHg (p less than 0.005) while there was no significant change after saline administration. Nine of the 14 patients receiving nalbuphine appeared to become more sedated, despite an improvement in ventilation. Pruritus was antagonized by 0.1 mg.kg-1 nalbuphine (p less than 0.006). There was no reversal of analgesia after administration of 0.3 mg.kg-1 nalbuphine.

The effectiveness of nalbuphine and hydroxyzine for the emergency treatment of severe headache

The present treatment for acute attacks of headache is empiric. Intramuscular nalbuphine (Nubain) and hydroxyzine (Vistaril) were assessed for pain relief in a prospective, double-blind clinical trial. Ninety-four patients were assigned randomly to treatment groups receiving nalbuphine 10 mg, nalbuphine 10 mg plus hydroxyzine 50 mg, hydroxyzine 50 mg, or placebo. The treatment groups were found to be adequately homogenous with regard to age, sex, type and duration of headaches, and history of prior narcotic use. All data were analyzed by one-way analysis of variance. Patients who had headaches diagnosed as other than classic migraine had significantly greater pain relief with nalbuphine compared to placebo (P less than .01). The combination of nalbuphine and hydroxyzine was not significantly more effective than other treatment groups. In 20 patients with classic migraine, none of the treatment regimens significantly outperformed placebo. There were no clinically significant adverse effects attributed to the study drugs. These findings are similar to others that showed a lack of efficacy of kappa receptor agonists in classic migraineurs. Nalbuphine appears to be clinically useful in other types of severe headache. This study does not support the routine addition of hydroxyzine for presumed synergistic effect.

Failure of Nalbuphine to Antagonize Morphine

The authors studied the respiratory and analgesic effects of nalbuphine (0.21 mg/kg, intravenous), naloxone (0.014 mg/kg, intravenous), and placebo (normal saline) when given after morphine (0.21 mg/kg, intravenous) in a double-blind, randomized fashion. Resting end-tidal CO2 (PETCO2), ventilatory and occlusion pressure responses to CO2 rebreathing, and pain threshold were measured in 12 healthy adult volunteers before, 5 min, and 30 min after morphine. Nalbuphine, naloxone, or saline were administered 55 min after morphine, and the above measurements were repeated 5 min later (60 min after morphine) as well as 90, 120, 180, and 240 min after morphine. Whereas naloxone reversed respiratory depression as measured by all three respiratory parameters, nalbuphine either further depressed (resting PETCO2) or did not affect (ventilatory and occlusion pressure responses to CO2 rebreathing) respiratory drive. Morphine produced a significant elevation of the pain threshold. Significant decreases in the pain threshold were seen only after naloxone. Saline and nalbuphine did not significantly alter the pain threshold. The data indicate that nalbuphine may not reliably antagonize moderate doses of morphine.

Effect of nalbuphine on intrabiliary pressure in the early postoperative period.

The effect of nalbuphine on common bile duct (CBD) pressure was studied by measurements through T-tubes on the first and second postoperative days after cholecystectomy and choledochotomy. Nalbuphine in a dose of 0.25 mg X kg-1 was injected intramuscularly in 11 patients, and changes in biliary pressure, heart and respiratory rate, blood pressure, and arterial blood gases were recorded during the subsequent four hours. The patients were free of pain, had stable common bile duct pressures and did not have any statistically significant changes in their vital signs. These results are similar to our previous observations during perioperative intravenous injection of nalbuphine. It is suggested that nalbuphine does not significantly change, or even may relax, the sphincter of Oddi, and can therefore be recommended as a safe analgesic in the postoperative period after extrahepatic biliary surgery.

Increased naloxone potency induced by pretreatment with morphine and nalbuphine in mice.

Both morphine and nalbuphine were effective in suppressing the abdominal constriction response induced by intraperitoneal injection of acetic acid in mice. On a weight to weight basis, nalbuphine was more potent than morphine in this test. However, the effect of nalbuphine was more effectively blocked by naloxone. Pretreatment with morphine 2.0 mg/kg subcutaneously did not alter the antinociceptive effect of either morphine or nalbuphine measured 3 h later. However, naloxone was about 1.4-fold more effective in antagonizing the antinociceptive effect of both drugs in morphine-pretreated mice than in saline-pretreated animals. Pretreatment with nalbuphine (1.0-2.0 mg/kg s.c.) did not alter the antinociceptive effect of either morphine or nalbuphine measured 3 h later, while naloxone effect was more effective in antagonizing the antinociceptive actions of morphine and nalbuphine. The increases in naloxone potency in antagonizing morphine after nalbuphine pretreatment were not dose-dependent on the amount of nalbuphine in the pretreatment and they were only marginally significant. In addition, these increases were much lower than that induced by morphine pretreatment. On the other hand, the naloxone effectiveness against nalbuphine itself was enhanced to a greater extent than that induced by morphine pretreatment. Furthermore, these increases in naloxone potency showed a dose-dependent relationship to the amount of nalbuphine used in the pretreatment. Based on these results, it was concluded that nalbuphine is an analgesic drug with properties in between those of the full agonist morphine and the partial agonist pentazocine.

Side effects of nalbuphine

Side effects of nalbuphine

Cardiovascular effects of nalbuphine in patients with coronary or valvular heart disease.

Although the hemodynamic changes produced by small doses of nalbuphine given to patients with cardiac disease are minimal, the cardiovascular effects of large doses which have been used as supplements for general anesthesia have not been investigated. Cardiovascular variables were measured after incremental doses of nalbuphine, up to 2 or 3 mg/kg in fourteen patients with coronary artery disease with normal left ventricular function and in seven patients with mitral valve disease. No significant changes in cardiac index, stroke work index, mean arterial pressure, pulmonary diastolic or wedge pressure, heart rate, or central venous pressure occurred in the preoperative period. However, nalbuphine alone did not produce surgical anesthesia and the addition of diazepam, nitrous oxide, or halothane was required in all patients. The addition of halothane coupled with surgical stimulation significantly decreased cardiac and stroke indices, increased mean arterial and pulmonary wedge pressures, and increased systemic vascular resistance in patients with coronary artery disease. In patients with mitral valve disease, following surgical incision, there were small but significant decreases in cardiac index and left ventricular stoke work index, and increases in systemic vascular resistance. Despite its lack of deleterious hemodynamic effects, the place of nalbuphine in the armamentarium of the anesthesiologist must be limited to use as a premedicant, as an adjunct to balanced anesthesia, or for postoperative pain relief.

Anesthetic Potency of Nalbuphine and Interaction with Morphine in Rats

The contribution to anesthesia by nalbuphine was determined in rats by measurement of the reduction in the anesthetic requirement for cyclopropane produced by increasing doses of nalbuphine while maintaining a constant level of anesthesia (MAC). The respiratory effect of nalbuphine was evaluated by measurement of arterial PCO2 at this constant MAG level. The response produced by the addition of morphine to a constant dose of nalbuphine in further reducing the cyclopropane anesthetic requirement was also evaluated, as was the effect on arterial PCO2. The anesthetic contribution of nalbuphine was dose dependent until a plateau contribution of 0.22 MAC was achieved. Arterial PCO2 increased to a plateau level of 48 torr with nalbuphine administration from a PCO2 of 41 torr with cyclopropane alone. Further increase in PCO2 did not occur until exceedingly high nalbuphine doses were used. Morphine did not supplement the anesthetic contribution of nalbuphine, and there was no increase in PCO2 when morphine was added in nalbuphine during cyclopropane anesthesia. These results suggest that nalbuphine produces analgesia by acting at kappa opioid receptors and that nalbuphine binds but produces minimal effects on mu opioid receptors within the central nervous system.