Other Opioid Antagonists

Naltrexone

Naltrexone is a μ-, δ- and κ-opioid receptor antagonist. It is longer acting than naloxone (plasma half-life of 8 to 12 hours versus 0.5 to 1.5 hours), and it is active when taken orally. Oral naltrexone (5–10 mg) reduces the frequency and severity of pruritus, nausea, and vomiting associated with epidural morphine without diminishing analgesia. Naltrexone, like naloxone, can stimulate the cardiovascular system.

Nalmefene

Like naloxone and naltrexone, nalmefene has a greater preference for μ- than for δ- and κ-receptors. Nalmefene is equipotent to naloxone. ^[512] It is long-acting after oral (0.5–3.0 mg/kg) and parenteral (0.2–2.0 mg/kg) administration. The bioavailability of nalmefene after oral administration is 40% to 50%, and peak plasma concentrations are reached in 1 to 2 hours. The mean terminal elimination half-life of nalmefene is 8.5 hours, compared with 1 hour for naloxone. Prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient-controlled analgesia with morphine.^[513]

Methylnaltrexone

Methylnaltrexone is the first quaternary ammonium opioid receptor antagonist that does not cross the blood-brain barrier. It can reverse adverse effects of opioid medications mediated by peripheral opioid receptors, whereas the opioid effects mediated by opioid receptors in the CNS, such as analgesia, are not affected. Delayed gastric emptying induced by morphine (0.09 mg/kg) could be attenuated by methylnaltrexone (0.3 mg/kg) in healthy volunteers.^[259] It was also reported that methylnaltrexone was effective for reversal of constipation due to chronic methadone use.^[514] Because methylnaltrexone does not cross the dura, it might have the potential to reverse the peripherally mediated side effects of epidural opioids.^[515]