29 In another study, behavioural changes, sweating, and yawning were observed in 14 healthy volunteers given 2–4 mg/kg naloxone, and these effects often lasted for a number of hours after its administration. In one early study on the use of naloxone to reverse morphine anaesthesia in non-opioid dependent, general surgical patients, acute withdrawal-like symptoms were observed to occur after the administration of 15 μg/kg naloxone. Second, opioid antagonists can precipitate acute withdrawal symptoms (AWS) in chronic opioid users 11, 23– 28 provoking an often violent reaction. Numerous case histories have revealed a 13-fold variation in rate of naloxone infusions given for prolonged overdoses. Unfortunately this is seldom known in clinical practice, 11 and instances have been reported where over 20 times the recommended doses of naloxone have been needed to counteract massive opioid overdoses, 12, 13 and even more in body packers. Recent evidence suggests that a dose of 13 µg/kg naloxone (approximately 1 mg in an 80 kg person) produces 50% receptor occupancy 10 however, this is also influenced by the dose of opioid ingested or injected. Naloxone has antagonist activity at all of the receptor types 9 and the amount needed to provide such an effect depends upon the number of receptors occupied. First, opioids exert their effect by binding to a series of receptors. There is also wide variation in the route of administration. Although naloxone has been used as a specific antidote for opioid poisoning since the 1960s, 8 there are variations in the recommended doses with the British National Formulary advising 0.8–2 mg boluses, repeated as necessary up to 10 mg for adults (10 µg/kg followed by 100 µg/kg boluses for children), and Poisindex suggesting 0.4–2 mg boluses.
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