Precipitated withdrawal, with opioids

Opioid antagonists bind to the opioid receptor with high affinity and have low efficacy. The pure antagonists block the effects of opioids at all opioid receptors. However, as previously discussed, the dose required for naloxone blockade of the jx-receptor versus the k-opioid receptor is several times as much. All opioid antagonists will precipitate withdrawal in opioid-dependent patients. 

Side-effects Dezocin induces j-opioid-type side-effects with nausea, vomiting and drowsiness. Overdoses may be treated with naloxone. The compound has a low abuse potential and is not under narcotic control. Because of its partial antagonistic properties dezocine can precipitate withdrawal in opioid-dependent subjects (Strain et al., 1996). 

Risk of precipitated withdrawal Nalmefene is known to produce acute withdrawal symptoms and, therefore, should be used with extreme caution in patients with known physical dependence on opioids or following surgery involving high uses of opioids. 

Mechanism of Action A narcotic agonist-antagonist that binds with opioid receptors in the CNS. May displace opioid agonists and competitively inhibit their action may precipitate withdrawal symptoms. Therapeutic Effect Alters the perception of and emotional response to pain. 

The non-precipitated withdrawal procedure represents a first screen for possible induction of drug dependence and has been shown to be sensitive to withdrawal effects with a variety of dependence-inducing agents including amphetamines, cocaine, opioids and benzodiazepines. It therefore possesses face validity. On the other hand, it is remarkably difficult, under the conditions of the protocol described, to show signs of withdrawal after treatment with agents such as nicotine... 

Two patients who were hospitalized with a diagnosis of opioid dependence received concomitant treatment with methadone 50 mg/day in one case, and levorpha-nol 14 mg/day in the other, each in association with risperidone. After several days, both had symptoms of opioid withdrawal despite having no change in their opioid doses (256). The withdrawal symptoms resolved soon after risperidone was withdrawn. According to the authors, this finding suggests that risperidone may precipitate opioid withdrawal in opioid-dependent patients. 

The availability of receptor knockout animals has also helped to illustrate cannabinoid-opioid interactions. CBi receptor knockout mice had greatly reduced morphine self-administration behavior and less severe naloxone-induced withdrawal signs than wild type animals, although the antinociceptive actions of morphine were unaffected in the knockout animals (40). The rimona-bant-precipitated withdrawal syndrome in THC-treated mice was significantly attenuated in animals with knockout of the pro-enkephalin gene (48). Knockout of the p opioid (OP3) receptor also reduced rimonabant-induced withdrawal signs in THC-treated mice, and there was an attenuated naloxone withdrawal syndrome in morphine-dependent CBi knockout mice (49,50). 

Lefetamine is an opioid receptor partial agonist, which combines the actions of amphetamines with opioid-Uke effects. It was a drug of abuse in Japan in the 1950s and later also in Italy (1). In 10 opiate addicts, lefetamine relieved acute opiate withdrawal symptoms and did not precipitate withdrawal symptoms in stable addicts (2). 

Finally, it must be borne in mind that some of the problems with opioids are treatable for example, naloxone can reverse respiratory depression, but care must be taken in opioid-dependent individuals, as it may precipitate opioid withdrawal. 

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