Opioid dependence withdrawal syndrome

Pentazocine dependence is associated with a mild opioid-hke withdrawal syndrome (8,9). 

The answer is c. (Hardman, p 546.) Pentazocine is a mixed agonist-antagonist of opioid receptors. When a partial agonist, such as pentazocine, displaces a full agonist, such as methadone, the receptor is less activated this leads to withdrawal syndrome in an opioid-dependent person. 

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

Severe opioid withdrawal syndromes Severe opioid withdrawal syndromes precipitated by accidental naltrexone ingestion have occurred in opioid-dependent individuals. Withdrawal symptoms usually appear within 5 minutes or less of ingestion and may last up to 48 hours. 

Naltrexone is generally taken once a day in an oral dose of 50 mg for treatment of alcoholism. An extended-release formulation administered as an IM injection once every 4 weeks is also effective. The drug can cause dose-dependent hepatotoxicity and should be used with caution in patients with evidence of mild abnormalities in serum aminotransferase activity. The combination of naltrexone plus disulfiram should be avoided, since both drugs are potential hepatotoxins. Administration of naltrexone to patients who are physically dependent on opioids precipitates an acute withdrawal syndrome, so patients must be opioid-free before initiating naltrexone therapy. Naltrexone also blocks the therapeutic effects of usual doses of opioids. 

Physical dependence is usually defined as the onset of withdrawal symptoms when the drug is abruptly removed. Withdrawal syndrome from opioid dependence is associated with a number of obvious and unpleasant symptoms (Table 14—3). In severe dependence, withdrawal symptoms become evident within 6 to 10 hours after the last dose of the drug, and symptoms reach their peak in the second or third day after the drug has been stopped. Withdrawal symptoms last approximately 5 days. This does not necessarily mean that the individual no longer desires the drug, only that the physical symptoms of withdrawal have ceased. Indeed, an addict may continue to crave the drug after months or years of abstinence. 

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). 

The neonatal abstinence syndrome occurs in 30-80% of infants whose mothers have taken opiates during pregnancy. The incidence is higher in those whose mothers have a history of opioid dependence and are taking methadone maintenance than in those who are taking methadone for chronic pain (39). The methadone blood concentration may be a useful predictor of the likelihood of severe withdrawal requiring treatment, but clinical assessment by a standardized scoring system is still required to determine the need to treat the neonatal abstinence syndrome (40). 

Babies born to mothers dependent on opioids may show a physical withdrawal syndrome. 

A low-efficacy opioid can reduce the effectiveness of a high-efficacy opioid by successfully competing with the latter for receptors. Partial agonist (agonist/antagonist) opioids, e.g. pentazocine, will also antagonise the action of other opioids, e.g. heroin, and may even induce the withdrawal syndrome in dependent subjects. 

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