Pentazocine withdrawal

Wu WH, Teng RJ, Shin HY. Neonatal pentazocine withdrawal syndrome—a case report of conservative treatment. Zhonghua Yi Xue Za Zhi (Taipei) 1988 42(3) 229-32. 

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. 

This class produces analgesia and has a ceiling effect on respiratory depression and lower abuse potential than morphine. However, psychotomimetic responses (e.g., hallucinations and dysphoria with pentazocine), a ceiling analgesic effect, and the propensity to initiate withdrawal in opioid-dependent patients have limited their widespread use. 

Patients receiving narcotics Pentazocine is a mild narcotic antagonist. Some patients previously given narcotics, including methadone for the daily treatment of narcotic dependence, have experienced withdrawal symptoms after receiving pentazocine. 

Tolerance to the analgesic effects of pentazocine develops. Withdrawal signs are milder than those seen with morphine, and they produce more excitatory effects. 

Nalbuphine hydrochloride is structurally related to oxymorphone and naloxone. It is approximately equipotent with morphine. Nalbuphine is metabolised in the liver to inactive metabolites. The plasma terminal half-life is approximately 5 h. The onset of analgesia is within 2-3 min of intravenous administration and 15 min after intramuscular injection, and lasts 3-6 h with an adult dose of 10 mg. With equi-analgesic doses, similar degrees of respiratory depression to that of morphine occur up to a dose of approximately 0.45 mg-kg-1. With higher doses a ceiling effect occurs. Sedation, possibly mediated by K-receptor activation, occasionally occurs. The incidence of psychotomimetic side effects is lower than with pentazocine. The abuse potential is low, but is can cause withdrawal symptoms in opioid-dependent subjects. It has occasionally been used to reverse opioid-induced respiratory depression. 

In the case of agents with mixed effects, withdrawal signs and symptoms can be induced after repeated administration followed by abrupt discontinuance of pentazocine, cyclazocine, or nalorphine, but the syndrome appears to be somewhat different from that produced by morphine and other agonists. Anxiety, loss of appetite and body weight, tachycardia, chills, increase in body temperature, and abdominal cramps have been noted. 

Strain, E.C. et al., Precipitated withdrawal by pentazocine in methadone-maintained volunteers, J. Pharmacol. Exp. Ther., 267, 624, 1993. 

Patients who have received hydromorphone for long periods of time or those with confirmed opioid dependency should not receive the so-called agonist/antagonist analgesics, such as nalbuphine, pentazocine, butorphanol, dezocine, and buprenorphine. The use of these drugs in these patients can intensify withdrawal symptoms. 

Severe pain in an opioid addict presents a special problem. High-efficacy opioid may be ineffective (tolerance) or overdose may result low-efficacy opioids will not only be ineffective but may induce withdrawal symptoms, especially if they have some antagonist effect, e.g. pentazocine. This leaves as drugs of choice nonsteroidal anti-inflammatory drugs (NSAIDs), e.g. indometacin, and nefopam (which is neither opioid nor NSAID). 

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. 

Some antihistamines, for example tripellenamine (often used in combination with pentazocine), have a particular abuse potential and are used by drug addicts. Psychiatric disturbances, dysphoria, depression, confusion, and hallucinations can occur while under the influence of an antihistamine or during drug withdrawal. Chronic parenteral abuse can cause skin lesions, muscular fibrosis, and vasculitis. 

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

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