Pentazocine administration

Pentazocine has been successfully used to relieve labour pain [201] and its obstetric use in place of pethidine is favoured by,its apparent inferior ability to pass the placental barrier [206]. A clinical trial of (+)- and (-)-pentazocine adds to the rare number of examples in which optical enantiomorphs have been evaluated [207]. In post-operative patients, response to 60 mg of the dextro isomer was less than that to 5 mg of morphine, while 25—29 mg of (-)-pentazocine was as effective as 10 mg of morphine. Hence most of the activity of the race-mate resides in the laevo isomer, as anticipated from results in animals [208]. Several studies of the distribution, excretion and metabolism of pentazocine have been made. Peak levels of the tritium-labelled drug (and its c/s-3-chloroallyl analogue) were present in the C.N.S. of a cat within 40 minutes of intramuscular administration [209], the comparable figure for morphine being 2 hours [210]. 

Absorption of pentazocine following oral administration is rapid. The onset of action occurs within approximately 15 minutes, and the half-life is 2 to 3 hours. Pentazocine is extensively metabolized in the liver and thus has a high first-pass effect following oral administration its half-life differs considerably from patient to patient. Oxidation of the methyl groups followed by conjugation to glucuronides in the liver terminates the effects of pentazocine. Excretion occurs through the kidney. 

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. 

Dosages and routes of administration Pentazocine is used as the hydrochloride or lactate in oral, parenteral and rectal formulations. Doses for the treatment of moderate to severe pain are in the range of 25-100 mg. 

Way and coworkers. Reviews of metabolism (51) and pharmacokinetics (97) of pentazocine have been published. The effect of route of administration on the disposition of pentazocine has been explored (27, 9,75,85,86). The metabolic pathways available to pentazocine are outlined in Figure 10. Also shown are urinary excretion data for the metabolites expressed as percent of administered dose. 

As nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate ALPE, the administration of NSAIDs should be avoided even after onset. When patients require analgesic agents, synthetic opioid agonist/antagonist analgesics (pentazocine hydrochloride or buprenorphine hydrochloride) should be administered. 

After i.m. administration of pentazocine, the peak plasma concentration is achieved at 30 min in the horse. Pentazocine has an elimination half-life of 97 min in ponies and 138 min in the horse (Davis Sturm 1970). After i.v. administration, pentazocine has been shown to be 80% bound to plasma protein. The glucuronide metabolite of pentazocine is cleared in the urine and pentazocine metabolites can be detected in the urine for up to 5 days in the horse. 

Gastrointestinal decontamination should be considered for patients who have ingested pentazocine only after initial supportive care has been provided and airway control has been assured. Activated charcoal (1 gkg ) may be administered. Syrup of ipecac is contraindicated after overdose with pentazocine due to the potential for rapid clinical deterioration. Gastric lavage is not indicated. Naloxone can be infused in an attempt to reverse respiratory and CNS depression. Naloxone administration may precipitate opioid withdrawal and should be administered slowly. Recent case series have demonstrated that naloxone may not result in clinical improvement in the majority of patients who have overdosed on pentazocine. 

In later investigations (1966) the impression that cyclazocine was not suitable as an analgetic was confirmed, but its use for the treatment of narcotic addicts was still favoured. The possibilities for pentazocine looked much brighter, and in 1967 pentazocine was released by the American Food and Drug Administration however, at very high doses some incidence of psychomimetic activity was observed. More recent investigations have demonstrated that, parenterally, the respiratory depression caused by pentazocine is equal to that shown by morphine, and also the absence of addictive properties has been questioned. Prolonged administration of pentazocine produces dependence like morphine. 

Sershen et al. (177) reported an involvement of serotonin receptors in the regulation of dopamine release by ibogaine. Thus, administration of ibogaine blocked the ability of a 5HT1B agonist (CGS-12066A [10 /xM]) to increase [3H]dopamine increase in striatal slices. In other studies, a concentration of ibogaine (1 ju.M) that was without effect on dopamine efflux inhibited both NMDA (25 /xM)- and ( )pentazocine (100 nM)-induced dopamine release in striatal slices (178). 

In subjects dependent on low doses of morphine (60 mg/day), nalbuphine precipitates an abstinence syndrome. Prolonged administration of nalbuphine can produce physical dependence. The withdrawal syndrome is similar in intensity to that seen with pentazocine. The potential for abuse of parenteral nalbuphine in subjects not dependent on p-receptor agonists probably is similar to that for parenteral pentazocine. 

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