Naltrexone injection

SKIN A 41-year-old female receiving subcutaneous naltrexone injections as part of her treatment for alcoholism presents with a painful skin lesion at the site of injection 1 week later. She was diagnosed with a cutaneous skin abscess, however skin biopsy confirmed development of Nicolau syndrome [92 ]. 

At the doses used, there is blockage of the effects of as much as 25 mg of injected heroin. Toxicity in heroin addicts is low, but some reported subtle adverse effects of naltrexone such as decreased energy (Hollister et al. 1981). Nonaddicted obese subjects have been known to develop markedly elevated transaminase levels at doses of 300 mg/day (Mitchell et al. 1987). The inference has been drawn that high doses are potentially hepatotoxic (Pfohl et al. 1986), and the drug is contraindicated in liver failure or acute hepatitis. 

P. D., Sustained release injectable naltrexone microcapsules, Basel, Switzerland, Controlled Release Society, Proc. 15th Int. Symp. Control. Rel. Bioact. Materials. 201-202, 1988. 

The rat has been previously used as a model animal for in vivo study of naltrexone (72). As shown in Figures 10 and 11, after an initial burst, the naltrexone plasma levels were 1.03 0.52 ng/mL/mg injected conjugate for P(HPG/LEU)-naltrexone-14-acetate and 0.70 0.39 ng/mL/mg injected conjugate for P(HPG/LEU)-naltrexone-3-acetate for 30 days. From these in vivo data, to achieve a similar plasma level in human, a subcutaneous injection dose of 100 to 500 mg can be predicted assuming that the volume of distribution of naltrexone per kilogram of body weight is of the same magnitude for both rats and humans. 

Figure 10. Plasma Levels of Naltrexone Following Injection of P(HPG/LEU)-Naltresone-3-acetate Conjugates (n=3).

Receptor blocker (long acting injectable version of naltrexone)... 

D PP, Tam YK, Young LT, et al Dthium decreases Gs, Gi-1 and Gi-2 alpha-subunit mRNA levels in rat cortex. Eur J Pharmacol 206 165-166, 1991 Debhch I, Yirmiya R Naltrexone reverses a long term depressive effect of a toxic lithium injection on saccharin preference. Physiol Behav 39 547-550, 1987 DebowitzMR Social phobia. Mod Probl Pharmacopsychiatry 22 141-173, 1987 Debowitz MR, Quitkin EM, Stewart JW, et al Phenelzine vs. imipramine in atypical depression a preliminary report. Arch Gen Psychiatry 41 669-677, 1984 liebowitz MR, Quitkin EM, Stewart JW, et al Antidepressant specificity in atypical depression. Arch Gen Psychiatry 45 129-137, 1988 Liebowitz MR, Schneier F, Campeas R, et al Phenelzine vs atenolol in social phobia. Arch Gen Psychiatry 49 290-300, 1992... 

Naltrexone, a relatively long-acting opioid receptor antagonist, blocks the effects at -opioid receptors (see Chapter 31). Studies in experimental animals first suggested a link between alcohol consumption and opioids. Injection of small amounts of opioids was followed by an increase in alcohol drinking, whereas administration of opioid antagonists inhibited self-administration of alcohol. 

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. 

Naltrexone [nal TREX own] has actions similar to those of naloxone. This drug has a longer duration of action than naloxone, and a single oral dose of naltrexone blocks the effect of injected heroin for up to 48 hours. Naltrexone is used in opiate-dependence maintenance programs and may also be beneficial in treating chronic alcoholism. 

Primary Physical Dependence capacity is measured on days 11 and 17 when all animals receive an injection of 10 mg/kg of naltrexone or naloxone i.p. in the morning. Signs of withdrawal are recorded during a 30 to 60 min period. Rats are scored for the presence or absence of withdrawal signs (e.g. diarrhea, wet-dog-type shaking) using standardized scoring. 

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