Naltrexone action

Substitution therapy with methadone or buprenorphine has been veiy successfiil in terms of harm reduction. Some opiate addicts might also benefit from naltrexone treatment. One idea is that patients should undergo rapid opiate detoxification with naltrexone under anaesthesia, which then allows fiuther naltrexone treatment to reduce the likelihood of relapse. However, the mode of action of rapid opiate detoxification is obscure. Moreover, it can be a dangerous procedure and some studies now indicate that this procedure can induce even more severe and long-lasting withdrawal symptoms as well as no improvement in relapse rates than a regular detoxification and psychosocial relapse prevention program. 

Naltrexone completely blocks the effects of IV opiates, as well as drugp with agonist-antagonist actions (butorphanol, nalbuphine, and pentazocine). The mechanism of action appears to be the same as that for naloxone... 

Naltrexone may produce withdrawal symptoms in those physically dependent on narcotics. The patient must not have taken any opiate for the last 7 to 10 days. Concurrent use of naltrexone with tiiioridazine may cause increased drowsiness and lethargy. Naltrexone may prevent the action of opioid antidiarrheals, antitus-sives, and analgesics. 

The opioid antagonists naloxone and naltrexone bind to aU three opioid receptors, p, K, and 8. These compounds are antagonists due to their inability to elicit downstream effects of these receptors once bound (Sarton et al. 2008 Yaksh and Rudy 1977). Interestingly, both antagonists have a high binding affinity for MORs. Naloxone is used to reverse the effects of an acute opioid overdose because of its rapid onset of action. Naltrexone elicits similar actions, but has a longer onset and duration of action and hence, is used for the maintenance of treatment for opioid addicts. 

The intoxicating effects of opioids appear to be due to their action as agonists on mu (p) receptors of the opioid neurotransmitter system. Competitive p opioid antagonists such as naloxone and naltrexone acutely reverse many of the adverse effects of opioids. To date we do not have specific antagonists for most other abused substances, so rapid pharmacologic reversal of intoxication is usually not possible. 

Another site of action for opioids is through the regulatory actions of the central nervous system (CNS) on the immune system. Substantial evidence supports the existence of a complex, bidirectional link between the CNS and the immune system (e.g., [65]). Experimental evidence indicates that morphine s immunomodulatory effects involve central opioid receptors. An initial study by Shavit and colleagues [12] found that systemic administration of morphine, but not N-methylmorphine (a form of morphine which does not readily penetrate the blood-brain barrier), produces a naltrexone-reversible suppression of splenic natural killer cell activity in the rat. That same study showed that intracerebroventricular (icv) administration of morphine dose-dependently suppresses... 

Hamann SR, Martin WR. (1994). Hyperalgesic and analgesic actions of morphine, U50-488, naltrexone, and (-)-lobeline in the rat brainstem. Pharmacol Biochem Behav. 47(1) 197-201. Hamann W, di Vadi PP. (1999). Analgesic effect of the cannabinoid analogue nabilone is not mediated by opioid receptors. Lancet 353(9152) 560. 

Naltrexone (ReVia). Naltrexone is a very potent antagonist of the actions of opiates. It has been used to reduce the rewarding effects of not only opiates but alcohol as well. Like buprenorphine, naltrexone appears to reduce craving for opiates by blocking their pleasurable effects. Naltrexone is not useful for detoxification and in fact worsens withdrawal. Naltrexone can be useful for maintenance treatment in those patients motivated to achieve total abstinence. It is taken at a constant dose of 50mg/day. A sustained-release depot formulation currently under development will likely help to overcome adherence issues that often undermine treatment for substance use disorders. 

Maintenance treatment Once the patient has been started on naltrexone, 50 mg every 24 hours will produce adequate clinical blockade of the actions of parenterally administered opioids. A flexible dosing regimen may be employed. Thus, patients may receive 50 mg every weekday with a 100 mg dose on Saturday, 100 mg every other day, or 150 mg every third day. 

Nalorphine and levallorphan are examples. For example in patients with postoperative pain the analgesic effects of 10 mg of nalorphine is about the same as 10 mg of morphine. On the other hand naloxone and naltrexone seem to have no agonistic activity and some antagonistic affinity for all types of opioid receptors. Although antagonists could be expected to have effects by altering the actions of endogenous opioid peptides mostly such effects are not discernable. 

The majority of their metabolites are inactive with a few notable exceptions, such as morphine-6-glucuronide, which produces an analgesic effect normeperidine and norpropoxyphene, which produce excitatory but not analgesic effects and 6-(3-naltexol, which is less active than naltrexone as an antagonist but prolongs the action of naltrexone. Excretion of the metabolites requires adequate renal function, since excretion by routes other than the urine are of minor importance. 

Naltrexone and nalmefene are structurally related to naloxone. Naltrexone is the /V-cyclopropy I methyl analogue of oxymorphone while nalmefene is the /V-allyl analogue. They have similar pharmacological properties to naloxone but with longer durations of action, with elimination half-lives in excess of 8 hours. They also have significant oral availability. They are used mainly in the management of addicts. 

Naltrexone Nonselective competitive antagonist of opioid receptors Reduced risk of relapse in individuals with alcoholism Available as an oral or long-action parenteral formulation Toxicity Gastrointestinal effects and liver toxicity will precipitate a withdrawal reaction in individuals physically dependent on opioids and will prevent the analgesic effect of opioids... 

Naltrexone, nalmefene Like naloxone but longer durations of action (10+ h) naltrexone is used in maintenance programs and can block heroin effects for up to 48 h ... 

Piminodine (Alvodine ), ethyl-4-phenyl-l-(3-phenylaminopropyl)piperidine-4-carboxylate ethanesulfonate, is reputed to be equal to morphine in analgesic potency, but relatively free of the latter s narcotizing action. It is administered in doses of 25 to 50 mg orally every 4 to 6 h, or in doses of 10 to 20 mg subcutaneously or intramuscularly every 4 h as needed. Piminodine is habit forming, requires a narcotic prescription, and should be used with the same precautions as other members of this group. Levallorphan tartrate, nalorphine, naloxone, or naltrexone are antidotes to it. 

Naloxone (Narcan) and naltrexone hydrochloride (Trexan) reverse the respiratory depressant action of narcotics related to morphine, meperidine, and methadone. They differ from other narcotic analgesics in several respects. Naloxone does not cause respiratory depression, pupillary constriction, sedation, or analgesia. However, it does antagonize the actions of pentazocine. Naloxone neither antagonizes the respiratory depressant effects of barbiturates and other hypnotics nor aggravates their depressant effects on respiration. Similar to nalorphine, naloxone precipitates an abstinence syndrome when administered to patients addicted to opiate-like drugs. 

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. 

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