Naloxone

Naloxone is a drug used to counter the effects of antagonist with qualitatively different effects, used for dependence treatment rather than emergency overdose treatment.

Pharmacodynamics

Naloxone has an extremely high affinity for μ-competitive antagonist, and its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at κ- and δ-opioid receptors.

Chemistry

Naloxone is allyl (prop-2-enyl) group. The name naloxone has been derived from N-allyl and oxymorphone.

Administration

Naloxone is injected, usually initially intravenously for fastest action. The drug acts after about two minutes, and its effects may last about 45 minutes. Other routes, including intramuscular injection, subcutaneous,endo-tracheal tube,and intranasal injection (use of a wedge device attached to the syringe to create a mist delivering the drug to the nasal mucosa) may also be utilized, although these are more likely in the prehospital setting.

Uses

Naloxone has been distributed as part of emergency kits to heroin users, and this has been shown to reduce rates of fatal overdose. Projects of this type are under way in San Francisco, New Mexico, Philadelphia, New York State, Baltimore, Boston, Los Angeles and Chicago, with pilot projects started in Scotland in 2006.

The drug also blocks the action of pain-lowering placebo pain-lowering response, both in clinical and experimental pain, if the placebo is administered together with a hidden or blind injection of naloxone.^[1]

While naloxone is still often used in emergency treatments for opioid overdose, its clinical use in the long-term treatment of opioid addiction is being increasingly superseded by naltrexone. Naltrexone is structurally similar but has a slightly increased affinity for κ-opioid receptors over naloxone, can be administered orally and has a longer duration of action.

Enteral naloxone has been successfully used in the reduction of gastritis and oesophagitis associated with opioid therapy in mechanically-ventilated acute care patients.

The effect of the hallucinogenic plant Salvia Divinorum and its primary active chemical Salvinorin-A, a κ-opioid agonist, can be inhibited by the pre-administration of naloxone. Naloxone has similar inhibitory effects on PCP, dextromethorphan.^{[citation needed]}

Naloxone is also being used as a secondary chemical in the Buprenorphine and 1 part Naloxone, while Subutex contains only Buprenorphrine.

Naloxone was added to Suboxone in an effort to dissuade patients from grinding up the Suboxone tablet and using it as part of a combination of opiates that the user would inject into their body. Intravenously administered Naloxone is supposed to block the effects of any opiates and cause the user to go into immediate withdrawal. However, buprenorphine has a higher affinity for the opiate receptors, and many users have reported that Suboxone is injectable without inducing withdrawal effects. Oral or sublingual administration affects only the gastronintestinal tract, and has the added benefit of helping to reverse constipation and lowered bowel motility caused by chronic medical use or abuse of a variety of opioids. Buprenorphine itself has less of an effect on the central nervous system and produces far less euphoria than other methadone, buprenorphine has only recently been approved for use in the management of pain, and likely restrictions on prescribing authority will be eased over time as buprenorphine sees wider use and acceptance by the medical profession, and concerns over diversion and abuse lessen.

The addition of naloxone to bruprenorphine in Suboxone tablets is intended to prevent misuse and abuse by injection. However, the Naloxone in Suboxone does cause side effects in some people. These side effects include, but are not limited to, asthenia, chills, headache, infection, pain, pain in the abdomen, back pain, withdrawal syndrome, Subutex, which does not contain any Naloxone. In this way, if for some reason the doctor moves the patient to Suboxone and the patient begins having side effects related to Naloxone, the doctor can easily move the patient back to Subutex.

For these reasons and others, it has been reported that Subutex is easier to withdraw from than is Suboxone.

Legal status

The patent for Naloxone has expired and the drug is currently available in various generic forms.

Identification

The salt has CAS 357-08-4 and the hydrochloride salt with 2 molecules of water has CAS 51481-60-8.

References