Methadone administration

Jannson Lm, DiPietro, J, Elko A. Fetal response to maternal methadone administration. Am J Obstet Gynaecol 2005 193(3) 611-7. 

Jellema JG. Hallucination during sustained-release morphine and methadone administration. Lancet... 

Three of the four subjects on the methadone study refused to continue with the experiments, an event which rarely happens at the U.S. Public Health Service laboratory in Lexmgton, Kentucky, after they had experienced the abstinence syndrome precipitated by iV-allylnormorphine. The acute syndrome precipitated by IV-allylnormorphine in methadone addicts contrasts strikingly with the mild changes which are observed after abrupt withdrawal of methadone. The subjects who refused to continue with the methadone study exhibited only lethargy, anorexia, and irritability during the first week after abrupt termination of methadone administration. N-Allylnormorphine failed to precipitate abstinence phenomena 3 days after completion of withdrawal of methadone by rapid reduction in the subject who continued with the study. 

X V 1 1 IM/SC/PO. Excreted more slowly than morphine (haif-life = 25h). Thus withdrawal symptoms are less intense, but prolonged. Plasma protein binding. Cross dependent with morphine (basis for narcotic detoxification). Tolerance develops readily. Less psychologically addicting than morphine. Detoxification is based on replacing heroin dependence with methadone dependence. Then slowly reducing methadone administration to zero. 

Table 2-2. Protocol for administration of clonidine for detoxification from short-acting opioids and methadone ...

Methadone is a p receptor agonist with special properties that make it particularly useful as a maintenance agent. Rehably absorbed orally, it does not reach peak concentration until about 4 hours after administration and maintains a large extravascular reservoir (Kreek 1979). These properties minimize acute euphoric effects. The reservoir results in a plasma half-life of 1—2 days, so there are usually no rapid blood level drops that could lead to withdrawal syndromes between daily doses. Effective blood levels are in the range of 200-500 ng/mL. Trough levels of 400 ng/mL are considered optimal (Payte and Khouri 1993). There is wide variability among individuals in blood levels with identical doses (Kreek 1979), and some have inadequate levels even with doses as high as 200 mg/day (Tennant 1987 Tenore 2003). 

FIG. 2. Comparison of the discriminative stimulus properties of LSD, morphine, and methadone when injected into the DRN of the rat. Rats were trained to discriminate LSD (120 ng/kg s.c.), cannulae implanted, and generalization from peripheral to central administration determined over a variety of doses of each drug. (Redrawn from the research of Rosecrans and Glennon, ref. 59.) A, I.C. saline, , I.C. morphine in morphine trained rats, O, I.C. saline, , I.C. LSD in LSD trained rats, , I.C. saline, , I.C. methadone in methadone trained rats. 

Methadone is an opioid analgesic that is available for oral and parenteral administration. It is used in severe pain, in palliative care and as an adjunct in the management of opioid dependence. Compared with morphine, it is less sedating and has a longer duration of action. It may lead to addiction and can still cause toxicity when used in adults with non-opioid dependency. Because of the long duration of action, in overdosage, patients need to be monitored for long periods. 

Methadone, used as an analgesic, may be dispensed in any licensed pharmacy. Methadone dispersible tablets are for oral administration only. This preparation contains insoluble excipients and therefore must not be injected. It is recommended that methadone dispersible tablets, if dispensed, be packaged in child-resistant containers and kept out of the reach of children to prevent accidental ingestion. 

Oral methadone is about one half as potent as parenteral. Oral administration results in a delay of onset, a lower peak, and an increased duration of analgesic effect. Duration of effect increases with repeated use because of cumulative effects. 

The treatment of opioid abuse and dependence aims also at preventing the social complications of abuse, especially infections linked to parenteral administration (HIV and HepB). It relies on the use of substimtive drugs that can be either pure agonists, or partial agonist-antagonists (methadone, buprenor-phine, naltrexone), with the objective of limiting receptor desensitization and the development of tolerance. Any success in the treatment of opiate dependence may stem as much from the re-establishment of healthcare contact and social reinsertion as from any treatment induced decrease in the abuse behaviour itself. 

L B. The most commonly used treatment and the most effective is to stabilize the patient with methadone and gradually reduce the maintenance dose until the patient is drug free. The administration of meperidine would reverse the abstinence syndrome but it is unlikely to help the patient terminate his opioid habit. The use of naltrexone would likely further precipitate the abstinence syndrome and without additional counseling, would not likely offer long-term beneht. 

There are not currently any medications that have been approved for treatment of MDMA addiction. In actuality, very few drugs of abuse have possible medical (pharmaceutical) treatments. Heroin addiction is one disease that is treatable by pharmaceutical means. Heroin addiction is often treated with methadone or levo-alpha-acetyl methadol (LAAM) administration. Similarly, alcohol addiction may be treated with pharmacological tools. However, most stimulants, such as cocaine, amphetamine, and MDMA, do not have medications available for treatment of addiction. 

Suppression of heroin self-administration in opioid-dependent volunteers has been found to be greater at doses over lOOmg (Donny et al. 2005), and this relates to the three-level effects of methadone, the implications of which we often have to contend with in our discussions with patients. Basically low doses of methadone will suppress opiate withdrawal symptoms in dependent individuals, and this is what a lot of patients mean when they say that their dose (which may be considered too low by us) holds them. In medium to high levels of methadone there is less craving for opiates, and then at the highest doses there will be full narcotic blockade (Donny et al. 2002), but as already indicated the users themselves may not wish to take such dosages. 

The concurrent administration of methadone to heroin addicts known to be recidivists has been questioned because of the increased risk of overdose death secondary to respiratory arrest. Buprenorphine, a partial M-receptor agonist with long-acting properties, has been found to be effective in opioid detoxification and maintenance programs and is presumably associated with a lower risk of such overdose fatalities. 

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