Morphine withdrawal, treatment

Recent studies in rat brains have investigated the role of chronic heroin and other narcotics on apoptosis. Chronic heroin and morphine treatment (as well as heroin/morphine withdrawal) resulted in changes in upregulation of Fas receptors as well as increased levels of dynamin. 

Kleber HD, Weissman MM, Rounsaville BJ, et al Imipramine as treatment for depression in addicts. Arch Gen Psychiatry 40 649-633, 1983 Kleber HD, Riordan CE, Rounsaville BJ, et al Clonidine in outpatient detoxification from methadone maintenance. Arch Gen Psychiatry 42 391-394, 1983 Kleber HD, Topazian M, Gaspari J, et al Clonidine and naltrexone in the outpatient treatment of heroin withdrawal. Am J Drug Alcohol Abuse 13 1-17, 1987 Kornetsky C. Brain stimulation reward, morphine-induced stereotypy, and sensitization implications for abuse. Neurosci Biobehav Rev 27 777-786, 2004 Kosten TR, Kleber HD Buprenorphine detoxification from opioid dependence a pilot study. Life Sci 42 633-641, 1988... 

There are two main treatments for the opiate withdrawal syndrome. One is replacement therapy with methadone or other X agonists that have a longer half-life than heroin or morphine, and produce mild stimulation rather than euphoria. They also produce cross-tolerance to heroin, lessening heroin s effect if patients relapse. Withdrawal is also treated with the 0C2 agonist clonidine, which inhibits LC neurons, thus counteracting autonomic effects of opiate withdrawal — such as nausea, vomiting, cramps, sweating, tachycardia and hypertension — that are due in part to loss of opiate inhibition of LC neurons. 

Morphine antagonists and partial agonists. The effects of opioids can be abolished by the antagonists naloxone or naltrexone (A), irrespective of the receptor type involved. Given by itself, neither has any effect in normal subjects however, in opioid-dependent subjects, both precipitate acute withdrawal signs. Because of its rapid presystemic elimination, naloxone is only suitable for parenteral use. Naltrexone is metabolically more stable and is given orally. Naloxone is effective as antidote in the treatment of opioid-induced respiratory paralysis. Since it is more rapidly eliminated than most opioids, repeated doses may be needed. Naltrexone may be used as an adjunct in withdrawal therapy. 

The use of opium dates to 4,000 b.c. At that time it was used for medicinal and recreational purposes mainly via inhalation. Today few opium-containing preparations are used, since the activity of opium is largely attributed to its morphine content. The preparations in use today are those that have constipative effects useful for the treatment of diarrhea. Preparations include pantopon, an injectable hydrochloride of opium alkaloids, and paregoric, a camphorated tincture of opium. Paregoric can be used to treat infants with opioid withdrawal signs following in utero exposure to opioids. 

The LC neurons express a variety of autoreceptors, which allow compounds such as clonidine to decrease, and others such as yohimbine to increase LC firing (Buccafusco, 1992). Clonidine is used in the treatment of opiate withdrawal, since it decreases LC firing during the withdrawal from morphine. 

Opium has been used as a medicine for hundreds of years, inevitably creating countless addicts. Scientists have conducted a never-ending search for effective cures for opium addiction, morphine addiction (morphinism), and heroin addiction. For most of its history, opium addiction was treated as a disease with no cure, and doctors concerned themseives with treating the symptoms of addiction rather than the root cause. As a result, other opiates were used to lessen the effects of withdrawal. The addict is placed on a regimen of opiates that slowly decrease over time, weaning the addict from his or her addiction. This process of treatment is still used today. 

It is inactive orally because of high first pass metabolism in liver. Metabolised by glucuronidation in liver. The main use of naloxone is in the treatment of acute opioid overdose (acute morphine poisoning). It also precipitates withdrawal syndrome when administered to morphine addicts. The constricted pupils of addicts dilate after administration of naloxone. This has been used as a diagnostic tool for opioid addiction. 

Methadone is widely used in the treatment of opioid abuse. Tolerance and physical dependence develop more slowly with methadone than with morphine. The withdrawal signs and symptoms occurring after abrupt discontinuance of methadone are milder, although more prolonged, than those of morphine. These properties make methadone a useful drug for detoxification and for maintenance of the chronic relapsing heroin addict. 

Dopamine Microdialysis in the Nucleus Accumbens During Acute and Chronic Morphine, Naloxone-Precipitated Withdrawal and Clonidine Treatment." Brain Research 566 348-50. 

Zharkovsky, A., Tottermann, A.M., Moisio, J., Aktee, L. Concurrent nimodipine attenuates the withdrawal signs and the increase of cerebral dihydropyridine binding after chronic morphine treatment in rats, Naunyn-Schmiedeberg s Arch. Pharmacol. 1993, 347, 483-486. 

Because any opiate derivative will suffice to soothe heroin cravings associated with withdrawal, methadone, a synthetic opiate that has no sedating side effects, has been an effective treatment for heroin and morphine addiction for more than 30 years. The medication is taken orally and suppresses narcotic withdrawal for a period of 24 to 36 hours. Methadone can be taken continuously for 10 years or longer with no harmful side effects. 

Butorphanol Tartrate With this drug, dependence, withdrawal, and interactions are similar to that of opioids. Butorphanol has less potential to produce dependence when compared with morphine, but it is a drug of abuse. Naloxone acts as an antagonist and can be used for the treatment of overdose.35... 

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