Methadone tolerance

Oral In 10 methadone-maintained inpatients, DXM (120, 240, and 480 mg/day for 4 days each to reduce methadone tolerance) induced some drowsiness no changes in subjective effects or ARCI several patients reported intoxication at the highest dose212... 

Volunteer postaddicts who receive subcutaneous or oral methadone daily develop partial tolerance to the nauseant, anorectic, miotic, sedative, respiratory-depressant, and cardiovascular effects of methadone. Tolerance develops more slowly to methadone than to morphine in some patients, especially with respect to the depressant effects this may be related in part to cumulative effects of the drug or its metabolites. Tolerance to the constipating effect of methadone does not develop as fully as tolerance to other effects. The behavior of addicts who use methadone parenterally is strikingly similar to that of morphine edicts, but many former heroin users treated with oral methadone show virtually no overt behavioral effects. 

Bleich A, Gelkopf M, Weizman T, et al Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel characteristics and a pharmacotherapeutic approach. Isr J Psychiatry Relat Sci 39 104-112, 2002 Bohn LM, Gainetdinov RR, Lin FT, et al Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 408 720— 723, 2000... 

Cross-tolerance A condition where an individual who is tolerant to the pharmacological effects of one member of a drug family also shows tolerance to other members of that family. Cross-dependence allows drug substitution during detoxification (e.g., methadone for heroin or clomethiazole for ethanol), so reducing the severity and potential danger of withdrawal symptoms. 

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. 

Opiates upper limit of tolerance test decrease dosage by 100 mg every 2-3 days Methadone 20-80 mg orally daily toper by 5-10 mg Al (methadone and... 

Unnecessary detoxification with drugs should be avoided if possible (e.g., if symptoms are tolerable). Heroin withdrawal reaches a peak within 36 to 72 hours, and methadone withdrawal peak is reached at 72 hours. 

Methadone maintenance is precisely what the name implies. Patients who will not or cannot tolerate being totally abstinent of opiates are maintained long-term on methadone replacement therapy. As noted previously, this continues the addiction but in a more controlled manner that averts the serious social and medical consequences of uncontrolled addiction. Daily doses for methadone maintenance range from 20mg/day to over lOOmg/day. 

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. 

A derivative of methadone, L-a-acetyl-methadol (LAAM) has been approved for the treatment of opioid addiction. In some addicts whose degree of tolerance is not known, the patient is first given methadone to stabilize the withdrawal signs and is then switched to LAAM. LAAM has an advantage over methadone in that it has a longer duration of action. Dosing is required only three times per week in most addicts to prevent withdrawal. 

The patient who uses methadone long-term may develop a tolerance to the drug s analgesic effect and physical dependence. 

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