Methadone effects

The time of onset, intensity, and duration of abstinence syndrome depend on the drug previously used and may be related to its biologic half-life. With morphine or heroin, withdrawal signs usually start within 6-10 hours after the last dose. Peak effects are seen at 36-48 hours, after which most of the signs and symptoms gradually subside. By 5 days, most of the effects have disappeared, but some may persist for months. In the case of meperidine, the withdrawal syndrome largely subsides within 24 hours, whereas with methadone several days are required to reach the peak of the abstinence syndrome, and it may last as long as 2 weeks. The slower subsidence of methadone effects is associated with a less intense immediate syndrome, and this is the basis for its use in the detoxification of heroin addicts. However, despite the... 

McCance-Katz EF, Rainey PM, Jatlow P, et al. Methadone effects on ZDV disposition (AIDS Clinical Trials Group 262). J Acquir Immune Defic Syndr Hum Retroviral 1998 18(5) 435 t43. 

Corkery J, Schifano F, Ghodse AH and Oyefeso A (2004) Methadone effects and its role in fatalities. Human Psychopharmacology Clinical and Experimental 19 565-576. Gilvarry E and Schifano F (2002) Medical use of buprenorphine in the UK. Special report prepared for the WHO, February, pp. 1-93. 

Geletko SM, Erickson AD. Decreased methadone effect after ritonavir initiation. Pharmacotherapy 2000 20(l) 93-4. 

Charney DS, Sternberg DE, Kleber HD, Heninger GR, Redmond DE Jr. The chnical nse of clonidine in abrupt withdrawal from methadone. Effects on blood pressure and specific signs and symptoms. Arch Gen Psychiatry 1981 38(ll) 1273-7. 

Both opioids and alcohol are CNS depressants, and there may be enhanced suppression of the medullary respiratory control centre. " Acute administration of alcohol appears to increase methadone effects due to inhibition... 

Methadone effects reduced or unaffected. A drug abuser with AIDS needed an increase in his levomethadone (7 -methadone) dosage from 40 to 60 mg daily, within a month of starting to take zidovudine 1 g daily. ... 

The effect of urinary pH on the clearance of methadone is an established interaction, but of uncertain importance. Be alert for any evidence of reduced methadone effects in patients whose urine becomes acidic because they are taking large doses of ammonium chloride. Lowering the urinary pH to 5 with ammonium chloride to increase the clearance can also be used to treat toxicity. Theoretically, urinary alkalinisers such as sodium bicarbonate and acetazolamide may increase the effect of methadone. 

Saxon A], ling W, EBUhouse M, Thomas C, Hasson A, Ang A, et al. Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health a randomized trial. Drug Alcohol Depend February 1,2013 128(l-2) 71-6. 

A common strategy for treating chronic opiate addiction iavolves the substitution of methadone which can either be provided as maintenance therapy or tapered until abstinence is achieved. Naltrexone and buprenorphine [52485-79-7] have also been used ia this manner. The a2 adrenergic agonist clonidine [4205-90-7] provides some rehef from the symptoms of opiate withdrawal, probably the result of its mimicking the inhibitory effect of opiates on the activity of locus coerukus neurons. 

Two opioids are used in the treatment and management of opiate dependence levomethadyl and methadone. Levomethadyl is given in an opiate dependency clinic to maintain control over the delivery of the drug. Because of its potential for serious and life-threatening proarrhythmic effects, levomethadyl is reserved for use in the treatment of addicted patients who have no response to other treatments. Levomethadyl is not taken daily the drug is administered three times a week (Monday/Wednesday/Thursday or Tuesday/Thursday/ Saturday). Daily use of the usual dose will cause serious overdose. 

Jerry Jbnes is to begin receiving methadone for the treatment of heroin dependency, tkrry asks why methadone, a narcotic, is effective in the treatment of narcotic dependency. How wouldyou explain this to the patient What information would be important to give this patient while he is in the methadone program ... 

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). 

LAAM (L-a-acetylmethadol or levomethadyl acetate) is a full agonist at the i opioid receptor with pharmacologic properties similar to those of methadone. A number of studies have demonstrated that treatment with LAAM results in reduction of opioid use and beneficial effects comparable to those achieved with methadone (Ling et al. 1978 Tennant et al. 1986 Zangwell et al. 1986). However, retention rates are higher in patients who take methadone doses of 80—100 mg/day. 

The approval of buprenorphine for the office-based treatment of opioid dependence represents a major departure from the earlier methadone clinic system. Physicians with addiction specialist credentials or those who have completed 8 hours of approved training can become qualified to treat up to 30 patients in their private offices. Stable patients may be given prescriptions for up to a month of medication. The combination buprenorphine/naloxone tablet is expected to have minimal risk for diversion. When taken subhnguaUy, as prescribed, naloxone has minimal biologic activity and does not interfere with the buprenorphine dose. However, if an attempt is made to inject the drug, the addict will experience the full antagonist effect of the naloxone. 

It is anticipated that buprenorphine will be an acceptable treatment for younger addicts and for individuals with smaller habits and shorter histories of dependence, thus permitting earlier intervention in the course of the addiction. Clinical experience suggests that buprenorphine is less effective for individuals with larger opioid habits. Methadone or LAAM remains the preferred medication for those patients. 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Bale RN, Zarconc VP, VanStone WW, et al Three therapeutic communities a prospective controlled study of narcotic addiction treatment process and two-year follow-up results. Arch Gen Psychiatry 41 185—191, 1984 Ball JC, Ross A The Effectiveness of Methadone Maintenance Treatment. New York, Springer-Verlag, 1991... 

Carroll KM, Ball SA, Nich C, et al Targeting behavioral therapies to enhance naltrexone treatment of opioid dependence. Arch Gen Psychiatry 38 755-761, 2001 Centers for Disease Control and Prevention Recommendation for prevention and control of hepatitis (virus (HCV) infection and HCV-related chronic disease. MMWR Recommendations and Reports 47(RR19) l-39, 1998 Charney DS, Steinberg DE, Kleber HD, et al The clinical use of clonidine in abrupt withdrawal from methadone. Arch Gen Psychiatry 38 1273-1277, 1981 Charney D S, Heninger OR, Kleber H D The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment of abrupt withdrawal from methadone. Am J Psychiatry 143 831-837, 1986... 

Gossop M, Bradley B, Phillips GT An investigation of withdrawal symptoms shown by opiate addicts during and subsequent to a 21 -day in-patient methadone detoxification procedure. Addict Behav 12 1-6, 1987 GreenJ, Jaffe JH Alcohol and opiate dependence. J Stud Alcohol 38 1274-1293,1977 Green L, Gossop M Effects of information on the opiate withdrawal syndrome. Br J Addict 83 305-309, 1988... 

Hubbard RL, Marsden ME, Rachal JV, et al Drug Abuse Treatment A National Study of Effectiveness. Chapel Hill, University of North Carolina Press, 1989 Hunt DE, Lipton DS, Goldsmith DS, et al It takes yom heart the image of methadone maintenance in the addict world and its effect on recruitment into treatment. Int J Addict 20 1751-1771, 1985-1986... 

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