Methadone use in patients with chronic renal disease
The Rockefeller University, 1230 York Avenue, New York, New York 10021 U.S.A.Drug and Alcohol Dependence (Impact Factor: 3.42). 04/1980; 5(3):197-205. DOI: 10.1016/0376-8716(80)90180-5
Methadone disposition was studied in three patients receiving chronic methadone treatment and having chronic renal disease: one oliguric patient during peritoneal dialysis, one anuric patient on hemodialysis, and one patient following renal transplantation. In all three patients plasma levels of methadone remained within the desired therapeutic range (0.09--0.68 microgram/ml) for the doses received (40-50 mg/day). Elimination of methadone and its metabolites was almost exclusively by the fecal route in the anuric patient. Less than 1% of the daily dose was removed by peritoneal dialysis or hemodialysis. There was no laboratory or clinical evidence for accumulation of either methadone or its metabolites, suggesting that methadone is an appropriate narcotic to use in patients with renal disease.
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ABSTRACT: This study evaluated levo-alpha-acetylmethadol hydrochloride (LAAM), a long-acting morphine-like (mu) agonist approved in 1993 to treat opiate dependence. Sprague-Dawley rate (20/sex/group) were gavaged with doses of 3.0-33.5 mg kg-1 for 30 days followed by a 14-day drug-free recovery period. Treatment-related effects included dose-dependent CNS depression, decreased food consumption and body weight gain, reddish urine and abdominal staining. Tolerance developed by day 7. Mortality was dose-dependent; deaths occurred predominantly during the first week. Increased alanine aminotransferase (SGOT, AST) and lactate dehydrogenase (LDH), observed only in high-dose males, were associated with findings in liver. Decreases in spleen/brain weight and increases in brain/body weight ratios were seen in both sexes. Decreases in weights of heart, liver and kidney achieved statistical significance only for high-dose groups. Kidneys of mid- and high-dose groups displayed intertubular mineral/crystal deposition, focal corticomedullary mineralization and focal regenerative tubular epithelium. Centrilobular hypertrophy was observed in livers of high-dose males and mid- and high-dose females. Following the recovery period, decreased body weights and increased brain/body weight ratios occurred in mid-dose males and low-dose females. Weights of liver and kidney and organ/brain weight ratios were decreased in mid-dose males. Histopathological findings observed in kidneys and livers had abated. In summary, acute and repeated administration of LAAM produced a spectrum of activity consistent with its profile as a long-acting pure mu-agonist which stimulates microsomal enzymes in rodents. Renal and hepatic effects seen in initially drug-naive rats treated with morphine-type agonists are not observed in tolerant individuals stabilized on mu-agonists to treat opiate dependence.
Article: Opioid rotation in cancer pain[Show abstract] [Hide abstract]
ABSTRACT: Some patients with cancer pain may develop uncontrolled adverse effects, including generalized myoclonus, delirium, nausea and vomiting, or severe sedation before achieving adequate analgesia during opioid dose titration. When aggressive attempts to provide prophylaxis against adverse effects fail, drug rotation should be considered, because sequential therapeutic trials can identify the most favorable drug. Experiences are accumulating demonstrating that opioid responsiveness to difficult pain syndromes should not be based on the results obtained by a single drug. Different mechanisms, including receptor activity, the asymmetry in cross-tolerance among different opioids, different opioid efficacies, and accumulation of toxic metabolites can explain the differences in analgesic or adverse effect responses among opioids in the clinical setting. Opioid rotation may be useful in opening the therapeutic window and establishing a more advantageous analgesia-toxicity relationship. By substituting opioids and using lower doses it is possible in most cases to reduce or relieve the symptoms of opioid toxicity and to manage highly tolerant patients with previous opioids while improving analgesia and, as a consequence, the opioid responsiveness. Conversion to alternative opioids poses some problems because previous conversion tables may be misleading. Because methadone is much more potent than previously described, any change should start at a lower equivalent dose. Different approaches have been proposed to avoid the problems caused by methadone’s long half-life and possible accumulation. This review will examine the rationale and the clinical aspects of opioid rotation on the basis of recent research.
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