Methadone analgesia

Manfredi PL, Gonzales GR, Cheville AL, Kornick C, Payne R. Methadone analgesia in cancer pain patients on chronic methadone maintenance therapy. J Pain Symptom Manage 2001 21(2) 169-74. 

Pruritus is a frequent adverse effect after intrathecal administration, with an incidence of one-third with bupre-norphine (122) and diamorphine (123) and over 70% for both diamorphine and morphine (124,125). In one stndy the incidence of pruritns was higher with morphine than with methadone analgesia was also snperior (124). Pruritus has also been reported with intrathecal pethidine (meperidine). Treatment was not reported to be necessary. This effect is not reported to occnr after intrathecal beta-endorphin (126,127). The mechanism of prnritns is not well understood and has been attribnted to a distnr-bance of thiamine metabolism (128) and to a distnrbance of afferent inpnt at snpraspinal as well as at spinal receptor sites (129). 

Codeine, hydrocodone, morphine, methadone, and oxycodone are substrates of the cytochrome P-450 isoenzyme CYP2D6.47 Inhibition of CYP2D6 results in decreased analgesia of codeine and hydrocodone due to decreased conversion to the active metabolites (e.g., morphine and hydromorphone, respectively) and increased effects of morphine, methadone, and oxycodone. Methadone is also a substrate of CYP3A4, and its metabolism is increased by phenytoin and decreased by cimetidine. CNS depressants may potentiate the sedative effects of opiates. 

Naloxone (Narcan) and naltrexone hydrochloride (Trexan) reverse the respiratory depressant action of narcotics related to morphine, meperidine, and methadone. They differ from other narcotic analgesics in several respects. Naloxone does not cause respiratory depression, pupillary constriction, sedation, or analgesia. However, it does antagonize the actions of pentazocine. Naloxone neither antagonizes the respiratory depressant effects of barbiturates and other hypnotics nor aggravates their depressant effects on respiration. Similar to nalorphine, naloxone precipitates an abstinence syndrome when administered to patients addicted to opiate-like drugs. 

Methadone has been used for intrathecal administration. Although this route can provide prolonged analgesia, the adverse effects have been reported to be unacceptable (SEDA-16, 81). 

Mercadante S, Casuccio A, Fulfaro F, Groff L, Boffi R, Villari P, Gebbia V, Ripamonti C. Switching from morphine to methadone to improve analgesia and tolerability in cancer patients a prospective study. J Clin Oncol 2001 19(11) 2898—904. 

Prieto-Alvarez P, Tello-Galindo I, Cuenca-Pena J, Rull-Bartomeu M, Gomar-Sancho C. Continuous epidural infusion of racemic methadone results in effective postoperative analgesia and low plasma concentrations. Can J Anaesth 2002 49(1) 25-31. 

After ingesting street drugs sold as PCP , THC , and methadone , three young men developed schizophreniform psychoses, analgesia, anesthesia, and amnesia (14). Except for the unusually long duration (2-4 weeks), these reactions resembled phencyclidine-induced psychoses. 

SAFETY PROFILE Poison by intravenous, subcutaneous, and intraperitoneal routes. Human systemic effects by ingestion hallucinations, distorted perceptions, and analgesia. Caution Abuse leads to habituation or addiction. When heated to decomposition it emits verj toxic fumes of Cr and NOx. See also METHADONE HYDROCHLORIDE. 

Methadone is a synthetic drug structurally and pharmacologically similar to morphine it acts mainly at the p-receptor. Methadone is largely metabolised to products that are excreted in the urine (t) 8 h). The principal feature of methadone is its duration of action. Analgesia may last for as long as 24 h. If used for chronic pain in palliative care (12-hourly) an opioid of short t) should be provided for breakthrough pain rather than an extra dose of methadone. 

Opioids are usually formulated as linctuses for antitussive use. Deciding on which agent to use depends largely on whether sedation and analgesia may be useful actions of the linctus. Hence methadone or diamorphine linctus may be preferred in patients with advanced bronchial carcinoma. In contrast, pholcodine, being nonsedating and nonaddictive, is widely incorporated into over-the-counter linctuses. 

Jacobson L, Chabal C, Brody MC, Ward RJ, Ireton RC. Intrathecal methadone and morphine for postoperative analgesia a comparison of the efficacy, duration, and side effects. Anesthesiology 1989 70(5) 742-6. 

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