Methadone gastrointestinal

Methadone has undergone a dramatic revival as a potent and clinically useful analgesic. It can be administered by the oral, intravenous, subcutaneous, spinal, and rectal routes. It is well absorbed from the gastrointestinal tract and its bioavailability far exceeds that of oral morphine. 

Methadone is a synthetic opioid, clinically available in the U.S. since 1947.8 It exists in the dextro- and levo-rotatory forms with the levo-isoform possessing approximately 8 to 50 times more pharmacological activity.27 34 Methadone acts on the CNS and cardiovascular system producing respiratory and circulatory depression. Methadone also produces miosis and increases the tone of smooth muscle in the lower gastrointestinal tract while decreasing the amplitude of contractions. It is used clinically for the treatment of severe pain and in maintenance programs for morphine and heroin addicts.34... 

Scientific research has shown that methadone and other opiates have specific areas, or sites, that they attach to in order to exert their influence on the brain and body. These sites, called receptors, are classified as mu, delta, and kappa, depending on what body functions they influence. Opiate activation of mu and delta receptors seems to influence mood, respiration, pain, blood pressure, and gastrointestinal functions. Kappa receptors appear to be more involved in the perception and aversion to pain. The degree of methadone s effect on these receptors can vary widely between individuals, however, there are certain effects that are almost universal. 

Actions The analgesic activity of methadone is equivalent to that of morphine. Methadone exhibits strong analgesic action when administered orally, in contrast to morphine, which is only partially absorbed from the gastrointestinal tract. The miotic and respiratory depressant actions of methadone have average half-lives of 24 hours. Like morphine, methadone increases biliary pressure, and is also constipating. 

Correct choice = A. Morphine causes increased cerebrospinal fluid pressure secondary to dilation of cerebral vasculature. Methadone can relieve withdrawal symptoms because opioids show cross sensitivity. It is administered parenterally because absorption from the gastrointestinal tract is unreliable. 

The results showed no correlation between hair levels and administered methadone dose (r = 0.14). We consider this lack of correlation with methadone dose not surprising, since it is known that the gastrointestinal absorption of methadone can vary greatly among individuals. This variability in absorption and uncertainty concerning pharmacokinetic parameters has no doubt contributed to the controversy about what constitutes hazardous overdosing or therapeutically ineffective underdosing with methadone. - We believe that hair analysis can potentially make important contributions to the resolution of this controversy. 

Methadone has Food and Drug Administration indications for the management of pain in adults and for adult narcotic addiction. Adverse events are those expected from opiate exposures gastrointestinal symptoms, CNS depression, and respiratory depression in larger doses, bradycardia, and constipation. Methadone appears to be fairly well tolerated by... 

Methadone is absorbed well from the gastrointestinal tract and can be detected in plasma within 30 minutes of oral ingestion it reaches peak concentrations at about 4 hours. After therapeutic doses, about 90% of methadone is bound to plasma proteins. Peak concentrations occur in the brain within 1 or 2 hours of SC or DVt administration, and this correlates well with the intensity and duration of analgesia. Methadone also can be absorbed from the buccal mucosa. 

B. Pharmacokinetics. Usually, peak effects occur within 2-3 hours, but absorption may be slowed by their pharmacologic effects on gastrointestinal motility. Most drugs have large volumes of distribution (3-5 Ukg). The rate of elimination is highly variable, from 1-2 hours for fentanyl derivatives versus 15-30 hours tor methadone. See also Tables 11-43 and 11-59. 

Kharasch ED, Hoffer C, Whittington D, Walker A, Bedynek PS. Methadone pharmacokinetics are independent of cytochrome P4503A (CYP3A) activity and gastrointestinal dmg transport insights from methadone interactions with ritonavir/indin-avir. Anesthesiology 2009 110 660-72. 

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