Therapy with opioids in liver or renal failure

Citation
I. Tegeder et al., Therapy with opioids in liver or renal failure, SCHMERZ, 13(3), 1999, pp. 183
Language
TEDESCO
art.tipo
Article
Categorie Soggetti
Neurology
Journal title
SCHMERZ
ISSN journal
0932-433X → ACNP
Volume
13
Issue
3
Year of publication
1999
Database
ISI
SICI code
0932-433X(199906)13:3<183:TWOILO>2.0.ZU;2-1
Abstract
In patients with renal or hepatic failure, the pharmacokinetics of opioids may be affected in several ways, leading to the necessity to correct the do se. The liver is the major site for biotransformation of most opioids. The major metabolic pathway is oxidation. Exceptions to this are morphine and b uprenorphine, which undergo primarily glucuronidation, and remifentanil whi ch is cleared by esther hydrolysis. The hydrophilic metabolites are predomi nantly excreted by the kidneys and may accumulate in patients with renal in sufficiency. Some metabolites such as morphine-6-glucuronide (M6G) or norme peridine are active opioid agonists. With high concentrations they may caus e narcotic effects or respiratory depression. In addition,special risks are known for normepridine that has been shown to exert neurotoxic effects wit h the risk of seizures. Few cases of respiratory depression following the a dministration of codeine, dihydrocodeine and tramdol have been reported. Th e elimination half-life of these drugs was prolonged. Lastly, the dispositi on of methadone, buprenorphine, fentanyl, sufentanyl and remifentanil appea rs to be unaffected in renal failure. In patients with hepatic cirrhosis it has been shown that oxidation of opioids is reduced, resulting in a decrea sed drug clearance (meperidine, propoxyphene, pentazocine, tramadol and alf entanil) and increased oral bioavailability due to reduced first-pass metab olism (meperidine, propoxyphene, pentazocine, dihydrocodeine). Although glu curonidation is thought to be less affected in liver cirrhosis, the clearan ce of morphine was found to be decreased and its oral bioavailability incre ased. The consequence of reduced drug metabolism is the risk of accumulatio n in the body, especially with repeated administrations. As for patients wi th renal failure, special risks are known for meperidine with potential acc umulation of normeperidine, which can cause seizures, and for propoxyphene for which several cases of hepatotoxicity have been reported. On the other hand, the analgesic activity of codeine and tilidine depends on transformat ion into the active metabolites, morphine and nortilidine. In the case of r educed metabolism in chronic liver disease, the analgesic action of these d rugs may be compromised. Lastly, the disposition of a few opioids, such as fentanyl, sufentanil, and remifentanil,appears to be unaffected in liver di sease.