Cholestasis and endogenous opioids: liver disease and exogenous opioid pharmacokinetics.
A class of endogenous opioids is upregulated in liver disease particular to cholestasis, which contributes to symptoms in liver disease such as pruritus, hypotension and encephalopathy. Symptoms associated with cholestasis are reversed or at least ameliorated by mu opioid receptor antagonists. Palliation of symptoms related to cholestatic liver disease also involves bile acid binding agents. Opioid receptor antagonists, unlike bile acid binding agents, have been reported to relieve multiple symptoms, except for pruritus, and improve liver function as demonstrated in experimental cholestasis. Exogenous opioid pharmacology is altered by liver disease. Dose reduction or prolongation of dose intervals is necessary depending on the severity of liver disease.
Davis
Mellar
M
The Harry R Horvitz Center for Palliative Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. davism6@ccf.org
D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D002779:Cholestasis / Q000188:drug therapy* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006501:Hepatic Encephalopathy / Q000188:drug therapy; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism; D017093:Liver Failure / Q000188:drug therapy / Q000378:metabolism; D009292:Narcotic Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D018847:Opioid Peptides / Q000378:metabolism; D011537:Pruritus / Q000188:drug therapy; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D051437:Renal Insufficiency / Q000150:complications
D000701:Analgesics, Opioid; D000924:Anticholesteremic Agents; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; D003577:Cytochrome P-450 Enzyme System