title: Opioid Drugs in Patients With Liver Disease: A Systematic Review.
abstract: BACKGROUND
  The liver, one of the most important organs of the body, is known to be responsible for several functions. The functional contribution of the liver to the metabolism of carbohydrates, protein, drugs and toxins, fats and cholesterol and many other biological processes are still unknown. Liver disorders are classified into two types: acute and chronic. Different drugs are used in liver diseases to treat and control pain. Most pain relief medications such as opioids are metabolized via the liver; therefore, the adverse reactions of drugs are probably higher for patients with liver disease. The current study aimed to evaluate the effects of opioid drugs on patients with liver disease; therefore, it is necessary to select suitable opioids for such patients.
  
  
  METHODS
  This review was written by referring to research literature including 70 articles and four textbooks published from 1958 to 2015 on various reputable sites. Searches were carried out on the key phrases of narcotic pain relievers (opioids), acute and chronic hepatic failure, opioid adverse drug reactions, drug-induced liver injury (DILI) and other similar keywords. References included a variety of research papers (descriptive and analytical), intervention and review articles.
  
  
  RESULTS
  In patients with liver disease, administration of opioid analgesics should be observed, accurately. As a general rule, lower doses of drugs should be administered at regular intervals based on the signs of drug accumulation. Secondly, the interactions of opioid drugs with different levels of substrates of the P450 cytochrome enzyme should be considered.
  
  
  CONCLUSIONS
  Pain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids. Opioids should be used cautiously since they can cause sedation, constipation and sudden encephalopathy effects. Since the clearance of these drugs in patients with hepatic insufficiency is decreased, the initial dose must be decreased, the intervals between doses should be increased and some patients need to be continuously assessed.
authors.affiliation: Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, IR Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Soleimanpour
authors.affiliation: Pain Research Center, Iran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Safari
authors.affiliation: Emergency Medicine Research Team, Tabriz University of Medical Sciences, Tabriz, IR Iran.
authors.forename: Kavous
authors.initials: K
authors.lastname: Shahsavari Nia
authors.affiliation: Tuberculosis and Lung Research Center, Tabriz University of Medical Sciences, Tabriz, IR Iran.
authors.forename: Sarvin
authors.initials: S
authors.lastname: Sanaie
authors.affiliation: Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran; Tehran Hepatitis Center, Tehran, IR Iran.
authors.forename: Seyed Moayed
authors.initials: SM
authors.lastname: Alavian
keywords: Adverse Drug Reactions; Liver Disease; Opioids