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Hepat Mon. The liver is one of the most important organs of the body since it plays important roles in several functions 1 , 2. The metabolism of carbohydrates glycogen storage and control , protein metabolism of albumin and many other proteins which play essential roles in homeostasis and the immune system , drugs and toxins metabolism based on the activity of cytochrome enzymes, etc. Obviously, hepatic impairments are vast and complicated. Liver disease is the tenth most common cause of death in the United States leading to deaths every year 5 , 6. Liver disorders are classified into two groups: acute and chronic. As disease initiates, liver cells are damaged or destroyed. If the injury is mild and reversible, then liver cells are reconstructed and the liver returns to its normal state; however, if the damage is severe, reconstruction does not happen and the damage to the liver is permanent. Permanent injuries cause fibrosis, liver destruction, loss of function, bleeding disorders, high portal pressure and damage, and or hepatic encephalopathy 7. In terms of etiology, the most important causes of acute liver disease in the world include viral infections and alcohol or drug toxicity especially in developed countries 5. Viral hepatitis B and C, alcohol, autoimmune hepatitis and genetic disorders are major causes of chronic liver dysfunction 1 , 4. The slow and prolonged causes of liver disease lead to increased number of patients. Since liver disease causes several systemic problems, it is necessary to look at the treatment type and particularly their pharmacodynamics. Cirrhosis is the twelfth most common cause of death in America. Patients with advanced chronic liver failure i. Because of the mentioned problems, patients with liver diseases are treated with several drugs. Moreover, they are periodically treated with surgery and endoscopic procedures which require the use of many analgesics, including opioids. Based on the importance of this issue for internists, a detailed discussion is formed known as drug-induced liver injury or drug-induced liver injury DILI Another important problem which patients with liver disease face is that unlike other diseases such as kidney failure, there is no numerical measure such as glomerular filtration rate or specific guidelines to determine the severity of the liver failure. Some classifications are provided according to serum albumin, bilirubin, coagulation time and the presence of ascites, but a comprehensive protocol is not developed yet 4 , Additionally, much of the research relies on the pharmacokinetic properties of drugs even at low doses , but sufficient knowledge about the potential harmful effects of drugs, particularly opioids, is not available. In fact, comprehensive information regarding pharmacodynamics is not available. Therefore, the administration of these drugs is more difficult Metabolic pathways of pain relief medications, including opioids, pass through the liver oxidation, de-alkylation, conversion, and combining. Therefore, in patients with reduced hepatic function, the metabolic pathways are affected and the toxicity probability of these drugs increases. Indeed, with liver disease in which the metabolic pathways of drugs are disturbed, they are exerted lowly and accumulate in plasma, which means that the half-life of the drug will increase in the body and the adverse drug reactions of this group of drugs appear more severe Albumin is a protein which binds to and facilitates the exertion of certain drugs. Albumin synthesis is decreased with liver disease; therefore, it leads to increased serum levels of some drugs. Thus, the risk of adverse drug reactions increases Drugs are a collection of natural and chemical morphine-like substances called opioids which bind to opioid receptors in synapses. They all work as neurotransmitters in the body endorphins by affecting the central nervous system that causes pain relieving There are two different types of chemical reactions in the liver metabolism of drugs. The first type is transfer-oxidation reaction that is catalyzed by the cytochrome P enzyme system and metabolizes most opioids. Clearance of opioids decreases in liver failure and their bioavailability increases. These changes may be considered as secondary outcomes of the reduction in liver blood flow the limitation of primary route of metabolism or the reduction of the cytochrome P enzymes levels. The second group of chemical reactions consists of conjugation and glucuronidation in the liver. The reactions are less affected, since the glucuronidase are preserved in patients with liver disease; moreover, extra-hepatic glucuronidation is less affected by the hepatic criteria, and the opioid metabolites are generally exerted by the kidneys. The reduction in the serum albumin level changes the quality of opioid distribution volumes that either increases or decreases the accumulation of drugs. Although there is no practical method to test or predict the clinical observations, at least a part of most opiates are metabolized by the liver. Therefore, the administration of opioids to patients with liver failure is high risk and requires precaution be taken to minimize their side effects 15 , The current study used articles that population P were over the age of eighteen and had liver disease, intervention I was use of opioid drugs and outcome O was: whether or not to use opioids in patients with liver disease. The present study is a systematic review. The research literature included 70 papers and four books published from to at various reliable data bases PubMed, Medline Ovid , Cochrane. Searches were performed on keywords such as opioid pain relievers opioids , hepatic failure, acute and chronic opioid adverse drug reactions, drug-induced liver injury DILI and other similar keywords. The primary search resulted in articles and four books. The irrelevant data including 75 irrelevant abstracts or full-text review, duplicate records and lack of access to the full-text of the articles or books were excluded. Resources included 17 review articles, 19 clinical trials, four randomized clinical trials, five case-control, four books, three cohort studies, six case reports or case series, one to the editor and one web site. Two independent authors managed and ran the data extraction and quality assessment. The quality of clinical trials, cohort studies and case control studies were assessed using CASP critical appraisal skills program with their checklists. Furthermore, for cross sectional studies STROBE strengthening the reporting of observational studies in epidemiology was used. In the current study, after the initial search and based on the titles found, a total of 93 potentially relevant papers were selected. After removing three duplicate studies, the abstracts of these papers were carefully studied and 16 papers were excluded as they did not meet the inclusion criteria. Finally 74 studies were included in the study Figure 1 , Tables 1 , 2 , 3 , 4 , 5 , and 6. The metabolism, effects, and adverse reactions of each opioid are discussed in the following paragraphs. Morphine is a very potent opioid. It is obtained from opium which is the most effective compound. Medicinal morphine products are available in three forms: oral tablets and capsules , parenteral intravenous, subcutaneous, and intramuscular and suppositories. Utilization through inhalation is also possible. Ninety percent of morphine is metabolized by the liver and excreted by the kidneys. M6G is an active quencher, which is a more potent analgesic than morphine; M3G has no analgesic effect, but it leads to neurotic adverse drug reactions neurotoxicity such as confusion. Morphine may also be metabolized into small amounts of neuro-morphine, codeine and hydro-morphine. Reducing morphine clearance from plasma and increasing the half-life of the drug in the blood are reported as consequences of its concentration 16 , Using morphine increases the levels of fasting bile acids in patients with nonalcoholic steatohepatitis; although metabolism of morphine does not change in these patients, morphine is eventually accumulated and leads to morphine poisoning 18 , The amount of morphine for pain relief was significantly lower in group three among the following three groups of patients who underwent surgery. Groups included: 1, kidney transplant donors; 2, patients with liver cirrhosis and hepatitis B or C; 3, patients with end-stage liver disease In one case, the use of slow-release oral morphine for pain relief led to hepatic encephalopathy in a patient with cirrhosis and liver cancer It was found that opioids, especially morphine and hydromorphone should be used with caution in older patients due to reduced liver and kidney function and underlying diseases It was found that morphine and fentanyl can be easily used in a child with cirrhosis who was a candidate for liver transplantation Slow-release morphine can be used with minimal doses and long intervals for pain relief in patients with liver cirrhosis due to hepatitis B and C treated by sclerotherapy The half-life of oral and intravenous morphine is increased in patients with severe hepatic cirrhosis; hence, it should be cautiously used in such patients Hepatic excretion of morphine is changed in patients with cirrhosis The final half-life of unchanged morphine not metabolized is also longer in patients with liver cirrhosis Removal of morphine storage is not affected by moderate and severe cirrhosis. However, morphine leads to mild sedation in these people, it does not lead to hepatic coma In patients with liver disease, the minimum dose of the drug should be used with the usual dose of medicine at regular intervals in the early stages. If the liver failure is progressive, the usual dose should still be used, but the medication interval should be extended Hydrocodone belongs to the group of long-acting or slow sustained release opioid analgesics. It is a semi-synthetic drug derived from codeine and is used as an analgesic antitussive 4 , 11 , Its drug products are available only in oral form or in combination with non-opioid drugs such as acetaminophen. Hydrocodone is a pre-drug that is metabolized into hydromorphone and oxymorphone by Cyp2D6 in the liver. Hydrocodone dosage titration is limited due to its non-narcotic composition 16 , 22 , In patients with hepatic failure, the half-life of hydromorphone is increased; therefore, overuse of these drugs can certainly be toxic for the liver Its pharmaceutical products are provided in the oral tablets and parenteral intramuscular, intravenous forms. However, none of these metabolites show considerable quencher activity. Oxycodone is administered in combination with paracetamol and its consumption leads to liver dysfunction Bioavailability of hydromorphone and oral oxycodone in patients with liver problems is dramatically increased; therefore, their doses should be reduced or the interval between administrations should be increased Codeine, or 3-methylmorphine, is an opioid which acts as an analgesic, antitussive, anti-hypertensive, anti-anxiety and sedative, and it has hypnotic effects. Its oral, suppository, or injection subcutaneous and intramuscular medication forms are available 11 , 13 , Codeine is converted to morphine by cytochrome p Cyp2D6 enzymes in the liver. Since codeine is not metabolized in patients with hepatic failure due to the reduced capacity of the enzyme , its analgesic effects may not appear in this group of patients; therefore, patients with hepatic failure should avoid taking these drugs 16 , Another analgesic instead of codeine is recommended to control pain in patients with liver failure 13 , Although codeine is frequently used to treat patients with liver failure, especially patients with cirrhosis, because of its conversion to morphine, serum levels can be highly variable Codeine can cause respiratory depression called morphinemia in patients with liver failure because of the accumulation of its metabolite 29 , Pethidine is a synthetic opioid. It has lower addictive properties than morphine. Oral tablets and parenteral intravenous, intramuscular medication forms are available 11 , 13 , In liver disease, the clearance of meperidine is reduced, and its half-life is prolonged. Seizure is a common adverse drug reaction of meperidine and normeperidine which may occur even at reduced dosages in patients with hepatic insufficiency 15 , In addition, this compound is responsible for the neurotoxic effects of hallucinogens and seizures of pethidine. Most pethidine metabolites are excreted in the form of glucuronic acid from the kidney; therefore, a more neurotoxic effect appears in kidney failures 16 , 31 , In renal failure, meperidine can cause seizure due to accumulation of its toxic metabolites i e, normeperidine, but it should be cautiously administered in liver failure In patients with lysosomal storage diseases such as Niemann-Pick, meperidine can be used for sedation of children to examine diagnosis and biopsy Normeperidine is the toxic metabolite of meperidine, excreted through the kidneys; therefore, it increases in patients with renal failure and cancer. In patients with liver cirrhosis, meperidine is decreased; thus its accumulation causes CNS suppression and hepatic encephalopathy Meperidine administration mode does not affect its metabolism. Meperidine production is lower in patients with cirrhosis due to impaired liver function and its toxic effects are lower, but its toxic effects appear due to cumulative effect and its narcotic effects on the CNS increase Methadone is a potent synthetic opiate drug which is less addictive than morphine and heroin. It is utilized as a maintenance drug for heroin addiction inhibition 11 , It has oral, parenteral intravenous, intramuscular , suppositories, inhalation and subcutaneous medicinal forms. It is metabolized by enzymes cyp3A4 and 1A2 in the liver; therefore, its clearance is reduced in severe hepatic insufficiency. Although methadone is a drug with a high affinity for binding to protein, it does not produce toxic metabolites 32 , 37 , Thus, it is better tolerated in patients with liver failure. If standard and regular doses of methadone are utilized, information shows no change in patients with mild to moderate hepatic insufficiency 16 , However, in patients with severe hepatic failure, the half-life of the drug increases, and it should be taken with caution 13 , In patients with hypoalbuminemia, the lowest dose should be given Methadone is contraindicated in severe liver disease Tramadol is known with the trade names Tramal, Tram and Biomadole. It is an opium-like pain killer that is considered as an opioid. Tramadol is administrated for relief of moderate to severe pain. The medicinal forms of this drug are available as tablets retard , drops, injections and suppositories 11 , 16 , Tramadol is metabolized by cyp3A4 and cyp2D6 in the liver, and it is excreted in the urine. When receiving mg of tramadol, the blood level of the drug reaches maximum amounts in two hours. The half-life of the drug is four to six hours. The compounds are metabolized to active metabolites in the liver which show the quencher effects. Since the metabolic enzymes of the liver are reduced in patients with liver failure, the drug may not be metabolized to its active metabolites that reduce the effects of the enzymes. Basically, the use of alternative materials for pain relief is recommended 13 , 31 , Similar side effects of other opium-like drugs are also observed in tramadol nausea, dizziness, drowsiness, dry mouth, delayed ejaculation, constipation, hypotension, sweating and itching. However, the risk of respiratory depression, which is the most fatal complication of these drugs, appears less with oral tramadol than with morphine 32 , 33 , The consumption of this drug causes nausea more than the consumption of other opioids because of the increased levels of serotonin. For people without physical dependency to opioids, the consumption of more than mg of tramadol will be dangerous. Seizure is one of the rare but serious adverse reactions of tramadol. Seizure is usually caused by utilizing too much of the drug in patients with epilepsy and brain injury, those who have kidney or liver problems, or people who are addicted to alcohol. In some studies, it is suggested that tramadol is one of the opiates administered in patients with severe and persistent pain of cirrhosis Its effects on peripheral pain pathways for inhibition of relative serotonin reuptake are low affinity for opioid receptors. Constipation appears because of the anticholinergic effects of tramadol. The use of tramadol in patients with liver failure has led to challenges 32 , 38 , 41 , High doses of tramadol caused the death of a year-old male with a painful rib fracture. Pathology revealed that it was because of acute liver failure due to fulminant liver necrosis. It was the first report of tramadol-induced hepatic failure Oral tramadol can be used for patients with primary cancer or metastatic liver cancer, provided that administration intervals are more, therefore, a dose of 50 mg every 12 hours can be effective and safe Buprenorphine is a semi-synthetic opioid derived from the baine. This drug is also useful to treat drug addicts 32 , The medicinal forms of buprenorphine include injectable intravenous, intramuscular , suppositories, sublingual, intranasal and transdermal forms. It is metabolized in the liver, processed by cyp2c8 and cyp3A4 to norbuprenorphine, and excreted through the kidneys and bile. In patients with severe cholestasis, the clearance of drugs which are metabolized in the liver, such as buprenorphine, are threatened 33 , 37 , Buprenorphine is a semi-synthetic opioid, more often used to treat heroin dependency withdrawal. Liver threatening complications are reported at therapeutic doses in a few patients with hepatitis C. Pathologic study revealed that mitochondria are mostly affected by toxic effects of buprenorphine In patients with hepatitis B or C, opioids may be used to reduce pain; however, in this group of patients liver function should be evaluated through tests Particularly in patients with hepatitis C, repeated intravenous administrations of buprenorphine will definitely cause liver damage A month study revealed that although treatment with buprenorphine or naloxone can lead to increased liver enzymes in the treatment of opioid dependents, it will not lead to liver damage, therefore, it can be used safely The use of nasal buprenorphine is increasing and one case was reported to cause hepatitis and renal failure Higher doses of buprenorphine can be used in end stage ill patients with progressive liver failure A study revealed that the use of buprenorphine in the first six months in patients with underlying hepatitis B and C slightly affects the increased serum levels of liver enzymes Transdermal buprenorphine can be effective in the treatment of pruritus in patients with primary biliary disease, but does not exacerbate liver complications Liver enzymes level are increased in patients with hepatitis C who are treated with buprenorphine; however, buprenorphine treatment is well tolerated by such patients and enzyme levels return to normal level after cessation of treatment Buprenorphine can be used for patients with hepatic porphyria, and has no effect on their liver function Buprenorphine should be cautiously used in patients with severe hepatic pruritus due to cholestasis Pentazocine is a synthetic drug which is the agonist or antagonist of opioids. Its drug forms include oral and intravenous IV The metabolism of pentazocine is hepatic, and it is excreted through the urine. It is more likely to cause illusions than morphine. In patients with the precedent of addiction, it causes withdrawal symptoms. The doses of this drug should be reduced in patients with hepatic insufficiency 13 , It is required to administer pentazocine cautiously in patients with diseases of the gallbladder and bile ducts 32 , Bioavailability of meperidine and pentazocine is increased in patients with liver cirrhosis; therefore, oral doses of these medications should be reduced in these patients, and when there is a need to repeat the dose in oral or intravenous mode, intervals should be prolonged between doses or repeated dose should be less than the initial dose The only drug product of dextropropoxyphene is the oral form available in combination with non-opioid drugs such as acetaminophen 11 , Evaluation of four patients showed that dextropropoxyphene and paracetamol combination can cause hepatotoxicity and can occur in form of cholestasis or cytolytic hepatitis or cholangitis, but the outcome of these patients is better as the discontinuation of the medication will lead to disappearance of the changes A study of 90 patients showed that dextropropoxyphene will cause hepatotoxicity; biopsies of patients demonstrated that the drug can cause centrilobular cholestasis The blood level of this drug increases in chronic liver disease which intensifies its effects 30 , 39 , Fentanyl is an opioid with a high absorption coefficient of the liver that binds to serum albumin. Fentanyl is available in TD, intramuscular IM , intravenous IV , oral, transmucosal, sublingual and buccal medicinal forms. This drug is mainly metabolized by the liver and is excreted through the kidneys 11 , Fentanyl is primarily metabolized by cyp3A4 and is distributed in the muscle and fat immediately after administration. Although the duration of its half-life, dose repetition and single-dose were prolonged, the single-dose pharmacokinetics of intravenous fentanyl in patients with liver failure did not change There is no information about its continuous infusion consumption 13 , Transdermal fentanyl is not adequately studied for the treatment of hepatic failure; however, it is assumed that liver failure can alter the permeability of the skin and drug absorption. The clinical relevance of this, however, has not been determined 17 , Although pharmacokinetics of phenyl pyridines such as fentanyl, sufentanil and remifentanil is not affected in patients with liver failure, all of them can cause hepatic encephalopathy, particularly in patients with severe liver failure In patients with liver cirrhosis who undergo general anesthesia, fentanyl pharmacokinetics is not initially affected Most opioids are metabolized in liver through glucuronidation, but fentanyl is cleared by the hydrolysis of ester Some experts recommend fentanyl as a proper opioid for liver failure, but that is an entirely empirical judgment 60 , 61 , It contains all pharmacokinetic properties of this class of drugs analgesic, hemodynamic stability, respiratory depression, muscle tightness, itching, nausea and vomiting 11 , 42 , It is available as an intravenous drug form. Unlike other opioids, Remifentanil has no hepatic metabolism; it is metabolized by nonspecific tissue and plasma esterase and is broken to remifentanil 42 , Since histamine is released during the drug administration, an antihistamine drug should be administered simultaneously 2 , Although pharmacokinetics of phenyl pyridines such as fentanyl, sufentanil and remifentanil are not affected in patients with liver failure, all of them can cause hepatic encephalopathy, particularly in patients with severe liver failure In a report about a year-old female with underlying liver and kidney problems who underwent hepatectomy, it was found that remifentanil can be quite effective and used safely In patients with severe impairment of the hepatic metabolism, remifentanil remains unchanged and does not cause hepatic encephalopathy. Therefore, it could be a good post-operative analgesic 64 , Remifentanil can be used for patients with severe liver dysfunction 66 , Sufentanil is a synthetic opioid that is 5- to times more potent than fentanyl. It is available in IV, IM, subcutaneous sub-Q , epidural, intrathecal, and transdermal patch in clinical trials drug forms. This drug is metabolized in the liver 2 , 11 , 13 , The half-life of an intravenous single dose of sufentanil does not change in liver failure Although pharmacokinetics of phenyl pyridines such as fentanyl, sufentanil and remifentanil are not affected in patients with liver failure, all of them can cause hepatic encephalopathy, particularly in patients with severe liver failure 31 , Sufentanil should be cautiously utilized in patients with hepatic insufficiency, similar to fentanyl and alfentanil This is also true regarding the continuous consumption of its infusion in the ICU 61 , Sufentanil can have a similar effect in a single dose on patients with uncomplicated liver cirrhosis and patients with normal liver function 67 , Alfentanil has a short-term effect, synthetic opioid fentanyl is 4 times faster than fentanyl. It is available as an intravenous medicinal form. Alfentanil is metabolized in the liver 32 , In patients with mild to moderate cirrhosis, the miosis created by alfentanil can be an alternative measure of the pharmacokinetic alfentanil In children with cholestatic liver disease, alfentanil can be easily used as an analgesic and the dose is similar to normal people and should not be changed A lower dose of this drug must be administrated to patients with chronic liver failure due to the reduced clearance of alfentanil and its concentration in the blood 33 , 61 , In patients with liver disease who need the pain medication relief, caution should be made in the administration of opioid analgesics. The correct dose of drug is the one which relieves the pain and has fewer adverse drug reactions 13 , As a general rule, it is necessary to use low doses of medication at regular intervals according to the signs of drug accumulation. Pain management in patients with liver problems has always been a challenge because of the effects of drugs, especially opioids 14 , Opioids should be used cautiously since it causes analgesia, sedation, constipation and sudden encephalopathy in patients with liver failure On the other hand, pain management in patients with cirrhosis is a difficult clinical challenge for health care providers 61 , Safely relieving the symptoms of pain is one of the tasks of health care providers. Moreover, it is believed that these precautions should be made by all health care providers involved in the treatment. Although it is recommended that opioids be used with caution, the fear of sudden encephalopathy and the sedative effects of these drugs are facts. The appropriate management of pain therapy in patients with liver failure who are candidates for liver transplantation is important in order to improve the performance and quality of life for this group of patients. For the patients with hepatic insufficiency who are not candidates for liver transplantation, palliative treatment is sometimes necessary and some opioids can be used 13 , Opiates can be safely used to reduce pain and distress even in patients with advanced liver disease, advanced kidney disease, lung disease, and heart disease, as these drugs are preferred to NSAID and other pain relief medications 14 , In various methods, low doses of opioids such as fentanyl are routinely used intravenously with a short half-life , oral or intravenous hydromorphone is used to relieve pain, and the researchers believe that these methods can be safe. Since clearance of these drugs is decreased in patients with hepatic insufficiency, the initial dose should be reduced while the intervals between doses increased, and in some cases there will be a need for continuous visits and control of vital signs. The adverse drug reactions of opioids can be reversed by naloxone 64 , The model for end-stage liver disease MELD. Anesthesiology and Pain Medicine. Circulatory changes in chronic liver disease. Am J Med. Harrison principle of internal medicine. Hoofnagle J. Autonomic dysfunction in end-stage liver disease manifested as defecation syncope: impact of orthotopic liver transplantation. Liver Transpl Surg. De Wolf AM. Int Anesthesiol Clin. Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med. Njoku DB. Drug-induced hepatotoxicity: metabolic, genetic and immunological basis. Int J Mol Sci. Review article: prescribing medications in patients with cirrhosis—a practical guide. AP and t. Acute-on-chronic liver failure: a review. Ther Clin Risk Manag. Pharmacokinetics of opioids in liver disease. Clin Pharmacokinet. Safe use of opioids to manage pain in patients with cirrhosis. Mayo Clin Proc. Therapeutic approaches for renal colic in the emergency department: a review article. Anesthesiology and pain medicine. Chandok N, Watt KD. Pain management in the cirrhotic patient: the clinical challenge. Rhee C, Broadbent AM. Palliation and liver failure: palliative medications dosage guidelines. J Palliat Med. Altered morphine glucuronide and bile acid disposition in patients with nonalcoholic steatohepatitis. Journal of Pharmacology and Experimental Therapeutics. Transplantation Proceedings. Gan To Kagaku Ryoho. Use of hydromorphone Dilaudid and morphine for patients with hepatic and renal impairment. Am J Ther. Kim TW, Harbott M. The use of caudal morphine for pediatric liver transplantation. Anesth Analg. Pharmacokinetics of controlled release morphine MST in patients with liver cirrhosis. Br J Anaesth. The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Br J Clin Pharmacol. Hepatic extraction of morphine is impaired in cirrhosis. Eur J Clin Pharmacol. Pharmacokinetics of unchanged morphine in normal and cirrhotic subjects. Normal metabolism of morphine in cirrhosis. The therapeutic use of analgesics in patients with liver cirrhosis: a literature review and evidence-based recommendations. Opioid-paracetamol prescription patterns and liver dysfunction: a retrospective cohort study in a population served by a US health benefits organization. Drug Saf. Analgesics in patients with hepatic impairment: pharmacology and clinical implications. Katzung BG, Antony J. Basic and Clinical Pharmacology. New York: McGraw-Hill; Liver biopsies in patients with lysosomal storage disease: experience with effective sedation. Indian J Pediatr. Central nervous system toxicity associated with meperidine use in hepatic disease. Presystemic metabolism of meperidine to normeperidine in normal and cirrhotic subjects. Clin Pharmacol Ther. Analgesia for the cirrhotic patient: a literature review and recommendations. J Gastroenterol Hepatol. Adv Emerg Nurs J. Murphy EJ. Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesth Intensive Care. Drug Alcohol Depend. Available from: www. Toxicologic Emergencies. Fatal hepatic failure following accidental tramadol overdose. Forensic Sci Int. Pharmacokinetics of oral tramadol in patients with liver cancer. J Opioid Manag. Acute liver and renal failure during treatment with buprenorphine at therapeutic dose. Digestive and Liver Disease. Postoperative pain relief after hepatic resection in cirrhotic patients: the efficacy of a single small dose of ketamine plus morphine epidurally. Donaher PA, Welsh C. Managing opioid addiction with buprenorphine. Am Fam Physician. Buprenorphine-naloxone treatment in opioid dependence and risk of liver enzyme elevation: Results from a month observational study. Am J Addict. Ann Pharmacother. High dose of buprenorphine in terminally ill patient with liver failure: Efficacy and tolerability. Transdermal buprenorphine may be effective in the treatment of pruritus in primary biliary cirrhosis. J Pain Symptom Manage. Am J Drug Alcohol Abuse. Buprenorphine Temgesic can be used in hepatic porphyria. Ann Fr Anesth Reanim. Buprenorphine and hepatic pruritus. Br J Clin Pract. Enhanced bioavailability of pethidine and pentazocine in patients with cirrhosis of the liver. Aust N Z J Med. Dextropropoxyphene induced hepatotoxicity: a report of nine cases. Journal of Hepatology. Fentanyl pharmacokinetics in anaesthetized patients with cirrhosis. Jin S. J, Jung J. Y, Noh M. H, Lee S. H, Lee E. K, Choi B. M, et al. Anesth Pain Med. Servin FS. Remifentanil: an update. Curr Opin Anaesthesiol. Dershwitz M, Rosow CE. The pharmacokinetics and pharmacodynamics of remifentanil in volunteers with severe hepatic or renal dysfunction. Use of remifentanil in a patient with chronic hepatic failure. Wilhelm W, Kreuer S. The place for short-acting opioids: special emphasis on remifentanil. Critical Care. Sufentanil pharmacokinetics in patients with cirrhosis. Alfentanil-induced miosis as a surrogate measure of alfentanil pharmacokinetics in patients with mild and moderate liver cirrhosis. Effects of cholestatic hepatic disease and chronic renal failure on alfentanil pharmacokinetics in children. Fairbank E. Opioid Use in LiverFailure. Available from: efairbank swh. Hypothermia after cardiac arrest as a novel approach to increase survival in cardiopulmonary cerebral resuscitation: a review. Iran Red Crescent Med J. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urology. Sensitivity of palm print, modified mallampati score and rule in prediction of difficult intubation. Int J Prev Med. We use cookies to provide you with the best possible experience. They also allow us to analyze user behavior in order to constantly improve the website for you. Hepatitis Monthly: Vol. Abstract Context: 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. Evidence Acquisition: This review was written by referring to research literature including 70 articles and four textbooks published from to 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 P 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. Context The liver is one of the most important organs of the body since it plays important roles in several functions 1 , 2. Hepatic Metabolism of Opioids There are two different types of chemical reactions in the liver metabolism of drugs. Evidence Acquisition 2. Data Sources The present study is a systematic review. Study Selection Searches were performed on keywords such as opioid pain relievers opioids , hepatic failure, acute and chronic opioid adverse drug reactions, drug-induced liver injury DILI and other similar keywords. Data Extraction and Quality Assessment Two independent authors managed and ran the data extraction and quality assessment. Results In the current study, after the initial search and based on the titles found, a total of 93 potentially relevant papers were selected. Table 1. Drugs Part 1. Table 2. Drugs Part 2. Table 3. Drugs Part 3. Table 4. Drugs Part 4. Drugs Year Pentazocine Tegeder et al. Table 5. Drug Part 5. Table 6. Drugs Part 6. Drugs Year Sufentanil Tegeder et al. References 1. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4. Leave a comment here:. Cookie Setting We use cookies to provide you with the best possible experience.

Socio-demographic characteristics of the addicted inmates of Qom and Tabriz prisons in Iran

Buy Heroin Tabriz

Official websites use. Share sensitive information only on official, secure websites. There is cultural support for opium in Iran, and also there is cultural tolerance for tobacco smoking, especially as water pipe smoking, in Iranian families. Alcohol, opium, and cannabis are the most frequently used illicit drugs, but there are new emerging problems with anabolic steroids, ecstasy, and stimulant substances, such as crystal methamphetamine. There is serious drug abuse problem among Iranian high school students. It could be due to role-modeling by parents — mainly fathers — and also cultural tolerance of some substances. Early onset of tobacco smoking, with a daily use rate between 4. Use of all types of drugs, except prescription drugs, is more prevalent among boys. Alcohol is the most frequently abused substance, with a lifetime rate of at least 9. Lifetime rates of opiate use — mostly opium — were between 1. As drug abuse is a frequent problem among Iranian high school students, it is necessary to design and implement drug prevention programs to protect them. Such programs, including life skills training and drug education, have been operating in recent years for Iranian students from kindergarten to the university level. There is a long history of opium use in Iran. Opium use as a recreational substance has been recorded for more than four centuries. One of the first scientific descriptions of opium use in Iran was written by Dr. Jacob Eduard Polak — , a Jewish Austrian physician who worked in Iran between and 1 among teachers of the first Iranian medical school. It is not forbidden and every Iranian who can afford its cost uses it daily. Adolescence is a particularly vulnerable period for initiation of drug use 2 , and younger age at first drug use significantly increases the likelihood of more serious drug problems 3. Iran has the highest rate of abuse of opiates in the world 6 , 7. In recent years, there has been increased use of heroin, crystal methamphetamine, and ecstasy. There is no direct standard survey for finding the prevalence of drug abuse in Iran. But there are surveys that help in estimating the drug use situation. The last nationwide survey of drug use in Iran, carried out in , was a rapid situational assessment RSA This study is based on interviews with drug abusers in treatment centers, the justice department system and prisons, as well as interviews with key informants. It is not a household survey and, therefore, interpretation of the data should consider their limitations. Unpublished data from this survey 8 showed that there are 1. Although traditional drugs of abuse in Iran are opium and cannabis, in recent years there has been more use of heroin, crystal methamphetamine, and ecstasy. In RSA , it is shown that The use of drugs by parents is a particular concern, as parental drug use is a risk factor for offspring Evidence has shown that family environment and mental health are inter-related in opiate addicts Spousal 13 and child abuse 14 are more frequent in drug abusers than the general population. Regarding age in this study, Main substances of use were opium all forms in Comparing these results with a previous RSA in , which found that the main substance was opium at This is the first time in the history of drug use in Iran that heroin use is more prevalent than opium use. Heroin is usually smoked, sniffed, or injected. In RSA , the usual way of drug use for Although the average Iranian drug-dependent person is likely to be married and employed, the average Iranian injection drug user is more likely to be unemployed and single or divorced RSA has shown that, compared with previous reports, there has been a decrease in cannabis use and an increase in crystal methamphetamine use as the main substance used among the total population of drug abusers. Crystal methamphetamine was the main substance in 3. In this article, we review published papers in international and domestic journals as well as existing unpublished data describing substance use by young people in Iran. There are four main studies on drug abuse in high school students in different parts of the country. Drug abuse in these studies is considered to be the use of any illicit substances, including alcohol, cannabis, opiates opium and heroin , ecstasy, and methamphetamine. Information about tobacco use is also included in these studies. In , Ziaaddini et al. This city is near the eastern border with Pakistan and Afghanistan and has a traditionally high rate of drug abuse. In this study Kerman Study , the rate for lifetime use of drugs in high school students was Also In another study, conducted in in Zanjan, a city in the northwest of the country Zanjan study , lifetime prevalence of drug abuse in high school students was The rate was significantly higher among boys than girls In this study, poor school performance, depression, and cigarette-smoking parents were associated with higher rates of drug abuse. Ahamdi and Hasani 21 in Shiraz — a large city located in the southern part of the country Shiraz study — have found rates of lifetime use and current use of drugs to be significantly higher among boys than among girls. In this study, pleasure seeking, modeling, and tension release were the most common reasons for drug use. In a study in Tabriz — another city in the northeast Tabriz study — among male high school students, There are two usual ways of using tobacco among Iranian adolescents: cigarette smoking and a water pipe. The latter has been a common practice for centuries, mostly in the Middle East, but its use appears to be widespread among high school students even in the United States 23 and European countries In the Zanjan study 20 , a history of water pipe tobacco smoking in high school students was twice that of cigarette smoking In Iran, like in most of the Middle Eastern and Islamic countries, there are traditional taboos and social behavioral limitations for girls. For example, in the Zanjan study 20 , lifetime history of cigarette smoking was more than three times higher for boys than for girls, but the sex difference for water pipe smoking was less see Table 1. It seems that smoking a water pipe is more tolerable in families compared with cigarettes, and its use does not bring the same degree of negative stigma for girls. One study in Lebanon has also shown a sex difference in cigarette smoking but not for water pipe smoking Smoking a water pipe is a socially acceptable practice for adolescents in Iran 20 , other Middle East countries 25 — 28 , and in western countries, even for athletes, who are traditionally considered at low risk for tobacco use 29 , and it appears acceptable for both boys and girls. Regular daily cigarette smoking was more prevalent than water pipe smoking The prevalence of daily smoking ranged from 4. There is also a study of middle school students grade 7 , with a mean age of 13 years, which shows 7. Although the purchasing of cigarettes is not allowed in Iran for people under the age of 18, clearly for many youth, the age of smoking onset is much younger. Age of smoking onset was Also there are studies that have shown an association between smoking and mental 35 and physical disorders In Iran, alcohol is considered an illicit drug and its use is banned for all age groups. Unfortunately this situation does not prevent its use among adolescents, and, in fact, alcohol is the most common illicit substance among Iranian high school students, especially among boys 20 — Two studies in Kerman have shown lifetime prevalences for alcohol between In RSA , in a cross-country study, the mean age of first alcohol use was In a study among high-risk grade 11students in Tehran, The rate of alcohol use was similar to the rate for tobacco smoking and much more than the rate for any other substance. In the Zanjan study, the lifetime history of alcohol use was 9. The rate was significantly lower in girls 3. In this study, 16 boys out of 6. Although alcohol consumption is illegal in Iran it is banned by Islam and unlike many other countries there is no alcohol advertising 39 to promote use by youth , it is customary to have alcohol at various parties and ceremonies. In the Kerman study, It seems that there is a tolerant atmosphere in these situations even for adolescents regarding alcohol use. In the Kerman study, among those students with lifetime experience of alcohol use, Whereas there is no comparative study between Muslims and other religious groups in Iran, some studies in Iran have shown that there is more tolerance for alcohol consumption among Christians than among Muslims Iran has a long border with Afghanistan, the biggest producer of opium in the world, and opium use has a centuries-old tradition in Iran Although there is negative stigma for heroin use, there is a traditional supporting culture for opium. In a household survey of people aged 15 and over, As Agahi and Spencer reported nearly three decades ago, the problem for Iranian adolescents is exposure to role models of drug abuse; such models are more likely to be an adult family member than an adolescent peer, a reversal of what is usually found in western countries Modeling is the second most common reason for drug use in the offspring of opium dependents Lifetime prevalence of opium and heroin use was 1. In this study, none of the high school students were current opiate users Ahmadi et al. In Kerman study, one fourth to one third of high school students who had lifetime experience of opiate use — opium or heroin — were daily users of it Although there is no cross-country study of youth drug use, it seems that the southeastern parts of the country, which border Pakistan and Afghanistan, show larger numbers of opioid users. In all studies, the rate of heroin use was far lower than the rate of opium use Table 2. Studies on the epidemiology of drug use in Iran show that all drugs are used more often by males than females 19 — 22 , The situation is the same for high school students. The Zanjan study reported that the lifetime prevalences of opium and heroin use in male students were 3. None of female students had a lifetime history of opium or heroin use. In the Kerman study, among high school students, lifetime history of opium use rates were The numbers for heroin use were 5. Cannabis is used in Iran in both the form of grass marijuana and hashish. Studies have reported lifetime history of cannabis use at 0. The Zanjan study showed a 2. The rate was 5. In the Kerman study, lifetime history of cannabis use was 8. Prevalence of daily cannabis use in this study was reported as 3. There is a lack of studies on methamphetamine or cocaine. Although the four most common substances used by high school students in Iran are tobacco, alcohol, cannabis and opium 19 — 22 , there have been some studies in recent years about other substances. Rates of lifetime and daily use of prescription sedatives mostly benzodiazepines were 2. In the Zanjan study, lifetime use rates for prescription narcotic drugs, including codeine and tramadol, were 9. Codeine is usually supplied and consumed as codeine-containing pain-killer tablets that mostly also contain acetaminophen. Both acetaminophen-codeine tablets and tramadol tablets are prescription drugs, but some pharmacies sell them without a prescription. Actually there are reports that acetaminophen-codeine tablets are one of the best selling drugs in Iran. Significant rates of use of prescription drugs by girls, who report very low rates of illicit drug use, suggest that prescription drug use is less stigmatized than illicit drug use. It is also an important concern that, like in other countries 47 , many users of these tablets are also abusing other substances. In the Zanjan study, the rate of lifetime and daily use of anabolic steroids was 6. Lifetime anabolic use was Shakeri et al. Sepehri et al. The prevalence of ecstasy use among 15—year-old people in Tehran was In another study on ecstasy use among high school students in Lahijan in the north of Iran, 2. The rate in boys 3. There is also one study that has shown that a large number of ecstasy users were high school or university students There are a large number of studies that have shown that various mental health disorders can be concordant with drug abuse problems. Zanganeh 53 stated that social isolation and lower socio-economic status can be associated with psychiatric disorders, including drug abuse. Emami et al. The frequency of such problems was higher in girls than in boys. Alcohol and drug use can be associated with high risk sexual behavior 55 and other risk-taking behaviors in Iranian adolescents 56 and can be a risk factor for HIV transmission. There is evidence that substance-using adolescents in Iran 19 and other countries 57 have greater psychological dysfunction. Childhood and family adverse events are also associated with more drug abuse problems in Iran and other countries 58 — Drug abuse is also reported in association with impulsivity 30 and delinquent antisocial behaviors in Iran 22 as well as other countries 61 — Adolescent drug use in Iran shows co-morbidity with mental disorders, especially depression and anxiety disorders. The Zanjan study, using the Beck depression inventory, found that Pathological anxiety was also more prevalent in high school students with a history of drug abuse, but it did not reach the significance threshold. Drug abuse also has been shown to be associated with academic problems There are very important drug problems among youth in Iran. As drug abuse and addiction are biopsychosocial problems, we should keep in mind relevant cultural factors and co-morbidities. It seems that parents and schools fail to play a significant role in primary prevention in Iran, and families in which the father is a drug user pose a very significant risk factor. Nearly half of drug-using university students in one study had been familiar with drugs since their adolescence Considering this fact and also the rule that earlier first drug use leads to more drug problems later in life, it is necessary to initiate preventive programs as early as possible. Adaptive motivational structure is important 67 , and it has been shown that behavioral control can help Iranian adolescents to resist drugs There are youth and family counseling programs in Iran that can be effective for behavior problems and, as DeJong et al. Although in Iran there are not yet comprehensive family-based or school-based drug prevention programs as in developed countries, some recent programs appear promising. Such programs include drug related life-skills training in kindergartens and primary schools, life skills training and drug education packages in high schools and universities, and parenting skills training programs promoting family bonding. Papers of particular interest, published within the annual period of review, have been highlighted as:. As a library, NLM provides access to scientific literature. Curr Opin Psychiatry. Published in final edited form as: Curr Opin Psychiatry. Find articles by Saeed Momtazi. Find articles by Richard A Rawson. PMC Copyright notice. The publisher's version of this article is available at Curr Opin Psychiatry. Cigarette Water pipe Girls Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Ziaaddini et al. Mohammadpoorasl et al. Nakhaee et al. Momtazi et al.

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