Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The liver is the major site of biotransformation for most opioids. Thus, the disposition of these drugs may be affected in patients with liver insufficiency. The major metabolic pathway for most opioids is oxidation. The exceptions are morphine and buprenorphine, which primarily undergo glucuronidation, and remifentanil, which is cleared by ester hydrolysis. Oxidation of opioids is reduced in patients with hepatic cirrhosis, resulting in decreased drug clearance [for pethidine (meperidine), dextropropoxyphene, pentazocine, tramadol and alfentanil] and/or increased oral bioavailability caused by a reduced first-pass metabolism (for pethidine, dextropropoxyphene, pentazocine and dihydrocodeine). Although glucuronidation is thought to be less affected in liver cirrhosis, and clearance of morphine was found to be decreased and oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in the body, especially with repeated administration. Lower doses or longer administration intervals should be used to remedy this risk. Special risks are known for pethidine, with the potential for the accumulation of norpethidine, a metabolite that can cause seizures, and for dextropropoxyphene, for which several cases of hepatotoxicity have been reported. On the other hand, the analgesic activity of codeine and tilidine depends on transformation into the active metabolites, morphine and nortilidine, respectively. If metabolism is decreased in patients with chronic liver disease, the analgesic action of these drugs may be compromised. Finally, the disposition of a few opioids, such as fentanyl, sufentanil and remifentanil, appears to be unaffected in liver disease.
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PMID:Pharmacokinetics of opioids in liver disease. 1045 81

Cigarette dependence is recognised as a life-threatening disorder which can be treated by behavioural support and/or medication. Bupropion hydrochloride sustained-release (Zyban trade mark, GlaxoSmithKline) is licensed in many countries including the US, Canada, UK, Australia and continental Europe to aid smoking cessation. The usual recommended dose is 150 mg b.i.d. taken for 7 - 14 days prior to the quit date, and then 6 - 8 weeks afterwards (figures vary across countries). Evidence from seven double-blind, placebo-controlled, randomised trials shows that it improves success at staying off cigarettes for at least 12 months by 9 - 10 percentage points. Taking into account estimates of subsequent cessation and relapse patterns in treated and untreated smokers, and the improvement in life-expectancy of smokers who manage to stop, the estimated cost/life/year saved from an episode of use of the medication is approximately UK pound 1000 or US$1500. Bupropion has CNS stimulant properties; the common side effects are dry mouth and sleep disturbance. Rare but serious side effects are anaphylactic/hypersensitivity reaction and seizure (both estimated at 1 in a 1000). The drug is contraindicated in patients with hypersensitivity to the drug or its metabolites, any seizure disorder, eating disorder, severe hepatic cirrhosis, history of bipolar disorder or in patients taking monoamine oxidase inhibitors. Extreme caution is advised where there are any predisposing factors that may reduce the seizure threshold. Bupropion sustained-release and nicotine replacement therapies are both considered as first-line treatments to aid smoking cessation. Ideally patients should also enrol in a structured behavioural support programme to boost their chances of success.
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PMID:Bupropion SR for smoking cessation. 1266 16

In patients with renal or hepatic failure, the pharmacokinetics of opioids may be affected in several ways, leading to the necessity to correct the dose. The liver is the major site for biotransformation of most opioids. The major metabolic pathway is oxidation. Exceptions to this are morphine and buprenorphine, which undergo primarily glucuronidation, and remifentanil which is cleared by esther hydrolysis. The hydrophilic metabolites are predominantly excreted by the kidneys and may accumulate in patients with renal insufficiency. Some metabolites such as morphine-6-glucuronide (M6G) or normeperidine are active opioid agonists. With high concentrations they may cause narcotic effects or respiratory depression. In addition, special risks are known for normepridine that has been shown to exert neurotoxic effects with the risk of seizures. Few cases of respiratory depression following the administration of codeine, dihydrocodeine and tramdol have been reported. The elimination half-life of these drugs was prolonged. Lastly, the disposition of methadone, buprenorphine, fentanyl, sufentanyl and remifentanil appears to be unaffected in renal failure. In patients with hepatic cirrhosis it has been shown that oxidation of opioids is reduced, resulting in a decreased drug clearance (meperidine, propoxyphene, pentazocine, tramadol and alfentanil) and increased oral bioavailability due to reduced first-pass metabolism (meperidine, propoxyphene, pentazocine, dihydrocodeine). Although glucuronidation is thought to be less affected in liver cirrhosis, the clearance of morphine was found to be decreased and its oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in the body, especially with repeated administrations. As for patients with renal failure, special risks are known for meperidine with potential accumulation 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 transformation into the active metabolites, morphine and nortilidine. In the case of reduced metabolism in chronic liver disease, the analgesic action of these drugs may be compromised. Lastly, the disposition of a few opioids, such as fentanyl, sufentanil, and remifentanil, appears to be unaffected in liver disease.
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PMID:[Therapy with opioids in liver or renal failure]. 1279 31

A 6-yr-old male patient underwent live related left lateral segment liver transplant for cryptogenic cirrhosis with portal hypertension. One month after the liver transplant the patient had an isolated liver transaminases increase. He was posted for percutaneous liver biopsy for suspected graft rejection under general anesthesia. The patient was administered ketamine 7 mg/kg along with glycopyrrolate 0.01 mg/kg IM in the preoperative area. He developed generalized tonic clonic seizures just before the biopsy and was treated with IV midazolam 1 mg and thiopental 60 mg. Percutaneous liver biopsy was obtained once the convulsions subsided. Both ketamine and cyclosporine have been implicated as having proconvulsant properties and may have been responsible for the seizures in our patient. Our experience prompted us to suggest that ketamine in a patient immunosuppressed with cyclosporine may not be safe and that alternative anesthetics may need to be considered for such procedures.
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PMID:Is ketamine a safe anesthetic for percutaneous liver biopsy in a liver transplant recipient immunosuppressed with cyclosporine? 1561 57

Metronidazole is a 5-nitroimidazole compound known as an antimicrobial agent widely used for the treatment of protozoal infection, anaerobic infection, Helicobacter pylori infection and hepatic encephalopathy. It may produce a number of neurologic side effects including peripheral neuropathy, seizure, encephalopathy, ataxic gait and dysarthritic speech. There have been ten or more reports of metronidazole-induced encephalopathy in the literatures including a few reports of brain imaging changes by magnetic resonance images (MRI). However, none of the case of metronidazole-induced encephalopathy in patients with hepatic encephalopathy has been reported yet. Recently, we experienced two cases of metronidazole-induced encephalopathy in patients with liver cirrhosis caused by chronic hepatitis B, which were diagnosed by brain MRI and MR spectroscopy. In this report, we present 2 cases of metronidazole-induced encephalopathy with MR imaging and MR spectroscopic changes including follow-up imaging performed after the discontinuation of the metronidazole with a review of the literatures.
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PMID:[Two cases of metronidazole-induced encephalopathy]. 1577 47

The clinical presentation of acute liver failure and hepatic encephalopathy (HE) in patients with cirrhosis differs significantly. The most serious neurological complication of acute liver failure is the development of devastating brain oedema. Therefore, intracranial pressure monitoring is urgently needed in these patients. Brain oedema is amplified by hypoglycemia, hypoxia and seizures, which are also frequent complications of acute liver failure. Therefore, these parameters must also be monitored. In contrast to acute liver failure in which cerebral dysfunction progresses rapidly, cognitive decline may be clinically undetectable for a long time in cirrhotic patients, until clinically overt symptoms such as psychomotor slowing, disorientation, confusion, extrapyramidal and cerebellar symptoms or a decrease in consciousness occur. Clinically, overt HE is preceded by minimal alterations of cerebral function that can only be detected by neuropsychological or neurophysiological measures, but which nevertheless interfere with the patient's daily living. Rapidly progressing spastic paraparesis (hepatic myelopathy) is a rare complication of cirrhosis. In contrast to HE, it does not respond to blood ammonia lowering therapies but must be considered as an indication for urgent liver transplantation. Cognitive dysfunction has recently been detected in hepatitis C virus (HCV)-infected patients with normal liver function. The patients presented with severe fatigue, cognitive dysfunction and mood disorders. Alterations in brain metabolites, as detected by magnetic resonance spectroscopy, indicated central nervous system alteration in these patients. In contrast to patients with HE, HCV-infected patients did not show motor symptoms or deficits in visual perception, but considerable deficits in attention and concentration ability.
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PMID:Neurological and neuropsychiatric syndromes associated with liver disease. 1625 35

Alpers syndrome was not clearly defined until the link between brain and liver disease was described. Alpers syndrome can now be clearly established as a disorder of oxidative metabolism related to mitochondrial dysfunction, and in most instances with an autosomal mode of inheritance. The symptoms and signs are discussed. The illness occurs in the first years of life with the sudden onset of intractable seizures associated with developmental delay, hypotonia, ataxia, cortical blindness, and hepatic failure, and death occurs within a short time. Treating the seizures with valproic acid can cause the rapid onset of liver failure and must be avoided. To establish a definite diagnosis, liver and muscle biopsies may be needed. The former shows bile duct proliferation with the evidence of cirrhosis, and the latter may support the involvement of the mitochondrial respiratory chain if there are ragged-red fibres. Genetic studies can show an association with mitochondrial DNA depletion and mutations in the polymerase gene. Cytochrome c oxidase deficiency has been demonstrated in some patients. Useful diagnostic tests include liver function tests, lactic acid levels in the blood and cerebrospinal fluid, electroencephalograms, computed tomography, and magnetic resonance imaging. The differential diagnosis will be from other forms of neuronal degeneration and disorders of mitochondrial function. There is no specific treatment, which must await further research into causes.
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PMID:Alpers syndrome: progressive neuronal degeneration of children with liver disease. 1710 92

We describe the first case of sirolimus-induced drug fever in a female liver transplant recipient, with a history of hepatitis C-induced end-stage liver cirrhosis in 1999. In 2005, six years after transplantation, she developed calcineurin inhibitor-induced renal function impairment. Immunosuppression was switched from tacrolimus to sirolimus. Two days after the intake of sirolimus, she developed daily fever spikes, but no infectious focus was found. Antibiotic therapy had no influence on the fever. After fourteen days, sirolimus was switched back to tacrolimus and the fever disappeared. In history, the patient developed ciclosporin-induced generalized seizures eleven days after liver transplantation, followed by the development of a motoric speech disorder. Magnetic resonance imaging (MRI) findings were consistent with leucoencephalopathy, therefore immunosuppressive therapy was changed from ciclosporin to tacrolimus and the neurologic symptoms improved significantly. Our case is the first reported case of sirolimus-induced drug fever. In addition, the patient showed the rare occurrence of ciclosporin-induced leukencephalopathy with seizures.
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PMID:Sirolimus-induced drug fever and ciclosporin-induced leukencephalopathia with seizures in one liver transplant recipient. 1802 6

Leukoencephalopathy with cerebral calcifications and cysts (LCC) was first reported in children who developed cognitive decline and variable extrapyramidal, cerebellar, and pyramidal signs, with or without seizures. Leukoencephalopathy with cerebral calcifications and cysts is characterized by progressive formation of brain cysts that can generate a mass effect simulating a neoplasm. Retinal changes that overlap with Coats disease, a microangiopathy with retinal telangiectasias and exudates, may also occur. We and others have reported LCC cases in adults. Neuroimaging shows diffuse leukoencephalopathy, multifocal calcifications especially of deep gray and white matter, multifocal enhancement, and variably sized cysts that may require surgical decompression. Biopsies adjacent to cysts have shown angiomatous and/or severely hyalinized blood vessels surrounded by myelin loss and gliosis, calcifications, and Rosenthal fibers. We report 2 additional adult-onset cases of LCC. Case 1 is a 40-year-old man who developed neurological symptoms and cirrhosis and died of acute gastrointestinal bleeding; he had numerous retinal microinfarcts at autopsy. Case 2 is a 55-year-old woman who was found by chance to have LCC; one and a half years later, her course remains benign. These cases expand the spectrum of adult-onset LCC, the etiology of which is unknown.
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PMID:Adult cases of leukoencephalopathy, cerebral calcifications, and cysts: expanding the spectrum of the disorder. 1928 8

The objective of this study is to review the presentation, outcome and aetiology of central pontine and extrapontine myelinolysis (CPEPM) in a tertiary hospital center. The study method is a case series and included identification of patients from University of Montreal Health Centre archives database (1995-2007). All diagnoses were confirmed by neuroimaging or brain autopsy. Twelve individuals (25-66 years old) presented heterogeneous manifestations. Co-morbidities included diabetes insipidus (n = 2), haemodialysis (n = 1), cirrhosis (n = 3), gastroenteritis (n = 2) and potomania (n = 1). Aetiologies included rapid correction of severe hyponatremia (n = 6)/acute hypernatremia (n = 1); immediate (n = 2) or remote (n = 1 with recurrent cirrhosis) orthotopic liver transplantation (OLT) with tacrolimus-induced immunosuppression (n = 3); and chronic alcoholism (n = 4, two with hyponatremia). Four individuals died acutely. Two were lost to follow-up. Six had good motor or cerebellar recovery. Neuropsychological evaluations (n = 5/6) revealed a subcortical/frontal dysfunction. Cognitive impairment represented the major remaining lasting sequel (n = 4). Three salient clinical syndromes were observed: (1) predominant cerebellar presentation in individuals with alcoholism (n = 4); (2) significant alteration of consciousness at presentation (n = 4), all resulting in death (OLT, n = 3); (3) seizures persisting after natremia correction (n = 2). Clinical presentation of CPEPM is heterogeneous and can even include seizures. Cognitive impairment should be screened as it is a significant factor limiting return to normal life.
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PMID:Central pontine and extrapontine myelinolysis: from epileptic and other manifestations to cognitive prognosis. 2014 34


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