psychiatric and psychotropic and benzodiazepines medicines and side effects investigation reports article outcomepsychiatric medicine and fatty liver diseasereported. Nefazodone Trazodone oct 2019 open for public to read open to public to read oct 2019
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psychiatric and psychotropic and benzodiazepines medicines and side effects investigation reports article outcomepsychiatric medicine and fatty liver diseasereported. Nefazodone Trazodone oct 2019 open for public to read open to public to read oct 2019
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psychiatric and psychotropic and benzodiazepines medicines and side effects investigation reports article outcome open to public to read oct 2019
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psychiatric and psychotropic and benzodiazepines medicines and side effects investigation reports article outcome open to public to read oct 2019
psychiatric and psychotropic and benzodiazepines medicines and side effects investigation reports article outcome open to public to read oct 2019
law psychiatric and psychotropic and benzodiazepines medicines and side effects investigation reports article outcome open to public to read oct 2019
Submitted by Unregistered User on Wed, 10/16/2019 - 17:42
Compared to other sedative-hypnotics, visits to the hospital involving benzodiazepines had a 66% greater odds of a serious adverse health outcome. This included hospitalization, patient transfer, or death, and visits involving a combination of benzodiazepines and non-benzodiapine receptor agonists had almost four-times increased odds of a serious health outcome.[28]
Cognitive effects[edit]
The short-term use of benzodiazepines adversely affects multiple areas of cognition, the most notable one being that it interferes with the formation and consolidation of memories of new material and may induce complete anterograde amnesia.[75] However, researchers hold contrary opinions regarding the effects of long-term administration
(While the definitive studies are lacking, the former view received support from a 2004 meta-analysis of 13 small studies.[103][104] This meta-analysis found that long-term use of benzodiazepines was associated with moderate to large adverse effects on all areas of cognition, with visuospatial memory being the most commonly detected impairment. Some of the other impairments reported were decreased IQ, visiomotor coordination, information processing, verbal learning and concentration. The authors of the meta-analysis[104] and a later reviewer[103] noted that the applicability of this meta-analysis is limited because the subjects were taken mostly from withdrawal clinics; the coexisting drug, alcohol use, and psychiatric disorders were not defined; and several of the included studies conducted the cognitive measurements during the withdrawal period.)
Long-term worsening of psychiatric symptoms[edit]
While benzodiazepines may have short-term benefits for anxiety, sleep and agitation in some patients, long-term (i.e., greater than 2–4 weeks) use can result in a worsening of the very symptoms the medications are meant to treat.
Controversial associations[edit]
Beyond the well established link between benzodiazepines and psychomotor impairment resulting in motor vehicle accidents and falls leading to fracture; research in the 2000s and 2010s has raised the association between benzodiazepines (and Z-Drugs) and other, as of yet unproven, adverse effects including dementia, cancer, infections, pancreatitis and respiratory disease exacerbations.[138]
Many drugs, including oral contraceptives, some antibiotics, antidepressants, and antifungal agents, inhibit cytochrome enzymes in the liver. They reduce the rate of elimination of the benzodiazepines that are metabolized by CYP450, leading to possibly excessive drug accumulation and increased side-effects. I
Veterinary use[edit]
Benzodiazepines are used in veterinary practice in the treatment of various disorders and conditions. As in humans, they are used in the first-line management of seizures, status epilepticus, and tetanus, and as maintenance therapy in epilepsy (in particular, in cats).[209][210][211] They are widely used in small and large animals (including horses, swine, cattle and exotic and wild animals) for their anxiolytic and sedative effects, as pre-medication before surgery, for induction of anesthesia and as adjuncts to anesthesia.[209][212]
References
Interactions[edit]
Individual benzodiazepines may have different interactions with certain drugs. Depending on their metabolism pathway, benzodiazepines can be divided roughly into two groups.
Many drugs, including oral contraceptives, some antibiotics, antidepressants, and antifungal agents, inhibit cytochrome enzymes in the liver. They reduce the rate of elimination of the benzodiazepines that are metabolized by CYP450, leading to possibly excessive drug accumulation and increased side-effects.
Taking benzodiazepines with alcohol, opioids and other central nervous system depressants potentiates their action. This often results in increased sedation, impaired motor coordination, suppressed breathing, and other adverse effects that have potential to be lethal.[78][161] Antacids can slow down absorption of some benzodiazepines; however, this effect is marginal and inconsistent.[78
Cancer[edit]
A Meta-analysis of observational studies has determined an association between benzodiazepine use and cancer, though the risk across different agents and different cancers varied significantly.[146] Furthermore, most of these studies were unable to control for confounding variables that may have influenced the relationship such as lifestyle exposures (i.e. tobacco, alcohol). In terms of experimental basic science evidence, an analysis of carcinogenetic and genotoxicity data for various benzodiazepines has suggested a small possibility of carcinogenesis for a small number of benzodiazepines.[147] A large, properly designed randomized controlled trial with appropriate follow-up in addition to further pharmacologic/toxicologic investigation is needed to confirm these preliminary findings.
Dementia[edit]
A number of studies have drawn an association between long-term benzodiazepine use and neuro-degenerative disease, particularly Alzheimer's disease.[139] It has been determined that long-term use of benzodiazepines is associated with increased dementia risk, even after controlling for protopathic bias.[11]
Long-term worsening of psychiatric symptoms[edit]
While benzodiazepines may have short-term benefits for anxiety, sleep and agitation in some patients, long-term (i.e., greater than 2–4 weeks) use can result in a worsening of the very symptoms the medications are meant to treat. Potential explanations include exacerbating cognitive problems that are already common in anxiety disorders, causing or worsening depression and suicidality,[110][111] disrupting sleep architecture by inhibiting deep stage sleep,[112] withdrawal symptoms or rebound symptoms in between doses mimicking or exacerbating underlying anxiety or sleep disorders,[110][111] inhibiting the benefits of psychotherapy by inhibiting memory consolidation and reducing fear extinction,[113][114][115] and reducing coping with trauma/stress and increasing vulnerability to future stress.[116] Anxiety, insomnia and irritability may be temporarily exacerbated during withdrawal, but psychiatric symptoms after discontinuation are usually less than even while taking benzodiazepines.[110][117] Functioning significantly improves within 1 year of discontinuation.[110][118]
Paradoxical effects[edit]
Paradoxical reactions, such as increased seizures in epileptics,[105] aggression, violence, impulsivity, irritability and suicidal behavior sometimes occur.[8] These reactions have been explained as consequences of disinhibition and the subsequent loss of control over socially unacceptable behavior. Paradoxical reactions are rare in the general population, with an incidence rate below 1% and similar to placebo.[7][106] However, they occur with greater frequency in recreational abusers, individuals with borderline personality disorder, children, and patients on high-dosage regimes.[107][108] In these groups, impulse control problems are perhaps the most important risk factor for disinhibition; learning disabilities and neurological disorders are also significant risks. Most reports of disinhibition involve high doses of high-potency benzodiazepines.[106] Paradoxical effects may also appear after chronic use of benzodiazepines.[109]
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Submitted by Unregistered User on Fri, 10/25/2019 - 22:14
americanLiverfoundation.org Nonalcoholic Fatty Liver Disease Nonalcoholic fatty liver disease (NAFLD) is the build up of extra fat in liver cells that is not caused by alcohol. It is normal for the liver to contain some fat. However, if more than 5% – 10% percent of the liver’s weight is fat, then it is called a fatty liver (steatosis). The more severe form of NAFLD is called nonalcoholic steatohepatitis (NASH). NASH causes the liver to swell and become damaged. The Liver’s Important Role As the quick quiz illustrates, there is a critical need for the American Liver Foundation throughout the year, but especially during Liver Awareness Month, to educate the general public about the important role the liver plays and how to maintain a healthy liver. ________________________________________ The Focus on Fatty Livers Intensifies Much of the Foundation’s emphasis during October continues to point to the cause and treatment for liver diseases like hepatitis A, B and C; cirrhosis, biliary atresia and liver cancer. But the Foundation is also tapping into the heightened awareness during Liver Awareness Month to draw attention to the alarming increase in the incidence of Non-Alcoholic Fatty Liver Disease (NAFLD), which, staggeringly, affects up to 25 percent of people in the United States. As its name suggests, NAFLD is the buildup of extra fat in the liver that isn’t caused by alcohol. It’s normal for the liver to contain some fat. But if more than 5 to 10 percent of the liver’s weight is fat, then it is called a “fatty liver.” Most often, NAFLD tends to develop in people who are overweight or obese or have diabetes, high cholesterol or high triglycerides. Sedentary behavior is another major contributing factor to the onset of NAFLD. For these reasons, concern continues to grow as one in 10 children—that’s seven million children in the United States—is estimated to have fatty livers. NALFD can become even more serious. It can progress to Non-Alcoholic Steatohepatitis (NASH), which means that along with the fat, there is inflammation and damage to the liver. A swollen liver may cause scarring (cirrhosis) over time and may even lead to liver cancer or liver failure. The Facts About Non-Alcoholic Fatty Liver Disease 1. As incredible as it may seem in pure numbers,Non-alcoholic Fatty Liver Disease (NAFLD) affects up to 25% of people in the United States. 2. NAFLD is the build-up of extra fat in liver cells that isn’t caused by alcohol. It’s normal for the liver to contain some fat. However, if more than 5 to 10% of the liver’s weight is fat, then it’s called a fatty liver (steatosis). 3. Who is likely to have NAFLD? It tends to develop in people who are overweight or obese, or have diabetes, high cholesterol or high triglycerides. Rapid weight loss and poor eating habits also may lead to NAFLD. But some people develop NAFLD even if they don’t have any risk factors. 4. Serious risks are linked to NAFLD. It may cause the liver to swell (steatohepatitis).Over time, a swollen liver may cause scarring (cirrhosis)—and may even lead to liver cancer or liver failure. 5. Strangely, NAFLD often has no symptoms. But when symptoms do occur, they may include fatigue, weakness, weight loss, loss of appetite, nausea, abdominal pain, spider-like blood vessels, yellowing of the skin and eyes (jaundice), itching, fluid build-up and swelling of the legs (edema) and abdomen (ascites), and mental confusion. 6. If there are no obvious symptoms, or if the symptoms may be due to any number of illnesses, how is NAFLD diagnosed? NAFLD is initially suspected if blood tests show high levels of liver enzymes. But, to be sure, other liver diseases are first ruled out through additional tests. Often, an ultrasound is used to confirm the NAFLD diagnosis. 7. How many kinds of treatments are there for NAFLD? How about none? In reality, that there are no medical treatments yet for NAFLD. 8. So if there are no known medical ways to cure NAFLD, can it be treated and, better yet, prevented? Yes, the good news is there are steps you can take to improve the health of your liver! – Eat a healthy diet – Lose weight if you’re overweight or obese – Exercise regularly – Control your diabetes – Avoid or at least limit alcohol intake – Only take medicines that you need, and carefully follow dosing recommendations – Try to lower your cholesterol and triglycerides 9. The more severe form of NAFLD is called non-alcoholic steatohepatitis (NASH). Most people with NASH are between the ages of 40 and 60. It’s more common in women than in men. Like NAFLD, NASH often has no symptoms and people can have it for years before symptoms occur. NASH is one of the leading causes of cirrhosis in adults in the United States. Up to 25% of adults with NASH may have cirrhosis. MORE INFORMATION IF YOU HAVE NAFLD OR NASH: Learning that you have nonalcoholic fatty liver disease, you’ll have a lot of questions. The American Liver Foundation is here to help. What to know about nonalcoholic fatty liver disease Last updated Thu 16 November 2017 Last updated Thu 16 Nov 2017 By Markus MacGill Reviewed by Daniel Murrell, MD Table of contents 1. Symptoms and stages 2. Causes and risk factors 3. Diagnosis 4. Treatment and management 5. Outlook Nonalcoholic fatty liver disease happens when there is too much fat in the liver, or steatosis. The condition is also known as fatty liver. There may be no symptoms in the early stages, but continued damage to the liver can lead to a more severe condition. Some people with nonalcoholic fatty liver disease (NAFLD) will develop nonalcoholic steatohepatitis (NASH). This can develop into cirrhosis, or scarring and dysfunction of the liver. Fatty liver is often related to obesity, high blood pressure, diabetes, and high cholesterol. NAFLD or NASH is not due to high alcohol consumption. Around 10 to 46 percent of people in the United States have fatty liver but no inflammation or damage. Between 3 and 12 percent have NASH. NAFLD is the most common cause of liver disease in western countries. Fatty liver can also occur during pregnancy, and cirrhosis can result from alcohol-related liver disease, but NAFLD is considered a separate diagnosis and doctors manage it differently. Fast facts about fatty liver disease • Nonalcoholic fatty liver disease (NAFLD) can occur if too much fat builds up in the liver. • Many people have a fatty liver with no symptoms, but, in some cases, it can progress to a more serious condition. • The exact cause is unknown, but obesity appears to be a risk factor. • Following a healthy, balanced diet that is low in sugar and trans fats may help prevent or even reverse the condition. • People with any type of liver disease should avoid alcohol or consume only very small amounts. Symptoms and stages Fatty liver disease often occurs with obesity, diabetes, and chronic kidney disease. The liver is important for removing toxins from the body. If it does not work properly, various symptoms can arise. If the body produces too much fat, or if the fat is not properly metabolized, it can build up in the liver. If too much fat builds up in the liver, this can cause fatty liver. If fat continues to accumulate, this can lead, in some cases, to NASH and eventually cirrhosis and liver failure. Fatty liver At a threshold level, more than 5 to 10 percent of the liver weight is fat. If more fat than this builds up in the liver, this is known as NAFLD, or simple fatty liver. It is not healthy, but it not necessarily severe enough to cause any problems, and the person will not usually notice any symptoms. Most people with simple fatty liver will not know they have it. They may only find out after being tested for some other condition, or because other risk factors suggest that a test is a good idea. Some 30 to 40 percent of adults in the U.S. have NAFLD. However, it is hard to establish an exact figure, as there is no one set of criteria for defining NAFLD. For most people, the condition does not progress beyond this stage. Nonalcoholic steatosis If fat continues to build up and the liver becomes inflamed, NASH results. In the U.S., this affects between 3 and 12 percent of adults. Around 75 percent of patients will have swelling in the liver, or hepatomegaly. Symptoms may include: • tiredness and fatigue, including muscle weakness and a lack of energy • discomfort and possibly swelling in the upper abdomen • weight loss • low appetite • nausea The symptoms can be vague, and they can resemble those of a number of other problems. Tests may be carried out to eliminate other conditions. Scientists are unsure why some people are more likely to develop NASH. Everything you need to know about cirrhosis Cirrhosis can result if fatty liver disease progresses to a more severe stage READ NOW Cirrhosis and liver failure In time, 10 to 25 percent of people with NASH will develop scarring or fibrosis, also known as cirrhosis, and liver failure. Symptoms include: • tiredness and weakness • nausea, vomiting, and diarrhea • tarry stools • abdominal swelling and pain • a yellowing of the skin and eyes, known as jaundice • confusion, difficulty focusing, memory loss, and hallucinations • itchy skin • bleeding and bruising easily In severe cases, a liver transplant may be necessary. US Doctor: Try This If You Have Belly Fat (It's Genius) Sponsored by Active PK SEE MORE Causes and risk factors A person with diabetes may have a higher risk of developing NAFLD. Exactly how and why fatty liver develops is not clear. It occurs when the body produces too much fat, or when it cannot process fat properly. Obesity is a clear risk factor. Around 70 percent of people with obesity have the condition, while 10 to 15 percent of people with a normal weight have it. Regardless of their weight, a person with "deep" abdominal fat is more likely to have a fatty liver. Other risk factors include: • diabetes • high cholesterol or high levels of fat in the blood • high blood pressure • high blood fats, or triglycerides People with metabolic syndrome, a condition that involves a clustering of the risk factors mentioned above, are at higher risk. Between 40 and 80 percent of people with type 2 diabetes have NAFLD. Researchers have found "growing evidence" that NAFLD is linked to cardiovascular disease (CVD) and chronic kidney disease (CKD). This means that those with NAFLD are also more likely to have diabetes and heart disease. While there are clear links between obesity and fatty liver, some people develop NAFLD without obesity. This suggests that there are other factors. These include: • genetic influences • smoking • older age • certain medications, such as steroids, and tamoxifen for cancer treatment • rapid weight loss • infections, such as hepatitis • exposure to some toxins Stay in the know. Get our free daily newsletter You’ve got questions. We’ve got answers. Expert, evidence-based advice delivered straight to your inbox to help you take control of your health Sign Up Your privacy is important to us. However, research suggests that "excess fat mass remains the most common background condition." NAFLD is also the most common form of long-term liver disease in children. A review published in 2016 states that it affects between 10 and 20 percent of pediatric patients and 50 to 80 percent of children with obesity. The scientists predict: "Within the next 10 years, it is expected to become the leading cause of liver pathology, liver failure, and indication for liver transplantation in childhood and adolescence in the Western world." Around 25 percent of pediatric patients with NASH will go on to develop cirrhosis within 10 years. Among those with obesity, the risk is higher. Diagnosis Early stage NAFLD does not usually produce symptoms, so diagnosis usually happens because of a routine blood test or because the person has the relevant risk factors. If the doctor suspects NAFLD, they will feel the abdominal area, to find out if there is any swelling. They will ask about diet and lifestyle and any use of medications, supplements, and alcohol. If tests suggest that there is damage to the liver or that the liver is swollen, the doctor must rule out other possible conditions, including alcoholic liver disease. Imaging scans, such as ultrasound, CT, and MRI can show up fat in the liver. A biopsy can confirm NAFLD, reveal the extent of the damage, and distinguish it from other types of liver problem. The doctor will use a needle to take a small tissue sample from the liver. Treatment and management There is no medical treatment for fatty liver, but lifestyle choices, such as achieving or maintaining a healthy weight, can reduce the risk and possibly reverse the damage, in the early stages. Dietary tips A diet that contains plenty of fresh food can help prevent liver damage. To reduce the risk of NAFLD, it is best to: • follow a balanced diet with moderate portions • eat plenty of fruits and vegetables • consume both proteins and carbohydrates, but limit fats and sugars • reduce salt intake • replace saturated and trans fats with monounsaturated and polyunsaturated fats The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) recommend the following dietary tips: • replace trans fats and animal fats with olive oil, flaxseed oil, corn, soybean, and safflower oils • eat oily fish instead of meat • avoid foods that are high in simple sugars, such as fructose, found in sweetened drinks, sports drinks, and juices • eat more foods that are low on the glycemic index (GI), such as fruits, vegetables, and whole grains • eat fewer high-GI foods, such as white bread and white rice • avoid alcohol or drink in moderation Scientists are looking at whether vitamin E may help, but more research is needed. Those who ae considering taking supplements or herbal remedies should always speak to a doctor first. A healthy diet and regular exercise will reduce the risk of a wide range of conditions, including diabetes and cardiovascular disease. Outlook For most people, a fatty liver does not usually cause serious problems. To some extent, the liver can repair itself, so switching to a healthy lifestyle will help. Researchers warn that NAFLD is on the increase, and if obesity continues to rise, it could become "an epidemic." Although simple fatty liver is not dangerous, without preventive action, some people will go on to develop NASH, and between 10 and 25 percent of adults with NASH will go on to develop cirrhosis within 10 years. In the U.S., fatty liver disease is the third cause of liver transplant, and it is on the rise. In addition, NAFLD is linked to CVD, CKD, and other conditions. Whether or not these can be reversed, even if the liver recovers, is not clear. The best way to treat and prevent it is through healthful lifestyle choices, with a varied and balanced diet and regular exercise. ________________________________________________________________________________ https://www.nhs.uk/conditions/non-alcoholic-fatty-liver-disease/ Non-alcoholic fatty liver disease (NAFLD) Non-alcoholic fatty liver disease (NAFLD) is the term for a range of conditions caused by a build-up of fat in the liver. It's usually seen in people who are overweight or obese. A healthy liver should contain little or no fat. It's estimated up to 1 in every 3 people in the UK has early stages of NAFLD, where there are small amounts of fat in their liver. Early-stage NAFLD does not usually cause any harm, but it can lead to serious liver damage, including cirrhosis, if it gets worse. Having high levels of fat in your liver is also associated with an increased risk of serious health problems, such as diabetes, high blood pressure and kidney disease. If you already have diabetes, NAFLD increases your chance of developing heart problems. If detected and managed at an early stage, it's possible to stop NAFLD getting worse and reduce the amount of fat in your liver. Stages of non-alcoholic fatty liver disease (NAFLD) NAFLD develops in 4 main stages. Most people will only ever develop the first stage, usually without realising it. In a small number of cases, it can progress and eventually lead to liver damage if not detected and managed. The main stages of NAFLD are: 1. simple fatty liver (steatosis) – a largely harmless build-up of fat in the liver cells that may only be diagnosed during tests carried out for another reason 2. non-alcoholic steatohepatitis (NASH) – a more serious form of NAFLD, where the liver has become inflamed; this is estimated to affect up to 5% of the UK population 3. fibrosis – where persistent inflammation causes scar tissue around the liver and nearby blood vessels, but the liver is still able to function normally 4. cirrhosis – the most severe stage, occurring after years of inflammation, where the liver shrinks and becomes scarred and lumpy; this damage is permanent and can lead to liver failure (where your liver stops working properly) and liver cancer It can take years for fibrosis or cirrhosis to develop. It's important to make lifestyle changes to prevent the condition getting worse. Am I at risk of non-alcoholic fatty liver disease (NAFLD)? You're at an increased risk of NAFLD if you: • are obese or overweight – particularly if you have a lot of fat around your waist (an "apple-like" body shape) • have type 2 diabetes • have high blood pressure • have high cholesterol • have metabolic syndrome (a combination of diabetes, high blood pressure and obesity) • are over the age of 50 • smoke But NAFLD has been diagnosed in people without any of these risk factors, including young children. Although it's very similar to alcohol-related liver disease (ARLD), NAFLD is not caused by drinking too much alcohol. Symptoms of non-alcoholic fatty liver disease (NAFLD) There are not usually any symptoms of NAFLD in the early stages. You probably will not know you have it unless it's diagnosed during tests carried out for another reason. Occasionally, people with NASH or fibrosis (more advanced stages of NAFLD) may experience: • a dull or aching pain in the top right of the tummy (over the lower right side of the ribs) • extreme tiredness • unexplained weight loss • weakness If cirrhosis (the most advanced stage) develops, you can get more severe symptoms, such as yellowing of the skin and the whites of the eyes (jaundice), itchy skin, and swelling in the legs, ankles, feet or tummy (oedema). How non-alcoholic fatty liver disease (NAFLD) is diagnosed NAFLD is often diagnosed after a blood test called a liver function test produces an abnormal result and other liver conditions, such as hepatitis, are ruled out. But blood tests do not always pick up NAFLD. The condition may also be spotted during an ultrasound scan of your tummy. This is a type of scan where sound waves are used to create an image of the inside of your body. If you're diagnosed with NAFLD, further tests may be needed to determine which stage you have. This may involve a special blood test or having another type of ultrasound scan (Fibroscan). Some people may also need a biopsy, where a small sample of liver tissue is taken using a needle so it can be analysed in a laboratory. Children and young people with an increased risk of NAFLD (those with type 2 diabetes or metabolic syndrome) should have an ultrasound scan of their liver every 3 years. Treatment for non-alcoholic fatty liver disease (NAFLD) Most people with NAFLD will not develop any serious problems, but if you're diagnosed with the condition it's a good idea to take steps to stop it getting any worse. There's currently no specific medication for NAFLD, but making healthy lifestyle choices can help. Treatment also may be recommended for associated conditions (high blood pressure, diabetes and cholesterol) or complications. You may be advised to have regular appointments with your doctor to check your liver function and look for signs of any new problems. Medicines There's not currently any medicine that can treat NAFLD, but various medicines can be useful in managing the problems associated with the condition. For example, your doctor may recommend medicine to treat high blood pressure, treat high cholesterol, treat type 2 diabetes and treat obesity. Liver transplant If you develop severe cirrhosis and your liver stops working properly, you may need to be put on the waiting list for a liver transplant. For adults, the average waiting time for a liver transplant is 135 days for transplants from recently deceased donors. Or it may be possible to have a transplant using a section of liver removed from a living donor. As the liver can regenerate itself, both the transplanted section and the remaining section of the donor's liver are able to regrow to a normal size. Find out more about liver transplants Things you can do if you have non-alcoholic fatty liver disease (NAFLD) Adopting a healthy lifestyle is the main way of managing NAFLD. For example, it can help to: • lose weight – you should aim for a BMI of 18.5 to 24.9 (use the BMI calculator to work out your BMI); losing more than 10% of your weight can remove some fat from the liver and improve NASH if you have it • eat a healthy diet – try to have a balanced diet high in fruits, vegetables, protein and carbohydrates, but low in fat, sugar and salt; eating smaller portions of food can help, too • exercise regularly – aim to do at least 150 minutes of moderate-intensity activity, such as walking or cycling, a week; all types of exercise can help improve NAFLD, even if you do not lose weight • stop smoking – if you smoke, stopping can help reduce your risk of problems such as heart attacks and strokes NAFLD is not caused by alcohol, but drinking may make it worse. It's therefore advisable to cut down or stop drinking alcohol. Page last reviewed: 19 November 2018 Next review due: 19 November 2021 Gi.org / Patients / Non-alcoholic Fatty Liver Disease (NAFLD) Non-alcoholic Fatty Liver Disease (NAFLD) 51Share GI Health and Disease Overview Non-alcoholic fatty liver disease (NAFLD) is a very common disorder and refers to a group of conditions where there is accumulation of excess fat in the liver of people who drink little or no alcohol. The most common form of NAFLD is a non serious condition called fatty liver. In fatty liver, fat accumulates in the liver cells. Although having fat in the liver is not normal, by itself it probably does not damage the liver. A small group of people with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH). In NASH, fat accumulation is associated with liver cell inflammation and different degrees of scarring. NASH is a potentially serious condition that may lead to severe liver scarring and cirrhosis. Cirrhosis occurs when the liver sustains substantial damage, and the liver cells are gradually replaced by scar tissue (see figure), which results in the inability of the liver to work properly. Some patients who develop cirrhosis may eventually require a liver transplant (surgery to remove the damaged liver and replace it with a “new” liver). Symptoms The majority of individuals with NAFLD have no symptoms and a normal examination. Children may exhibit symptoms such as abdominal pain, which may be in the center or the right upper part of the abdomen, and sometimes fatigue. However, other causes of abdominal pain and fatigue should be considered. On physical examination the liver might be slightly enlarged and some children may have patchy, dark discoloration of the skin present (acanthosis nigricans) most commonly over the neck and the under arm area. Causes of NAFLD/NASH NAFLD is part of the metabolic syndrome characterized by diabetes, or pre-diabetes (insulin resistance), being overweight or obese, elevated blood lipids such as cholesterol and triglycerides, as well as high blood pressure. Not all patients have all the manifestations of the metabolic syndrome. Less is known about what causes NASH to develop. Researchers are focusing on several factors that may contribute to the development of NASH. These include: Oxidative stress (imbalance between pro-oxidant and anti-oxidant chemicals that lead to liver cell damage) Production and release of toxic inflammatory proteins (cytokines) by the patient’s own inflammatory cells, liver cells, or fat cells Liver cell necrosis or death, called apoptosis Adipose tissue (fat tissue) inflammation and infiltration by white blood cells Gut microbiota (intestinal bacteria) which may play a role in liver inflammation Risk Factors NAFLD is a very common disorder affecting and may affect as many as one in three to one in five adults and around one in ten children in the United States. Obesity is thought to be the most common cause of fatty infiltration of the liver. Some experts estimate that about two thirds of obese adults and half of obese children may have fatty liver. About 2 to 5 percent of adult Americans and up to 20 percent of those who are obese may suffer from the more severe condition NASH. The number of children who have NASH is not known. The presence of type 2 diabetes and other conditions associated with insulin resistance, such as polycystic ovarian syndrome are know risk factors for the development of fatty liver and NASH. Screening/Diagnosis The diagnosis of NAFLD is usually first suspected in an overweight or obese person who is found to have mild elevations in their liver tests during a routine blood testing or incidentally detected on radiologic investigations such as abdominal ultrasound or CT scan. Some experts are now recommending that every obese child or adolescent should have these liver enzymes checked. However NAFLD can be present with normal liver blood tests. The diagnosis of NAFLD is confirmed by imaging studies, most commonly a liver ultrasound, showing accumulation of fat in the liver. Fat accumulation in the liver can also be caused by excess alcohol intake, certain medications, viral hepatitis, autoimmune liver disease, and metabolic or inherited liver disease. These need to be excluded as causes of fatty liver disease in order to confirm the diagnosis of NAFLD. Currently, the only reliable way of telling whether a person has NASH or simple fatty liver is by a liver biopsy. In this procedure, a small needle is inserted through the skin after local anesthesia is given to obtain a small piece of the liver for microscopic evaluation. NASH is diagnosed when examination of this piece of liver under the microscope shows fatty infiltration of the liver in addition to inflammation and different degrees of scarring. If only fat is present, then the diagnosis of simple fatty liver is made. The liver biopsy provides essential information regarding the degree of scarring within the liver, which would not be apparent on a blood test, ultrasound, or an x-ray alone. Liver biopsy rarely can be associated with serious risks including bleeding and patients should discuss the risks and benefits of the procedure with their physician. Treatment of NAFLD/NASH A few studies have suggested that weight loss may be associated with regression of fat within the liver. Therefore, the most important recommendations for people with fatty liver are to lose weight if they are overweight or obese, increase their physical activity, follow a balanced diet and avoid alcohol and unnecessary medications. New evidence suggests that Mediterranean diet (rich in monounsaturated fatty acids) may be more beneficial than low fat diet. Drinking coffee seems to decrease the risk of having fatty liver in large cohort studies. In patients with NASH, the more severe form of NAFLD, these same recommendations may be helpful. It is also important to control diabetes and treat elevated cholesterol levels when appropriate. Development of medications that could treat NAFD and NASH is an area of intense research. Recent trials in adult and children have shown that vitamin E (an anti-oxidant) could help improve NASH in non-diabetic patients. Strategies currently being evaluated by physicians and scientists to decrease the amount of fat/ inflammation in the liver include: Weight reduction (diet + exercise, medications, surgery) Lipid lowering medications Insulin sensitizers (medications) Decrease the amount of liver inflammation by administering anti-oxidant medications, anti-apoptotic medications and anti-cytokine medications Author(s) and Publication Date(s) Naim Alkhouri, MD, and Marsha H. Kay, MD, FACG, The Cleveland Clinic, Cleveland, OH – Updated December 2012. Ariel E. Feldstein, MD, and Marsha H. Kay, MD, FACG, Cleveland Clinic Foundation, Cleveland, OH – Published January 2006. American Liver Foundation American Association for the Study of Liver Disease Patient Flyer Non-Alcoholic Fatty Liver Disease & The Mediterranean Diet Advancing gastroenterology, improving patient care kesackett32463whitelady(5'3)(5'21/2) information articles found in internet under google oct 2019
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psychiatric medicines and how it causes non-alcoholic fatty liver disease by raising the triglyceride and cholesterol level and by causing weight gain plus metabolic trouble this is open for public to read oct 2019
6 Medications That Can Cause High Triglycerides
By Cindy Kuzma
Key Takeaways
• Almost one-third of American adults have high triglycerides, which can be harmful to your health.
• Certain medications can influence your triglyceride levels. These include some blood pressure medicines, corticosteroids, antipsychotics, isotretinoin, HIV treatments, and estrogen.
• Always talk with your health care provider before starting or stopping any medications.
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Medical Reviewers: William C. Lloyd III Last Review Date: 2018 Jan 17
3. Antipsychotics
Though they were developed to treat schizophrenia, bipolar disorder, and other severe forms of mental illness, health care providers now prescribe these drugs to children and adults for a wide range of psychological complaints. These range from autism and attention deficit hyperactivity disorder (ADHD) to conduct disorder and Tourette’s syndrome.
Newer antipsychotics—including aripiprazole (Abilify), olanzapine (Zyprexa) quetiapine (Seroquel), and risperidone (Risperdal)—may raise triglyceride levels. However, first-generation antipsychotics, such as chlorpromazine (Thorazine) and haloperidol (Haldol), don’t have this effect.
Medications That Increase Cholesterol Levels
By Jennifer Moll, PharmD
Updated October 04, 2019
Medically reviewed by Richard N. Fogoros, MD
More in High Cholesterol
18 Both valproate and drug-induced weight gain appear to raise serum insulin levels; the resulting hyperinsulinemia further stimulates ovarian androgen production.17,19
Psychotropic Drugs Related to Diabetes and High Blood Sugar
Diabetes Complications / By AngelicaMD / Diabetes
What Are Psychotropic Drugs?
Psychotropic drugs are medications prescribed to improve a patient’s mood, perception, behavior and emotions. These may consist of:
• Antipsychotics for the treatment of schizophrenia
• Atypical antipsychotic drugs for bipolar disorders
• Antidepressants like monoamine oxidase inhibitors (MAOIs) such as phenelzine and isocarboxazid
• Selective serotonin reuptake inhibitors (SSRIs) like venlafaxine and paroxetine
• Mood stabilizers like lithium and sodium valproate
These drugs usually act by improving the balance of natural chemicals in the brain known as neurotransmitters and by blocking receptors to which these substances interact.
Side Effects of Psychotropic Drugs Related to Diabetes
Among the side effects related to diabetes noted with the use of psychotropics are:
• Weight gain, elevated body mass index (BMI) and obesity
• Increased blood sugar levels (hyperglycemia)
• Increased insulin levels (hyperinsulinemia)
• Diabetic ketoacidosis
• Elevated total cholesterol and triglycerides
Diabetes-related side effects have been observed to occur rapidly with the use of psychotropic drugs, most especially with typical antipsychotics like clonazepine and olanzapine. The risk for these side effects seem to be less for atypical antipsychotics like risperidone, quetiapine and ziprasidone although there have been fewer studies done on these drugs.
The side effects psychotropic drugs related to diabetes and high blood sugar have been established after observations that these effects start right after the commencement of their intake and the rapid disappearance or improvement of these effects after withdrawal of the drugs or switching to other drugs.
How Do Psychotropic Drugs Increase Blood Sugar Levels?
The mechanisms proposed on how antipsychotics, antidepressants and other mood-altering drugs affect blood sugar levels and lead to diabetes include:
• Weight gain – the onset of type 2 diabetes is often associated with a significant increase in BMI and obesity which occur after the intake of psychotropics
• Insulin resistance – a decrease in glucose utilization by the cells despite elevations of insulin production leads to high blood sugar levels
• Rapid and disproportionate increase in leptin levels (a substance released from fat cells) – leads to an imbalance of hypothalamic hormone regulation; this effect inhibits the normal effect of leptin which is to suppress the appetite and cause the breakdown of fat cells
Management of Diabetes and Psychotropic Drug Intake
Patients who need effective control of symptoms of schizophrenia, bipolar disorders, chronic depression and other behavioral and mood problems usually benefit from the intake of psychotropic drugs which may need several weeks or months to work. However, diabetes-related side effects such as high blood sugar levels, weight gain and high cholesterol levels may occur in these patients.
• Switching to psychotropic meds with less diabetes-related side effects like risperidone
How Do Psychotropic Drugs Increase Blood Sugar Levels?
The mechanisms proposed on how antipsychotics, antidepressants and other mood-altering drugs affect blood sugar levels and lead to diabetes include:
• Weight gain – the onset of type 2 diabetes is often associated with a significant increase in BMI and obesity which occur after the intake of psychotropics
• Insulin resistance – a decrease in glucose utilization by the cells despite elevations of insulin production leads to high blood sugar levels
• Rapid and disproportionate increase in leptin levels (a substance released from fat cells) – leads to an imbalance of hypothalamic hormone regulation; this effect inhibits the normal effect of leptin which is to suppress the appetite and cause the breakdown of fat cells
Antipsychotics and metabolic adverse events
Recently, the focus on the tolerability of antipsychotics has shifted from extrapyramidal syndrome (EPS) toward adverse effects on body weight and related metabolic consequences that seem to be more common with atypical than with typical antipsychotics.20 The concerns about weight gain are fueled by ample evidence that increased body weight and obesity, particularly increased visceral fat agglomeration, are associated with greatly increased risks for diabetes, dyslipidemia, and hypertension (the metabolic syndrome; see Table 1) and are related to increased coronary heart disease morbidity and mortality.21,22 In addition, antipsychotic-induced weight gain has been associated with a lower quality of life23 and impaired medication adherence.24
Data suggest that there is an increased prevalence of obesity, diabetes, and dyslipidemia in patients with schizophrenia and bipolar disorder compared with the general population. Increased relative risk estimates range from 2 to 3 times the risk for obesity25,26 and diabetes27,28 to 4 to 5 times the risk for dyslipidemia.22 Likewise, prevalence rates for the metabolic syndrome and for calculated 10-year coronary heart disease events have been shown to be about twice as high in patients with schizophrenia29-31 and in patients with mixed diagnoses receiving atypical antipsychotics.32 Rates in patients with bipolar disorder have also been higher than in the general population, although they seem to be less elevated than in patients with schizophrenia.33
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].
Antipsychotic Agents
Last Update: July 20, 2017.
Go to:
OVERVIEW
Psychotic disorders include schizophrenia, the manic phase of manic-depressive illness (bipolar illness), acute psychosis and other conditions marked by acute, severe agitation. The antipsychotic medications are invaluable adjuncts to the treatment of psychosis and bipolar illness and have revolutionized management of these conditions.
The antipsychotic agents in clinical use include the phenothiazines and structurally similar compounds such as thioxanthenes, benazepines, butyrophenones, diphenylbutylpiperidines and miscellaneous similar heterocyclic compounds. The antipsychotic medications are usually classified into conventional and atypical agents, based upon relative risks for extrapyramidal side effects that are greater with the older, conventional agents. They are also referred to as first and second generation antipscyhotic agents.
The initial antipsychotic medications introduced into clinical practice were the phenothiazines, but they have been largely replaced in recent years by the atypical agents. Phenothiazines in current use (with initial brand names and date of first approval) include chlorpromazine (Thorazine: 1957, the initial prototype antipsychotic agent), fluphenazine (Prolixin: 1972), perphenazine (Trilafon: 1957), prochlorperazine (Compazine: 1956, used mostly as therapy of nausea rather than psychosis), thioridazine (Mellaril: 1978), and trifluoperazine (Stelazine: 1959). Miscellaneous conventional antipsychotic medications include haloperidol (Haldol: 1967), loxapine (Loxitane: 1976), molindone (Moban: 1974) and pimozide (Orap: 1984, used largely for Tourette syndrome). Lithium is also frequently discussed in the context of antipsychotic therapies, although its major use is for stabilization of bipolar illness.
The atypical antipsychotic agents are more recently introduced drugs that generally have greater potency and fewer extrapyramidal side effects. Currently, these are the most commonly used antipsychotic agents. They include aripiprazole (Abilify: 2002), asenapine (Saphris: 2007), brexpiprazole (Rexulti: 2015), cariprazine (Vraylar: 2016), clozapine (Clozaril: 1975-79, 1989), iloperidone (Fanapt: 2010), lurasidone (Latuda: 2010), olanzapine (Zyprexa: 1996), paliperidone (Invega: 2006), pimavanserin (Nuplazid: 2016), quetiapine (Seroquel: 1997), risperidone (Risperdal: 1993) and ziprasidone (Geodon: 2001). Some of these agents are also used to treat bipolar illness and major depression.
The phenothiazines are well established causes of drug induced liver disease and typically cause a cholestatic injury arising within 1 to 4 weeks of starting treatment. Indeed, during the 1960s and early 1970s, chlorpromazine was one of the most common causes of drug induced liver disease ("Thorazine jaundice"). The other phenothiazines were found to cause a similar cholestatic hepatitis, although much less frequently than chlorpromazine. The other conventional antipsychotic medications have been linked to liver injury only rarely, if at all, and do not exhibit a characteristic signature pattern of injury. Many but not all of the atypical antipsychotic medications have been linked to serum enzyme elevations during therapy, but clinically apparent liver injury with jaundice from these agents is very rare.
• First Generation
o Phenothiazines
 Chlorpromazine, Fluphenazine, Perphenazine, Prochlorperazine, Thioridazine, Trifluoperazine
o Other
 Haloperidol, Lithium, Loxapine, Molindone, Pimozide
• Second Generation (Atypicals)
o Aripiprazole, Asenapine, Brexpiprazole, Cariprazine, Clozapine, Iloperidone, Lurasidone, Olanzapine, Paliperidone, Pimavanserin, Quetiapine, Risperidone, Ziprasidone
Go to:
ANNOTATED BIBLIOGRAPHY
References updated: 20 July 2017
• Zimmerman HJ. Neuroleptic drugs. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 483-91.
High cholestrerol and high triglyceride levels caused from certain medicine taken and psychiatric is one of them(caused non-alcoholic fatty liver disease)
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Non-alcoholic fatty liver disease (NAFLD)
Non-alcoholic fatty liver disease (NAFLD) is the term for a range of conditions caused by a build-up of fat in the liver. It's usually seen in people who are overweight or obese.
A healthy liver should contain little or no fat. It's estimated up to 1 in every 3 people in the UK has early stages of NAFLD, where there are small amounts of fat in their liver.
Early-stage NAFLD does not usually cause any harm, but it can lead to serious liver damage, including cirrhosis, if it gets worse.
Having high levels of fat in your liver is also associated with an increased risk of serious health problems, such as diabetes, high blood pressure and kidney disease.
If you already have diabetes, NAFLD increases your chance of developing heart problems.
If detected and managed at an early stage, it's possible to stop NAFLD getting worse and reduce the amount of fat in your liver.
Stages of non-alcoholic fatty liver disease (NAFLD)
NAFLD develops in 4 main stages.
Most people will only ever develop the first stage, usually without realising it.
In a small number of cases, it can progress and eventually lead to liver damage if not detected and managed.
The main stages of NAFLD are:
1. simple fatty liver (steatosis) – a largely harmless build-up of fat in the liver cells that may only be diagnosed during tests carried out for another reason
2. non-alcoholic steatohepatitis (NASH) – a more serious form of NAFLD, where the liver has become inflamed; this is estimated to affect up to 5% of the UK population
3. fibrosis – where persistent inflammation causes scar tissue around the liver and nearby blood vessels, but the liver is still able to function normally
4. cirrhosis – the most severe stage, occurring after years of inflammation, where the liver shrinks and becomes scarred and lumpy; this damage is permanent and can lead to liver failure (where your liver stops working properly) and liver cancer
It can take years for fibrosis or cirrhosis to develop. It's important to make lifestyle changes to prevent the condition getting worse.
Am I at risk of non-alcoholic fatty liver disease (NAFLD)?
You're at an increased risk of NAFLD if you:
• are obese or overweight – particularly if you have a lot of fat around your waist (an "apple-like" body shape)
• have type 2 diabetes
• have high blood pressure
• have high cholesterol
• have metabolic syndrome (a combination of diabetes, high blood pressure and obesity)
• are over the age of 50
• smoke
But NAFLD has been diagnosed in people without any of these risk factors, including young children.
Although it's very similar to alcohol-related liver disease (ARLD), NAFLD is not caused by drinking too much alcohol.
Symptoms of non-alcoholic fatty liver disease (NAFLD)
There are not usually any symptoms of NAFLD in the early stages. You probably will not know you have it unless it's diagnosed during tests carried out for another reason.
Occasionally, people with NASH or fibrosis (more advanced stages of NAFLD) may experience:
• a dull or aching pain in the top right of the tummy (over the lower right side of the ribs)
• extreme tiredness
• unexplained weight loss
• weakness
If cirrhosis (the most advanced stage) develops, you can get more severe symptoms, such as yellowing of the skin and the whites of the eyes (jaundice), itchy skin, and swelling in the legs, ankles, feet or tummy (oedema).
How non-alcoholic fatty liver disease (NAFLD) is diagnosed
NAFLD is often diagnosed after a blood test called a liver function test produces an abnormal result and other liver conditions, such as hepatitis, are ruled out.
But blood tests do not always pick up NAFLD.
The condition may also be spotted during an ultrasound scan of your tummy.
This is a type of scan where sound waves are used to create an image of the inside of your body.
If you're diagnosed with NAFLD, further tests may be needed to determine which stage you have. This may involve a special blood test or having another type of ultrasound scan (Fibroscan).
Some people may also need a biopsy, where a small sample of liver tissue is taken using a needle so it can be analysed in a laboratory.
Children and young people with an increased risk of NAFLD (those with type 2 diabetes or metabolic syndrome) should have an ultrasound scan of their liver every 3 years.
Treatment for non-alcoholic fatty liver disease (NAFLD)
Most people with NAFLD will not develop any serious problems, but if you're diagnosed with the condition it's a good idea to take steps to stop it getting any worse.
There's currently no specific medication for NAFLD, but making healthy lifestyle choices can help.
Treatment also may be recommended for associated conditions (high blood pressure, diabetes and cholesterol) or complications.
You may be advised to have regular appointments with your doctor to check your liver function and look for signs of any new problems.
Medicines
There's not currently any medicine that can treat NAFLD, but various medicines can be useful in managing the problems associated with the condition.
For example, your doctor may recommend medicine to treat high blood pressure, treat high cholesterol, treat type 2 diabetes and treat obesity.
Liver transplant
If you develop severe cirrhosis and your liver stops working properly, you may need to be put on the waiting list for a liver transplant.
For adults, the average waiting time for a liver transplant is 135 days for transplants from recently deceased donors.
Or it may be possible to have a transplant using a section of liver removed from a living donor.
As the liver can regenerate itself, both the transplanted section and the remaining section of the donor's liver are able to regrow to a normal size.
Find out more about liver transplants
Things you can do if you have non-alcoholic fatty liver disease (NAFLD)
Adopting a healthy lifestyle is the main way of managing NAFLD.
For example, it can help to:
• lose weight – you should aim for a BMI of 18.5 to 24.9 (use the BMI calculator to work out your BMI); losing more than 10% of your weight can remove some fat from the liver and improve NASH if you have it
• eat a healthy diet – try to have a balanced diet high in fruits, vegetables, protein and carbohydrates, but low in fat, sugar and salt; eating smaller portions of food can help, too
• exercise regularly – aim to do at least 150 minutes of moderate-intensity activity, such as walking or cycling, a week; all types of exercise can help improve NAFLD, even if you do not lose weight
• stop smoking – if you smoke, stopping can help reduce your risk of problems such as heart attacks and strokes
NAFLD is not caused by alcohol, but drinking may make it worse. It's therefore advisable to cut down or stop drinking alcohol.
Page last reviewed: 19 November 2018
Next review due: 19 November 2021
Olanzapine and Zyprexa side effects and more
Neuroleptic Malignant Syndrome (NMS)
NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. Rare cases reported as NMS have also been received in association with olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.
Hyperglycaemia and diabetes
Hyperglycaemia and/or development or exacerbation of diabetes, occasionally associated with ketoacidosis or coma, has been reported uncommonly, including some fatal cases (see section 4.8). In some cases, a prior increase in body weight has been reported, which may be a predisposing factor. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g., measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually thereafter. Patients treated with any antipsychotic medicines, including ZYPREXA/ZYPREXA VELOTAB, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly, e.g., at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter.
Lipid alterations
Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled clinical trials (see section 4.8). Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders. Patients treated with any antipsychotic medicines, including ZYPREXA/ZYPREXA VELOTAB, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g., at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter.
Anticholinergic activity
Lactose
ZYPREXA tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Sudden cardiac death
In postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in patients with olanzapine. In a retrospective observational cohort study, the risk of presumed sudden cardiac death in patients treated with olanzapine was approximately twice the risk in patients not using antipsychotics. In the study, the risk of olanzapine was comparable to the risk of atypical antipsychotics included in a pooled analysis
4.8 Undesirable effects
Summary of the safety profile
Adults
The most frequently (seen in ≥ 1% of patients) reported adverse reactions associated with the use of olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 4.4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma glutamyltransferase, high uric acid, high creatine phosphokinase and oedema.
Tabulated list of adverse reactions
Musculoskeletal and connective tissue disorders
Arthralgia9 Rhabdomyolysis11
Weight gain1 Elevated cholesterol levels2,3
Elevated glucose levels4
Elevated triglyceride levels2,5
Glucosuria
Increased appetite Development or exacerbation of diabetes occasionally associated with ketoacidosis or coma, including some fatal cases (see section 4.4) 11 Hypothermia12
Skin and subcutaneous tissue disorders
Rash Photosensitivity reaction
Alopecia Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Investigations
Elevated plasma prolactin levels8 Increased alkaline phosphatase10
High creatine phosphokinase11
High Gamma Glutamyltransferase10
High uric acid 10 Increased total bilirubin
1Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. Following short-term treatment (median duration 47 days), weight gain ≥ 7% of baseline body weight was very common (22.2%); ≥ 15% was common (4.2%); and ≥ 25% was uncommon (0.8%). Patients gaining ≥ 7%, ≥ 15% and ≥ 25% of their baseline body weight with long-term exposure (at least 48 weeks) were very common (64.4%, 31.7% and 12.3% respectively).
2Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline.
Investigations
Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels16.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you have:
• unusual movement (a common side effect that may affect up to 1 in 10 people) mainly of the face or tongue;
• blood clots in the veins (an uncommon side effect that may affect up to 1 in 100 people) especially in the legs (symptoms include swelling, pain, and redness in the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in breathing. If you notice any of these symptoms seek medical advice immediately;
• a combination of fever, faster breathing, sweating, muscle stiffness and drowsiness or sleepiness (the frequency of this side effect cannot be estimated from the available data).
Very common side effects (may affect more than 1 in 10 people) include weight gain; sleepiness; and increases in levels of prolactin in the blood. In the early stages of treatment, some people may feel dizzy or faint (with a slow heart rate), especially when getting up from a lying or sitting position. This will usually pass on its own but if it does not, tell your doctor.
Common side effects (may affect up to 1 in 10 people) include changes in the levels of some blood cells, circulating fats and early in treatment, temporary increases in liver enzymes; increases in the level of sugars in the blood and urine; increases in levels of uric acid and creatine phosphokinase in the blood; feeling more hungry; dizziness; restlessness; tremor; unusual movements(dyskinesias); constipation; dry mouth; rash; loss of strength; extreme tiredness; water retention leading to swelling of the hands, ankles or feet; fever; joint pain; and sexual dysfunctions such as decreased libido in males and females or erectile dysfunction in males.
Uncommon side effects (may affect up to 1 in 100 people) include hypersensitivity (e.g. swelling in the mouth and throat, itching, rash); diabetes or the worsening of diabetes, occasionally associated with ketoacidosis (ketones in the blood and urine) or coma; seizures, usually associated with a history of seizures (epilepsy); muscle stiffness or spasms (including eye movements); restless legs syndrome; problems with speech; stuttering; slow heart rate; sensitivity to sunlight; bleeding from the nose; abdominal distension; memory loss or forgetfulness; urinary incontinence; lack of ability to urinate; hair loss; absence or decrease in menstrual periods; and changes in breasts in males and females such as an abnormal production of breast milk or abnormal growth.
Rare side effects (may affect up to 1 in 1000 people) include lowering of normal body temperature; abnormal rhythms of the heart; sudden unexplained death; inflammation of the pancreas causing severe stomach pain, fever and sickness; liver disease appearing as yellowing of the skin and white parts of the eyes; muscle disease presenting as unexplained aches and pains; and prolonged and/or painful erection.
Very rare side effects include serious allergic reactions such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). DRESS appears initially as flu-like symptoms with a rash on the face and then with an extended rash, high temperature, enlarged lymph nodes, increased levels of liver enzymes seen on blood tests and an increase in a type of white blood cells (eosinophilia).
While taking olanzapine, elderly patients with dementia may suffer from stroke, pneumonia, urinary incontinence, falls, extreme tiredness, visual hallucinations, a rise in body temperature, redness of the skin and have trouble walking. Some fatal cases have been reported in this particular group of patients.
In patients with Parkinson's disease ZYPREXA may worsen the symptoms.
This for post use cut out of articles by me oct 2019
from Katrine elizabethsackett 32463whitelady32463(5'3)(5'21/2)
oct 2019
psychiatric medicine and fatty liver disease oct 2019 open for public to read
Submitted by Unregistered User on Tue, 10/29/2019 - 13:29
law psychiatric medicine and fatty liver disease oct 2019 open for public to read
Submitted by Unregistered User on Mon, 10/28/2019 - 00:46
americanLiverfoundation.org
Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is the build up of extra fat in liver cells that is not caused by alcohol. It is normal for the liver to contain some fat. However, if more than 5% – 10% percent of the liver’s weight is fat, then it is called a fatty liver (steatosis). The more severe form of NAFLD is called nonalcoholic steatohepatitis (NASH). NASH causes the liver to swell and become damaged.
The Liver’s Important Role
As the quick quiz illustrates, there is a critical need for the American Liver Foundation throughout the year, but especially during Liver Awareness Month, to educate the general public about the important role the liver plays and how to maintain a healthy liver.
________________________________________
The Focus on Fatty Livers Intensifies
Much of the Foundation’s emphasis during October continues to point to the cause and treatment for liver diseases like hepatitis A, B and C; cirrhosis, biliary atresia and liver cancer.
But the Foundation is also tapping into the heightened awareness during Liver Awareness Month to draw attention to the alarming increase in the incidence of Non-Alcoholic Fatty Liver Disease (NAFLD), which, staggeringly, affects up to 25 percent of people in the United States.
As its name suggests, NAFLD is the buildup of extra fat in the liver that isn’t caused by alcohol. It’s normal for the liver to contain some fat. But if more than 5 to 10 percent of the liver’s weight is fat, then it is called a “fatty liver.”
Most often, NAFLD tends to develop in people who are overweight or obese or have diabetes, high cholesterol or high triglycerides. Sedentary behavior is another major contributing factor to the onset of NAFLD.
For these reasons, concern continues to grow as one in 10 children—that’s seven million children in the United States—is estimated to have fatty livers.
NALFD can become even more serious. It can progress to Non-Alcoholic Steatohepatitis (NASH), which means that along with the fat, there is inflammation and damage to the liver. A swollen liver may cause scarring (cirrhosis) over time and may even lead to liver cancer or liver failure.
The Facts About Non-Alcoholic Fatty Liver Disease
1. As incredible as it may seem in pure numbers,Non-alcoholic Fatty Liver Disease (NAFLD) affects up to 25% of people in the United States.
2. NAFLD is the build-up of extra fat in liver cells that isn’t caused by alcohol. It’s normal for the liver to contain some fat. However, if more than 5 to 10% of the liver’s weight is fat, then it’s called a fatty liver (steatosis).
3. Who is likely to have NAFLD? It tends to develop in people who are overweight or obese, or have diabetes, high cholesterol or high triglycerides. Rapid weight loss and poor eating habits also may lead to NAFLD. But some people develop NAFLD even if they don’t have any risk factors.
4. Serious risks are linked to NAFLD. It may cause the liver to swell (steatohepatitis).Over time, a swollen liver may cause scarring (cirrhosis)—and may even lead to liver cancer or liver failure.
5. Strangely, NAFLD often has no symptoms. But when symptoms do occur, they may include fatigue, weakness, weight loss, loss of appetite, nausea, abdominal pain, spider-like blood vessels, yellowing of the skin and eyes (jaundice), itching, fluid build-up and swelling of the legs (edema) and abdomen (ascites), and mental confusion.
6. If there are no obvious symptoms, or if the symptoms may be due to any number of illnesses, how is NAFLD diagnosed? NAFLD is initially suspected if blood tests show high levels of liver enzymes. But, to be sure, other liver diseases are first ruled out through additional tests. Often, an ultrasound is used to confirm the NAFLD diagnosis.
7. How many kinds of treatments are there for NAFLD? How about none? In reality, that there are no medical treatments yet for NAFLD.
8. So if there are no known medical ways to cure NAFLD, can it be treated and, better yet, prevented? Yes, the good news is there are steps you can take to improve the health of your liver!
– Eat a healthy diet
– Lose weight if you’re overweight or obese
– Exercise regularly
– Control your diabetes
– Avoid or at least limit alcohol intake
– Only take medicines that you need, and carefully follow dosing recommendations
– Try to lower your cholesterol and triglycerides
9. The more severe form of NAFLD is called non-alcoholic steatohepatitis (NASH). Most people with NASH are between the ages of 40 and 60. It’s more common in women than in men. Like NAFLD, NASH often has no symptoms and people can have it for years before symptoms occur. NASH is one of the leading causes of cirrhosis in adults in the United States. Up to 25% of adults with NASH may have cirrhosis.
MORE INFORMATION IF YOU HAVE NAFLD OR NASH: Learning that you have nonalcoholic fatty liver disease, you’ll have a lot of questions. The American Liver Foundation is here to help.
What to know about nonalcoholic fatty liver disease
Last updated Thu 16 November 2017 Last updated Thu 16 Nov 2017
By Markus MacGill
Reviewed by Daniel Murrell, MD
Table of contents
1. Symptoms and stages
2. Causes and risk factors
3. Diagnosis
4. Treatment and management
5. Outlook
Nonalcoholic fatty liver disease happens when there is too much fat in the liver, or steatosis. The condition is also known as fatty liver.
There may be no symptoms in the early stages, but continued damage to the liver can lead to a more severe condition.
Some people with nonalcoholic fatty liver disease (NAFLD) will develop nonalcoholic steatohepatitis (NASH). This can develop into cirrhosis, or scarring and dysfunction of the liver.
Fatty liver is often related to obesity, high blood pressure, diabetes, and high cholesterol. NAFLD or NASH is not due to high alcohol consumption.
Around 10 to 46 percent of people in the United States have fatty liver but no inflammation or damage. Between 3 and 12 percent have NASH. NAFLD is the most common cause of liver disease in western countries.
Fatty liver can also occur during pregnancy, and cirrhosis can result from alcohol-related liver disease, but NAFLD is considered a separate diagnosis and doctors manage it differently.
Fast facts about fatty liver disease
• Nonalcoholic fatty liver disease (NAFLD) can occur if too much fat builds up in the liver.
• Many people have a fatty liver with no symptoms, but, in some cases, it can progress to a more serious condition.
• The exact cause is unknown, but obesity appears to be a risk factor.
• Following a healthy, balanced diet that is low in sugar and trans fats may help prevent or even reverse the condition.
• People with any type of liver disease should avoid alcohol or consume only very small amounts.
Symptoms and stages
Fatty liver disease often occurs with obesity, diabetes, and chronic kidney disease.
The liver is important for removing toxins from the body. If it does not work properly, various symptoms can arise.
If the body produces too much fat, or if the fat is not properly metabolized, it can build up in the liver.
If too much fat builds up in the liver, this can cause fatty liver. If fat continues to accumulate, this can lead, in some cases, to NASH and eventually cirrhosis and liver failure.
Fatty liver
At a threshold level, more than 5 to 10 percent of the liver weight is fat.
If more fat than this builds up in the liver, this is known as NAFLD, or simple fatty liver. It is not healthy, but it not necessarily severe enough to cause any problems, and the person will not usually notice any symptoms.
Most people with simple fatty liver will not know they have it. They may only find out after being tested for some other condition, or because other risk factors suggest that a test is a good idea.
Some 30 to 40 percent of adults in the U.S. have NAFLD. However, it is hard to establish an exact figure, as there is no one set of criteria for defining NAFLD.
For most people, the condition does not progress beyond this stage.
Nonalcoholic steatosis
If fat continues to build up and the liver becomes inflamed, NASH results. In the U.S., this affects between 3 and 12 percent of adults.
Around 75 percent of patients will have swelling in the liver, or hepatomegaly.
Symptoms may include:
• tiredness and fatigue, including muscle weakness and a lack of energy
• discomfort and possibly swelling in the upper abdomen
• weight loss
• low appetite
• nausea
The symptoms can be vague, and they can resemble those of a number of other problems. Tests may be carried out to eliminate other conditions.
Scientists are unsure why some people are more likely to develop NASH.
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Cirrhosis and liver failure
In time, 10 to 25 percent of people with NASH will develop scarring or fibrosis, also known as cirrhosis, and liver failure.
Symptoms include:
• tiredness and weakness
• nausea, vomiting, and diarrhea
• tarry stools
• abdominal swelling and pain
• a yellowing of the skin and eyes, known as jaundice
• confusion, difficulty focusing, memory loss, and hallucinations
• itchy skin
• bleeding and bruising easily
In severe cases, a liver transplant may be necessary.
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Causes and risk factors
A person with diabetes may have a higher risk of developing NAFLD.
Exactly how and why fatty liver develops is not clear. It occurs when the body produces too much fat, or when it cannot process fat properly.
Obesity is a clear risk factor. Around 70 percent of people with obesity have the condition, while 10 to 15 percent of people with a normal weight have it.
Regardless of their weight, a person with "deep" abdominal fat is more likely to have a fatty liver.
Other risk factors include:
• diabetes
• high cholesterol or high levels of fat in the blood
• high blood pressure
• high blood fats, or triglycerides
People with metabolic syndrome, a condition that involves a clustering of the risk factors mentioned above, are at higher risk.
Between 40 and 80 percent of people with type 2 diabetes have NAFLD.
Researchers have found "growing evidence" that NAFLD is linked to cardiovascular disease (CVD) and chronic kidney disease (CKD).
This means that those with NAFLD are also more likely to have diabetes and heart disease.
While there are clear links between obesity and fatty liver, some people develop NAFLD without obesity. This suggests that there are other factors.
These include:
• genetic influences
• smoking
• older age
• certain medications, such as steroids, and tamoxifen for cancer treatment
• rapid weight loss
• infections, such as hepatitis
• exposure to some toxins
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However, research suggests that "excess fat mass remains the most common background condition."
NAFLD is also the most common form of long-term liver disease in children. A review published in 2016 states that it affects between 10 and 20 percent of pediatric patients and 50 to 80 percent of children with obesity.
The scientists predict:
"Within the next 10 years, it is expected to become the leading cause of liver pathology, liver failure, and indication for liver transplantation in childhood and adolescence in the Western world."
Around 25 percent of pediatric patients with NASH will go on to develop cirrhosis within 10 years. Among those with obesity, the risk is higher.
Diagnosis
Early stage NAFLD does not usually produce symptoms, so diagnosis usually happens because of a routine blood test or because the person has the relevant risk factors.
If the doctor suspects NAFLD, they will feel the abdominal area, to find out if there is any swelling. They will ask about diet and lifestyle and any use of medications, supplements, and alcohol.
If tests suggest that there is damage to the liver or that the liver is swollen, the doctor must rule out other possible conditions, including alcoholic liver disease.
Imaging scans, such as ultrasound, CT, and MRI can show up fat in the liver.
A biopsy can confirm NAFLD, reveal the extent of the damage, and distinguish it from other types of liver problem. The doctor will use a needle to take a small tissue sample from the liver.
Treatment and management
There is no medical treatment for fatty liver, but lifestyle choices, such as achieving or maintaining a healthy weight, can reduce the risk and possibly reverse the damage, in the early stages.
Dietary tips
A diet that contains plenty of fresh food can help prevent liver damage.
To reduce the risk of NAFLD, it is best to:
• follow a balanced diet with moderate portions
• eat plenty of fruits and vegetables
• consume both proteins and carbohydrates, but limit fats and sugars
• reduce salt intake
• replace saturated and trans fats with monounsaturated and polyunsaturated fats
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) recommend the following dietary tips:
• replace trans fats and animal fats with olive oil, flaxseed oil, corn, soybean, and safflower oils
• eat oily fish instead of meat
• avoid foods that are high in simple sugars, such as fructose, found in sweetened drinks, sports drinks, and juices
• eat more foods that are low on the glycemic index (GI), such as fruits, vegetables, and whole grains
• eat fewer high-GI foods, such as white bread and white rice
• avoid alcohol or drink in moderation
Scientists are looking at whether vitamin E may help, but more research is needed. Those who ae considering taking supplements or herbal remedies should always speak to a doctor first.
A healthy diet and regular exercise will reduce the risk of a wide range of conditions, including diabetes and cardiovascular disease.
Outlook
For most people, a fatty liver does not usually cause serious problems. To some extent, the liver can repair itself, so switching to a healthy lifestyle will help.
Researchers warn that NAFLD is on the increase, and if obesity continues to rise, it could become "an epidemic."
Although simple fatty liver is not dangerous, without preventive action, some people will go on to develop NASH, and between 10 and 25 percent of adults with NASH will go on to develop cirrhosis within 10 years.
In the U.S., fatty liver disease is the third cause of liver transplant, and it is on the rise.
In addition, NAFLD is linked to CVD, CKD, and other conditions. Whether or not these can be reversed, even if the liver recovers, is not clear.
The best way to treat and prevent it is through healthful lifestyle choices, with a varied and balanced diet and regular exercise.
________________________________________________________________________________
https://www.nhs.uk/conditions/non-alcoholic-fatty-liver-disease/
Non-alcoholic fatty liver disease (NAFLD)
Non-alcoholic fatty liver disease (NAFLD) is the term for a range of conditions caused by a build-up of fat in the liver. It's usually seen in people who are overweight or obese.
A healthy liver should contain little or no fat. It's estimated up to 1 in every 3 people in the UK has early stages of NAFLD, where there are small amounts of fat in their liver.
Early-stage NAFLD does not usually cause any harm, but it can lead to serious liver damage, including cirrhosis, if it gets worse.
Having high levels of fat in your liver is also associated with an increased risk of serious health problems, such as diabetes, high blood pressure and kidney disease.
If you already have diabetes, NAFLD increases your chance of developing heart problems.
If detected and managed at an early stage, it's possible to stop NAFLD getting worse and reduce the amount of fat in your liver.
Stages of non-alcoholic fatty liver disease (NAFLD)
NAFLD develops in 4 main stages.
Most people will only ever develop the first stage, usually without realising it.
In a small number of cases, it can progress and eventually lead to liver damage if not detected and managed.
The main stages of NAFLD are:
1. simple fatty liver (steatosis) – a largely harmless build-up of fat in the liver cells that may only be diagnosed during tests carried out for another reason
2. non-alcoholic steatohepatitis (NASH) – a more serious form of NAFLD, where the liver has become inflamed; this is estimated to affect up to 5% of the UK population
3. fibrosis – where persistent inflammation causes scar tissue around the liver and nearby blood vessels, but the liver is still able to function normally
4. cirrhosis – the most severe stage, occurring after years of inflammation, where the liver shrinks and becomes scarred and lumpy; this damage is permanent and can lead to liver failure (where your liver stops working properly) and liver cancer
It can take years for fibrosis or cirrhosis to develop. It's important to make lifestyle changes to prevent the condition getting worse.
Am I at risk of non-alcoholic fatty liver disease (NAFLD)?
You're at an increased risk of NAFLD if you:
• are obese or overweight – particularly if you have a lot of fat around your waist (an "apple-like" body shape)
• have type 2 diabetes
• have high blood pressure
• have high cholesterol
• have metabolic syndrome (a combination of diabetes, high blood pressure and obesity)
• are over the age of 50
• smoke
But NAFLD has been diagnosed in people without any of these risk factors, including young children.
Although it's very similar to alcohol-related liver disease (ARLD), NAFLD is not caused by drinking too much alcohol.
Symptoms of non-alcoholic fatty liver disease (NAFLD)
There are not usually any symptoms of NAFLD in the early stages. You probably will not know you have it unless it's diagnosed during tests carried out for another reason.
Occasionally, people with NASH or fibrosis (more advanced stages of NAFLD) may experience:
• a dull or aching pain in the top right of the tummy (over the lower right side of the ribs)
• extreme tiredness
• unexplained weight loss
• weakness
If cirrhosis (the most advanced stage) develops, you can get more severe symptoms, such as yellowing of the skin and the whites of the eyes (jaundice), itchy skin, and swelling in the legs, ankles, feet or tummy (oedema).
How non-alcoholic fatty liver disease (NAFLD) is diagnosed
NAFLD is often diagnosed after a blood test called a liver function test produces an abnormal result and other liver conditions, such as hepatitis, are ruled out.
But blood tests do not always pick up NAFLD.
The condition may also be spotted during an ultrasound scan of your tummy.
This is a type of scan where sound waves are used to create an image of the inside of your body.
If you're diagnosed with NAFLD, further tests may be needed to determine which stage you have. This may involve a special blood test or having another type of ultrasound scan (Fibroscan).
Some people may also need a biopsy, where a small sample of liver tissue is taken using a needle so it can be analysed in a laboratory.
Children and young people with an increased risk of NAFLD (those with type 2 diabetes or metabolic syndrome) should have an ultrasound scan of their liver every 3 years.
Treatment for non-alcoholic fatty liver disease (NAFLD)
Most people with NAFLD will not develop any serious problems, but if you're diagnosed with the condition it's a good idea to take steps to stop it getting any worse.
There's currently no specific medication for NAFLD, but making healthy lifestyle choices can help.
Treatment also may be recommended for associated conditions (high blood pressure, diabetes and cholesterol) or complications.
You may be advised to have regular appointments with your doctor to check your liver function and look for signs of any new problems.
Medicines
There's not currently any medicine that can treat NAFLD, but various medicines can be useful in managing the problems associated with the condition.
For example, your doctor may recommend medicine to treat high blood pressure, treat high cholesterol, treat type 2 diabetes and treat obesity.
Liver transplant
If you develop severe cirrhosis and your liver stops working properly, you may need to be put on the waiting list for a liver transplant.
For adults, the average waiting time for a liver transplant is 135 days for transplants from recently deceased donors.
Or it may be possible to have a transplant using a section of liver removed from a living donor.
As the liver can regenerate itself, both the transplanted section and the remaining section of the donor's liver are able to regrow to a normal size.
Find out more about liver transplants
Things you can do if you have non-alcoholic fatty liver disease (NAFLD)
Adopting a healthy lifestyle is the main way of managing NAFLD.
For example, it can help to:
• lose weight – you should aim for a BMI of 18.5 to 24.9 (use the BMI calculator to work out your BMI); losing more than 10% of your weight can remove some fat from the liver and improve NASH if you have it
• eat a healthy diet – try to have a balanced diet high in fruits, vegetables, protein and carbohydrates, but low in fat, sugar and salt; eating smaller portions of food can help, too
• exercise regularly – aim to do at least 150 minutes of moderate-intensity activity, such as walking or cycling, a week; all types of exercise can help improve NAFLD, even if you do not lose weight
• stop smoking – if you smoke, stopping can help reduce your risk of problems such as heart attacks and strokes
NAFLD is not caused by alcohol, but drinking may make it worse. It's therefore advisable to cut down or stop drinking alcohol.
Page last reviewed: 19 November 2018
Next review due: 19 November 2021
Gi.org / Patients / Non-alcoholic Fatty Liver Disease (NAFLD)
Non-alcoholic Fatty Liver Disease (NAFLD)
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GI Health and Disease
Overview
Non-alcoholic fatty liver disease (NAFLD) is a very common disorder and refers to a group of conditions where there is accumulation of excess fat in the liver of people who drink little or no alcohol. The most common form of NAFLD is a non serious condition called fatty liver. In fatty liver, fat accumulates in the liver cells. Although having fat in the liver is not normal, by itself it probably does not damage the liver. A small group of people with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH). In NASH, fat accumulation is associated with liver cell inflammation and different degrees of scarring. NASH is a potentially serious condition that may lead to severe liver scarring and cirrhosis. Cirrhosis occurs when the liver sustains substantial damage, and the liver cells are gradually replaced by scar tissue (see figure), which results in the inability of the liver to work properly. Some patients who develop cirrhosis may eventually require a liver transplant (surgery to remove the damaged liver and replace it with a “new” liver).
Symptoms
The majority of individuals with NAFLD have no symptoms and a normal examination. Children may exhibit symptoms such as abdominal pain, which may be in the center or the right upper part of the abdomen, and sometimes fatigue. However, other causes of abdominal pain and fatigue should be considered. On physical examination the liver might be slightly enlarged and some children may have patchy, dark discoloration of the skin present (acanthosis nigricans) most commonly over the neck and the under arm area.
Causes of NAFLD/NASH
NAFLD is part of the metabolic syndrome characterized by diabetes, or pre-diabetes (insulin resistance), being overweight or obese, elevated blood lipids such as cholesterol and triglycerides, as well as high blood pressure. Not all patients have all the manifestations of the metabolic syndrome. Less is known about what causes NASH to develop. Researchers are focusing on several factors that may contribute to the development of NASH. These include:
Oxidative stress (imbalance between pro-oxidant and anti-oxidant chemicals that lead to liver cell damage)
Production and release of toxic inflammatory proteins (cytokines) by the patient’s own inflammatory cells, liver cells, or fat cells
Liver cell necrosis or death, called apoptosis
Adipose tissue (fat tissue) inflammation and infiltration by white blood cells
Gut microbiota (intestinal bacteria) which may play a role in liver inflammation
Risk Factors
NAFLD is a very common disorder affecting and may affect as many as one in three to one in five adults and around one in ten children in the United States. Obesity is thought to be the most common cause of fatty infiltration of the liver. Some experts estimate that about two thirds of obese adults and half of obese children may have fatty liver. About 2 to 5 percent of adult Americans and up to 20 percent of those who are obese may suffer from the more severe condition NASH. The number of children who have NASH is not known. The presence of type 2 diabetes and other conditions associated with insulin resistance, such as polycystic ovarian syndrome are know risk factors for the development of fatty liver and NASH.
Screening/Diagnosis
The diagnosis of NAFLD is usually first suspected in an overweight or obese person who is found to have mild elevations in their liver tests during a routine blood testing or incidentally detected on radiologic investigations such as abdominal ultrasound or CT scan. Some experts are now recommending that every obese child or adolescent should have these liver enzymes checked. However NAFLD can be present with normal liver blood tests. The diagnosis of NAFLD is confirmed by imaging studies, most commonly a liver ultrasound, showing accumulation of fat in the liver. Fat accumulation in the liver can also be caused by excess alcohol intake, certain medications, viral hepatitis, autoimmune liver disease, and metabolic or inherited liver disease. These need to be excluded as causes of fatty liver disease in order to confirm the diagnosis of NAFLD. Currently, the only reliable way of telling whether a person has NASH or simple fatty liver is by a liver biopsy. In this procedure, a small needle is inserted through the skin after local anesthesia is given to obtain a small piece of the liver for microscopic evaluation. NASH is diagnosed when examination of this piece of liver under the microscope shows fatty infiltration of the liver in addition to inflammation and different degrees of scarring. If only fat is present, then the diagnosis of simple fatty liver is made. The liver biopsy provides essential information regarding the degree of scarring within the liver, which would not be apparent on a blood test, ultrasound, or an x-ray alone. Liver biopsy rarely can be associated with serious risks including bleeding and patients should discuss the risks and benefits of the procedure with their physician.
Treatment of NAFLD/NASH
A few studies have suggested that weight loss may be associated with regression of fat within the liver. Therefore, the most important recommendations for people with fatty liver are to lose weight if they are overweight or obese, increase their physical activity, follow a balanced diet and avoid alcohol and unnecessary medications. New evidence suggests that Mediterranean diet (rich in monounsaturated fatty acids) may be more beneficial than low fat diet. Drinking coffee seems to decrease the risk of having fatty liver in large cohort studies. In patients with NASH, the more severe form of NAFLD, these same recommendations may be helpful. It is also important to control diabetes and treat elevated cholesterol levels when appropriate. Development of medications that could treat NAFD and NASH is an area of intense research. Recent trials in adult and children have shown that vitamin E (an anti-oxidant) could help improve NASH in non-diabetic patients. Strategies currently being evaluated by physicians and scientists to decrease the amount of fat/ inflammation in the liver include:
Weight reduction (diet + exercise, medications, surgery)
Lipid lowering medications
Insulin sensitizers (medications)
Decrease the amount of liver inflammation by administering anti-oxidant medications, anti-apoptotic medications and anti-cytokine medications
Author(s) and Publication Date(s)
Naim Alkhouri, MD, and Marsha H. Kay, MD, FACG, The Cleveland Clinic, Cleveland, OH – Updated December 2012.
Ariel E. Feldstein, MD, and Marsha H. Kay, MD, FACG, Cleveland Clinic Foundation, Cleveland, OH – Published January 2006.
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Non-Alcoholic Fatty Liver Disease & The Mediterranean Diet Advancing gastroenterology, improving patient care
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Risperidone
Last Update: June 4, 2018.
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OVERVIEW
Introduction
Risperidone is an atypical antipsychotic that is used widely in the treatment of mania and schizophrenia. Risperidone therapy is associated with serum aminotransferase elevations and in rare instances has been linked to clinically apparent acute liver injury.
Background
Risperidone (ris per' i done) is a benzisoxazole derivative which appears to act as a dopamine type 2 (D2) and serotonin (5-HT2) receptor antagonist. Risperidone is indicated for treatment of schizophrenia and as monotherapy or combination therapy for acute manic or mixed episodes of bipolar I disorder in adults. Risperidone is also used for management of irritability with autistic disorder in children and adolescents. Risperidone was approved for use in the United States in 1993 and it is still widely used. Risperidone is available as tablets of 0.25, 0.5, 1, 2, 3 and 4 mg generically and under the brand name of Risperdal. Oral solutions for pediatric use are available as are orally disintegrating tablets and formulations for parenteral administration. The typical initial dose in adults is 1 mg once or twice daily, with increase in dose to as high as 8 mg daily based upon indications, efficacy and tolerance. Common side effects include somnolence, fatigue, restlessness, dizziness, dry mouth, increased saliva, constipation, increased appetite and weight gain. Rare, but potentially severe adverse events include cerebrovascular events, tardive dyskinesia, neuroleptic malignant syndrome, orthostatic hypotension, suicidal ideation and behavior, seizures, diabetes and agranulocytosis.
Hepatotoxicity
Liver test abnormalities may occur in up to 30% of patients on long term therapy with risperidone, usually arising within the first 8 weeks of treatment. The ALT elevations are usually mild, transient and may resolve even with continuation of medication. Instances of more marked ALT and alkaline phosphatase elevations, with or without symptoms and with or without jaundice, have also been reported. The onset of injury typically occurs within a few days of starting risperidone and resolves rapidly with stopping. Instances of acute liver injury with jaundice arising several months and even years after starting risperidone have also been reported. The pattern of serum enzyme elevations is typically cholestatic, but cases with hepatocellular and mixed patterns have also been described. Immunoallergic manifestations (rash, fever, eosinophilia) are rare; a case of autoimmune hepatitis apparently triggered by risperidone therapy was been published, but most cases do not have autoimmune features.
Likelihood score: C (probable rare cause of clinically apparent liver injury).
Mechanism of Injury
The mechanism by which risperidone causes serum ALT elevations is not known. Risperidone is extensively metabolized by the cytochrome P450 system (CYP 2D6) to its active metabolite. Some instances of liver injury may be due to nonalcoholic fatty liver disease caused by weight gain that occurs in at least one-quarter of treated patients and can be as much as 30 kg, generally during the first 1 to 2 years of therapy. In large series, however, the minor ALT elevations that occur on therapy have not correlated well with weight gain.
Outcome and Management
The serum aminotransferase elevations that occur on risperidone therapy are usually self-limited and often do not require dose modification or discontinuation of therapy. No instances of acute liver failure or vanishing bile duct syndrome have been attributed to risperidone. A single case of autoimmune hepatitis due to risperidone has been published. There may be some cross reactivity to liver injury between risperidone and quetiapine, but usually not with clozapine and olanzapine.
Drug Class: Antipsychotic Agents, Atypicals
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PRODUCT INFORMATION
REPRESENTATIVE TRADE NAMES
Risperidone – Generic, Risperdal®
DRUG CLASS
Antipsychotic Agents
COMPLETE LABELING
Product labeling at DailyMed, National Library of Medicine, NIH
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CHEMICAL FORMULA AND STRUCTURE
DRUG CAS REGISTRY NUMBER MOLECULAR FORMULA STRUCTURE
Risperidone 106266-06-2
C23-H27-F-N4-O2
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ANNOTATED BIBLIOGRAPHY
References updated: 04 June 2018
• Meyer JM. Pharmacotherapy of psychosis and mania. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 417-56.
(Textbook of pharmacology and therapeutics).
• Benazzi F. Risperidone-induced hepatotoxicity. Pharmacopsychiatry 1998; 31: 241. [PubMed]
(25 year old woman treated with increasing doses of risperidone [to 6 mg/day] had 20 kg weight gain and fatigue; ALT rose from 13 [pre] to 277 U/L [month 4] without jaundice and fell to normal 1 month after stopping drug).
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].
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Olanzapine
Last Update: January 26, 2014.
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OVERVIEW
Introduction
Olanzapine is an atypical antipsychotic that is used currently in the treatment of schizophrenia and bipolar illness. Olanzapine is not infrequently associated with serum aminotransferase elevations during therapy and there have been rare instances of clinically apparent acute liver injury linked to its use.
Background
Olanzapine (oh lan' za peen) is a thienobenzodiazepine derivative which appears to act as a dopamine (D1-4) and serotonic (5-HT2A/2C and 5-HT6) receptor antagonist. Olanzapine was approved for use in schizophrenia in the United States in 1996 and continues to be used for this indication. Olanzapine is also used in mood disturbances of bipolar I disorder and in combination with other agents for treatment of resistant depression in adults. Olanzapine is available as tablets of 2.5, 5, 7.5, 10, 15 and 20 mg generically and under the brand name Zyprexa; formulations for parenteral use and orally disintegrating tablets are also available, as are fixed combinations with antidepressants such as fluoxetine (Symbyax and generics). A typical dose regimen is 5 to 20 mg daily, starting with a low dose and increasing cautiously. Common side effects include sedation, increased appetite, weight gain, constipation, orthostatic hypotension, dizziness, dry mouth, weakness and akathisia (restlessness).
Hepatotoxicity
Liver test abnormalities have been reported to occur in 10% to 50% of patients on long term therapy with olanzapine. These abnormalities are usually mild, asymptomatic and transient, and can reverse even with continuation of medication. In addition, instances of more marked elevations in serum aminotransferase levels and clinically apparent hepatitis with jaundice have been reported in patients taking olanzapine. The pattern of serum enzyme elevations has ranged from hepatocellular to mixed and even cholestatic. Allergic manifestations (rash, fever, eosinophilia) and autoimmune markers are uncommon. The time to onset of liver injury with olanzapine therapy has varied widely, from a few weeks to a year after starting. In all cases, the injury has resolved rapidly with drug discontinuation. Cases with a long latency and accompanied by significant weight gain may represent nonalcoholic fatty liver disease, rather than olanzapine hepatotoxicity.(zyprexa and olanzapine/thienobenzodiazepine)
Mechanism of Injury
The mechanism by which olanzapine causes serum aminotransferase elevations is not known. Some instances of ALT elevations occurring on olanzapine therapy may be due to nonalcoholic fatty liver disease caused by weight gain that occurs in at least one-quarter of treated patients generally during the first 1 to 2 years of therapy. Weight gain averages 1 kg/month and can be extreme (20 to 30 kg). Olanzapine has extensive hepatic metabolism, partially via the cytochrome P450 system, and some cases of clinically apparent hepatotoxicity may be due to production of a toxic intermediate of metabolism.
Outcome and Management
The serum aminotransferase elevations that occur on olanzapine therapy are usually self-limited and rarely require dose modification or discontinuation of therapy. No instances of acute liver failure, chronic liver disease or vanishing bile duct syndrome have been attributed to olanzapine. Switching to other atypical antipsychotics is occasionally, but not always associated with recurrence of hepatic injury.
Drug Class: Antipsychotic Agents, Atypicals
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CASE REPORT
Case 1. Acute liver injury due to olanzapine.
[Modified from: Domínguez-Jiménez JL, Puente-Gutiérrez JJ, Pelado-García EM, Cuesta-Cubillas D, García-Moreno AM. Liver toxicity due to olanzapine. Rev Esp Enferm Dig 2012; 104: 617-8. PubMed Citation]
A 47 year old patient with a history of paranoid schizophrenia developed jaundice 11 months after starting olanzapine (10 mg daily). She had a vague history of alcoholic liver disease. Laboratory test results showed a total bilirubin of 7.5 mg/dL, ALT 173 U/L and alkaline phosphatase of 178 U/L (Table). Olanzapine was stopped and haloperidol started in its place. Tests for viral hepatitis and autoantibodies were negative. Within 2 weeks, serum bilirubin levels had fallen and all test results returned to normal when she was seen 3 months later.
Key Points
Medication: Olanzapine
Pattern: Mixed (R=3.0)
Severity: 3+ (jaundice and hospitalization)
Recovery: 3 months
Other medications: None mentioned
Laboratory Values
Time After Starting Time After Stopping ALT (U/L) GGT (U/L) Bilirubin (mg/dL)
Other
11 months 0 173 178 7.5 Admission
2 weeks 775 181 2.7
12 months 6 weeks 79 161 0.6 Haloperidol
14 months 14 weeks 9 80 0.4
Normal Values <42 <130 <1.2
Comment
A brief case report with missing information but somewhat typical presentation of drug induced liver injury with a mixed hepatocellular-cholestatic pattern. Olanzapine is a common cause of transient serum aminotransferase elevations, but has rarely been implicated in cases of clinically apparent liver injury with jaundice.
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PRODUCT INFORMATION
REPRESENTATIVE TRADE NAMES
Olanzapine – Zyprexa®
DRUG CLASS
Antipsychotic Agents
COMPLETE LABELING
Product labeling at DailyMed, National Library of Medicine, NIH
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CHEMICAL FORMULA AND STRUCTURE
DRUG CAS REGISTRY NUMBER MOLECULAR FORMULA STRUCTURE
Olanzapine 132539-06-1
C17-H20-N4-S
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ANNOTATED BIBLIOGRAPHY
References updated: 26 January 2014
• Meyer JM. Pharmacotherapy of psychosis and mania. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman.s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 417-56.
(Textbook of pharmacology and therapeutics).
• Larry D, Ripault MP. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 443-62.
(Review of hepatotoxicity of psychiatric agents mentions that olanzapine has rarely been implicated in causing clinically apparent hepatic toxicity).
• Beasley CM, Tollefoson GD, Tran PV. Safety of olanzapine. J Clin Psychiatry 1997; 10: 7-13. [PubMed]
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Trazodone
Last Update: December 15, 2013.
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OVERVIEW
Introduction
Trazodone is a serotoninergic modulating antidepressant that is used in therapy of depression, aggressive behavior and panic disorder. Trazodone therapy can be associated with transient, usually asymptomatic elevations in serum aminotransferase levels and has been linked to rare instances of clinically apparent acute liver injury.
Background
Trazodone (traz' oh done) is a triazolopyridine derivative whose mechanism of action is believed to be inhibition of serotovcnin and norepinephrine reuptake, which results in increased levels and activity of these neurotransmitters. Trazodone was approved for use in major depressive disorder in the United States in 1981 and remains in wide use, with more than 15 million prescriptions being filled yearly. Trazodone is also used off-label for control of aggressive behavior and for panic disorder. Trazodone is available in tablets of 50, 75, 100, 150 and 300 mg in several generic forms. The recommended dosage for depression in adults is 150 in divided doses that can be increased in 50 mg amounts to a maximum of 600 mg daily. An extended release formulation is also available in 150 mg tablets (Oleptro) which is given once daily. Common side effects of trazodone are drowsiness, fatigue, dizziness, headache, dry mouth, blurred vision, nausea, decreased libido, increased appetite and weight gain.
Hepatotoxicity
Liver test abnormalities occur in a proportion of patients on trazodone, but elevations are usually modest and usually do not require dose modification or discontinuation. Rare instances of acute, clinically apparent episodes of liver injury with marked liver enzyme elevations with or without jaundice have been reported in patients on trazodone. The onset of injury is varies from a few days to 6 months and the pattern of serum enzyme elevations is usually hepatocellular, but mixed and cholestatic forms have also been described. Several cases have had immunoallergic features (rash, fever, eosinophilia), but these were not prominent. Autoimmune (autoantibodies) features are uncommon. Rare instances of acute liver failure and death from trazodone have been reported. Nefazodone, an antidepressant similar in structure and mechanism of action to trazodone, was approved for use in 1998, but is currently not commonly used because of multiple reports of acute hepatocellular injury, with a high mortality rate arising 2 weeks to 6 months after starting therapy.
Mechanism of Injury
The mechanism by which trazodone causes liver injury is not known. Trazodone is extensively metabolized by the liver, mainly via the cytochrome P450 system (CYP3A4), and hepatotoxicity may be mediated by toxic intermediates of its metabolism. Trazodone is susceptible to multiple drug-drug interactions.
Outcome and Management
The serum aminotransferase elevations that occur on trazodone therapy are usually self-limited and do not require dose modification or discontinuation of therapy. Rare instances of acute liver failure and chronic hepatitis have been attributed to trazodone therapy. Persons with intolerance to trazodone may have similar reactions to other antidepressants, and careful monitoring is warranted if other such agents are used.
Drug Class: Antidepressant Agents
Other Drugs in the Subclass: Nefazodone
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CASE REPORT
Case 1. Acute hepatitis due to trazodone.
[Modified from: Fernandes NF, Martin RR, Schenker S. Trazodone-induced hepatotoxicity: a case report with comments on drug-induced hepatotoxicity. Am J Gastroenterol 2000; 95: 532-5. PubMed Citation]
A 38 year old woman with rheumatoid arthritis developed itching followed by jaundice approximately 18 months after starting trazodone. She was also receiving prednisone (10 mg daily), methotrexate, hydroxychloroquine, nabumetone, propoxyphene, folate, birth control pills and alendronate, but had been on this regimen for many years. She had no history of liver disease or known risk behaviors for acquiring hepatitis and did not drink alcohol. On examination, she was jaundiced but had no rash, fever or signs of chronic liver disease. Laboratory results showed a bilirubin of 11.0 mg/dL with marked elevations in serum aminotransferase levels (Table). Her liver tests had been normal on routine testing several months previously. Tests for hepatitis A, B and C were negative as were autoantibodies. An abdominal ultrasound showed no evidence of biliary obstruction. A liver biopsy showed intrahepatic cholestasis, modest inflammation, and ballooning degeneration but no fat or fibrosis. Trazodone was stopped, and she began to improve rapidly. She was discharged from the hospital, but one week later restarted trazodone. After two days she had a return of her symptoms and jaundice. Within two weeks of stopping trazodone for the second time, she had no symptoms of liver disease and her liver tests were near-normal.
Key Points
Medication:
Trazodone
Pattern:
Hepatocellular (R=5.8)
Severity:
3+ (jaundice, hospitalization)
Latency:
Initially 18 months, with rechallenge 3 days
Recovery:
Within 1 month
Other medications:
Prednisone, methotrexate, hydroxychloroquine, nabumetone, propoxyphene, folate, birth control pills, alendrolate.
Laboratory Values
Time After Starting
Time After Stopping
ALT
(U/L)
Alk P
(U/L)
Bilirubin
(mg/dL)
Other
12 months
13
64
0.8
Routine testing
Onset of pruritus and jaundice 18 months after starting trazodone
18 months
0
1092
206
11.0
3 days
786
191
8.7
Discharged from hospital and shortly after restarted trazodone
10 (0) days
1476
259
10.3
15 (5) days
466
202
3.3
19 (9) days
146
154
2.4
23 (13) days
55
108
1.6
30 (20) days
43
93
1.4
51 (41) days
17
71
0.9
Normal Values
<48
<125
<1.2
• Numbers in parentheses indicate the days after stopping the second time.
Comment
Trazodone has been linked to rare cases of hepatic injury. The onset of injury is generally after several months and is typically hepatocellular, although cases with a shorter latency and with a cholestatic pattern of serum enzyme elevations have been described. In this case, the long latency period was atypical of trazodone and not characteristic of drug induced liver disease in general. Furthermore, the patient was taking other potentially hepatotoxic drugs (methotrexate, nabumetone). What makes the likelihood of trazodone being the cause of the injury was the inadvertent rechallenge that led to a rapid worsening of the injury. Furthermore, the liver biopsy showed no evidence of methotrexate injury and had changes that were considered typical of drug induced liver injury. The hepatic injury rapidly resolved with stopping therapy.
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PRODUCT INFORMATION
REPRESENTATIVE TRADE NAMES
Trazodone – Desyrel®
DRUG CLASS
Antidepressant Agents
COMPLETE LABELING
Product labeling at DailyMed, National Library of Medicine, NIH
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CHEMICAL FORMULA AND STRUCTURE
DRUG
CAS REGISTRY NUMBER
MOLECULAR FORMULA
STRUCTURE
Trazodone
19794-93-5
C19-H22-Cl-N5-O
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ANNOTATED BIBLIOGRAPHY
References updated:15 December 2013
Zimmerman HJ. Antidepressants. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 493-8.
(Expert review of hepatotoxicity published in 1999; trazodone is listed as potentially causing either cholestatic or hepatocellular injury having been implicated in at least 6 cases, including instances of chronic hepatitis).
Larrey D, Ripault MP. Hepatotoxicity of psychotropic drugs and drugs of abuse. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 443-62.
(Review of hepatotoxicity of antidepressants mentions that trazodone can cause immunoallergic liver injury with a latency of a few days to 1.5 year and with variable patterns of enzyme elevations).
O'Donnell JM, Shelton RC. Pharmacotherapy of depression and anxiety disorders. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological b
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