What are the Signs and Symptoms of Hepatotoxicity?

Hepatotoxicity from drugs is sometimes difficult to diagnose because the signs and symptoms vary so much from one drug to the next and symptoms often resemble other commonly diagnosed illnesses. This can present a problem for health professionals because drug induced liver damage is the number one reason that approved drugs are pulled from the market. Nurses can aid in the early detection of hepatotoxicity by knowing some of the signs and by being proactive in patient diagnosis of the drug intake in order to discontinue the drug as soon as possible. Discontinuing the drug can reduce the severity of hepatotoxicity.

The signs and symptoms of drug induced hepatotoxicity can be as mild as a change in liver function tests presenting no viable symptoms in the patient, to full blown hepatotoxicity and liver failure. The earlier the problem is diagnosed, the greater chance of survival for the patient. There is usually an increase in the liver function tests when hepatotoxicity is present. The problem with this is that many drugs on the market increase the AST and ALT levels in patients, knowing when the increase is substantial enough to have to discontinue the drug is essential. A drug should be discontinued if the ALT levels are elevated more than two times the normal limit while the AST levels remain within normal limits or slightly elevated. An increase in bilirubin levels will follow the increase in ALT levels as the condition worsens.

Many drugs present the symptoms of rash, fever and an increase in eosinophils in the blood when ALT levels are increased (this happens in about 30% of cases). The symptoms usually occur within 4 weeks of starting a drug and can seize 8 weeks out.

Although a difference of signs and symptoms can vary so much from one drug to the next, and one patient to the next some common signs associated with drug induced hepatotoxicity include:

Non-specific symptoms-- ones that may not directly pinpoint the problem.

• fatigue
• weakness
• vague abdominal pain
• loss of appetite

Signs and symptoms specific for hepatotoxicity--

• Jaundice
• Itching
• Easily bruising

When the liver is severely damaged cirrhosis can occur. Symptoms of cirrhosis include--

• Edema (often times in the legs)
• Mental confusion
• Kidney failure
• Gastrointestinal bleeding
• Vulnerability to bacteria infections

Some drugs may cause hepatitis (inflammation of liver cells that can result in the death of the cells. Symptoms of hepatitis include-

• Loss of appetite
• Nausea
• Vomiting
• Fever
• Weakness
• Fatigue
• Abdominal pain

Hepatotoxicity caused by the intake of commonly used drugs can be difficult to diagnose due to the vast number of symptoms the patient may experience. That is why it is extremely important for a nurse to get a thorough medical history report from every patient outlining the drugs, herbs, vitamins and over the counter medications that they are consuming. The treatment for each different hepatotoxicity case can vary as well but the first and best solution is to discontinue the drug that is causing the liver damage. Often times this will eliminate the symptoms but there are times where the damage is too extensive or that an antidote to a particular drug may be administered. Treatment is then varied on an individual basis.

Sources:

http://www.medicinenet.com/drug_induced_liver_disease/article.htm

http://emedicine.medscape.com/article/169814-overview

OTC Pain Relievers-The hidden Danger

What is an NSAID?
NSAID stands for Non-steroidal Anti-inflammatory Drugs, which include commonly, used over-the-counter drugs like aspirin, ibuprofen and naproxen. These are drugs that people use everyday for common issues such as headaches, arthritis, cramps, or even as daily therapy for heart attack and stroke prevention.

What’s in a name? Know what’s in the Medications you take!
How do you know if you’re using an NSAID? Here is a list of the most common seen on over-the-counter shelves:
Aspirin (two brand names: Bayer, St. Joseph)
Ibuprofen (two brand names: Advil, Motrin)
Ketoprofen (one brand name: Orudis KT)
Naproxen (one brand name: Aleve)

Side Effects
Common side effects for these types of drugs are: nausea, vomiting, diarrhea, constipation, rash, headache, etc. However, the most serious side effects are:
Kidney failure
LIVER FAILURE
Ulcers
Prolonged bleeding after injury or surgery.

Who is at risk?
When used as directed or as prescribed by a doctor, these drugs are safe. Hepatotoxicity is uncommon, but persons with cirrhosis and advanced liver disease should avoid NSAIDs since the can worsen liver function. Also, persons taking other hepatotoxic drugs, persons with autoimmune disease should consult there healthcare professional before using NSAIDs. Your risk of hepatotoxicity with NSAIDs is increased when taken with other drugs that affect the liver, so understanding if NSAIDs are compatible with your medication is essential before using. Alcohol use is also a factor, if you have 3 or more alcoholic drinks a day, you should not take NSAIDs.

Importance of Communication
Many people may not think to list the commonly used drugs when talking with there healthcare professional, as they may not use these products everyday. Nevertheless, it’s important to ask or mention that you take Advil, Aleve or Bayer Aspirin for minor aches and pains when speaking with your healthcare professional to avoid any dangerous drug interactions and increased risk to your health and liver.

A Thought to Take Away
Diclofenac, and particularly sulindac, (both NSAIDs) are reported to be more commonly associated with hepatotoxicity

Some products contain both acetaminophen and aspirin (brand names: Excedrin Extra Strength, Excedrin Migraine, Vanquish), which could increase your risk.

Resources for You
http://www.medicinenet.com/nonsteroidal_antiinflammatory_drugs/article.htm
http://www.wonderdrug.com/index.html
http://familydoctor.org/online/famdocen/home/otc-center/otc-medicines/862.printerview.html
http://www.nlm.nih.gov/medlineplus/painrelievers.html
http://www.fda.gov/CDER/drug/infopage/ibuprofen/adult.htm
http://www.medicinenet.com/drug_induced_liver_disease/page8.htm
http://qjmed.oxfordjournals.org/cgi/content/full/96/11/787

Herbal Hepatotoxicity

Herbal supplements are being used more and more frequently due to media hype and to some of the great benefits they have been shown to provide. They are also a nice alternative to individuals looking to self medicate, or to save on health care costs. There seems to be a misconception to the general public that herbs are somehow safer than other drugs because they are natural. While some herbs may provide beneficial outcomes, they can become dangerous by themselves or in combination with other pharmaceuticals since they are not as tightly mandated by the FDA as other drugs are. The public should make themselves aware of potential drug reactions when using herbal supplements in order to protect themselves from possible complications such as hepatotoxicity. Nurses also need to become aware of possible drug/herb reactions in order to teach patients about the potential hazards of self medicating. Patients should always give their physicians a full list of herbal supplements they are taking as a first line of defense against complications and nurses should remember to ask details about herbal supplements when getting a medical history report because many people do not think of the herbs they consume as "medications" that they are taking.

One example of a possibly deadly combination of herbal supplements and medication that can cause hepatotoxicity is acetaminophen in combination with the herbs Echinacia and kava or the herbs that have salicylate (willow and meadowsweet). Echinacia is used for a variety of medicinal purposes such as burns, urinary tract infections, colon cancer and many others so it is used by a large number of Americans who are looking for a way to self medicate. Although it has many beneficial side effects, it's use with acetaminophen can prove to be fatal. There have been no real experimental studies to make this evidence concrete yet health care professionals should be aware of the growing trend of this drug/herb reaction. Kava also is used for a number of different purposes such as anxiety, muscles spasms and depression but also has the same potential for hepatotoxicity as does Echinacia when used in combination with acetaminophen or even alone. There has been a report in the United States of a young woman who required a liver transplant after using Kava. Willow and meadowsweet should also be monitored for their potential hepatotoxicity effects.

Green tea extract is a common over the counter herbal supplement used for weight loss purposes and has also been shown to create hepatotoxicity in humans.

While it is apparent that herbal supplements do provide some benefits to people, they should be taken with caution as we are still learning about possible side effects of hepatotoxicity when some are used alone or in combination with other common medications such as acetaminophen.





Green tea extract (Green Lite): suspected association with hepatotoxicity. (2007). Canadian Adverse Reaction Newsletter, Retrieved March 29, 2009, from CINAHL Plus with Full Text database.

Abebe, W. (2002, December). Herbal medication: potential for adverse interactions with analgesic drugs. Journal of Clinical Pharmacy & Therapeutics, 27(6), 391-401. Retrieved March 29, 2009, from CINAHL Plus with Full Text database.

Complications from Alcohol-Induced Liver Disease

For most people, one drink a day will not cause alcohol-induced liver damage. It is when that limit is exceeded and constantly abused that leads to disease. It is important for the public to know the safe level of intake and to be aware of the harm that drinking can cause to our liver. This means that women can have one drink a day and men can have two. It may be alarming to hear but excessive alcohol consumption is the most important cause of illness and death from liver disease in the United States.

How our liver works: When we consume alcohol our liver breaks it down so we can excrete it from our body. When we intake more than our liver can handle, an imbalance occurs and therefore our liver can not break down our proteins, fats, and carbohydrates like normal.

Alcohol consumption can cause diseases like alcoholic hepatitis, cirrhosis, and fatty liver.

Alcoholic hepatitis is inflammation of the liver and 35% of heavy drinkers develop it. Symptoms include: vomiting, fever, jaundice, loss of appetite, nausea, and abdominal pain and tenderness. You can reverse alcoholic hepatitis if you stop drinking.

Alcoholic cirrhosis is the most severe type of these three diseases. Cirrhosis means that the liver has replaced normal, healthy liver tissue with scar tissue. About 10-20% of heavy drinkers develop cirrhosis. Symptoms are same as alcoholic hepatitis. However, it is not reversible. Cirrhosis can stabilize if you stop drinking.

Fatty liver occurs when our liver has a build up of fat cells. The only symptom is discomfort in you upper abdomen. Fatty liver happens with everyone who heavily drinks but will improve after you stop drinking.

Complications of severe alcohol-induced liver disease you need to know:

• Accumulation of fluid in the abdomen

• Bleeding from veins in the esophagus

• Enlarged spleen

• High blood pressure in the liver

• Changes in mental function, and coma

• Kidney failure

• Liver cancer

What does this all mean??

We have to take care of our liver. If you don't, complications can be life-threatening. Therefore, follow the recommended intake of alcohol. And most importantly, if you do have alcohol-induced liver disease, STOP DRINKING!

http://pubs.niaaa.nih.gov/publications/aa19.htm http://www.liverfoundation.org/education/info/alcohol/

THE MOST COMMON CAUSE OF ACUTE LIVER FAILURE: TYLENOL

Tylenol (acetaminophen) may seem harmless to many people, but when taken in excess it can lead to damaging results, maybe even death. The exact mechanism of action of Tylenol is unknown. However, we do know that it elevates the pain threshold and acts as a pain and fever reducer. Tylenol related hepatotoxicity can be very common because it is an ingredient found in many prescribed and over-the-counter drugs. It is used to treat a variety of issues such as:

Muscle aches
Headaches
Back pain
Colds
Fever

There is no set “level” of Tylenol that will cause toxicity because the drug affects everyone differently. So, to avoid hepatotoxicity: TYLENOL MUST BE TAKEN AS DIRECTED. Early signs of this condition would include nausea, vomiting, anorexia, and abdominal pain, and usually appear within 24 hours of toxicity. If you know that you have taken more than the recommended dose and you experience any of these symptoms, contact your physician immediately! Chronic symptoms will take a little longer to appear and may include GI bleeding and mental changes. If left untreated, hepatotoxicity may result in death. Alcohol taken in addition to Tylenol will increase the risk of hepatotoxicity. Some medications that contain acetaminophen:

Anacin-3
Percocet
Liquiprin
Panadol
Tempra

Tylenol is a useful and effective drug that must be taken seriously. Some important facts include:

The FDA recommends that children under 4 years old should not be given Tylenol.
Home treatment will not cure Tylenol related hepatotoxicity. Immediate hospital treatment is a MUST.

If medical treatment is received within 8 hours of toxicity, recovery will most likely occur.
Tylenol should not be used for more than 10 days.
The dose for a child is based on age and weight.
Tylenol can be used during pregnancy when taken as directed by a physician.

About 500 deaths per year are due to overdoses of acetaminophen.

Tylenol-induced liver toxicity is the most common form of acute liver failure observed in the United States today.

The dosage of Tylenol for children will be different than for that of adults. You must be careful when giving children Tylenol.

http://www.tylenol.com/

http://www.nlm.nih.gov/medlineplus/ency/article/002598.htm

http://www.medicinenet.com/acetaminophen/artical.htm

http://www.merk.com/mmpe/sec21/ch326/ch326c.html

http://www.migraines.org/treatment/protylnl.htm

http://www.aasld.org/yourliver/Pages/acetaminophen.aspx

STEROIDS CAN CAUSE LIVER DAMAGE

Although the non-medical use of anabolic steroids is illegal, it is becoming more and more common. Anabolic steroids are synthetic derivatives of testosterone, the male sex hormone. They help in the development of muscles because they retain the body’s intake of dietary protein. This is what grabs the attention of many people, especially athletes. The use of anabolic steroids can improve both the physical appearance and athletic performance of those who take them. There are two types of steroids: those that can be injected and those that can be taken orally. Some side effects of steroid abuse include:

Agression
Acne
Prostate enlargement in males
Stunted growth
Muscular dystrophy
Blood clotting changes
Birth defects
And…
LIVER DAMAGE

One of the long term side effects of steroids abuse is severe liver damage, especially in oral steroids. This is because most everything you ingest orally must eventually filter through your liver. The chemicals in anabolic steroids have the ability to damage liver cells, decreasing their ability to breakdown wastes and excrete them from the body. The use of steroids can also cause tumors, which can lead to many severe complications.
During the beginning of steroid-induced hepatotoxicity, jaundice is very common. Jaundice involves the yellow discoloration of eyes and skin due to the accumulation of bile in the blood. Bile is a yellow or green substance secreted by the liver that helps in absorption and digestion.
Steroids in the news:

http://www.nytimes.com/2007/11/16/sports/baseball/16bonds.html
http://www.usdoj.gov/dea/pubs/pressrel/pr121505.html
http://www.nytimes.com/2005/01/14/sports/baseball/14baseball.html
http://www.dallasnews.com/s/dws/img/03-05/030305asteroids.pdf
http://health.usnews.com/usnews/health/healthday/071213/report-finds-widespread-steroid-use-in-baseball.htm

Interesting facts about steroids:
There are more than 100 types of anabolic steroids.
Steroid abuse among adolescents is on the rise.
Most people would probably assume that the only steroid users are men. However, the Rimrock Foundation states that: steroid use is growing most rapidly among young women.
When taken by adolescents, steroids can prematurely halt growth.

http://espn.go.com/special/s/drugsandsports/steroids.html
http://www.nida.nih.gov/Infofacts/Steroids.html
http://www.usdoj.gov/dea/concern/steroids.html
http://www.articlesbase.com/supplements-and-vitamins-articles/anabolic-steroid-side-effects-36049.html
http://www.rimrock.org/resources/steroids.shtml#extent

Strattera

Strattera
http://www.strattera.com/index.jsp

Strattera is an FDA approved drug for the treatment of ADHD (Attention Deficit Hyperactivity Disorder). This drug is often used as a second line, which means it is given to patients who are not responding to the normal first-line medications prescribed.

What sets it apart from other ADHD drugs? Strattera is not a stimulant, which reduces the risk that it will be abused or given to someone it’s not prescribed for. This also means it can be used for patients who are not responding to stimulant-type ADHD treatments.

Recent news released this March, announces Pharmac has approved funding for this new type of drug, making it the first non-stimulant ADHD medication to receive funding of this kind. With this news and the excitement over reduced addictive properties, we may see an increase of Heathcare Professional using this medication when they suspect misuse of other ADHD prescriptions.

http://www.nzdoctor.co.nz/news?article=c10ca00d-f471-45c8-9287-2429c8478cc5

In 2005 the FDA instructed Eli Lilly (the company that produces Strattera) to add a warning to the product that it can cause liver damage in both adults and children, which could lead to liver failure.

http://www.youtube.com/watch?v=wVAVo8e-kOY

Increased risked of liver damage is given to persons taking other drugs known to induce hepatotoxicity.

https://www.changehealthcare.com/rx_brands/drug_interactions/13796

Antiepileptic Drug-Induced Liver Injury

Liver injury is commonly observed in patients that are prescribed anti-epileptic (AED) medications. These drugs may lead to acute liver failure. Sometimes patients may asymptomatic.
A hypersensitivity to any of these AED medications may lead to Hepatotoxicity:
Phenytoin~ Can occur in less than 1% of patients and may result in liver death.
Carbamazepine~ Patients with reactions are immediately taken off the drug with
no further reactions.
Valproate~ There is two types: Valproate therapy-dose-related and idiosyncratic, which is usually irreversible causing serve Hepatotoxicity.
Valporic Acid~ Hepatotoxicity is rare in the acute overdose setting.

Patients who need a greater dosage of their AED medication will have their baseline liver enzymes checked and will be monitored while they are taking their AEDs.

http://www.theannals.com/cgi/content/abstract/23/1/13
http://www.medscape.com/viewarticle/417938
http://www.ncbi.nlm.nih.gov/pubmed/3939742
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1432377