Thursday, October 2, 2008

Diabetes and Hepatotoxicity

Did you know that diabetes is the 6th most common cause of death in the United States according to the CDC? Yeah, diabetes is a serious problem! But, if you think being diagnosed with type I or type II diabetes was worse enough, several drugs associated with diabetes can cause hepatotoxicity. Lets take a closer look!

Of the many drugs on the market today, the following 4 groups of drugs have been known to cause liver toxicity.

As you can see, Troglitazone was pulled off the market in 2000. This particular medication caused many deaths. “When considered as a whole, the pre-marketing clinical data and post-marketing safety data from Rezulin as compared to similar, alternative diabetes drugs indicate that continued use of Rezulin now poses an unacceptable risk to patients," said Dr. Janet Woodcock, Director of FDA's Center for Drug Evaluation and Research. But not only does troglitazone cause severe liver damage, any TZD does! Look at this tid bit of info, http://www.med.umich.edu/diabetes/profs/Page%206%20-%20Oral%20Medications-TZD.pdf. They help insulin work better in muscle and fat; they lower insulin resistance and have a small effect on slowing the release of sugar from the liver. Here are some side effects that might be helpful to you.

  • Headache
  • Muscle aches
  • Swelling or fluid retention

Looking back at the chart, a large class of liver damaging drugs is the sulfonylureas. They work by stimulating the beta cell in the pancreas to release more insulin.This class of drug is dangerous because they are extensively metabolized in the liver. In fact, Glimepiride (Amaryl), has an extremely high protein binding percentage of 99.5%! You can see how this might affect a patient, especially is they are taking other medications too. A common side effect of sulfonylurea drugs are low blood sugar, so one must need a lot of carbohydrates in their diet. Look at some of these other side effect as well.


  • skin reactions
  • stomach upset
  • increased sensitivity to the sun
  • brownish urine

Now let’s look at alpha-glucose inhibitors. These are more commonly known as starch blockers. The actions of these drugs are to slow or block the breakdown of starches and certain sugars in the intestines. This slows the rise in blood sugar levels following a meal, so this medication should be taken with food. "Although acarbose-induced hepatotoxicity appears to be uncommon, diabetic patients receiving long-term acarbose therapy should be closely monitored for this adverse effect." “patients and clinicians should recognize that dietary management is the principal consideration in the management of diabetes mellitus and that antidiabetic therapy is used only as an adjunct to, and not as a substitute for or a convenient means to avoid, proper dietary management.” So no matter what, proper nutrition is the key to this drug! If one does not begin to properly take care of themselves, or if a nurse doesn’t realize what the patient is eating, they may witness these signs and symptoms.

  • Intestinal gas
  • Diarrhea
  • Abdominal pain

http://www.cdc.gov/nchs/FASTATS/lcod.htm
http://www.uspharmacist.com/index.asp?show=article&page=8_2281.htm
http://www.fda.gov/bbs/topics/NEWS/NEW00721.html
http://www.med.umich.edu/diabetes/profs/Page%206%20-%20Oral%20Medications-TZD.pdf http://www.pharmgkb.org/do/serve?objId=PA10390&objCls=Drug#tabview=tab1
http://www.pharmgkb.org/do/serve?objId=PA449761&objCls=Drug#tabview=tab1
http://www.med.umich.edu/1libr/aha/umoral.htm
http://www.ashp.org/mngrphs/AHFS/a396015.htm

Watching out for Tylenol and other pain meds!



ACETAMINOPHEN

INTRODUCTION


Pain relievers and fever reducers have always been the most frequently used medications and, we can count on Acetaminophen, commonly known as Tylenol as the most well known over the counter analgesic. It is also doctors’ first choice of drugs for pain relief, and is considered safe if used as recommended. But, overdose and toxicity can be a real big problem when it comes to Tylenol because of the fact that many people have misconceptions that this over the counter drug is very safe and harmless. Acetaminophen overdose can lead to serious consequences like liver damage and death.

HISTORY:

According to the FDA, more than 200 million persons take acetaminophen each year and about 200 of these die of serious liver damage due to toxicity. Statistics in the medscape website state that Americans take over 8 billion pills (tablets or capsules) of Tylenol each year and, the National Hospital Discharge Survey (NHDS) indicates that there are an average of 26,256 hospitalizations per year related to acetaminophen overdoses.
Acetaminophen was to blame for 28 percent of the liver poisonings in 1998, but it caused 51 percent of cases in 2003. The Food and Drug Administration has been more concerned about with the liver risk, warning two years ago that more than 56,000 emergency-room visits a year are because of acetaminophen overdoses and that 100 people die annually from unintentionally taking too much. It has placed regulations on companies to place labels about acetaminophen content in all medications.


PRINCIPLE OF OPERATION:

Acetaminophen overdose occurs when one consumes more than 4000mg of acetaminophen in one day. So, simply taking 2 extra strength Tylenol tablets, 500mg each, 4 times a day can cause acetaminophen toxocity. People accidentally overdose themselves when combining it with other medications that contain acetaminophen in them. Heavy drinkers who mix acetaminophen with alcohol are at high risk for acetaminophen toxicity because combining acetaminophen with more than three alcoholic drinks a day can lead to toxicity.There are many ways one can overdose acetaminophen unintentionally like taking acetaminophen in combination with more than 3 alcoholic drinks a day, varying dosing schedules and formulations of recommended drug in infants and children and combining it with other medications that contain acetaminophen as one of their drugs like: Anacin-3, Liquiprin, Panadol, Percocet, Decongestants, Tempra, and various other cold/flu medications


Signs and Symptoms of toxicity:
Initial symptoms may be flu-like, so doctors may not prompt for overdose treatment.
Sudden fever
Nausea and vomiting
Abdominal pain
Diarrhea
Irritability
Jaundice
Sweating
Coma
Convulsions.
But symptoms do not occur until 12 or more hours after acetaminophen consumption.
Require immediate assistance to the emergency, within 8 hours.


Prognosis:
If not treated, overdose can lead to LIVER FAILURE and DEATH.

Three clinical stages (phases) of acetaminophen-induced liver injury have been described.

During the first phase, that is, the initial 12 to 24 hours after the consumption, the person may feel very nauseated and vomiting. The second Phase which is next 24 to 48 hrs, the person feels normally well considering the fact that he/she threw-up most of the medication. The next 48 to 72 hrs which is the third phase, liver blood test abnormalities begin to appear. Most concerning would be high levels of AST AND ALT, which is very common with this type of liver injury. If the damage is bad enough and there is a sever acid build up in the blood, kidney damage or coma then death is almost certain and in these cases liver transplant is mostly suggested.


SAFETY ADVICE:

  • Read all the drug labels and add up all your acetaminophen, avoiding more than 4,000 milligrams a day (more than 200 other drugs contain acetaminophen as one of their ingredients.)


  • For extra safety, avoid alcohol when you are taking Tylenol or any other acetaminophen containing medications.


  • Do not switch formulations or vary dosing schedules with different strengths of liquid drugs.


  • Always follow the dosage recommendations and, ask the health care provider if you have any doubts.


  • Make sure to report early if you notice any signs and symptoms of toxicity or, if you accidentally overdose on any medications.

“www.druginfo,com.” < http://www.druginfonet.com/acetamin.htm.>
“www.medline Plus”
<http://www.nlm.nih.gov/medlineplus/ency/article/002598.htm>
http://www.medscape.com”./ < http://www.medscape.com/viewarticle/557074
http://www.medicinenet.com/tylenol_liver_damage/page6.htm

Alcohol and Complications


Most people have heard that drinking alcohol is bad for the liver. While not a drug used for healing individuals (even though they may think it helps!), alcohol remains a dangerous, if not the MOST dangerous commonly used drug.

The liver has a tough job- it has to filter out toxins, break down byproducts, and process many drugs! While it's trying to perform this huge function, alcohol consumption adds to the burden!
Look at this picture. Can you believe that drinking can do this massive damage! People tend to miss or ignore the dangers of drinking. Anything you put in the body has to be processed and broken down, or REMOVED. Alcohol must be broken down in the liver!

Alcohol is a predominant cause of liver problems, from fatty liver disease to liver fibrosis to cirrhosis.

Excessive drinking is bad. Period. But many different complications come about when you mix alcohol with other substances. For example, people who drink heavily and take acetaminophen may see a compound effect in the liver. That means your liver is getting hurt even more! My point with this post is to show that 1) alcohol itself is bad on the liver and 2) alcohol in COMBINATION with other drugs can add up to way more damage.

Did you know that daily drinkers have at more of a risk that binge drinkers? People who have a problem with drinking, or have lived ten or twenty years with constant damage to their livers have an increased risk for cirrhosis of the liver.

If you think you have a problem with drinking, check out
this site. While abstinence and portion control are major factors in preventive health, there has been substantial research on other supplements and drugs that actually help the liver. Milk thistle, PPC, and other antioxidant 'good guys' come to mind. While my team does not condone alcohol abuse, the treatments outlined in that site may offer some options to people who are trying to improve or save their liver function!


Herbal Hepatotoxicity


A lot of people do not know the harm in herbal medicines. Did you know that hepatotoxicity from herbal medicines is a growing worldwide problem and has been clearly linked to cases of acute liver failure? I didn’t either. I have always thought herbals were safe and natural but that is just what the media persuades us to think. The main concern with taking herbals is that many people choose to not share this critical information with their doctor and therefore drug-herb toxicity can occur. So be smart and always inform your doctor what you are using. Hepatotoxicity from herbals is somewhat rare but it is a growing problem and people need to be aware of the potential problems. In Asia herbals are more frequently used, and therefore responsible for the condition.

Kava and Spirulina, Teucrium, Setarud, Sweet clover, Poke root, Green tea leaf, and Buckthorn are just a few of herbals that have been known to cause hepatotoxicity.


Here are some helpful websites to check out if you would like to read more information about herbal hepatotoxicity.

http://www.natap.org/2005/HCV/101105_01.htm
http://content.herbalgram.org/ogdenpress/herbalgram/articleview.asp?a=2783

Wednesday, October 1, 2008

HEPATOTOXICITY inducing DRUGS

[A*K*A DILT (drug-induced liver toxicity)]

Here are a few drugs that you may have encountered or are familiar with.

Just a reminder :Too much of something can be dangerous or too little of something can also be dangerous!!

Drugs that may cause ACUTE DOSE-DEPENDENT LIVER DAMAGE
(resembling acute viral hepatitis)
acetaminophen
salicylates (doses over 2 grams daily)
Drugs that may cause ACUTE DOSE-INDEPENDENT LIVER DAMAGE
(resembling acute viral hepatitis)

acebutolol
atenolol
ketoconazole
naproxen
sulfonamides
ethambutol
penicillins
tricyclic antidepressants
ibuprofen
and more.....

Drugs that may cause ACUTE FATTY INFILTRATION OF THE LIVER

adrenocortical steroids
phenothiazines
sulfonamides
antithyroid drugs
phenytoin
tetracyclines
isoniazid
salicylates
valproic acid
methotrexate

Drugs that may cause CHOLESTATIC JAUNDICE
erythromycin
amoxicillin/clavulanate
diazepam
gold
cephalosporins
oral contraceptives
methyltestosterone
tricyclic antidepressants
nonsteroidal
anti-inflammatory drugs
and more......

Drugs that may cause LIVER GRANULOMAS
(chronic inflammatory nodules)
gold
phenytoin
aspirin
carbamazepine
isoniazid
sulfonamides
penicillin
and more.....
Drugs that may cause CHRONIC LIVER DISEASE
acetaminophen (chronic use, large doses)
dantrolene
methyldopa
isoniazid
nitrofurantoin


Drugs that may cause LIVER CIRRHOSIS or FIBROSIS
(scarring)
methotrexate
terbinafine HCI (Lamisil, Sporanox)

nicotinic acid

Drugs that may cause CHRONIC CHOLESTASIS
(resembling primary biliary cirrhosis)
chlorpromazine/valproic acid (combination)
imipramine
thiabendazole
phenothiazines
tolbutamide
chlorpropamide/erythro-mycin (combination)
phenytoin
Drugs that may cause LIVER TUMORS
(benign and malignant)

anabolic steroids
oral contraceptives
thorotrast
danazol
testosterone


Drugs that may cause DAMAGE TO LIVER BLOOD VESSELS

anabolic steroids
vitamin A (excessive doses)

carmustine
mitomycin

cyclophosphamide/cyclo-sporine (combination)
oral contraceptives

and more.....




*Some drugs are listed in more than one category